Nanopore-Based Metagenomic Sequencing in Respiratory Tract Infection:A Developing Diagnostic Platform

Respiratory tract infection (RTI) remains a significant cause of morbidity and mortality across the globe. The optimal management of RTI relies upon timely pathogen identification via evaluation of respiratory samples, a process which utilises traditional culture-based methods to identify offending microorganisms. This process can be slow and often prolongs the use of broad-spectrum antimicrobial therapy, whilst also delaying the introduction of targeted therapy as a result. Nanopore sequencing (NPS) of respiratory samples has recently emerged as a potential diagnostic tool in RTI. NPS can identify pathogens and antimicrobial resistance profiles with greater speed and efficiency than traditional sputum culture-based methods. Increased speed to pathogen identification can improve antimicrobial stewardship by reducing the use of broad-spectrum antibiotic therapy, as well as improving overall clinical outcomes. This new technology is becoming more affordable and accessible, with some NPS platforms requiring minimal sample preparation and laboratory infrastructure. However, questions regarding clinical utility and how best to implement NPS technology within RTI diagnostic pathways remain unanswered. In this review, we introduce NPS as a technology and as a diagnostic tool in RTI in various settings, before discussing the advantages and limitations of NPS, and finally what the future might hold for NPS platforms in RTI diagnostics.</p

Integración entre servicios de salud y comunidad. Evaluación cualitativa de servicios de primer nivel de atención de la ciudad de Corrientes

La integración entre el equipo de salud y su comunidad de referencia es una de las condiciones operativas, y conceptuales, de la Atención Primaria de la Salud. Con el fin de evaluarla, se realizó una investigación en las Salas de Atención Primaria de la Salud de la Ciudad de Corrientes. Se utilizó un método exploratorio orientado desde una perspectiva interpretativa-cualitativa. 30 alumnos de la Carrera de Medicina de la Universidad Nacional del Nordeste fueron capacitados a tal efecto. Se realizaron observaciones in situ y entrevistas semi-estructuradas al personal de salud y a usuarios de las salas. Se realizó un análisis de contenido, esquematizado en un sistema de categorías preestablecidas y enriquecido con subcategorias inducidas a partir del análisis de la información. Como facilitadores para la integración, se encontró por parte del personal del equipo: conocimiento de los problemas de la zona, residencia en el barrio, buena accesibilidad a la atención y respuesta adecuada a la demanda; y por parte de la población: predisposición a participar. Como barreras para la integración: diferencias de conceptos respecto al rol del primer nivel de atención entre equipo de salud y comunidad y escasa integración de algunos profesionales. Se concluyó con que existen factores favorecedores importantes que habría que aprovechar y potenciar; en tanto, habría que trabajar sobre las barreras, comenzando por el rol fundamental que para esto tiene el equipo de salud. La mejor identificación de categorías que ha permitido este trabajo propicia la realización de estudios de mayor profundidad

Evolución de la demanda ambulatoria del sector público de la Ciudad de Corrientes en el período 1991-2013

La estrategia de atención primaria de la salud (APS) promueve fuertemente el rol del primer nivel de atención (PNA) como puerta de entrada al sistema; siendo su utilización un indicador de importancia que tiene dentro del sistema. A fin de evaluar la tendencia y distribución de demanda ambulatoria del subsector público en la ciudad de Corrientes (CCtes.), se analizaron las consultas externas del período 1991-2013 según los Anuarios de Estadísticas de la Provincia. Se utilizaron datos censales y proyecciones de población. Se evaluó la tendencia de utilización mediante el número de consultas en ambos niveles y tasas poblacionales. En el período la población de la CCtes. creció un 81,20 %; en tanto, el incremento de las consultas fue del 51,66 %: un 99,27 % las hospitalarias y 21,55 % las del PNA. En el primer trienio del período las consultas fueron superiores en el PNA. Luego la relación se invirtió y sólo volvió a superar el PNA al hospital en dos oportunidades: en el año 1998 y el período 2004-2007. Finalmente, se observa una recuperación en los últimos cuatro años observados. Las tasas provinciales pasaron de 3,5 a 5,0 consultas/habitantes/año; en tanto en la CCtes. pasó de 5,0 a 5,2 consultas/habitantes/año. Se concluye que en la CCtes., según las tasas, la utilización no ha variado y que el PNA no ha ocupado un lugar de relevancia en la atención ambulatoria.

Laser-induced breakdown spectroscopy applied to cattle compost for phosphorus quantification

Purpose Agronomic and environmental reasons force farmers to know the total P concentration of composted cattle manure. Laser-Induced Breakdown Spectroscopy seems proper to obtain such information. For logistic reasons (carriage, storage, field application, etc.), a dry matter characterization is also needed.Method Thirty samples of feedlot compost at different stages of stability and maturity were studied. Samples were dried at 50°C for dry matter characterization. As a reference method to determine total P concentration, wet digestion and colorimetry were employed. The area of the P I line emission obtained by laser-induced ablation of the samples was measured to estimate the total P concentration. Randomized calibrations through a modified version of the Kennard-Stone algorithm based on the Mahalanobis distance were performed.Results Dry matter varied from 40% to 90%, and no pattern was found related to compost origin, maturity, or stability. The total P concentration of the studied compost ranged from 1800 ppm up to 11200 ppm. Almost 80% of the calibration fittings have an R2 ≥ 0.895. The mean validation error was less than 22% for about 80% of the calibrations, with a mean prediction error bound to 40%. Discarding outliers, the errors were reduced to 19% and 30%, respectively.Conclusion Water content must be considered in addition to other characterizations due to logistic implications. Calibrations with a 30 percent of prediction error were achieved, which seems enough as a first approximation to predict the total P content in compost for utilization in farms to recycle nutrients

Modeling the Cerebellar Microcircuit: New Strategies for a Long-Standing Issue

The cerebellar microcircuit has been the work bench for theoretical and computational modeling since the beginning of neuroscientific research. The regular neural architecture of the cerebellum inspired different solutions to the long-standing issue of how its circuitry could control motor learning and coordination. Originally, the cerebellar network was modeled using a statistical-topological approach that was later extended by considering the geometrical organization of local microcircuits. However, with the advancement in anatomical and physiological investigations, new discoveries have revealed an unexpected richness of connections, neuronal dynamics and plasticity, calling for a change in modeling strategies, so as to include the multitude of elementary aspects of the network into an integrated and easily updatable computational framework. Recently, biophysically accurate realistic models using a bottom-up strategy accounted for both detailed connectivity and neuronal non-linear membrane dynamics. In this perspective review, we will consider the state of the art and discuss how these initial efforts could be further improved. Moreover, we will consider how embodied neurorobotic models including spiking cerebellar networks could help explaining the role and interplay of distributed forms of plasticity. We envisage that realistic modeling, combined with closed-loop simulations, will help to capture the essence of cerebellar computations and could eventually be applied to neurological diseases and neurorobotic control systems

Nuclear phospholipase Cβ1 interactome: a morphological and proteomic approach

Inositide-dependent phospholipase Cβ1 (PI-PLCβ1b) has two isoforms generated by alternative splicing (PI-PLCβ1a and PI-PLCβ1b). In murine erythroleukemia (MEL) cells both the isoforms are present within the nucleus, but PI-PLCβ1b is exclusively nuclear. Our group has demonstrated that PI-PLCβ1 nuclear localisation is crucial for its function, although the mechanism by which PI-PLCβ1 is imported into the nucleus has never been carefully investigated. The purpose of the present study was to get more insights on the protein interactome of PI-PLCβ1b, namely the proteins present in the nucleus. Immuno-affinity purification coupled with tandem mass spectrometry analysis have been used to purify and identify PI-PLCβ1b interaction binding partners from Friend’s erythroleukemia isolated nuclei. Gene ontology and protein-protein interaction network were performed to analyze data. Some interactions were already characterized, such as the binding with the splicing factor SRp20 and the lamin B. Among the proteins identified, the binding of eEF1A and prohibitin 2 with PI-PLCβ1b was confirmed by western blot analysis. Of particular interest was the identification of importin a, importin b1 and Ran, which interact with PI-PLCβ1b. These proteins are believed to be involved in the import mechanism from the cytoplasm to the nucleus. Further analysis by overexpressing both wild type and cytoplasmatic mutant of PI-PLCβ1, suggests that importin b1 is responsible for the localisation of PI-PLCβ1b in the nucleus, giving new insight into the mechanism of trafficking of this signaling molecule