Exploring the Immunomodulatory Moonlighting Activities of Acute Phase Proteins for Tolerogenic Dendritic Cell Generation

The acute phase response is generated by an overwhelming immune-inflammatory process against infection or tissue damage, and represents the initial response of the organism in an attempt to return to homeostasis. It is mediated by acute phase proteins (APPs), an assortment of highly conserved plasma reactants of seemingly different functions that, however, share a common protective role from injury. Recent studies have suggested a crosstalk between several APPs and the mononuclear phagocyte system (MPS) in the resolution of inflammation, to restore tissue integrity and function. In fact, monocyte-derived dendritic cells (Mo-DCs), an integral component of the MPS, play a fundamental role both in the regulation of antigen-specific adaptive responses and in the development of immunologic memory and tolerance, particularly in inflammatory settings. Due to their high plasticity, Mo-DCs can be modeled in vitro toward a tolerogenic phenotype for the treatment of aberrant immune-inflammatory conditions such as autoimmune diseases and allotransplantation, with the phenotypic outcome of these cells depending on the immunomodulatory agent employed. Yet, recent immunotherapy trials have emphasized the drawbacks and challenges facing tolerogenic Mo-DC generation for clinical use, such as reduced therapeutic efficacy and limited in vivo stability of the tolerogenic activity. In this review, we will underline the potential relevance and advantages of APPs for tolerogenic DC production with respect to currently employed immunomodulatory/immunosuppressant compounds. A further understanding of the mechanisms of action underlying the moonlighting immunomodulatory activities exhibited by several APPs over DCs could lead to more efficacious, safe, and stable protocols for precision tolerogenic immunotherapy

Synthesis and catalytic activity of well-defined Co(i) complexes based on NHC–phosphane pincer ligands

A new methodology for the preparation of Co(I)–NHC (NHC = N-heterocyclic carbene) complexes, namely, [Co(PCNHCP)(CO)2][Co(CO)4] (1) and [Co(PCNHCP)(CO)2]BF4 (2), has been developed (PCNHCP = 1,3-bis(2-(diphenylphosphanyl)ethyl)-imidazol-2-ylidene). Both complexes can be straightforwardly prepared by direct reaction of their parent imidazolium salts with the Co(0) complex Co2(CO)8. Complex 1 efficiently catalyses the reductive amination of furfural and levulinic acid employing silanes as reducing agents under mild conditions. Furfural has been converted into a variety of secondary and tertiary amines employing dimethyl carbonate as the solvent, while levulinic acid has been converted into pyrrolidines under solventless conditions. Dehydrocoupling of the silane to give polysilanes has been observed to occur as a side reaction of the hydrosilylation process

ESTELLE: A Method to Analyze Automatically the Performance of Telecontrol Protocols in SCADA Systems

This paper presents the use of ESTELLE, a formal description technique, as a method to calculate automatically the performance of telecontrol protocols in SCADAsystems. Some specific primitives are added to the ESTELLE description language in order to achieve that goal. As an example, we analyze the performance of a telecontrol protocol. The results from this method are compared to performance measurements obtained from analytical and simulated solutionsMinisterio de Ciencia y Tecnología TIC 2000-111

The impact of class imbalance in classification performance metrics based on the binary confusion matrix

A major issue in the classification of class imbalanced datasets involves the determination of the most suitable performance metrics to be used. In previous work using several examples, it has been shown that imbalance can exert a major impact on the value and meaning of accuracy and on certain other well-known performance metrics. In this paper, our approach goes beyond simply studying case studies and develops a systematic analysis of this impact by simulating the results obtained using binary classifiers. A set of functions and numerical indicators are attained which enables the comparison of the behaviour of several performance metrics based on the binary confusion matrix when they are faced with imbalanced datasets. Throughout the paper, a new way to measure the imbalance is defined which surpasses the Imbalance Ratio used in previous studies. From the simulation results, several clusters of performance metrics have been identified that involve the use of Geometric Mean or Bookmaker Informedness as the best null-biased metrics if their focus on classification successes (dismissing the errors) presents no limitation for the specific application where they are used. However, if classification errors must also be considered, then the Matthews Correlation Coefficient arises as the best choice. Finally, a set of null-biased multi-perspective Class Balance Metrics is proposed which extends the concept of Class Balance Accuracy to other performance metrics

Ingeniería de características para la clasificación de señales sonoras

Muchos autores han demostrado que el canto de anuros puede ser un indicador del cambio climático. Por esta razón, la clasificación del sonido del canto de anuros se ha convertido en un tema importante para biólogos y otros científicos del clima. A lo largo de este artículo se describirá la investigación que se llevará a cabo para encontrar el mejor camino de realizar una clasificación automática de los cantos de anuros.Several authors have shown that the sounds of anurans can be used as an indicator of climate change. For this purpose anuran sound automatic classification has become an important issue for biologists and other climate scientists. In this paper, we will describe the research to find the best way to perform an automatic classification of anurans sounds.Plan Propio de la Universidad de Sevilla Proyecto: 2017/0000096

Representación óptima del espectro de llamadas de anuros en sistemas de control ambiental utilizando redes de sensores inalámbricos

El análisis y la clasificación de los sonidos producidos por determinadas especies animales, en particular los anuros, han revelado que son un potente indicador de la existencia del cambio climático. Es por lo que los sistemas de monitorización ambiental que utilizan redes de sensores inalámbricos son de gran interés para obtener indicadores del calentamiento global. El presente documento se centra en este proceso de extracción de características explorando tres alternativas: el MPEG- 7 estandarizado, los Filter Bank Energy (Energía de Bancos de Filtros, FBE) y los Mel Frequency Cepstral Coefficients (Coeficientes Cepstrales de Frecuencia de Mel, MFCC). Además, se consideran diferentes valores para cada opción en la extracción de las características del espectro.The analysis and classification of the sounds produced by certain animal species, in particular anurans, have revealed that they are a powerful indicator of the existence of climate change. Environmental monitoring systems using wireless sensor networks are of great interest for global warming indicators. This paper focuses on this feature extraction process by exploring three alternatives: the standardised MPEG-7, Filter Bank Energy (FBE) and Mel Frequency Cepstral Coefficients (MFCC). In addition, different values are considered for each option in the extraction of spectrum characteristics

Baropodometric association of the first metatarsal bone in medial tibial stress syndrome

[Resumen] Objetivos: El síndrome de estrés tibial medial (SETM) es una lesión de sobreuso por estrés mecánico, que se localiza por lo general en el borde postero-medial de la tibia. El objetivo de este estudio es cuantificar la diferencia baropodométrica existente en la primera cabeza metatarsal entre dos grupos. Métodos: Se analizaron las huellas de 30 participantes, de los cuales 15 padecían SETM y 15 controles. Se trata de un estudio observacional en el que se obtuvieron las huellas baropodométricas de los participantes, caminando sobre una plataforma de presiones. Se cuantificó la presión plantar media y la integral presión/tiempo que estaba recibiendo cada paciente en la primera cabeza metatarsal. Realizamos la prueba t-student para muestras independientes con el objetivo de definir las diferencias. Resultados: Los resultados de la variable presión plantar media muestran diferencias estadísticamente significativas entre los 2 grupos (p=0,001 para pie izquierdo y p=0,001 para pie derecho). Por el contrario no se observaron diferencias estadísticamente significativas para la variable integral presión/tiempo en ambos grupos (p=0,327 para pie izquierdo y p=0,300 para pie derecho). Conclusiones: Según nuestro estudio, los resultados obtenidos concluyen que el SETM se ocasiona con mayor frecuencia en personas con una disminución significativa de la presión plantar en la cabeza del primer metatarsiano medida en plataforma baropodométrica. Consideramos que son necesarios más estudios que evidencien esta relación biomecánica mediante plantillas instrument[Abstract] Objectives: Medial tibial stress syndrome (MTSS) is a mechanical stress overuse lesion, which is usually located at the post-medial border of the tibia. This study aims to quantify the baropodometric difference in the first metatarsal head between two groups. Methods: For the study 30 patient footprints were analyzed. Among them, half were affected by MTSS and the other half were controls. The baropodometric footprint samples were obtained by walking barefooted over a platform. While the patients were walking the average plantar pressure and the integral ratio pressure/time was quantified. The T-student test was performed in independent samples in order to define the differences. Results: The average plantar pressure results show statistically significant differences amongst the 2 groups (p=0.001 for the left foot and p=0.001 for the right foot). On the other hand, there were not any significant differences for the integral pressure/time variable in both groups (p=0.327 for the left foot and p=0.300 for the right foot). Conclusion: By having done this study, we can affirm that the MTSS is more frequent in persons with a significant plantar pressure decrease in the first metatarsal head measured in the baropodometric platform. We consider the need for further studies that prove this biomechanical connection through instrumented insoles

Usefulness of circulating microRNAs for the prediction of early preeclampsia at first-trimester of pregnancy

To assess the usefulness of circulating microRNAs (miRNAs) as non-invasive molecular biomarkers for early prediction of preeclampsia, a differential miRNA profiling analysis was performed in first-trimester pooled sera from 31 early preeclampsia patients, requiring delivery before 34 weeks of gestation, and 44 uncomplicated pregnancies using microfluidic arrays. Among a total of 754 miRNAs analyzed, the presence of 63 miRNAs (8%) was consistently documented in the sera from preeclampsia and control samples. Nevertheless, only 15 amplified miRNAs (2%) seemed to be differentially, although modestly, represented (fold change range: 0.4-1.4). After stem loop RT-qPCR from individual samples, the statistical analysis confirmed that none of the most consistent and differentially represented miRNAs (3 overrepresented and 4 underrepresented) were differentially abundant in serum from preeclamptic pregnancies compared with serum from normal pregnancies. Therefore, maternal serum miRNA assessment at first-trimester of pregnancy does not appear to have any predictive value for early preeclampsia

Effect of Preoperative Infusion of Levosimendan on Biomarkers of Myocardial Injury and Haemodynamics After Paediatric Cardiac Surgery: A Randomised Controlled Trial

Trial registry number: EudraCT 2012-005310-19.Key Points A randomised controlled trial was conducted to test the hypothesis that preoperative infusion of levosimendan would decrease myocardial injury biomarkers (troponin I and B-type natriuretic peptide) after paediatric cardiac surgery more efficiently than placebo. Troponin I and B-type natriuretic peptide levels were higher with placebo at 12 and 24 h after cardiopulmonary bypass, but the differences were not statistically significant. Lactic acid level was significantly lower and oxygen delivery (DO2) was significantly higher at 12 and 24 h after surgery in Levosimendan group. The results highlight the importance of this new drug and its possible benefit with regard to myocardial injury; however, evaluation in larger, adequately powered trials is needed to determine the efficacy of levosimendan.Objective The aim was to test the hypothesis that preoperative infusion of levosimendan would decrease patients’ cardiac biomarker profiles during the immediate postoperative stage (troponin I and B-type natriuretic peptide levels) more efficiently than placebo after cardiopulmonary bypass. Methods In a randomised, placebo-controlled, double-blinded study, 30 paediatric patients were scheduled for congenital heart disease surgery. 15 patients (50%) received prophylactic levosimendan and 15 patients (50%) received placebo from 12 h before cardiopulmonary bypass to 24 h after surgery. Results Troponin I levels were higher in the placebo group at 0, 12, and 24 h after cardiopulmonary bypass, although the mean differences between the study groups and the 95% confidence intervals (CIs) for troponin I levels did not present statistically significant differences at any of the three time points considered (mean differences [95% CIs] − 3.32 pg/ml [− 19.34 to 12.70], − 2.42 pg/ml [− 19.78 to 13.95], and − 79.94 pg/ml [− 266.99 to 16.39] at 0, 12, and 24 h, respectively). A similar lack of statistically significant difference was observed for B-type natriuretic peptide (mean differences [95% CIs] 36.86 pg/dl [− 134.16 to 225.64], − 350.79 pg/dl [− 1459.67 to 557.45], and − 310.35 pg/dl [− 1505.76 to 509.82]). Lactic acid levels were significantly lower with levosimendan; the mean differences between the study groups and the 95% CIs for lactate levels present statistically significant differences at 0 h (− 1.52 mmol/l [− 3.19 to − 0.25]) and 12 h (− 1.20 mmol/l [− 2.53 to − 0.10]) after cardiopulmonary bypass. Oxygen delivery (DO2) was significantly higher at 12 h and 24 h after surgery (mean difference [95% CI] 627.70 ml/min/m2 [122.34–1162.67] and 832.35 ml/min/m2 [58.15 to 1651.38], respectively). Conclusions Levosimendan does not significantly improve patients’ postoperative troponin I and B-type natriuretic peptide profiles during the immediate postoperative stage in comparison with placebo, although both were numerically higher with placebo. Levosimendan, however, significantly reduced lactic acid levels and improved patients’ DO2 profiles. These results highlight the importance of this new drug and its possible benefit with regard to myocardial injury; however, evaluation in larger, adequately powered trials is needed to determine the efficacy of levosimendan

Multi-Etiological Nature of Tuberculosis-Like Lesions in Condemned Pigs at the Slaughterhouse.

Tuberculosis-like lesions (TBL) in pigs have been associated with microorganisms other than mycobacteria. In this work a histopathological and microbiological evaluation of TBL in pigs is shown. A total of 352 samples belonging to 171 pigs totally condemned at slaughterhouse due to generalized TBL were sampled and selected for analysis. Pyogranulomatous (56.2%) and granulomatous lesions (20.2%) were observed in all analysed organs. Most of the granulomas observed in both lymph nodes and lungs belonged to more advanced stages of development (stages III and IV) whereas in the liver and the spleen most of lesions belonged to intermediate stages (stages II and III). Different microorganisms were simultaneously detected from TBL in the 42.7% of the animals. Mycobacterium tuberculosis complex (MTC) (38%), coryneform bacteria (40.3%) and streptococci (28.1%) were the main groups of microorganisms detected after bacteriological analysis, with Trueperella pyogenes and Streptococcus suis as the most frequently isolated species. Mycobacteria belonging to MTC were the most frequently detected pathogens in granulomatous and pyogranulomatous lesions in submandibular lymph nodes (32.7%) and coryneform bacteria were the microorganisms more frequently isolated from lungs (25.9%) and spleen samples (37.2%). These results may provide new insights into the pathogenesis and diagnosis of this pathology. The importance of coryneform bacteria and streptococci in such processes must be evaluated in future studies