Paper-based chromatic toxicity bioassay by analysis of bacterial ferricyanide reduction

Water quality assessment requires a continuous and strict analysis of samples to guarantee compliance with established standards. Nowadays, the increasing number of pollutants and their synergistic effects lead to the development general toxicity bioassays capable to analyse water pollution as a whole. Current general toxicity methods, e.g. Microtox®, rely on long operation protocols, the use of complex and expensive instrumentation and sample pre-treatment, which should be transported to the laboratory for analysis. These requirements delay sample analysis and hence, the response to avoid an environmental catastrophe. In an attempt to solve it, a fast (15 min) and low-cost toxicity bioassay based on the chromatic changes associated to bacterial ferricyanide reduction is here presented. E. coli cells (used as model bacteria) were stably trapped on low-cost paper matrices (cellulose-based paper discs, PDs) and remained viable for long times (1 month at -20 °C). Apart from bacterial carrier, paper matrices also acted as a fluidic element, allowing fluid management without the need of external pumps. Bioassay evaluation was performed using copper as model toxic agent. Chromatic changes associated to bacterial ferricyanide reduction were determined by three different transduction methods, i.e. (i) optical reflectometry (as reference method), (ii) image analysis and (iii) visual inspection. In all cases, bioassay results (in terms of half maximal effective concentrations, EC50) were in agreement with already reported data, confirming the good performance of the bioassay. The validation of the bioassay was performed by analysis of real samples from natural sources, which were analysed and compared with a reference method (i.e. Microtox). Obtained results showed agreement for about 70% of toxic samples and 80% of non-toxic samples, which may validate the use of this simple and quick protocol in the determination of general toxicity. The minimum instrumentation requirements and the simplicity of the bioassay open the possibility of in-situ water toxicity assessment with a fast and low-cost protocolPostprint (author's final draft

Thyroid hormone regulation of gene expression in the developing rat fetal cerebral cortex: Prominent role of the Ca2+/calmodulin-dependent protein kinase IV pathway

11 p., 6 figures, 1 table and references.Thyroid hormones influence brain development through regulation of gene expression mediated by nuclear receptors. Nuclear receptor concentration increases rapidly in the human fetus during the secondtrimester,aperiod of high sensitivity of the brain to thyroidhormones.In the rat, the equivalent period is the last quarter of pregnancy. However, little is known about thyroid hormone action in the fetal brain, and in rodents, most thyroid hormone-regulated genes have been identified during the postnatal period. To identify potential targets of thyroid hormone in the fetal brain,weinduced maternal and fetal hypothyroidism by maternal thyroidectomy followed by antithyroid drug (2-mercapto-1-methylimidazole) treatment. Microarray analysis identified differentially expressed genes in the cerebral cortex of hypothyroid fetuses on d 21 after conception. Gene function analysis revealed genes involved in the biogenesis of the cytoskeleton, neuronal migration and growth,and branching of neurites. Twenty percent of the differentially expressed genes were related to each other centered on the Ca2 and calmodulin-activated kinase (Camk4) pathway.Camk4was regulated directly by T3 in primary cultured neurons from fetal cortex, and the Camk4 protein was also induced by thyroid hormone. No differentially expressed genes were recovered when euthyroid fetuses from hypothyroid mothers were compared with fetuses from normal mothers. Although the resultsdonot rule out a specific contribution from the mother, especially at earlier stages of pregnancy, they indicate that the main regulators of thyroid hormone-dependent, fetal brain gene expression near term are the fetal thyroid hormones.This work was supported by Grants BFU2005-01740, SAF2008-01168, and SAF2006-14068 from the Ministry of Science and Innovation, Spain, by the European Union Integrated Project CRESCENDO (LSHM- CT-2005-018652), and by the Center for Biomedical Research on Rare Diseases (CIBERER). D.D. was supported by the I3P program of the Consejo Superior de Investigaciones Científicas, Spain, and by a postdoctoral fellowship from The Japanese Society for the Promotion of Science. D.N. was supported by a predoctoral fellowship of the Spanish Ministry of Science and Innovation.Peer reviewe

Thyroid hormone regulation of gene expression in the developing rat fetal cerebral cortex: Prominent role of the Ca2+/calmodulin-dependent protein kinase IV pathway

Thyroid hormones influence brain development through regulation of gene expression mediated by nuclear receptors. Nuclear receptor concentration increases rapidly in the human fetus during the secondtrimester,aperiod of high sensitivity of the brain to thyroidhormones.In the rat, the equivalent period is the last quarter of pregnancy. However, little is known about thyroid hormone action in the fetal brain, and in rodents, most thyroid hormone-regulated genes have been identified during the postnatal period. To identify potential targets of thyroid hormone in the fetal brain,weinduced maternal and fetal hypothyroidism by maternal thyroidectomy followed by antithyroid drug (2-mercapto-1-methylimidazole) treatment. Microarray analysis identified differentially expressed genes in the cerebral cortex of hypothyroid fetuses on d 21 after conception. Gene function analysis revealed genes involved in the biogenesis of the cytoskeleton, neuronal migration and growth, and branching of neurites. Twenty per cent of the differentially expressed genes were related to each other centered on the Ca2+ and calmodulin-activated kinase (Camk4) pathway.Camk4was regulated directly by T3 in primary cultured neurons from fetal cortex, and the Camk4 protein was also induced by thyroid hormone. No differentially expressed genes were recovered when euthyroid fetuses from hypothyroid mothers were compared with fetuses from normal mothers. Although the resultsdonot rule out a specific contribution from the mother, especially at earlier stages of pregnancy, they indicate that the main regulators of thyroid hormone-dependent, fetal brain gene expression near term are the fetal thyroid hormones.Ministerio de Ciencia e Innovación (España)European CommissionCentro de Investigación Biomédica en Enfermedades Raras (España)Consejo Superior de Investigaciones Científicas (España)The Japanese Society for the Promotion of ScienceDepto. de Biología CelularFac. de Ciencias BiológicasTRUEpu

Paper-based chromatic toxicity bioassay by analysis of bacterial ferricyanide reduction

Water quality assessment requires a continuous and strict analysis of samples to guarantee compliance with established standards. Nowadays, the increasing number of pollutants and their synergistic effects lead to the development general toxicity bioassays capable to analyse water pollution as a whole. Current general toxicity methods, e.g. Microtox®, rely on long operation protocols, the use of complex and expensive instrumentation and sample pre-treatment, which should be transported to the laboratory for analysis. These requirements delay sample analysis and hence, the response to avoid an environmental catastrophe. In an attempt to solve it, a fast (15 min) and low-cost toxicity bioassay based on the chromatic changes associated to bacterial ferricyanide reduction is here presented. E. coli cells (used as model bacteria) were stably trapped on low-cost paper matrices (cellulose-based paper discs, PDs) and remained viable for long times (1 month at -20 °C). Apart from bacterial carrier, paper matrices also acted as a fluidic element, allowing fluid management without the need of external pumps. Bioassay evaluation was performed using copper as model toxic agent. Chromatic changes associated to bacterial ferricyanide reduction were determined by three different transduction methods, i.e. (i) optical reflectometry (as reference method), (ii) image analysis and (iii) visual inspection. In all cases, bioassay results (in terms of half maximal effective concentrations, EC50) were in agreement with already reported data, confirming the good performance of the bioassay. The validation of the bioassay was performed by analysis of real samples from natural sources, which were analysed and compared with a reference method (i.e. Microtox). Obtained results showed agreement for about 70% of toxic samples and 80% of non-toxic samples, which may validate the use of this simple and quick protocol in the determination of general toxicity. The minimum instrumentation requirements and the simplicity of the bioassay open the possibility of in-situ water toxicity assessment with a fast and low-cost protoco

Complex Care Needs in Multiple Chronic Conditions: Population Prevalence and Characterization in Primary Care. A Study Protocol

Background: Chronicity, and particularly complex care needs for people with chronic diseases is one of the main challenges of health systems. Objective: To determine the population prevalence of people with chronic diseases and complex care needs and to characterize these needs considering features of health and social complexity in Primary Care. Design: Cross-sectional population-based study. Scope: Patients who have one or more chronic health conditions from three Primary Care urban centres of a reference population of 43.647 inhabitants older than 14 years old. Methodology: Data will be obtained from the review of electronical medical records. Complexity will be defined by: 1) the independent clinical judgment of primary care physicians and nurses and 2) the aid of three complexity domains (clinical and social). Patients with advanced chronic disease and limited life prognosis will be also described. Conclusions: This research protocol intends to describe and analyse complex care needs from a primary care professional perspective in order to improve knowledge of complexity beyond multimorbidity and previous consumption of health resources. Knowing about health and social complexity with a more robust empirical basis could help for a better integration of social and health policies and a more proactive and differentiated care approach in this most vulnerable population

Informe sobre el impacto verde europeo desde un enfoque de sistema alimentario sostenible

Fundación Triptolemos es una entidad privada que promueve el desarrollo del Sistema Alimentario Global Sostenible y contribuye con sus acciones a la optimización del sistema alimentario, a alcanzar una alimentación adecuada para toda la población, a mejorar la confianza del ciudadano y a la dignificación del sector. Sus actividades están avaladas por la Cátedra UNESCO "Science and Innovation for Sustainable Development: Global Food Production and Safety". El patronato de la Fundación reunido el 9 de febrero de 2021, aprobó redactar un informe sobre el impacto del Pacto Verde Europeo (Green Deal), desde un enfoque de sistema alimentario global en un contexto de cambio climático. Se invitó a participar a expertos en sus diversas áreas y a los investigadores de las 26 universidades y del Consejo Superior de Investigaciones Científicas de entre los miembros que conforman el patronato. Este informe está alineado con la visión de sistema alimentario de Fundación Triptolemos, con la intención de contribuir, como miembro de la sociedad civil, al desarrollo de una política alimentaria integral en la UE siguiendo el dictamen del Comité Económico y Social Europeo. Cada uno de los 6 capítulos contiene al inicio una pequeña introducción. Habida cuenta de la complejidad de los temas tratados y del número de investigadores, puede suceder que un solo hecho influya en varios conceptos y pueda darse por ello, alguna repetición con enfoques diferentes.Peer reviewe

Contemporary use of cefazolin for MSSA infective endocarditis: analysis of a national prospective cohort

Objectives: This study aimed to assess the real use of cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) in the Spanish National Endocarditis Database (GAMES) and to compare it with antistaphylococcal penicillin (ASP). Methods: Prospective cohort study with retrospective analysis of a cohort of MSSA IE treated with cloxacillin and/or cefazolin. Outcomes assessed were relapse; intra-hospital, overall, and endocarditis-related mortality; and adverse events. Risk of renal toxicity with each treatment was evaluated separately. Results: We included 631 IE episodes caused by MSSA treated with cloxacillin and/or cefazolin. Antibiotic treatment was cloxacillin, cefazolin, or both in 537 (85%), 57 (9%), and 37 (6%) episodes, respectively. Patients treated with cefazolin had significantly higher rates of comorbidities (median Charlson Index 7, P <0.01) and previous renal failure (57.9%, P <0.01). Patients treated with cloxacillin presented higher rates of septic shock (25%, P = 0.033) and new-onset or worsening renal failure (47.3%, P = 0.024) with significantly higher rates of in-hospital mortality (38.5%, P = 0.017). One-year IE-related mortality and rate of relapses were similar between treatment groups. None of the treatments were identified as risk or protective factors. Conclusion: Our results suggest that cefazolin is a valuable option for the treatment of MSSA IE, without differences in 1-year mortality or relapses compared with cloxacillin, and might be considered equally effective