Validation and shortcomings of the most common mouse model of chronic rhinosinusitis with nasal polyps

BACKGROUND: Chronic rhinosinusitis (CRS) is a highly prevalent airway disease worldwide. Whereas eosinophilic CRS with nasal polyps (eCRSwNP) represents its most severe phenotype, pathogenic mechanisms remain poorly understood despite a wide spectrum of in vitro and in vivo experimental models. A mouse model of experimental ovalbumin (OVA)-induced airway allergy with coadministration of Staphylococcus aureus enterotoxin B (SEB) has been widely used to study eosinophilic eCRSwNP. This study revisits the features of this model and its suitability for studying eCRS. METHODOLOGY: We implemented the most used eCRSwNP mouse model based on OVA+SEB intranasal challenges. Readouts including inflammatory features by (immuno)histology of the sinonasal epithelium (NP formation, eosinophils, epithelial and basement membrane thickness, fibrosis, goblet cells, Charcot-Leyden crystals (CLC)-like, tight junctions) and IgE production by enzyme-linked immunosorbent assay (ELISA), were compared to features of the corresponding human disease. RESULTS: The OVA+SEB model induced eosinophilic inflammation of upper and lower airways, with epithelial and basement membrane thickening, goblet cell hyperplasia and subepithelial fibrosis in the sinuses, along increased IgE production. Except local IgE in nasal lavage (NL), which was only increased in OVA+SEB group, all other features did not differ between OVA and OVA+SEB groups. Macro- or microscopic NP were not detected. CONCLUSIONS: With the notable exception of local IgE production, the addition of SEB did not induce additional inflammatory or structural change in the sinuses from mice exposed to and challenged with OVA. This model might represent a model for severe upper airway allergy rather than a specific model of human eCRSwNP.

Anaphylaxis: Mediators, Biomarkers, and Microenvironments.

The life-threatening nature of anaphylactic reactions has increased interest in discovering new biomarkers that could improve diagnosis and prevention. However, the diverse nature of the clinical features and the etiology and pathogenesis of anaphylaxis hinder the identification of valuable molecular indicators of disease. Most studies on anaphylaxis focus on the immune system. Anaphylactic reactions are characterized primarily by IgE-mediated activation of mast cells and basophils and release of mediators. Determination of serum tryptase levels is the main in vitro test used to confirm the reaction, although there are no biomarkers that can predict it. Nevertheless, recent research has postulated that alternative pathways, cell types, and systems are involved. Consequently, various molecular products have been explored and considered potential biomarkers, although none of them are yet used in clinical practice. The products that are altered in patients with anaphylaxis include vasoactive agents, proteases, proteoglycans, lipids, interleukins, cytokines, products of the complement-contact and coagulation systems, circulating proteins, extracellular vesicles, microRNAs, and metabolites. The recognition of biological processes and molecular pathways affecting the microenvironments involved in anaphylaxis will considerably improve clinical practice and the identification of better molecular markers. We offer a broad review of the various mediators described in anaphylaxis, consider their usefulness as potential biomarkers of this pathological event, and examine their role in the molecular basis of the reaction.

Microbialites show a distinct cyanobacterial phylogenetic structure and functional redundancy in Bacalar lagoon and Cenote Azul sinkhole, Yucatan Peninsula, Mexico.

Cyanobacterial components of microbialites from two geographically close systems, the Bacalar lagoon (BL) and the Cenote Azul sinkhole (CA) in Quintana Roo, Mexico, were characterized. BL and CA systems were studied along a longitudinal gradient (north to south) and a depth gradient (5-30 m), respectively. Microscopic observations, 16S rRNA amplicon sequencing, and shotgun metagenomics were used to characterize Cyanobacteria. Both systems showed similar metabolic/functional profiles but harbored completely different cyanobacterial taxa. BL was dominated by Nostocales, including a population of previously undescribed Chakia sp., while CA was dominated by an unknown taxon of Chroococcales, comprising 70% of relative abundance through all depths. Interestingly, cyanobacterial assemblages in microbialites exhibited phylogenetic overdispersion in most of the BL sites, while CA sites exhibited phylogenetic clustering, these differences were attributed to depth/light conditions and possibly different times of geological formation for BL and CA systems.

First detection of SARS-CoV-2 variant B.1.1.529 (Omicron) in Ecuador.

The National Institute of Research and Public Health reported the first local record of the Omicron variant detected in Ecuador. A fully vaccinated subject returned from South Africa with a negative RT-PCR. We present the cumulative frequency of the variants in Ecuador and a phylogenetic analysis of this new Omicron.

Anaphylaxis: Mediators, Biomarkers, and Microenvironments

The life-threatening nature of anaphylactic reactions has increased interest in discovering new biomarkers that could improve diagnosis and prevention. However, the diverse nature of the clinical features and the etiology and pathogenesis of anaphylaxis hinder the identification of valuable molecular indicators of disease. Most studies on anaphylaxis focus on the immune system. Anaphylactic reactions are characterized primarily by IgE-mediated activation of mast cells and basophils and release of mediators. Determination of serum tryptase levels is the main in vitro test used to confirm the reaction, although there are no biomarkers that can predict it. Nevertheless, recent research has postulated that alternative pathways, cell types, and systems are involved. Consequently, various molecular products have been explored and considered potential biomarkers, although none of them are yet used in clinical practice. The products that are altered in patients with anaphylaxis include vasoactive agents, proteases, proteoglycans, lipids, interleukins, cytokines, products of the complement-contact and coagulation systems, circulating proteins, extracellular vesicles, microRNAs, and metabolites. The recognition of biological processes and molecular pathways affecting the microenvironments involved in anaphylaxis will considerably improve clinical practice and the identification of better molecular markers. We offer a broad review of the various mediators described in anaphylaxis, consider their usefulness as potential biomarkers of this pathological event, and examine their role in the molecular basis of the reaction (AU)

Response of RAW 264.7 and J774A.1 macrophages to particles and nanoparticles of a mesoporous bioactive glass: A comparative study.

Mesoporous bioactive glasses (MBGs) are bioceramics designed to induce bone tissue regeneration and very useful materials with the ability to act as drug delivery systems. MBGs can be implanted in contact with bone tissue in different ways, as particulate material, in 3D scaffolds or as nanospheres. In this work, we assessed the effects of particles of mesoporous bioactive glass MBG-75S and mesoporous nanospheres NanoMBG-75S on RAW 264.7 and J774A.1 macrophages, which present different sensitivity and are considered as ideal models for the study of innate immune response. After evaluating several cellular parameters (morphology, size, complexity, proliferation, cell cycle and intracellular content of reactive oxygen species), the action of MBG-75S particles and NanoMBG-75S on the polarization of these macrophages towards the pro-inflammatory (M1) or reparative (M2) phenotype was determined by the expression of specific M1 (CD80) and M2 (CD206, CD163) markers. We previously measured the adsorption of albumin and fibrinogen on MBG-75S particles and the production of pro-inflammatory cytokines as TNF-α and IL-6 by macrophages in response to these particles. This comparative study demonstrates that particles of mesoporous bioactive glass MBG-75S and mesoporous nanospheres NanoMBG-75S allow the appropriated development and function of RAW 264.7 and J774A.1 macrophages and do not induce polarization towards the M1 pro-inflammatory phenotype. Therefore, considering that these mesoporous biomaterials offer the possibility of loading drugs into their pores, the results obtained indicate their high potential for use as drug-delivery systems in bone repair and osteoporosis treatments without triggering an adverse inflammatory response.

Perspectiva de mujeres mexicanas sobre lactancia materna asociada al cambio del modelo cultural / Mexican women breastfeeding perspective associated with the cultural model change / Perspectiva das mulheres mexicanas sobre a aleitamento materno associado ao câmbio do modelo cultural

RESUMEN Introducción: La lactancia materna es importante para el desarrollo saludable del recién nacido. A pesar de sus beneficios, la decisión de no amamantar se incrementa entre las mujeres de la Ciudad de México debido a la influencia de la globalización y del cambio de modelo cultural moderno al posmoderno. Objetivo: Comprender la perspectiva de las mujeres mexicanas sobre el ofrecer y abandonar la lactancia materna asociada al cambio del modelo cultural. Metodología: Se llevó a cabo un estudio cualitativo con enfoque exploratorio, descriptivo: participaron 12 diadas (madre-hijo lactante), residentes de la Ciudad de México, quienes ofrecieron y abandonaron la lactancia materna. Se realizaron entrevistas en profundidad. Los datos obtenidos se grabaron, transcribieron y codificaron para garantizar el rigor de la investigación. Resultados: Se reconocieron dos categorías que sustentan el por qué las mujeres brindan o abandonan la lactancia materna, vistas desde el modelo cultural. En el modelo moderno las mujeres consideran una convicción sentida el ofrecer lactancia materna, reconocen los beneficios de dicho alimento para su hijo; mientras que, en el modelo posmoderno, las mujeres tienen una convicción negativa de amamantar. Conclusiones: Al asociar la lactancia materna con modelos culturales, en el moderno se considera la lactancia como un deber, mientras que en el posmoderno un derecho. Al encontrarnos en transición entre ambos modelos, las mujeres están influenciadas por discursos y prácticas culturales que en ocasiones son contradictorias. Comprender estos fenómenos permitirá diseñar estrategias efectivas desde la enfermería para fomentar la lactancia materna.

ABSTRACT Introduction: Breastfeeding is an important activity for the healthy development of the newborn, but nevertheless the benefits, the decision of women to avoid breastfeeding is becoming more prevalent in Mexico City. Perhaps this decision is the result of the influence of the globalization process with its cultural model change from the modern to the postmodern. Objective: To better understand the perspective of Mexican women regarding breastfeeding or not breastfeeding and the relationship of this decision with the cultural model change. Methodology: This is a qualitative, descriptive, and exploratory study on 12 mothers in Mexico City, who decided to terminate breastfeeding their babies. In-Depth interviews were conducted. The gathered data were recorded, transcribed, and coded in order to procure rigour of research. Results: Two categories related to the cultural model that reflect why women breastfeed or not were identified. In the modern model, women consider breastfeeding as a solid conviction which has benefits to their babies, while in the postmodern model, women tend to have a negative image of breastfeeding. Conclusions: From the association of breastfeeding with the cultural models, in the modern model, women consider breastfeeding as a duty, while in the postmodern one, women consider breastfeeding as a right. Currently, we are in a transition between these possibly contradicting cultural models. Therefore, better understanding these phenomena can help nursing professionals design strategies which can foster a healthy decision on breastfeeding.

RESUMO Introdução: O aleitamento materno é importante para o desenvolvimento saudável do recém-nascido. Apesar de seus benefícios, a decisão de não amamentar aumenta entre as mulheres da Cidade do México devido à influência da globalização e da mudança do modelo cultural moderno para o pós-moderno. Objetivo: Compreender a perspectiva das mulheres mexicanas sobre a oferta e o abandono do aleitamento materno associado à mudança do modelo cultural. Metodologia: Realizou-se um estudo qualitativo com abordagem exploratória e descritiva: participaram 12 díades (mãe-filho em lactação), residentes na Cidade do México, que ofereceram e abandonaram a amamentação. Entrevistas em profundidade foram realizadas. Os dados obtidos foram gravados, transcritos e codificados para garantir o rigor da pesquisa. Resultados: Foram reconhecidas duas categorias que sustentam porque as mulheres oferecem ou abandonam a amamentação, visto a partir do modelo cultural. No modelo moderno, as mulheres consideram o fato da amamentação uma convicção sincera, reconhecem os benefícios dessa alimentação para o filho; enquanto no modelo pós-moderno as mulheres têm uma convicção negativa de amamentar. Conclusões: Ao associar o aleitamento materno aos modelos culturais, no moderno amamentar é considerado um dever, enquanto na pós-moderna um direito. Ao encontrarmos em transição entre os dois modelos, as mulheres são influenciadas por discursos e práticas culturais que às vezes são contraditórios. Compreender esses fenômenos permitirá o desenho de estratégias de enfermagem eficazes para promover o aleitamento materno.

Prevención de extubación no programada en pacientes con ventilación mecánica invasiva / Prevention of non-programed tube-extractions among patients with invasive mechanical ventilation / Prevenção de extubação não programada em pacientes com ventilação mecânica invasiva

Introducción Las extubaciones no programadas constituyen un evento adverso frecuente y de alto impacto, en la mayoría de los casos la presencia de este evento se relaciona con factores como la vía aérea, ventilación mecánica, nivel de sedación, estado y actividad mental del paciente, entre otros también prevenibles. Por ello, se establece un indicador de calidad para prevenir extubaciones no programadas en pacientes con ventilación mecánica invasiva y tubo endotraqueal. Objetivo Realizar la validación de contenido del indicador y describir el nivel de cumplimiento para la prevención de extubaciones no programadas en pacientes con ventilación mecánica invasiva en un hospital de tercer nivel de la Ciudad de México, con el propósito de dar a conocer nuevos aportes en materia de prevención. Metodología Estudio cuantitativo y descriptivo, con una muestra no probabilística a conveniencia conformada por 46 procesos observados durante el turno matutino en tres servicios de hospitalización. Resultados Se encontró que el 96% de los procesos observados arrojaron un nivel de prevención medio para las extubaciones no programadas. Al evaluar el índice de eficiencia global del indicador, se obtuvo un resultado del 59.8%, lo cual muestra que las acciones para prevenir una extubación no programada se cumplen en un porcentaje muy bajo. Conclusiones Se detectó una omisión de funciones por los profesionales de la salud en la prevención de este evento, por lo que se propuso un plan de mejora para la institución con el propósito de disminuir los eventos relacionados a las extubaciones.

Introduction Non-programed extubation, constitute a frequent high impact adverse event involving issues on the airway, mechanical ventilation, sedation level, patient´s mental activity, among others. Because of this, a quality indicator is established in order to help prevent non-programed extubation among patients with invasive mechanical ventilation and endotracheal tube. Objective To perform a validation of content on this indicator in a third level hospital of the City of Mexico, and describe the level of adherence to its components in order to prevent non-programed extubation among patients with invasive mechanical ventilation and endotracheal tube, and share the resulting contributions in the area of prevention. Methodology This is a quantitative and descriptive study with a non-probabilistic sample by convenience of 46 processes which were observed during the morning shifts in three hospitalization services. Results It was found that 96% of the processes observed showed an insufficient level of prevention of non-programed extubation. The assessment of the efficiency related to indicator´s components showed a 59.8% compliance, suggesting that the actions to prevent non-programed extubation are not sufficiently taken. Conclusions An important related omission by health professionals regarding the prevention of this kind of adverse events was detected, and thus, a corresponding improvement plan for the institution was proposed.

Introdução As extubaçãos não programadas constituem um evento adverso frequente e de alto impacto, na maioria dos casos, a presença deste evento relaciona-se com fatores como a via aérea, ventilação mecânica, nível de sedação, estado e atividade mental do paciente, entre outros, também preveníeis. Por isso, estabelece-se um indicador de qualidade para prevenir extubaçãos não programadas em pacientes com ventilação mecânica invasiva e tubo endotraqueal. Objetivo Realizar a validação de conteúdo do indicador e descrever o nível de cumprimento para a prevenção de extubaçãos não programadas em pacientes com ventilação mecânica invasiva em um hospital de terceiro nível da Cidade do México, com o propósito de dar a conhecer novas contribuições em matéria de prevenção. Metodologia Estudo quantitativo e descritivo, com uma amostra não probabilística a conveniência, conformada por 46 processos observados durante o turno matutino em três serviços de hospitalização. Resultados Encontrou-se que o 96% dos processos observados revelaram um nível de prevenção médio para as extubaçãos não programadas. Avaliando o índice de eficiência global do indicador, obteve-se um resultado do 59.8%, o qual mostra que as ações para prevenir uma extubação não programada cumprem-se em uma porcentagem muito baixa. Conclusões Identificou-se uma omissão de funções pelos profissionais da saúde na prevenção deste evento, pelo que se propus um plano de melhora para a instituição com o propósito de diminuir os eventos relacionados às extubaçãos.

Lactancia materna desde el modelo cultural: perspectivas de mujeres de la Ciudad de México / Breastfeeding from the cultural model: perspective of women in Mexico City

Introducción: El abandono de la LME tiene importantes implicaciones en la salud y en la sociedad. Se estima que durante los primeros 6 meses de vida a nivel mundial el 34.8% de lactantes recibe LME, en América latina el 40% mientras que México tiene el más bajo índice, con una disminución en los últimos 6 años del 22.3% al 14.4%, a pesar de los esfuerzos y programas diseñados para revertirlo. La lactancia materna está bajo la influencia de la globalización y del cambio del modelo cultural moderno al posmoderno, lo cual influye directamente en sus prácticas, generado un impacto negativo en niños, madres, familias y sociedad en general. Objetivos: Comprender la perspectiva de las mujeres de la Ciudad de México sobre lactancia materna desde el modelo cultural. Metodología: El estudio fue cualitativo exploratorio, los informantes fueron mujeres que ofrecieron y negaron LME de la Ciudad de México entre 15 y 49 años con bebés menores de 2 años. La selección de la muestra fue intencional. Utilizamos como técnicas: entrevistas a profundidad, guías de observación y se aplicó un análisis categorial al material recolectado en la observación. Resultados: En el modelo cultural moderno la LME se considera un deber encontramos 3 tipos de mujeres: la que se encuentra en un entorno favorable y tiene profunda convicción en dar LME (tipo 1); la que tiene profunda convicción de dar LME y lo hace a pesar de encontrarse en un entorno vinculado al modelo postmoderno el cual presionan para no hacerlo (tipo 2) y la que tiene profunda convicción de no hacerlo pero lo hace debido a la presión de su entorno vinculado al modelo moderno(tipo 3). Vinculadas al entorno cultural postmoderno asociado a no brindar LME por ser un derecho encontramos 3 tipos de mujeres: la que tiene profunda convicción de no dar LME porque es su derecho y se encuentra en un entorno favorable a esta práctica (tipo 4); la que tiene profunda convicción de no dar LME y no la brinda, a pesar de encontrarse en un entorno ligado al modelo moderno que presiona a brindarlo (tipo 5)la que tiene la profunda convicción de hacerlo, pero no lo hace debido a la presión de su entorno vinculado al modelo postmoderno(tipo 6). Conclusiones: Asociando la LME con modelos culturales concluimos que en el modelo cultural moderno se considera la LME como un deber, mientras que en el postmoderno un derecho. Al encontrarnos en transición entre un modelo y otro, las mujeres están influenciadas por discursos y prácticas culturales que en ocasiones son contradictorias. Comprender estos fenómenos nos permitirá diseñar estrategias efectivas desde la enfermería para aumentar la LME.

Introduction: The abandonment of the exclusive breastfeeding (EB) has important implications for health and society. It is estimated that during the first 6 months of life worldwide, 34.8% of infants receive EB, in Latin America 40%, while Mexico has the lowest index, with a decrease in the last 6 years of 22.3% to 14.4%, despite efforts and programs designed to reverse it. The Breastfeeding is under the influence of globalization and the change from the modern to the postmodern cultural model, which directly influence their practices, generating negative impact on children, mothers, families and society in general. Objective: Understand the perspective of women in Mexico City on breastfeeding from the cultural model. Methods: The study was qualitative exploratory, the informants were women who offered and denied EB in Mexico City with ages between 15 and 49 years old with infants under 2 years. The sample was selected intentional. We used as techniques: depth interviews, observation guides and a categorical analysis was applied to the material collected in the observation. Results: In the modern cultural model where the EB is considered as a duty we find 3 types of women: the woman who is in a favorable environment and has a deep conviction to give EB (type 1); the woman who has deep conviction to give EB and she does it in spite of being in an environment linked to the postmodern model which presses for not to do it (type 2) and the woman who has the deep conviction to do it, but she don't give due to the pressure of its environment linked to the postmodern model (type 3). Linked to the cultural postmodern environment associated to not provide EB by being a right we find 3 types of women: the woman who is deeply convinced for not give EB because it is their right and she is in an environment favorable to this practice (type 4); The woman who has deep conviction of not give EB and does not offer it, in spite of being in an environment linked to the modern model that presses to offer it (type 5) and the woman who has deep conviction for don't do it, but she do it due to the pressure of its environment linked to the modern model (type 6). Conclusions: Associating the EB with cultural models we conclude that in the modern cultural model the EB is considered as a duty, while in the postmodern one as a right. As we find ourselves in the transition from one model to another, women are influenced by cultural discourses and practices that are sometimes contradictory. Understand these phenomena will allow us design effective strategies from a point of view of the nursing to increase the EB.

Tratamiento microquirúrgico de la neuralgia trigeminal en mayores de 70 años, estudio de eficacia y seguridad / Microsurgical treatment of trigeminal neuralgia in patients older than 70 years: An efficacy and safety study

Introducción: El incremento de la incidencia de la neuralgia del trigémino (NT) con la edad junto con el creciente envejecimiento poblacional obligan a valorar las opciones de tratamiento quirúrgico de la NT refractaria en pacientes mayores. Métodos: Se revisó retrospectivamente una serie consecutiva de pacientes mayores de 70 años con NT refractaria tratados mediante descompresión microvascular (DMV) entre 1997 y 2015. Los resultados según la escala de dolor facial del Barrow Neurological Institute (BNI score), así como las complicaciones quirúrgicas, se compararon con los de pacientes menores de 70 años operados durante el mismo período. Resultados: Fueron intervenidos 40 pacientes mayores de 70 años (media 74,8 años). A los 34 meses de seguimiento medio, el 73% de los pacientes presentaba ausencia completa del dolor sin medicación (BNI I) y el 85% tenía un control del dolor sin o con medicación (BNI I-III). Comparando con 85 pacientes menores de 70 años intervenidos en el mismo período no se demostró una asociación significativa entre la edad y la obtención de un control del dolor (BNI I-III), pero sí entre la edad mayor de 70 años y la desaparición del dolor (BNI I; p = 0,03). La estancia media en mayores de 70 años fue significativamente mayor (p = 0,04), aunque la tasa de complicaciones posquirúrgicas fue similar a la de los pacientes más jóvenes. Conclusiones: Las personas de edad avanzada con NT refractaria pueden beneficiarse de un tratamiento mediante DMV con una probabilidad de éxito y unos riesgos equiparables a los de personas más jóvenes (AU)

Introduction: The increasing incidence of trigeminal neuralgia (TN) with age together with population ageing call for reexamination of surgical treatment options for refractory TN in elderly patients. Methods: Retrospective review of a consecutive series of patients older than 70 who underwent microvascular decompression (MVD) for refractory TN between 1997 and 2015. Outcomes based on the Barrow Neurological Institute pain intensity score (BNI score) and surgical complications were compared to those of patients younger than 70 undergoing MVD in the same period. Results: Forty patients older than 70 (mean = 74.8 years) underwent interventions. At a mean follow-up time of 34 months, 73% of the patients presented complete absence of pain without medication (BNI I) and 85% had good pain control with or without medication (BNI I-III). A comparison of these patients with the 85 patients younger than 70 treated surgically during the same period did not find a significant association between age and achievement of pain control (BNI I-II). However, there was a significant association between age older than 70 and complete pain relief (BNI I; P=.03). The mean hospital stay in patients over 70 was also significantly longer (P=.04), although the postsurgical complication rate was similar to that in younger patients. Conclusions: Elderly patients with refractory TN may benefit from treatment with MVD and the probability of success and surgical risk are comparable to those in younger patients (AU)

Revascularización mediante aterectomía direccional en isquemia crítica de miembro inferior. Primera experiencia ecuatoriana / Revascularization through directional atherectomy in critical inferior limb ischemia: first Ecuadorian experience

Introducción: La aterectomía direccional es una técnica mínimamente invasiva que puede ser utilizada para evitar la amputación de los miembros inferiores en caso de isquemia crítica. Caso: Se presenta la primera experiencia en Ecuador, realizada en una paciente diabética e insuficiente renal. Este procedimiento logró repermeabilizar el segmento femoropoplíteo izquierdo con éxito. Discusión: La aterectomía direccional es una alternativa eficaz, mínimamente invasiva, para evitar la amputación de miembros inferiores en pacientes isquemia crítica y múltiples comorbilidades. Palabras clave: Aterectomía, isquemia, miembro inferior, pie diabético.

Introduction: Directional atherectomy is a minimally invasive technique that can be used to avoid lower limb amputation due to critical ischemia. Case report: This is the first experience in Ecuador, using this technique in a diabetic patient with chronic renal failure. The procedure achieved successful recanalization of the left femoropopliteal artery. Discusion: Directional atherectomy seems to be an alternative to avoid limb amputation in patients with critical ischemia and several comorbidities.

Microsurgical treatment of trigeminal neuralgia in patients older than 70 years: An efficacy and safety study. / Tratamiento microquirúrgico de la neuralgia trigeminal en mayores de 70 años, estudio de eficacia y seguridad.

INTRODUCTION: The increasing incidence of trigeminal neuralgia (TN) with age together with population ageing call for reexamination of surgical treatment options for refractory TN in elderly patients. METHODS: Retrospective review of a consecutive series of patients older than 70 who underwent microvascular decompression (MVD) for refractory TN between 1997 and 2015. Outcomes based on the Barrow Neurological Institute pain intensity score (BNI score) and surgical complications were compared to those of patients younger than 70 undergoing MVD in the same period. RESULTS: Forty patients older than 70 (mean = 74.8 years) underwent interventions. At a mean follow-up time of 34 months, 73% of the patients presented complete absence of pain without medication (BNI I) and 85% had good pain control with or without medication (BNI I-III). A comparison of these patients with the 85 patients younger than 70 treated surgically during the same period did not find a significant association between age and achievement of pain control (BNI I-II). However, there was a significant association between age older than 70 and complete pain relief (BNI I; P=.03). The mean hospital stay in patients over 70 was also significantly longer (P=.04), although the postsurgical complication rate was similar to that in younger patients. CONCLUSIONS: Elderly patients with refractory TN may benefit from treatment with MVD and the probability of success and surgical risk are comparable to those in younger patients.

MicroRNA changes through Müller glia dedifferentiation and early/late rod photoreceptor differentiation.

Cell-type determination is a complex process driven by the combinatorial effect of extrinsic signals and the expression of transcription factors and regulatory genes. MicroRNAs (miRNAs) are non-coding RNAs that, generally, inhibit the expression of target genes and have been involved, among other processes, in cell identity acquisition. To search for candidate miRNAs putatively involved in mice rod photoreceptor and Müller glia (MG) identity, we compared miRNA expression profiles between late-stage retinal progenitor cells (RPCs), CD73-immunopositive (CD73+) rods and postnatal MG. We found a close similarity between RPCs and CD73+ miRNA expression profiles but a divergence between CD73+ and MG miRNA signatures. We validated preferentially expressed miRNAs in the CD73+ subpopulation (miR-182, 183, 124a, 9(∗), 181c and 301b(∗)) or MG (miR-143, 145, 214, 199a-5p, 199b(∗), and 29a). Taking advantage of the unique capacity of MG to dedifferentiate into progenitor-like cells that can be differentiated to a rod phenotype in response to external cues, we evaluated changes of selected miRNAs in MG-derived progenitors (MGDP) during neuronal differentiation. We found decreased levels of miR-143 and 145, but increased levels of miR-29a in MGDP. In MGDPs committed to early neuronal lineages we found increased levels of miR-124a and upregulation of miR-124a, 9(∗) and 181c during MGDP acquisition of rod phenotypes. Furthermore, we demonstrated that ectopic miR-124 expression is sufficient to enhance early neuronal commitment of MGDP. Our data reveal a dynamic regulation of miRNAs in MGDP through early and late neuronal commitment and miRNAs that could be potential targets to exploit the silent neuronal differentiation capacity of MG in mammals.

Glutamate-induced epigenetic and morphological changes allow rat Müller cell dedifferentiation but not further acquisition of a photoreceptor phenotype.

Müller cells are not only the main glial cell type in the retina but also latent progenitor/stem cells, which in pathological conditions can transdifferentiate to a neuronal phenotype and regenerate the neurons lost in a mature retina. Several signal transduction pathways can induce the dedifferentiation of mature Müller cells to a progenitor-like state, including that stimulated by glutamate. However, the precise molecular mechanisms by which terminally differentiated cells are initially primed to acquire multipotency remain unclear. In the present study, we have characterized early genetic and epigenetic events that occur immediately after glutamate-induced dedifferentiation of fully differentiated Müller cells is initiated. Using Müller cell-enriched cultures from postnatal rats, we demonstrate that glutamate triggers a rapid dedifferentiation response characterized by changes in cell morphology coupled to the induction of progenitor cell marker gene expression (e.g., nestin, lin28 and sox2) within 1h. Dedifferentiation involved the activation of N-methyl-d-aspartate and type II metabotropic glutamate receptors, as well as global DNA demethylation (evident through the decrease in methyl-CpG-binding protein 2 immunoreactivity) and an increase in gadd45-ß gene expression; although, early progenitor gene expression was only partially inhibited by pharmacological impairment of DNA methylation. Importantly, the expression of Müller glia identity genes (i.e., glutamine synthetase; cellular retinaldehyde binding protein, CRALBP) is retained through the process. Dedifferentiated Müller cells held an early neuronal differentiation potential similar to that observed in retinal progenitor-enriched cultures but, contrary to the latter, dedifferentiated Müller cells failed to further differentiate into mature photoreceptor lineages. We speculate that, in spite of the initial triggering of the dedifferentiation pathways, these cells may exhibit a certain degree of epigenetic memory that precludes them from further differentiation.

Three new sensitive and specific heat-shock protein 70 PCRs for global Leishmania species identification.

The heat-shock protein 70 gene (hsp70) has been exploited for Leishmania species identification in the New and Old World, using PCR followed by restriction fragment length polymorphism (RFLP) analysis. Current PCR presents limitations in terms of sensitivity, which hampers its use for analyzing clinical and biological samples, and specificity, which makes it inappropriate to discriminate between Leishmania and other trypanosomatids. The aim of the study was to improve the sensitivity and specificity of a previously reported hsp70 PCR using alternative PCR primers and RFLPs. Following in silico analysis of available sequences, three new PCR primer sets and restriction digest schemes were tested on a globally representative panel of 114 Leishmania strains, various other infectious agents, and clinical samples. The largest new PCR fragment retained the discriminatory power from RFLP, while two smaller fragments discriminated less species. The detection limit of the new PCRs was between 0.05 and 0.5 parasite genomes, they amplified clinical samples more efficiently, and were Leishmania specific. We succeeded in significantly improving the specificity and sensitivity of the PCRs for hsp70 Leishmania species typing. The improved PCR-RFLP assays can impact diagnosis, treatment, and epidemiological studies of leishmaniasis in any setting worldwide.

NRF2, cancer and calorie restriction.

The transcription factor NF-E2-related factor (NRF2) is a key regulator of several enzymatic pathways, including cytoprotective enzymes in highly metabolic organs. In this review, we summarize the ongoing research related to NRF2 activity in cancer development, focusing on in vivo studies using NRF2 knockout (KO) mice, which have helped in defining the crucial role of NRF2 in chemoprevention. The lower cancer protection observed in NRF2 KO mice under calorie restriction (CR) suggests that most of the beneficial effects of CR on the carcinogenesis process are likely mediated by NRF2. We propose that future interventions in cancer treatment would be carried out through the activation of NRF2 in somatic cells, which will lead to a delay or prevention of the onset of some forms of human cancers, and subsequently an extension of health- and lifespan.

Heat-shock protein 70 PCR-RFLP: a universal simple tool for Leishmania species discrimination in the New and Old World.

INTRODUCTION: Species typing in leishmaniasis gains importance in diagnostics, epidemiology, and clinical studies. A restriction fragment length polymorphism (RFLP) assay of PCR amplicons from a partial heat-shock protein 70 gene (hsp70) had been described for the New World, allowing identification of some species. METHODS: Based on an initial in silico analysis of 51 hsp70 sequences, most of which we recently determined in the frame of a phylogenetic study, species-specific restriction sites were identified. These were tested by PCR-RFLP on 139 strains from 14 species, thereby documenting both inter- and intra-species variability. RESULTS: Our assay could identify Leishmania infantum, L. donovani, L. tropica, L. aethiopica, L. major, L. lainsoni, L. naiffi, L. braziliensis, L. peruviana, L. guyanensis, and L. panamensis by applying 2 subsequent digests. L. mexicana, L. amazonensis, and L. garnhami did not generate species-specific restriction fragment patterns. CONCLUSION: Currently no assay is available for global Leishmania species discrimination. We present a universal PCR-RFLP method allowing identification of most medically relevant Old and New World Leishmania species on the basis of a single PCR, obviating the need to perform separate PCRs. The technique is simple to perform and can be implemented in all settings where PCR is available.

Perfil de preferencias de aprendizaje de alumnos y profesores de medicina. Elemento a considerar en la enseñanza / Profile of learning preferences of students and professors of medicine. Element to consider in teaching

Introducción. Es importante que alumnos y profesores comprendan y desarrollen habilidades que favorezcan un mejor aprendizaje. Para ello se debe identificar sus perfiles de aprendizaje. Sujetos y métodos. Con autorización del autor se aplicó el cuestionario VARK a 530 alumnos y 27 profesores del primer año de la carrera de Medicina en la Universidad Nacional Autónoma de México. Las respuestas al cuestionarios e procesaron con la metodología establecida por el autor. Se utilizó la prueba exacta de Fisher para identificar diferencias entre ambos perfiles. Mediante análisis inferencial se buscó asociación por género y con el promedio de calificaciones, así como entre profesor y alumnos. Resultados. El 31% de alumnos presentó una modalidad, y el 69%, más de una; de éstos, el 14% desarrolló las cuatro modalidades. El 41% fueron visual/cinestésicos, y el 64% desarrolló una o dos modalidades. De los profesores, el 26% manifestó una modalidad, y el 74%, más de una; de ellos, el 4% tuvo las cuatro modalidades. No se encontraron diferencias estadísticamente significativas entre mujeres y hombres, ni entre los grupos matutinos, vespertinos o de alto rendimiento. Conclusiones. Este primer acercamiento permitió tener una visión general de las preferencias de aprendizaje de la población estudiada. Los resultados permitirán que cuando profesores y alumnos reconozcan su estilo de aprendizaje, podrán enriquecer su práctica docente y acercarla a las necesidades de sus alumnos, y con ello mejorar el proceso de enseñanza y los resultados del aprendizaje (AU)

Introduction. It is important for students and teachers to identify their learning profiles. Subjects and methods. The consent of the author was solicited to translate and apply the ARK questionnaire to 530 students and 27 professors of Public Health course, which is given at first year medical students. Fisher’s exact test was used to identify the existence of differences between the learning profiles of the professors and the learning modalities of the students and then both compared with the averages of grades separated by group. By means of inferential analysis the association between gender and group characteristics with the average grades looked for. Results.31%, of the students displayed a single modality of learning, and 69% declared more than one learning modality; and of these last ones 14% said they development all four modalities. It is interesting to note that 41% are visual/kinesthetic and64% of the students displayed of one to two modalities. About the teachers 26% used only one teaching modality, 74% used more than one, and 4% used all four modalities. There were no statistical significance differences between women and men neither between, morning and afternoon groups nor with high performance groups. Conclusions. This first approach allowed us to have a general vision of the preferences of learning in the studied population. When the teacher identifies how their students learn and also recognizes his/her own, he/she can enrich their educational practice, and approach it to the necessities of the students and, that way improve the teaching process and better the student’s results (AU)

In vitro and in vivo cytokeratin patterns of expression in bioengineered human periodontal mucosa.

BACKGROUND AND OBJECTIVE: Development of human oral mucosa substitutes by tissue engineering may provide new therapeutic tools for the management of periodontal diseases. In this study we evaluated a fibrin-agarose human oral mucosa substitute both in vitro and in vivo. MATERIAL AND METHODS: In vitro bioengineered oral mucosa substitutes were developed from irrelevant biopsy samples of human oral gingiva. In vivo evaluation of the constructed tissues was performed by implantation into athymic nude mice. The expression of several epithelial markers was assessed by microarray analysis and immunohistochemistry. RESULTS: Bioengineered oral mucosa samples kept in vitro developed a multilayered epithelium that expressed several cytokeratins, including some markers of simple epithelia (cytokeratins 7, 8 and 18), along with markers of stratified epithelia (cytokeratins 5 and 13) and of cell proliferation (proliferating cell nuclear antigen). Bioengineered tissues grafted in vivo onto nude mice exhibited very good biointegration with the host, showing a cytokeratin expression pattern that was very similar to that of normal native oral mucosa controls. Histological analysis of the artificial tissues demonstrated that oral mucosa substitutes evaluated in vivo were structurally mature, showing some typical structures of human native oral mucosa such as rete ridges and chorial papillae, along with numerous blood vessels at the fibrin-agarose stromal substitute. These structures were absent in samples evaluated in vitro. CONCLUSION: The results indicate that this model of human oral mucosa, constructed using fibrin-agarose scaffolds, shows similarities to native oral mucosa controls and imply that bioengineered oral mucosa substitutes could eventually be used clinically.

Hydroxylation of demethoxy-Q6 constitutes a control point in yeast coenzyme Q6 biosynthesis.

Coenzyme Q is a lipid molecule required for respiration and antioxidant protection. Q biosynthesis in Saccharomyces cerevisiae requires nine proteins (Coq1p-Coq9p). We demonstrate in this study that Q levels are modulated during growth by its conversion from demethoxy-Q (DMQ), a late intermediate. Similar conversion was produced when cells were subjected to oxidative stress conditions. Changes in Q(6)/DMQ(6) ratio were accompanied by changes in COQ7 gene mRNA levels encoding the protein responsible for the DMQ hydroxylation, the penultimate step in Q biosynthesis pathway. Yeast coq null mutant failed to accumulate any Q late biosynthetic intermediate. However, in coq7 mutants the addition of exogenous Q produces the DMQ synthesis. Similar effect was produced by over-expressing ABC1/COQ8. These results support the existence of a biosynthetic complex that allows the DMQ(6) accumulation and suggest that Coq7p is a control point for the Q biosynthesis regulation in yeast.