Dental restoration operative time and analysis of the internal gap of conventional resins (Incremental Technique) vs. Bulk Fill (Single-Increment Technique): In vitro study.

Background: To determine the operative time and the internal restoration gap in the restoration-tooth interface in the cavity floor using an incremental technique for conventional resins and the single-increment technique for the bulk fill resin. Material and Methods: In this in vitro experimental study, the internal gaps of the restoration-tooth interfaces in the cavity floors of two conventional resins and two bulk fill resins were microscopically analyzed, and the restoration times of the single-increment technique and the incremental technique were determined. Results: Bulk fill resins had smaller internal gap (63.31 µm) than conventional resins (333.14 µm). Regarding the restoration time, the single-increment technique obtained the best results in operative time (3.52 minutes), with significant differences relative to the incremental technique. Conclusions: The Tetric N-Ceram bulk fill resin presented better performance than conventional resins relative to the internal gap of the restoration-tooth interface in the cavity floor. In addition, the single-increment technique presented a short clinical restoration time. Key words:Composite, internal gap, restoration technique.

Genome-wide DNA methylation analysis of aggressive behaviour: a longitudinal population-based study.

BACKGROUND: Human aggression is influenced by an interplay between genetic predisposition and experience across the life span. This interaction is thought to occur through epigenetic mechanisms, inducing differential gene expression, thereby moderating neuronal cell and circuit function, and thus shaping aggressive behaviour. METHODS: Genome-wide DNA methylation (DNAm) levels were measured in peripheral blood obtained from 95 individuals participating in the Estonian Children Personality Behaviours and Health Study (ECPBHS) at 15 and 25 years of age. We examined the association between aggressive behaviour, as measured by Life History of Aggression (LHA) total score and DNAm levels both assessed at age 25. We further examined the pleiotropic effect of genetic variants regulating LHA-associated differentially methylated positions (DMPs) and multiple traits related to aggressive behaviours. Lastly, we tested whether the DNA methylomic loci identified in association with LHA at age 25 were also present at age 15. RESULTS: We found one differentially methylated position (DMP) (cg17815886; p = 1.12 × 10-8 ) and five differentially methylated regions (DMRs) associated with LHA after multiple testing adjustments. The DMP annotated to the PDLIM5 gene, and DMRs resided in the vicinity of four protein-encoding genes (TRIM10, GTF2H4, SLC45A4, B3GALT4) and a long intergenic non-coding RNA (LINC02068). We observed evidence for the colocalization of genetic variants associated with top DMPs and general cognitive function, educational attainment and cholesterol levels. Notably, a subset of the DMPs associated with LHA at age 25 also displayed altered DNAm patterns at age 15 with high accuracy in predicting aggression. CONCLUSIONS: Our findings highlight the potential role of DNAm in the development of aggressive behaviours. We observed pleiotropic genetic variants associated with identified DMPs, and various traits previously established to be relevant in shaping aggression in humans. The concordance of DNAm signatures in adolescents and young adults may have predictive value for inappropriate and maladaptive aggression later in life.

Noción y postura sobre la eutanasia de médicos y enfermeras en un hospital público de Santiago de Chile

Propósito/Contexto. El estudio se propone explorar la concepción de la eutanasia en los discursos de médicos y enfermeras, sus aspectos constitutivos, posturas y creencias, considerando que para avanzar en la discusión sobre la eutanasia se requiere conocer las nociones de quienes atienden al paciente al final de la vida. Metodología/Enfoque. Diseño cualitativo con análisis de contenido triangulado por las investigadoras, de 11 entrevistas en profundidad a profesionales de un hospital chileno. Resultados/Hallazgos. Se distinguen nociones etimológicas, ético-legales y operacionales de la eutanasia, además, los aspectos constitutivos (enfermedad no curativa, sufrimiento, voluntariedad y contexto médico) generan interrogantes que deben atenderse. Discusión/Conclusiones/Contribuciones. Es necesario instalar el tema en los equipos de salud y generar acuerdos socionormativos y ético-legales que sustraigan el peso de las decisiones en los individuos o los equipos profesionales.

Purpose/Background. To explore the notion of euthanasia and the positions and beliefs of doctors and nurses considering that a discussion about euthanasia requires knowing the notions of those who care for patients at the end of life. Methodology/Approach. Within a qualitative design, interviews were conducted with 11 professionals from a Chilean hospital. A content analysis was made and was triangulate by researchers. Results/Findings. Etymological, ethical-legal and operational notions of euthanasia are distinguished. Core aspects of euthanasia -non-curative disease, suffering, voluntariness and the medical context-raise questions that must be addressed. Discussion/Conclusions/Contributions. It is necessary to install the topic in the health teams and generate socio-normative ethical-legal agreements that remove the weight of the decisions in the individuals or professional teams.

Finalidade/Contexto. O estudo visa explorar a concepção da eutanásia nos discursos de médicos e enfermeiros, os seus aspectos constituintes, posições e crenças, considerando que para avançar a discussão sobre a eutanásia é necessário conhecer as noções daqueles que cuidam do doente no fim da vida. Metodologia/Aproximação. Concepção qualitativa com análise de conteúdo triangulada pelos investigadores, de 11 entrevistas em profundidade com profissionais de um hospital chileno. Resultados/Descobertas. Distinguem-se noções etimológicas, ético-legais e operacionais de eutanásia, e os aspectos constitutivos (doença não curativa, sofrimento, voluntariedade e contexto médico) levantam questões que precisam de ser abordadas. Discussão/Conclusões/Contribuições. É necessário levantar a questão nas equipas de saúde e gerar acordos sócio-normativos e ético-jurídicos que eliminem o peso da tomada de decisões de indivíduos ou equipas profissionais.

Crystal structure of a trigonal polymorph of aqua-dioxidobis(pentane-2,4-dionato-κ2 O,O')uranium(VI).

The title compound, [UO2(acac)2(H2O)] consists of a uran-yl(VI) unit ([O=U=O]2+) coordinated to two monoanionic acetyl-acetonate (acac, C5H7O2) ligands and one water mol-ecule. The asymmetric unit includes a one-half of a uranium atom, one oxido ion, one-half of a water mol-ecule and one acac ligand. The coordination about the uranium atom is distorted penta-gonal-bipyramidal. The acac ligands and Ow atom comprise the equatorial plane, while the uranyl O atoms occupy the axial positions. Inter-molecular hydrogen bonding between complexes results in the formation of two-dimensional hexa-gonal void channels along the c-axis direction with a diameter of 6.7 Å. The monoclinic (P21/c space group) polymorph was reported by Alcock & Flanders [(1987). Acta Cryst. C43, 1480-1483].

Haploinsufficiency of the Attention-Deficit/Hyperactivity Disorder Risk Gene St3gal3 in Mice Causes Alterations in Cognition and Expression of Genes Involved in Myelination and Sialylation.

Genome wide association meta-analysis identified ST3GAL3, a gene encoding the beta-galactosidase-alpha-2,3-sialyltransferase-III, as a risk gene for attention-deficit/hyperactivity disorder (ADHD). Although loss-of-function mutations in ST3GAL3 are implicated in non-syndromic autosomal recessive intellectual disability (NSARID) and West syndrome, the impact of ST3GAL3 haploinsufficiency on brain function and the pathophysiology of neurodevelopmental disorders (NDDs), such as ADHD, is unknown. Since St3gal3 null mutant mice display severe developmental delay and neurological deficits, we investigated the effects of partial inactivation of St3gal3 in heterozygous (HET) knockout (St3gal3 ±) mice on behavior as well as expression of markers linked to myelination processes and sialylation pathways. Our results reveal that male St3gal3 HET mice display cognitive deficits, while female HET animals show increased activity, as well as increased cognitive control, compared to their wildtype littermates. In addition, we observed subtle alterations in the expression of several markers implicated in oligodendrogenesis, myelin formation, and protein sialylation as well as cell adhesion/synaptic target glycoproteins of ST3GAL3 in a brain region- and/or sex-specific manner. Taken together, our findings indicate that haploinsufficiency of ST3GAL3 results in a sex-dependent alteration of cognition, behavior and markers of brain plasticity.

Precisión de los sistemas de impresión digital intraoral en odontología restauradora: Una revisión de la literatura / Accuracy of Intraoral Digital Impression Systems in Restorative Dentistry: A Review of the Literature

Abstract: La impresión intraoral permite al odontólogo obtener directamente los datos de las piezas dentales que se requiera rehabilitar, otorgándole mayor precisión y eliminando así de la fase clínica la toma de impresión y la fabricación del modelo, aspectos sensibles a errores. El objetivo de la presente revisión es identificar el sistema de impresión digital intraoral más preciso y además identificar los factores que afectan a la precisión de esta en odontología restauradora. Mediante una revisión bibliográfica con búsqueda en las bases de datos de PubMed y Embase se obtuvieron 153 artículos, luego de la evaluación cualitativa se incluyeron en la revisión 14 que cumplieron con los criterios de inclusión y exclusión. Se determinó que la experiencia del dentista, la convergencia en la preparación dental y la terminación cervical son determinantes al momento de la toma de impresión digital, sin embargo, el uso o no de polvo no es relevante. El sistema de impresión digital Lava C.O.S., iTero y True definition son los más precisos dependiendo siempre del tipo de rehabilitación a realizar.

Abstract: Digital impresión allows the dentist to directly obtain the data of the dental pieces that neet to be rehabilitated, giving it greater precisión and thus eliminating the impression and manufacturing of the dental model, error-sensitive aspects of the clinical phase. The aim of this review is to identify the most accurate intraoral digital impression system and identifiy the factors that affect the accuracy in the restorative dentistry. Through a bibliographic review with search in PubMed and Embase databases, 153 articles were obtained, after qualitative evaluation they were included in the revisión 14 that met the inclusion and exclusion criteria. It was determined that the experience of the dentist, the convergence in the dental preparation and the cervical termination are decisive at the accuracy of the digital impression, however, the use or not of dust is not relevant. The Lava C.O.S., iTero and True definition are the most accurate always depending on the type of rehabilitation to be performed.

Experiencias y percepciones sobre rehabilitación comunitaria en la región metropolitana de Chile Estudio Cualitativo / Experiences and perceptions about community-based rehabilitation in the Metropolitan Region of Chile: Qualitative study

INTRODUCCIÓN: La rehabilitación basada en la comunidad (RBC) busca mejorar el acceso a la rehabilitación y la inclusión social de las personas con discapacidad. Los escasos estudios realizados muestran experiencias heterogéneas en su implementación. El objetivo de este estudio fue describir las experiencias y percepciones sobre RBC de profesionales sanitarios, personas con discapacidad y familiares participantes en centros de atención primaria de la Región Metropolitana de Chile. MÉTODOS: Se realizó un estudio cualitativo exploratorio-descriptivo. A través de un muestreo de caso típico se seleccionaron profesionales sanitarios, hombres y mujeres con discapacidad física y familiares. Se desarrollaron 16 entrevistas grupales semiestructuradas, 4 por cada grupo. Se realizó análisis de contenido semántico mediante codificación inductiva y deductiva. RESULTADOS: La RBC es valorada positivamente por las personas con discapacidad y familiares. Sin embargo, los profesionales consideran que es insuficiente para lograr la inclusión social. DISCUSIÓN: Existen barreras y facilitadores para la implementación de la RBC. Su ubicación en la Atención Primaria permite flexibilidad en la atención. No obstante, se centra en intervenciones de rehabilitación física, relegando la salud integral y el trabajo intersectorial a un segundo plano. Se requiere capacitar a los equipos sanitarios para proveer una rehabilitación integral, que contribuya a la inclusión social de las personas con discapacidad

Experiencias y percepciones sobre discapacidad y participación social en centros de rehabilitación comunitaria de Chile / Experiences and perceptions on disability and social participation in community rehabilitation centers in Chile

Resumen Este estudio busca describir experiencias y percepciones sobre discapacidad y participación social de personas con discapacidad y profesionales sanitarios de centros de rehabilitación comunitaria de la Región Metropolitana de Chile. Se realizó un estudio cualitativo con muestreo teórico de actores claves en cuatro centros. Se realizaron 16 grupos focales y análisis de contenido semántico. Las experiencias de personas con discapacidad son diversas, existen elementos comunes como la homologación de la dependencia con la discapacidad y el reconocimiento de barreras sociales. Las percepciones sobre discapacidad representan los modelos individual y social, esto último se evidencia en las injusticias y discriminaciones. La participación social es intensa y afectiva en el centro de salud, sin embargo, otros espacios de participación son escasos. Las concepciones sobre discapacidad y niveles de participación señalan la necesidad de más lineamientos, capacitación y recursos para la efectiva implementación de la rehabilitación comunitaria.

Abstract This study seeks to describe experiences and perceptions about disability and social participation of people with disabilities and professionals who are part of community rehabilitation centers in the Metropolitan Region of Chile. A qualitative study was carried out with a theoretical sampling of key actors from 4 community rehabilitation centers. 16 focus groups were conducted and a semantic content analysis was applied. The experiences of people with disabilities are diverse, there are common elements such as dependency made equivalent to disability and recognition of social barriers. Perceptions of disability represent individual and social models. The latter appears when injustices and discrimination are experienced. Social participation linked to the center is intense and affective. However, other participation spaces are scarce. The concepts of disability and levels of social participation show the need for more guidelines, training and resources for an effective implementation of community rehabilitation.

Stress-induced aggression in heterozygous TPH2 mutant mice is associated with alterations in serotonin turnover and expression of 5-HT6 and AMPA subunit 2A receptors.

BACKGROUND: The contribution of gene-environment interactions that lead to excessive aggression is poorly understood. Environmental stressors and mutations of the gene encoding tryptophan hydroxylase-2 (TPH2) are known to influence aggression. For example, TPH2 null mutant mice (Tph2-/-) are naturally highly aggressive, while heterozygous mice (Tph2+/-) lack a behavioral phenotype and are considered endophenotypically normal. Here we sought to discover whether an environmental stressor would affect the phenotype of the genetically 'susceptible' heterozygous mice (Tph2+/-). METHODS: Tph2+/- male mice or Tph2+/+ controls were subjected to a five-day long rat exposure stress paradigm. Brain serotonin metabolism and the expression of selected genes encoding serotonin receptors, AMPA receptors, and stress markers were studied. RESULTS: Stressed Tph2+/- mice displayed increased levels of aggression and social dominance, whereas Tph2+/+ animals became less aggressive and less dominant. Brain tissue concentrations of serotonin, its precursor hydroxytryptophan and its metabolite 5-hydroxyindoleacetic acid were significantly altered in all groups in the prefrontal cortex, striatum, amygdala, hippocampus and dorsal raphe after stress. Compared to non-stressed animals, the concentration of 5-hydroxytryptophan was elevated in the amygdala though decreased in the other brain structures. The overexpression of the AMPA receptor subunit, GluA2, and downregulation of 5-HT6 receptor, as well as overexpression of c-fos and glycogen-synthase-kinase-3ß (GSK3-ß), were found in most structures of the stressed Tph2+/- mice. LIMITATIONS: Rescue experiments would help to verify causal relationships of reported changes. CONCLUSIONS: The interaction of a partial TPH2 gene deficit with stress results in pathological aggression and molecular changes, and suggests that the presence of genetic susceptibility can augment aggression in seemingly resistant phenotypes.

Community-Based Rehabilitation (CBR) in primary care centers in Chile.

OBJECTIVE: To describe the implementation status of the Community-Based Rehabilitation in Chile. METHODS: Quantitative, transversal and descriptive study. The scope was constituted by the 66 community-based rehabilitation centers in the Chilean Metropolitan Region that implemented Community-Based Rehabilitation until December 2016. The sampling was based on a census method, so all the community centers were contacted. A self-administered questionnaire designed based on the Community-Based Rehabilitation matrix defined by the World Health Organization was applied. The questionnaire was answered on-line by the coordinators of the strategy in their respective centers. The data analysis was performed using descriptive statistics. RESULTS: A heterogeneous level of implementation of Community-Based Rehabilitation was identified, specifically in terms of the components of the matrix described by the World Health Organization. The most implemented component was Health; the Social, Livelihood and Empowerment components were moderately implemented; and the Education component was the least implemented. CONCLUSION: The implementation of Community-Based Rehabilitation is mainly based on the Health component. The level implementation of the other components of the matrix needs to be increased, as well as interdisciplinary and intersectoral strategies to achieve greater social inclusion of people with disabilities.

Community-based rehabilitation (CBR) in primary care centers in Chile / Rehabilitación basada en la comunidad (RBC) en centros de atención primaria en Chile

ABSTRACT OBJECTIVE To describe the implementation status of the Community-Based Rehabilitation in Chile. METHODS Quantitative, transversal and descriptive study. The scope was constituted by the 66 community-based rehabilitation centers in the Chilean Metropolitan Region that implemented Community-Based Rehabilitation until December 2016. The sampling was based on a census method, so all the community centers were contacted. A self-administered questionnaire designed based on the Community-Based Rehabilitation matrix defined by the World Health Organization was applied. The questionnaire was answered on-line by the coordinators of the strategy in their respective centers. The data analysis was performed using descriptive statistics. RESULTS A heterogeneous level of implementation of Community-Based Rehabilitation was identified, specifically in terms of the components of the matrix described by the World Health Organization. The most implemented component was Health; the Social, Livelihood and Empowerment components were moderately implemented; and the Education component was the least implemented. CONCLUSION The implementation of Community-Based Rehabilitation is mainly based on the Health component. The level implementation of the other components of the matrix needs to be increased, as well as interdisciplinary and intersectoral strategies to achieve greater social inclusion of people with disabilities.

RESUMEN OBJETIVO Describir el estado de implementación de la Rehabilitación Basada en la Comunidad en Chile. MÉTODOS Estudio cuantitativo, transversal y descriptivo. El universo estuvo conformado por los 66 centros comunitarios de rehabilitación de la Región Metropolitana de Chile que implementaron la Rehabilitación Basada en la Comunidad hasta diciembre de 2016. El muestreo tuvo intención censal, por lo que se contactaron todos los centros comunitarios. Se aplicó un cuestionario autoadministrado diseñado con base a la matriz de Rehabilitación Basada en la Comunidad definida por la Organización Mundial de la Salud. El cuestionario fue respondido on-line por los coordinadores de la estrategia en sus respectivos centros. El análisis de datos se realizó utilizando estadígrafos descriptivos. RESULTADOS Se identificó un nivel heterogéneo de implementación de la Rehabilitación Basada en la Comunidad, específicamente en cuanto a los componentes de la matriz descrita por la Organización Mundial de la Salud. El componente más implementado fue Salud; los componentes Social, Subsistencia y Fortalecimiento fueron medianamente implementados; y el componente Educación fue el menos implementado. CONCLUSIÓN La implementación de la Rehabilitación Basada en la Comunidad se basa principalmente en el componente Salud. Se requiere aumentar el nivel de implementación de los otros componentes de la matriz, así como de estrategias interdisciplinarias e intersectoriales para lograr una mayor inclusión social de las personas con discapacidad.

Dosis atípica de bevacizumab en un paciente con síndrome de Osler-Weber-Rendu / Atypical dose of bevacizumab in a patient with Osler-Weber Rendu syndrome

Resumen El síndrome de Osler-Weber-Rendu es una enfermedad de transmisión autosómica dominante. Si bien el síntoma más común es la epistaxis, existen muchas alteraciones viscerales que deben considerarse al momento del estudio. Los anti-VEFG son un pilar en el tratamiento, aunque no existe consenso acerca de la dosis a administrar. Comunicamos el caso de un paciente con síndrome de Osler-Weber-Rendu atendido en el servicio de Medicina Interna del Hospital Regional de Puebla, al que se prescribió una dosis atípica de bevacizumab con buena respuesta terapéutica.

Abstract Osler-Weber-Rendu syndrome is an autosomical dominant condition. Although epistaxis is the most frequent symptom, many other visceral implications have to be considered while the workup takes place. While Anti-VEGF are the cornerstone of the treatment, there is no consensus regarding the specific dose to be administered. We communicate de case of a patient with Osler-Weber-Rendu syndrome attended at our Hospital in which we prescribed an atypical dose of bevacizumab with good outcome.

Streptozotocin Impairs Proliferation and Differentiation of Adult Hippocampal Neural Stem Cells in Vitro-Correlation With Alterations in the Expression of Proteins Associated With the Insulin System.

Rats intracerebroventricularily (icv) treated with streptozotocin (STZ), shown to generate an insulin resistant brain state, were used as an animal model for the sporadic form of Alzheimer's disease (sAD). Previously, we showed in an in vivo study that 3 months after STZ icv treatment hippocampal adult neurogenesis (AN) is impaired. In the present study, we examined the effects of STZ on isolated adult hippocampal neural stem cells (NSCs) using an in vitro approach. We revealed that 2.5 mM STZ inhibits the proliferation of NSCs as indicated by reduced number and size of neurospheres as well as by less BrdU-immunoreactive NSCs. Double immunofluorescence stainings of NSCs already being triggered to start with their differentiation showed that STZ primarily impairs the generation of new neurons, but not of astrocytes. For revealing mechanisms possibly involved in mediating STZ effects we analyzed expression levels of insulin/glucose system-related molecules such as the glucose transporter (GLUT) 1 and 3, the insulin receptor (IR) and the insulin-like growth factor (IGF) 1 receptor. Applying quantitative Real time-PCR (qRT-PCR) and immunofluorescence stainings we showed that STZ exerts its strongest effects on GLUT3 expression, as GLUT3 mRNA levels were found to be reduced in NSCs, and less GLUT3-immunoreactive NSCs as well as differentiating cells were detected after STZ treatment. These findings suggest that cultured NSCs are a good model for developing new strategies to treat nerve cell loss in AD and other degenerative disorders.

1,2,4,5-Benzenetetracarboxylic acid: a versatile hydrogen bonding template for controlling the regioselective topochemical synthesis of head-to-tail photodimers from stilbazole derivatives.

The crystal engineering of hydrogen bonded organic assemblies based on 1,2,4,5-benzenetetracarboxylic acid (H4bta) and stilbazole derivatives (1-10) is exploited to provide regio-controlled [2 + 2] photocycloadditions in the solid state. Single crystal X-ray diffraction analyses have revealed that all the arrays are built-up from the self-assembly of the (H2bta)2- dianion with two stilbazolium cations via O-HO- and N+-HO- charge-assisted H-bonding synthons: (4-Hstilbazolium+)2(H2bta2-). The dianion displays an interesting diversity of H-bonding motifs. Such structural flexibility allowed us to obtain four structure-types defined by the preferential formation of intramolecular or intermolecular hydrogen bonds between carboxylate-carboxylic groups. In these ionic assemblies two predominant structural H-bonding patterns were observed. The first pattern is characterised by the formation of intramolecular H-bonds in the dianion, leading to discrete assemblies based on ternary arrays. The second hydrogen pattern consists of 2-D hydrogen networks built-up from the self-assembly of anions via intermolecular H-bonds that are linked to the cations. Two additional examples, in which the dianion is self-assembled in two types of ribbons, were also observed. Another supramolecular feature predominant in all these arrays is the stacking of the cations in a head-to-tail fashion, which is controlled via cation-π interactions. These arrays are photoactive in the solid state upon UV-irradiation leading to the regioselective synthesis of rctt-cyclobutane head-to-tail-isomers in high to quantitative yield. In this work, the template tolerance either to steric or electronic effects by changing the number or positions of the supramolecular interactions exerted by distinctive functional groups was also explored. In addition, assemblies bearing 2-chloro (7 and 8) and 3-chloro-4-stilbazole (1 and 9) crystallize in two different crystalline forms, leading to novel examples of supramolecular isomers with similar solid state reactivity.

Evaluación del consumo de antimicrobianos en una Unidad de Neonatologia: un trabajo en equipo para promover el uso racional de antimicrobianos / Evaluation of antimicrobial consumption in a Neonatology Unit: a team work to promote the rational use of antibiotics

Resumen Antecedentes: Los antimicrobianos (ATM) son uno de los medicamentos más utilizados en recién nacidos (RN) hospitalizados. El uso indiscriminado de ATM trae consecuencias negativas como son el predominio de bacterias resistentes a los ATM usualmente utilizados y asociaciones individuales a morbilidad relevante como son la displasia broncopulmonar, enterocolitis necrosante, sepsis tardía y/o muerte. Objetivo: Registrar y evaluar las tendencias del uso de ATM a lo largo del tiempo en RN hospitalizados en el Servicio de Neonatología (SRN) del Complejo Asistencial Dr. Sótero del Río, con el fin de objetivar los cambios en la práctica habitual de la indicación de ATM. Un objetivo secundario fue evaluar el impacto de estas conductas sobre la resistencia antimicrobiana. Métodos: Estudio de cohorte, prospectivo, observacional, unicéntrico, en todos los pacientes hospitalizados entre enero de 2011 y diciembre de 2014. Se registró el peso al nacer, días de hospitalización, indicación y días de uso de ATM para cada paciente. El uso de ATM fue cuantificado por medio de distintas tasas: días de indicación de un o más ATM para el consumo global (TUA), sumatoria total de días de uso (STUA) como para los ATM más frecuentemente utilizados. Cada tasa calculada por 100 días hospitalizados. Además, se registró la susceptibilidad antimicrobiana de las bacterias más frecuentemente aisladas en nuestro servicio: Staphylococcus coagulasa negativa (SCN) y bacilos gramnegativos (BGNs). Resultados: El 34,7% de los pacientes hospitalizados recibió algún tipo de antimicrobiano, correspondiendo 32,3% a antibacterianos. El ATM más utilizado fue ampicilina (20,2% del total) y luego cefadroxilo (11,6%). El TUA no cambió entre 2011 y 2014. La STUA disminuyó en 10,7% entre 2011 y 2014 (p < 0,05). En el análisis por rangos de peso, en el grupo < 750 g disminuyó la tendencia de uso de vancomicina (descenso de uso en 9,9%) y un aumento de 18,8% para metronidazol. Por otra parte, hubo un aumento en el uso del régimen de piperacilina/tazobactam en el grupo > 1.500 g. Al evaluar la susceptibilidad antimicrobiana, hubo una disminución de la susceptibilidad a cloxacilina en SCN entre 2011 y 2014 desde 27 a 10,3%, respectivamente. Para BGN hubo una disminución desde 76,9 a 40,5% en la susceptibilidad a cefalosporinas de tercera generación, principalmente debido a Klebsiella pneumoniae que pasó a ser el BGN predominante, con un aumento de 6,7 a 50% en los años 2011 y 2014, respectivamente. Para Klebsiella pneumoniae la susceptibilidad a cefalosporinas de tercera generación descendió desde 77 a 22%. Por último, amikacina mostró una actividad sobre 85% en todos los BGNs entre 2011 y 2014. Conclusiones: Es recomendable planificar y mantener un registro continuo del consumo de ATM tanto como terapia y profilaxis, idealmente llevar el TUA, el STUA y siendo categorizado por tipo de ATM y rango de peso de los RN. En forma concomitante, es de considerable importancia analizar y evaluar la susceptibilidad de microorganismos. Es esencial que un equipo interdisciplinario prepare este registro, y que continuamente proporcione retroalimentación a los profesionales que mantienen el funcionamiento de las unidades de cuidados neonatales.

Background: Antibiotics (ATB) are drugs widely used in hospitalized newborns. The indiscriminate use of ATBs promote the rise of resistant bacteria to the most commonly indicated antimicrobials. In addition, ATB prescription presents associations to morbidity, such as bronchopulmonary dysplasia, necrotizing enterocolitis, late sepsis and even death. All of the above leads to an increase in health care costs. Aim: To record and to evaluate trends of antibiotic use over time in hospitalized NB in the Neonatology Unit at Dr. Sótero del Río Hospital, in order to objectify the changes in the usual practice of the ATM indication. A secondary objective was to assess its impact on antimicrobial resistance. Methods: Cohort, observational, prospective unicenter study which included all hospitalized patients between January 2011 and December 2014. Birth weight, hospitalization days, ATB indication and days of ATB use were recorded for each patient. The use of ATB was quantified by means of different rates; days of indication of one or more ATBs for global consumption (RUA), total sum of days of use (TSUA) and for the most frequently used ATBs. Each calculated rate for 100 days hospitalized. In addition, the antimicrobial susceptibility of the most frequently isolated bacteria in our service: coagulase-negative Staphylococcus (SCN) and Gram-negative bacilli (BGN) were recorded continuously. Results: The 34.7% of the hospitalized patients received some type of antimicrobial agent. ATBs were 32.3% of medicines used. The most widely used was ampicillin (with 20.2% of the total) and cefadroxyl (with 11.6%). The RUA did not change during the study time, but STUA decreased by 10.7% between 2011 and 2014 with p < 0.05. When subgroup analyzes were divided by weight ranges, in the < 750 g group, the use of vancomycin decreased in use by 9.9% and an increase of 18.8% for metronidazole was observed. On the other hand, there was an increase in the use of the piperacillin-tazobactam regimen in the range > 1,500 g. When evaluating antimicrobial susceptibility, there was a decrease in susceptibility for oxacillin in SCN between 2011 and 2014 from 27% to 10.3% respectively. In addition, for Gram negative there was a decrease from 76.9% to 40.5% in susceptibility to third generation cephalosporins, mainly due to Klebsiella pneumoniae, which became the predominantly isolated BGN with an increase of 6.7% to 50% between 2011 and 2014, respectively. For K. pneumoniae the loss of susceptibility to third generation cephalosporins decreased from 77% to 22%. Finally, amikacin showed an activity over 85% in all BGNs between 2011 and 2014. Conclusions: It is advisable to plan and to maintain a continuous record of ATB consumption, as well as therapy and prophylaxis, being categorized by ATB type and range of newborn weight. It is of considerable importance to analyze and to evaluate the susceptibility of microorganisms. It is essential that an interdisciplinary team prepare this recording, and to continuously provide feedback to professionals who maintain the functioning of neonatal care units.

Interactions of a prenylated flavonoid from Dalea elegans with fluconazole against azole- resistant Candida albicans.

BACKGROUND: The prenylated flavonoid 2', 4'-dihydroxy-5'-(1'″, 1'″-dimethylallyl)-8-prenylpinocembrin (8PP, formerly 6PP) shows antifungal activity, inhibits rhodamine 6G efflux and reverses fluconazole (FCZ) resistance in azole-resistant Candida albicans overexpressing cdr1, cdr2 and mdr1 transporters. PURPOSE AND DESIGN: In this paper, we tried to characterize 8PP in vitro interactions on the cell growth and lethality of C. albicans. We also initiated preliminary in vivo toxicological studies on mice. METHODS: The effects of 8PP and FCZ on cell growth and viability of C. albicans were evaluated by CLSI guidelines. The checkerboard assay was used to search for interactions on cell growth. The time-kill assay was used to study fungicidal effects. Acute toxicity was evaluated at a single dose schedules. RESULTS: From the checkerboard design, and using a starting inoculum of 103CFU/ml, the fractional inhibitory concentration (FIC) of FCZ and 8PP could be determined as 0.11 and 0.50, respectively, with a FIC index value (FICI) of 0.61. This FICI and the isobologram showing a concave shape suggests an additive interaction between them. At a higher starting inoculum (105CFU/ml), C. albicans growth and viability were decreased by FCZ, 8PP and their combination in a concentration-dependent way. For FCZ, minimum fungicidal concentration (MFC) and FC50 (the concentration that kills 50% of the fungal cells) were 4-fold reduced (280-70µM) in combination with 125µM 8PP. A decrease of 3 log units in viable counts with respect to control was reached (3.65 ± 1.05 ‰, p< 0.0001). Thus, both fungistatic compounds when combined achieved an almost complete fungicidal effect at lower concentrations respecting of each of them alone. In preliminary toxicological assessment, lethal dose 50% (LD50) for 8PP by the i.p. route was 357 and 245mg/kg, for female and male adult albino mice, respectively. FCZ LD50 was 785 and 650mg/kg for female and male animals, respectively CONCLUSIONS: In vitro results suggest additive interactions between 8PP and FCZ with respect to C. albicans cell growth. Besides killing per se, 8PP helps FCZ to achieve an almost complete fungicidal effect, which would be crucial to eradicate fungal infections.

[Evaluation of antimicrobial consumption in a Neonatology Unit: a team work to promote the rational use of antibiotics]. / Evaluación del consumo de antimicrobianos en una Unidad de Neonatologia: un trabajo en equipo para promover el uso racional de antimicrobianos.

BACKGROUND: Antibiotics (ATB) are drugs widely used in hospitalized newborns. The indiscriminate use of ATBs promote the rise of resistant bacteria to the most commonly indicated antimicrobials. In addition, ATB prescription presents associations to morbidity, such as bronchopulmonary dysplasia, necrotizing enterocolitis, late sepsis and even death. All of the above leads to an increase in health care costs. AIM: To record and to evaluate trends of antibiotic use over time in hospitalized NB in the Neonatology Unit at Dr. Sótero del Río Hospital, in order to objectify the changes in the usual practice of the ATM indication. A secondary objective was to assess its impact on antimicrobial resistance. METHODS: Cohort, observational, prospective unicenter study which included all hospitalized patients between January 2011 and December 2014. Birth weight, hospitalization days, ATB indication and days of ATB use were recorded for each patient. The use of ATB was quantified by means of different rates; days of indication of one or more ATBs for global consumption (RUA), total sum of days of use (TSUA) and for the most frequently used ATBs. Each calculated rate for 100 days hospitalized. In addition, the antimicrobial susceptibility of the most frequently isolated bacteria in our service: coagulase-negative Staphylococcus (SCN) and Gram-negative bacilli (BGN) were recorded continuously. RESULTS: The 34.7% of the hospitalized patients received some type of antimicrobial agent. ATBs were 32.3% of medicines used. The most widely used was ampicillin (with 20.2% of the total) and cefadroxyl (with 11.6%). The RUA did not change during the study time, but STUA decreased by 10.7% between 2011 and 2014 with p < 0.05. When subgroup analyzes were divided by weight ranges, in the < 750 g group, the use of vancomycin decreased in use by 9.9% and an increase of 18.8% for metronidazole was observed. On the other hand, there was an increase in the use of the piperacillin-tazobactam regimen in the range > 1,500 g. When evaluating antimicrobial susceptibility, there was a decrease in susceptibility for oxacillin in SCN between 2011 and 2014 from 27% to 10.3% respectively. In addition, for Gram negative there was a decrease from 76.9% to 40.5% in susceptibility to third generation cephalosporins, mainly due to Klebsiella pneumoniae, which became the predominantly isolated BGN with an increase of 6.7% to 50% between 2011 and 2014, respectively. For K. pneumoniae the loss of susceptibility to third generation cephalosporins decreased from 77% to 22%. Finally, amikacin showed an activity over 85% in all BGNs between 2011 and 2014. CONCLUSIONS: It is advisable to plan and to maintain a continuous record of ATB consumption, as well as therapy and prophylaxis, being categorized by ATB type and range of newborn weight. It is of considerable importance to analyze and to evaluate the susceptibility of microorganisms. It is essential that an interdisciplinary team prepare this recording, and to continuously provide feedback to professionals who maintain the functioning of neonatal care units.

Differential effects of prenatal stress in female 5-HTT-deficient mice: towards molecular mechanisms of resilience.

Prenatal stress (PS) exposure is known to increase the risk of developing emotional disorders like major depression in later life. However, some individuals do not succumb to adversity following developmental stress exposure, a phenomenon referred to as resilience. To date, the molecular mechanisms explaining why some subjects are vulnerable and others more resilient to PS are far from understood. Recently, we have shown that the serotonin transporter (5-HTT) gene may play a modulating role in rendering individuals susceptible or resilient to PS. However, it is not clear which molecular players are mediating the interaction between PS and the 5-Htt genotype in the context of vulnerability and resilience to PS. For this purpose, we performed a microarray study with the help of Affymetrix GeneChip® Mouse Genome 430 2.0 Array, in which we separated wild-type and heterozygous 5-Htt-deficient (5-Htt+/-) PS offspring into susceptible and resilient offspring according to their performance in the forced swim test. Performance-oriented LIMMA analysis on the mRNA expression microarray data was followed by subsequent Spearman's correlation analysis linking the individual qRT-PCR mRNA expression data to various anxiety- and depression-related behavioral and neuroendocrine measures. Results indicate that, amongst others, Fos-induced growth factor (Figf), galanin receptor 3 (Galr3), growth hormone (Gh) and prolactin (Prl) were differentially expressed specifically in resilient offspring when compared to controls, and that the hippocampal expression of these genes showed several strong correlations with various measures of the hypothalamus-pituitary-adrenal axis (re)activity. In conclusion, there seems to be an intricate interplay between the expression of Figf, Galr3, Gh and Prl and neuroendocrine regulation, which may be critical in mediating resilience to PS exposure. More insight into the exact role of these molecular players may significantly enhance the development of new treatment strategies for stress-related emotional disorders.

A new semisynthetic derivative of sauroine induces LTP in hippocampal slices and improves learning performance in the Morris Water Maze.

Two semisynthetic acetyl derivatives of the alkaloid sauroine from Huperzia saururus, monoacetyl sauroine, and diacetyl sauroine (DAS) were obtained and their chemical structures were analyzed by NMR. While monoacetyl sauroine is the typical product of acetylation, DAS is an unexpected derivative related to the keto-enol formation of sauroine. Recordings of field excitatory post-synaptic potentials from the CA1 region of rat hippocampal slices showed that only DAS acutely applied induced chemical long-term potentiation (LTP) in a dose-dependent manner with an EC50 of 1.15 ± 0.09 µM. This effect was blocked by 10 µM D(-)-2-amino-5-phosphonopentanoic acid (AP5), suggesting dependence on the NMDA receptor. DAS significantly increased NMDA receptor-dependent excitatory post-synaptic currents without affecting α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor-dependent currents. Repetitive administration of DAS improved visuo-spatial learning in the Morris Water Maze. In slices from rats tested in the Morris Water Maze, LTP resulting from electrical synaptic stimulation was 2.5 times larger than in controls. Concentration of DAS measured in the brain after repetitive administration was 29.5 µM. We conclude that slices perfused with DAS display a robust NMDA receptor-dependent chemical LTP. During chronic treatment, DAS enhances learning abilities through a metaplastic mechanism as revealed by the augmentation of LTP in slices. DAS, therefore, may be a promising compound as a nootropic therapeutic drug. A semisynthetic derivative of sauroine, diacetyl sauroine (DAS), induces chemical long-term potentiation in rat hippocampal slices increasing the NMDA receptor-dependent current. 2 mg/kg prior to each session in a Morris Water Maze (MWM) improves behavior performance. In slices prepared from the tested rats the electrical stimulation-dependent long-term potentiation (LTP) was greatly enhanced. Therefore, DAS may have potency as a nootropic drug against the memory decline.

Usefulness of adalimumab in the treatment of refractory uveitis associated with juvenile idiopathic arthritis.

PURPOSE: To assess the efficacy and safety of adalimumab in patients with juvenile idiopathic arthritis (JIA) and associated refractory uveitis. DESIGN: Multicenter, prospective case series. METHODS: Thirty-nine patients (mean [SD] age of 11.5 [7.9] years) with JIA-associated uveitis who were either not responsive to standard immunosuppressive therapy or intolerant to it were enrolled. Patients aged 13-17 years were treated with 40 mg of adalimumab every other week for 6 months and those aged 4-12 years received 24 mg/m(2) body surface. RESULTS: Inflammation of the anterior chamber (2.02 [1.16] versus 0.42 [0.62]) and of the posterior segment (2.38 [2.97] versus 0.35 [0.71] decreased significantly between baseline and the final visit (P < 0.001). The mean (SD) macular thickness at baseline was 304.54 (125.03) µ and at the end of follow-up was 230.87 (31.12) µ (P < 0.014). Baseline immunosuppression load was 8.10 (3.99) as compared with 5.08 (3.76) at the final visit (P < 0.001). The mean dose of corticosteroids also decreased from 0.25 (0.43) to 0 (0.02) mg (P < 0.001). No significant side effects requiring discontinuation of therapy were observed. CONCLUSION: Adalimumab seems to be an effective and safe treatment for JIA-associated refractory uveitis and may reduce steroid requirement.