The Proteomic Signature of Intestinal Acute Rejection in the Mouse.

Intestinal acute rejection (AR) lacks a reliable non-invasive biomarker and AR surveillance is conducted through frequent endoscopic biopsies. Although citrulline and calprotectin have been suggested as AR biomarkers, these have limited clinical value. Using a mouse model of intestinal transplantation (ITx), we performed a proteome-wide analysis and investigated rejection-related proteome changes that may eventually be used as biomarkers. ITx was performed in allogenic (Balb/C to C57Bl) and syngeneic (C57Bl) combinations. Graft samples were obtained three and six days after transplantation (n = 4/time point) and quantitative proteomic analysis with iTRAQ-labeling and mass spectrometry of whole tissue homogenates was performed. Histology showed moderate AR in all allografts post-transplantation at day six. Nine hundred and thirty-eight proteins with at least three unique peptides were identified in the intestinal grafts. Eighty-six proteins varying by >20% between time points and/or groups had an alteration pattern unique to the rejecting allografts: thirty-seven proteins and enzymes (including S100-A8 and IDO-1) were significantly upregulated whereas forty-nine (among other chromogranin, ornithine aminotransferase, and arginase) were downregulated. Numerous proteins showed altered expression during intestinal AR, several of which were previously identified to be involved in acute rejection, although our results also identified previously unreported proteome changes. The metabolites and downstream metabolic pathways of some of these proteins and enzymes may become potential biomarkers for intestinal AR.

Soluble silica stimulates osteogenic differentiation and gap junction communication in human dental follicle cells.

Several studies have indicated that dietary silicon (Si) is beneficial for bone homeostasis and skeletal health. Furthermore, Si-containing bioactive glass biomaterials have positive effects on bone regeneration when used for repair of bone defects. Si has been demonstrated to stimulate osteoblast differentiation and bone mineralisation in vitro. However, the mechanisms underlying these effects of Si are not well understood. The aim of the present study was to investigate the effects of soluble Si on osteogenic differentiation and connexin 43 (CX43) gap junction communication in cultured pluripotent cells from human dental follicles (hDFC). Neutral Red uptake assay demonstrated that 25 µg/ml of Si significantly stimulated hDFC cell proliferation. Dosages of Si above 100 µg/ml decreased cell proliferation. Alizarin Red staining showed that osteogenic induction medium (OIM) by itself and in combination with Si (25 µg/ml) significantly increased mineralisation in hDFC cultures, although Si alone had no such effect. The expression of osteoblast-related markers in hDFC was analysed with RT-qPCR. OSX, RUNX2, BMP2, ALP, OCN, BSP and CX43 genes were expressed in hDFC cultured for 1, 7, 14 and 21 days. Expression levels of BMP-2 and BSP were significantly upregulated by OIM and Si (25 µg/ml) and were also induced by Si alone. Notably, the expression levels of OCN and CX43 on Day 21 were significantly increased only in the Si group. Flow cytometric measurements revealed that Si (50 µg/ml) significantly increased CX43 protein expression and gap junction communication in hDFC. Next-generation sequencing (NGS) and bioinformatics processing were used for the identification of differentially regulated genes and pathways. The influence of OIM over the cell differentiation profile was more prominent than the influence of Si alone. However, Si in combination with OIM increased the magnitude of expression (up or down) of the differentially regulated genes. The gene for cartilage oligomeric matrix protein (COMP) was the most significantly upregulated. Genes for the regulator of G protein signalling 4 (RGS4), regulator of G protein signalling 2 (RGS2), and matrix metalloproteinases (MMPs) 1, 8, and 10 were also strongly upregulated. Our findings reveal that soluble Si stimulates Cx43 gap junction communication in hDFC and induces gene expression patterns associated with osteogenic differentiation. Taken together, the results support the conclusion that Si is beneficial for bone health.

Whole exome sequencing reveals mutations in NARS2 and PARS2, encoding the mitochondrial asparaginyl-tRNA synthetase and prolyl-tRNA synthetase, in patients with Alpers syndrome.

Alpers syndrome is a progressive neurodegenerative disorder that presents in infancy or early childhood and is characterized by diffuse degeneration of cerebral gray matter. While mutations in POLG1, the gene encoding the gamma subunit of the mitochondrial DNA polymerase, have been associated with Alpers syndrome with liver failure (Alpers-Huttenlocher syndrome), the genetic cause of Alpers syndrome in most patients remains unidentified. With whole exome sequencing we have identified mutations in NARS2 and PARS2, the genes encoding the mitochondrial asparaginyl-and prolyl-tRNA synthetases, in two patients with Alpers syndrome. One of the patients was homozygous for a missense mutation (c.641C>T, p.P214L) in NARS2. The affected residue is predicted to be located in the stem of a loop that participates in dimer interaction. The other patient was compound heterozygous for a one base insertion (c.1130dupC, p.K378 fs*1) that creates a premature stop codon and a missense mutation (c.836C>T, p.S279L) located in a conserved motif of unknown function in PARS2. This report links for the first time mutations in these genes to human disease in general and to Alpers syndrome in particular.

Distribución de Aedes aegypti y Aedes albopictus en Guatemala 2016 / Distribution of Aedes aegypti and Aedes albopictus in Guatemala 2016

Los recientes brotes de zika y chikungunya en Guatemala, y el continuo padecimiento de dengue, hacen necesario generar preguntas respecto a la presencia de los vectores de arbovirus, Aedes aegypti y A. albopictus, en este país. Los reportes publicados previamente, señalan la presencia de estos vectores en cuatro departamentos de Guatemala. El objetivo de este estudio fue actualizar los reportes de A. aegypti y A. albopictus en Guatemala para informar con datos robustos a las agencias de salud. Se utilizaron datos del Programa de Enfermedades Transmitidas por Vectores del Ministerio de Salud Pública y Asistencia Social, que contiene principalmente información sobre la presencia de estadios larvales de los vectores. Los sitios de colecta de los mosquitos fueron validados usando herramientas de Sistemas de Información Geográfica, generando mapas de distribución de ambas especies de vectores en todo el país. Los resultados incluyen la presencia de A. aegypti en 21 departamentos y A. albopictus en 11. Aedes aegypti fue reportado en zonas bajas con tolerancias a altas temperaturas (32.3-34.8°C), mientras A. albopictus se reportó en zonas con mayor precipitación y en mayores altitudes (2,301 m). Se concluye en un notable incremento en la distribución de estas dos especies en Guatemala, basados en los informes del primer trimestre 2016 del Programa de Enfermedades Transmitidas por Vectores colectados en época seca. Se discuten la oportunidad de integrar a la academia con los programas actuales de vigilancia epidemiológica para abordar las necesidades de investigación de estos vectores a nivel nacional.

Recent outbreaks of zika and chikungunya in Guatemala, and the continued burden of dengue, make necessary to generate novel questions regarding the presence of arboviruses vectors, Aedes aegypti and A. albopictus, in this country. Reports published before this manuscript, indicated the presence of these vectors in four departments of Guatemala. The aim of this study was to update the reports of A. aegypti and A. albopictus in Guatemala to better inform health agencies. We used data from the Programa de Enfermedades Transmitidas por Vectores, which mainly contains information about the presence of larval stages of vectors. Sites of mosquito collection were validated using geographic information systems tools, generating maps of both vector species' occurrence across the country. The results include A. aegypti presence in 21 departments and A. albopictus in 11. Aedes aegypti was reported in lowlands with high temperature tolerance, while A. albopictus was reported in drier zones and in higher altitudes (2,301 m). We conclude a notable increase in the distribution of these two species in Guatemala, based on the reports of the first quarter of 2016 of the Program of Vector-borne Diseases collected during the dry season. We discuss the opportunity to integrate the academy with epidemiological surveillance programs to address theresearch needs of these vectors at the national level

Prevalencia y características del síndrome de agotamiento profesional (SAP) en docentes de tres colegios públicos de Bogotá (Colombia) / Prevalence and Characteristics of Burnout Syndrome among Teachers of Three Public Schools in Bogotá (Colombia)

Introducción: El síndrome de agotamiento profesional (SAP) o burnout tiene gran importancia y prevalencia entre los trabajadores de la salud y está parcialmente estudiado entre los docentes. Objetivo: Determinar la prevalencia y las características asociadas al SAP en tres colegios públicos de Bogotá. Método: Se realizó un diseño de corte transversal, tipo encuesta, en tres colegios públicos de Bogotá. Se evaluaron los docentes mediante el Inventario de Maslach para agotamiento profesional y un cuestionario diseñado para evaluar factores sociodemográficos, personales y laborales. Resultados: Se realizaron 343 encuestas, de 367 previstas, para un índice de respuesta del 93,4%. Se halló que el SAP tiene una prevalencia de 15,4% para los docentes y que podría aumentar a 29,7% si se tiene en cuenta que dos de los tres dominios del SAP están por encima del percentil 30. Un 25,3% de los docentes presentaron cansancio emocional alto. La prevalencia de SAP fue menor en docentes mayores de 55 años, con 21 a 30 años de experiencia; en aquellos que solamente trabajan una jornada, y en los que tienen cargos directivos. Es menos frecuente en docentes casados y en aquellos que tienen más hijos. Conclusión: El SAP es frecuente en docentes y requiere intervenciones de salud mental que lleven a mejorar la interacción docente-alumno.

Introduction: Burnout syndrome is highly prevalent among health care professionals, but has only been partially studied in teachers. Objective: To determine the characteristics associated to burnout syndrome in teachers of three public schools in the city of Bogotá (Colombia). Method: Teachers were evaluated according to the Maslach Inventory for Burnout and a questionnaire designed to evaluate socio-demographic, personal and job-related factors. Results: 343 out of 367 questionnaires were completed, giving a response index of 93.4%. It was noted that burnout syndrome had a prevalence of 15.4% in teachers but it could actually rise to 29.7% if the fact is taken into account that two out of three domains of burnout syndrome were above the 30th percentile. 25.3% of the teachers had high emotional tiredness. The prevalence of burnout syndrome was lower in teachers over 55 years of age with 21 to 30 years of working experience, also in those who worked less hours a day and in those with high directive positions. It was also less frequent in married teachers and in those who have more children. Conclusion: Burnout syndrome is frequent in teachers and requires interventions in mental health in order to improve the teacher-student relationship.