Estado nutricional, obesidad y eventos en pacientes con fibrilación auricular / Nutrition status, obesity and outcomes in patients with atrial fibrillation

Introducción y objetivos Se ha descrito un efecto protector paradójico de la obesidad en pacientes con fibrilación auricular (FA) cuya mecanismo no está claro. El objetivo de este estudio fue determinar el impacto del estado nutricional y el índice de masa corporal (IMC) en el pronóstico de los pacientes con FA. Métodos Se realizó un estudio de cohortes retrospectivo de pacientes con FA entre 2014 y 2017 de una única área sanitaria en España. La escala CONUT se utilizó para evaluar el estado nutricional. La asociación del IMC y escala CONUT con la mortalidad se analizó por regresión de Cox. La asociación con eventos embólicos y hemorrágicos se evaluó mediante análisis de riesgos competitivos. Resultados Entre los 14.849 pacientes, se observó sobrepeso y obesidad en 42,6% y 46,0%, respectivamente, mientras que malnutrición en 34,3%. Durante un seguimiento medio de 4,4 años, 3.335 pacientes murieron, 984 pacientes sufrieron un evento embólico y 1.317 una hemorragia. El IMC se asoció inversamente con la mortalidad, embolias y hemorragias en el análisis univariado; sin embargo, esta asociación se perdió después del ajuste por edad, sexo, comorbilidades y escala CONUT (HR para el combinado de eventos 0,98; IC95%, 0,95-1,01; p=0,719). Por el contrario, la escala CONUT si se asoció con la mortalidad, la embolia y la hemorragia (HR = 1,15; IC95%, 1,14-1,17; p<0,001). Conclusiones El IMC no fue un predictor independiente de eventos en pacientes con FA, a diferencia del estado nutricional, que mostró una fuerte asociación con la mortalidad, la embolia y la hemorragia (AU)

Introduction and objectives A paradoxical protective effect of obesity has been previously reported in patients with atrial fibrillation (AF). The aim of this study was to determine the impact of nutritional status and body mass index (BMI) on the prognosis of AF patients. Methods We conducted a retrospective population-based cohort study of patients with AF from 2014 to 2017 from a single health area in Spain. The CONUT score was used to assess nutritional status. Cox regression models were used to estimate the association of BMI and CONUT score with mortality. The association with embolism and bleeding was assessed by a competing risk analysis. Results Among 14 849 AF patients, overweight and obesity were observed in 42.6% and 46.0%, respectively, while malnutrition was observed in 34.3%. During a mean follow-up of 4.4 years, 3335 patients died, 984 patients had a stroke or systemic embolism, and 1317 had a major bleeding event. On univariate analysis, BMI was inversely associated with mortality, embolism, and bleeding; however, this association was lost after adjustment by age, sex, comorbidities, and CONUT score (HR for composite endpoint, 0.98; 95%CI, 0.95-1.01; P=.719). Neither obesity nor overweight were predictors of mortality, embolism, and bleeding events. In contrast, nutritional status—assessed by the CONUT score—was associated with mortality, embolism and bleeding after multivariate analysis (HR for composite endpoint, 1.15; 95%CI, 1.14-1.17; P<.001). Conclusion BMI was not an independent predictor of events in patients with AF in contrast to nutritional status, which showed a strong association with mortality, embolism, and bleeding (AU)

Study of the Use of Antinematode Drugs, Mebendazole and Pyrantel, in Galicia (Spain) from 2016 to 2020.

To the best of our knowledge, there is no study on the use of drugs focused on the consumption of antinematode drugs in any region of the world. In the present study, we analyzed and evaluated the use of mebendazole and pyrantel in the provinces of Galicia (Spain), as well as described the variability of the consumption of both drugs between these provinces from 2016 to 2020. A descriptive, cross-sectional, and retrospective study of the consumption of these drugs, expressed in defined daily dose per 1000 inhabitants per day (DHD), was carried out. The DHD values for both drugs were small, although clearly higher, both on average and in variability, in the case of mebendazole. The difference in the mean DHD between both drugs and the geographical differences observed was statistically significant. The seasonal differences were statistically significant for both active principles, with lower values in summer. The active principle most consumed in all the provinces and years was mebendazole. The main consequence of the excessive use of this drug compared to pyrantel may be the increased risk of the development of resistance and of therapeutic failure, as well as the consequent limitation of pharmacological options in the future.

Balance entre el efecto de los eventos embólicos frente a los hemorrágicos en la mortalidad de los pacientes ancianos con fibrilación auricular / Trade-off between the effects of embolic versus bleeding events on mortality in elderly patients with atrial fibrillation

Introducción y objetivos: La toma de decisiones clínicas sobre la anticoagulación de pacientes ancianos con fibrilación auricular (FA) requiere que se considere no solo la incidencia de eventos embólicos y hemorrágicos, sino también el riesgo de muerte tras esos efectos adversos. Nuestro objetivo es analizar el balance con respecto a la mortalidad entre los eventos embólicos y hemorrágicos en pacientes ancianos con FA. Métodos: Se analizó a todos los pacientes de 75 o más años de un área de salud española diagnosticados de FA entre 2014 y 2017 (n=9.365). El riesgo de muerte se estimó utilizando modelos de Cox que incluyeron los episodios embólicos y hemorrágicos como variables dependientes del tiempo. Resultados: Durante una mediana de seguimiento de 4,0 años, los eventos se asociaron con mayor mortalidad, tanto los embólicos (HR=2,39; IC95%, 2,12-2,69) como los hemorrágicos (HR=1,79; IC95%, 1,64-1,96). El riesgo de muerte fue un 33% mayor después de una embolia que después de una hemorragia (rRR=1,33; IC95%, 1,15-1,55), aunque con accidente isquémico transitorio el riesgo fue menor que con hemorragia (rRR=0,79; IC95%, 0,63-0,99). La mortalidad tras una hemorragia intracraneal fue similar que tras una embolia mayor (RR=1,00; IC95%, 0,75-1,29). Conclusiones: En los pacientes de edad avanzada con FA, los eventos embólicos parecen estar asociados con una mayor mortalidad que las hemorragias extracraneales, salvo los accidentes isquémicos transitorios. Con hemorragia intracraneal, el riesgo de muerte es similar al de una embolia mayor (AU)

Introduction and objectives: Clinical decision-making on anticoagulation in elderly patients with atrial fibrillation (AF) requires clinicians to consider not only the incidence of embolic and bleeding events, but also the risk of death following these adverse events. We aimed to analyze the trade-off between embolic and bleeding events with respect to mortality in elderly patients with AF. Methods: The study cohort comprised all patients aged ≥ 75 years from a Spanish health area diagnosed with AF between 2014 and 2017 (n=9365). The risk of death was investigated using Cox proportional hazards models, including embolic and bleeding events as time-dependent binary indicators. Results: During a median follow-up of 4.0 years, both embolic and bleeding events were associated with a higher risk of death (adjusted HR, 2.39; 95%CI, 2.12-2.69; and adjusted HR, 1.79; 95%CI, 1.64-1.96, respectively). The relative risk of death was 33% higher following an embolism than following a bleeding event (rRR, 1.33; 95%CI, 1.15-1.55), although for transient ischemic attack the risk was lower than for bleeding (rRR, 0.79; 95%CI, 0.63-0.99). The risk of death associated with intracranial hemorrhage was similar to that of major embolisms (RR, 1.00; 95%CI, 0.75-1.29). Conclusions: In elderly AF patients, embolic events appeared to be associated with a higher risk of mortality than extracranial bleeding, except for transient ischemic attacks, which have a better prognosis. For ICH, the mortality risk was similar to that of major embolism (AU)

Reconstrucción de la vía aérea principal mediante el uso de prótesis sintéticas integrables / Reconstruction of the main airway through the use of integrable synthetic prosthesis

Uno de los principales problemas que plantea el tratamiento quirúrgico de las lesiones traqueales es la limitación existente en la longitud del segmento que es posible resecar. Actualmente, se puede extirpar con seguridad el 50% de la tráquea como máximo. Lesiones más extensas no se pueden beneficiar de este tratamiento y es necesario utilizar técnicas alternativas, en la mayoría de los casos paliativas. Una posible solución a este problema es la interposición de algún elemento que sustituya el segmento traqueal resecado. Se ha realizado un estudio experimental en animales, sustituyendo segmentos traqueales de distinta longitud por prótesis cilíndricas de politetrafluoroetileno. Posteriormente, se ha realizado un seguimiento y sacrificio de los animales estudiando los cambios histológicos. Los resultados obtenidos muestran la posibilidad técnica de la sustitución de la vía aérea por segmentos de material protésico. En el seguimiento evolutivo de los animales, parece existir una relación directa entre la longitud del implante y la aparición de estenosis traqueal a dicho nivel, tanto en los estudios morfológicos macroscópicos como en los estudios realizados con microscopía óptica. Sin embargo, por el momento, la mortalidad perioperatoria es elevada y, si bien se puede atribuir a la curva de aprendizaje, la traslación de los resultados a una posible práctica clínica no es recomendable

One of the main problems arising from the surgical treatment of tracheal lesions is the existing limitation in the length of segment that can be resected. Currently, a maximum of 50% of the trachea can be safely removed. More extensive lesions cannot benefit from this treatment and alternative techniques must be used, which are palliative in most cases. The interposition of an element which substitutes the segment of resected trachea is a possible solution for this problem. An experimental animal study has been conducted, substituting tracheal segments varying in length with cylindrical polytetrafluoroethylene prostheses. Later, a follow-up was done and the animals were sacrificed to study histological changes. The results show the technical possibility of substituting the airway with segments of prosthetic material. In the monitoring of the animals, there seems to be a direct relationship between the length of the implant and the appearance of tracheal stenosis at the implant site, both in the macroscopic morphological studies and the studies completed with optical microscopy. However, for the time being, perioperative mortality is high and, although it can be attributed to the learning curve, applying the results to possible clinical practice is not recommended

Pharmacokinetic model of florfenicol in turbot (Scophthalmus maximus): establishment of optimal dosage and administration in medicated feed.

The pharmacokinetics of florfenicol (FF) in turbot (Scophthalmus maximus) was studied after single intravenous (10 mg kg-1 ) and oral (100 mg kg-1 ) administration. The plasma concentration-time data of florfenicol were described by an open one-compartment model. The elimination half-life (t1/2 ) was estimated to be 21.0 h, and the total body clearance, Cl, was determined as 0.028 L kg h-1 . The apparent volume distribution (Vd ) was calculated to be 0.86 L kg-1 and the mean residence time (MRTiv ) was 30.2 h. Following oral administration, the maximum plasma concentration (Cmax ) of 55.4 µg mL-1 was reached at 12 h (Tmax ). The absorption constant (ka ) was 0.158 h-1 . The bioavailability was estimated to be 57.1%. The low bioavailability observed at higher doses was explained by the saturation of the mechanisms of absorption. The drug absorption process was limited by its inherent low solubility, which limited the amount of available FF absorbed in the gastrointestinal tract. Based on the pharmacokinetic data, an optimal dosing schedule for FF administration is hereby provided. Based on the minimum inhibitory concentration found for susceptible strains of Aeromonas salmonicida, oral FF administration of first, an initial dose of 30 mg FF kg-1 , followed by 6 maintenance doses at 18 mg kg-1 /daily could be effective against furunculosis in turbot.

Metodología geométrica para la evaluación de la saturación arterial de oxígeno en pacientes de la Unidad de Cuidados Intensivos / Geometric methodology for the saturation evaluation arterial oxygen in patients of the Care Unit Intensive

Introducción: En cardiología, la aplicación de teorías, como la de los sistemas dinámicos y la geometría fractal, han generado nuevos diagnósticos matemáticos que diferencian, de manera geométrica y cuantitativa, el comportamiento normal del enfermo a partir de la ocupación del atractor caótico cardíaco. El objetivo de este estudio fue desarrollar, en el contexto de la teoría de los sistemas dinámicos, una metodología de evaluación de la saturación arterial de oxígeno para pacientes en la Unidad de Cuidados Intensivos. Materiales y Métodos: Se seleccionaron 10 pacientes con diferentes enfermedades, provenientes de la Unidad de Cuidados Intensivos, a los cuales se les registró la saturación arterial de oxígeno durante su estancia en la Unidad, y se construyeron atractores caóticos en el mapa de retardo. Posteriormente, se establecieron cuantificaciones de los valores mínimos y máximos del atractor. Resultados: Los valores máximos y mínimos de los atractores de la saturación de oxígeno variaron entre el 100% y el 70%, para los pacientes que fallecieron, mientras que para aquellos que vivieron, se mantuvo entre el 99% y el 85%. Conclusiones: Se observó un comportamiento caótico asociado a la saturación arterial de oxígeno, cuantificable a partir de los valores máximos y mínimos hallados de la totalidad del atractor, estableciendo una nueva medida matemática y física del paciente crítico en la Unidad de Cuidados Intensivo (AU)

Introduction: In cardiology, the application of theories, such as dynamical systems and fractal geometry, has generated new mathematical diagnoses that differentiate geometrically and quantitatively the normal from the diseased behavior through the occupation of the cardiac chaotic attractor. The objective of this study was to develop, in the context of the dynamical systems theory, a methodology for the evaluation of arterial oxygen saturation in patients of the Intensive Care Unit. Materials and Methods: Ten patients with different pathologies from the Intensive Care Unit were selected. The arterial oxygen saturation was recorded during their stay in the Intensive Care Unit and chaotic attractors were built in the delay map. Subsequently, quantifications of the minimum and maximum values of the attractor were established. Results: The maximum and minimum values of the oxygen saturation attractors varied between 100% and 70% for patients who died, whereas for those who lived, saturation values between 99% and 85% were maintained. Conclusions: A chaotic behavior associated with arterial oxygen saturation, quantifiable through the maximum and minimum values found in the entire attractor, was observed, establishing a new mathematical and physical measurement of the critical patient in the Intensive Care Unit.(AU)

A 50-gene signature is a novel scoring system for tumor-infiltrating immune cells with strong correlation with clinical outcome of stage I/II non-small cell lung cancer

Purpose: To identify a novel system for scoring intratumoral immune response that can improve prognosis and therapy decisions in early stage non-small cell lung cancer (NSCLC). Methods/patients: Eighty-four completely resected stage I/II NSCLC without adjuvant therapy were classified by expression profiling using whole genome microarrays. An external cohort of 162 tumors was used to validate the results. Immune cells present in tumor microenvironment were evaluated semiquantitatively by CD20, CD79, CD3, CD8, CD4 and CD57 immunostaining. Univariate and multivariate analyses of variables associated with recurrence-free survival were performed. Results: Initial molecular classification identified three clusters, one with significantly better RFS. A reduced two-subgroup classification and a 50-gene predictor were built and validated in an external dataset: high and low risk of recurrence patients (HR = 3.44; p = 0.001). Analysis of the predictor´s genes showed that the vast majority were related to a B/plasma cell immune response overexpressed in the low-risk subgroup. The predictor includes genes coding for unique B lineage-specific genes, functional elements or other genes that, although non-restricted to this lineage, have strong influence on B-cell homeostasis. Immunostains confirmed increased B-cells in the low-risk subgroup. Gene signature (p < 0.0001) and CD20 (p < 0.05) were predictors for RFS, while CD79 and K-RAS mutations showed a tendency. Conclusions: Favorable prognosis in completely resected NSCLC is determined by a B-cell-mediated immune response. It can be differently scored by a 50-gene expression profile or by CD20 immunostaining. That prognosis information not reflected by traditional classifications may become a new tool for determining individualized adjuvant therapies (AU)

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Effects of fire and three fire-fighting chemicals on main soil properties, plant nutrient content and vegetation growth and cover after 10 years.

The study addresses a knowledge-gap in the long-term ecological consequences of fire and fire-fighting chemicals. Ten years after a prescribed fire and the application of three fire-fighting chemicals, their effects on the soil-plant system were evaluated. Five treatments were established: unburnt soils (US) and burnt soils treated with water alone (BS), foaming agent (BS+Fo), Firesorb (BS+Fi) and ammonium polyphosphate (BS+Ap). Soils (0-2 cm depth) and foliar material of shrubs (Erica umbellata, Pterospartum tridentatum and Ulex micranthus) and trees (Pinus pinaster) were analysed for total N, δ(15)N, and soil-available and plant total macronutrients and trace elements. Soil pH, NH4(+)-N and NO3(-)-N; pine basal diameter and height; and shrub cover and height were also measured. Compared with US plots, burnt soils had less nitrates and more Mo. Although differences were not always significant, BS+Ap had the highest levels of soil available P, Na and Al. Plants from BS+Ap plots had higher values of δ(15)N (P. pinaster and E. umbellata), P (all species), Na (P. tridentatum and U. micranthus) and Mg (E. umbellata and P. tridentatum) than other treatments; while K in plants from BS+Ap plots was the highest among treatments for P. pinaster and the lowest for the shrubs. Pines in US plots were higher and wider than in burnt treatments, except for BS+Ap, where the tallest and widest trees were found, although half of them were either dead (the second highest mortality after BS+Fi) or had a distorted trunk. BS+Ap was the treatment with strongest effects on plants, showing E. umbellata the lowest coverage and height, P. tridentatum the highest coverage, U. micranthus one of the lowest coverages and being the only treatment where Genista triacanthos was absent. Consequently, it is concluded that both fire and ammonium polyphosphate application had significant effects on the soil-plant system after 10 years.

A 50-gene signature is a novel scoring system for tumor-infiltrating immune cells with strong correlation with clinical outcome of stage I/II non-small cell lung cancer.

PURPOSE: To identify a novel system for scoring intratumoral immune response that can improve prognosis and therapy decisions in early stage non-small cell lung cancer (NSCLC). METHODS/PATIENTS: Eighty-four completely resected stage I/II NSCLC without adjuvant therapy were classified by expression profiling using whole genome microarrays. An external cohort of 162 tumors was used to validate the results. Immune cells present in tumor microenvironment were evaluated semiquantitatively by CD20, CD79, CD3, CD8, CD4 and CD57 immunostaining. Univariate and multivariate analyses of variables associated with recurrence-free survival were performed. RESULTS: Initial molecular classification identified three clusters, one with significantly better RFS. A reduced two-subgroup classification and a 50-gene predictor were built and validated in an external dataset: high and low risk of recurrence patients (HR = 3.44; p = 0.001). Analysis of the predictor´s genes showed that the vast majority were related to a B/plasma cell immune response overexpressed in the low-risk subgroup. The predictor includes genes coding for unique B lineage-specific genes, functional elements or other genes that, although non-restricted to this lineage, have strong influence on B-cell homeostasis. Immunostains confirmed increased B-cells in the low-risk subgroup. Gene signature (p < 0.0001) and CD20 (p < 0.05) were predictors for RFS, while CD79 and K-RAS mutations showed a tendency. CONCLUSIONS: Favorable prognosis in completely resected NSCLC is determined by a B-cell-mediated immune response. It can be differently scored by a 50-gene expression profile or by CD20 immunostaining. That prognosis information not reflected by traditional classifications may become a new tool for determining individualized adjuvant therapies.

Evaluación físico matemática de la dinámica cardiaca arrítmica mediante la aplicación de la ley exponencial caótica / Physical mathematical evaluation of the arrhythmic cardiac dynamic by means of the application of the chaotic exponential law / Avaliação físico matemática da dinâmica cardíaca arrítmica mediante a aplicação da lei exponencial caótica

Objetivo: confirmar la aplicabilidad clínica de la ley exponencial de ayuda diagnóstica específicamente en arritmias y evaluar la concordancia diagnóstica del mismo con respecto al Gold Estándar, por medio del cálculo de la sensibilidad, especificidad y el coeficiente Kappa. Metodología: se realizó un estudio de 40 Holter, 10 corresponden a sujetos normales y 30 diagnosticados con diferentes tipos de arritmias. Se realizó una simulación teórica de todas las frecuencias cardiacas de mínimo 21 horas a partir de los valores máximos y mínimos de frecuencias registrados, para construir el atractor de la dinámica cardiaca. Seguidamente se calculó la dimensión fractal del atractor y se cuantificó la ocupación espacial de cada uno ellos en el espacio generalizado de Box-counting. Finalmente, se aplicaron los parámetros matemáticos que diferencian dinámicas cardiacas normales de enfermas y agudas, así como en evolución hacia la enfermedad. Resultados: los casos con arritmias diagnosticados matemáticamente con dinámica aguda fueron seis, se encontraron 24 casos entre los rangos de 73 y 200 de ocupación de la rejilla Kp, que corresponden a casos de evolución hacia agudización de la dinámica. El diagnóstico físico-matemático, después de ser comparado con el Gold Estándar, presentó una sensibilidad y especificidad del 100% y un coeficiente Kappa de uno. Conclusiones: la aplicación de esta metodología al estudio de la dinámica cardiaca caótica, evidencia su utilidad como herramienta de ayuda diagnóstica para la predicción y prevención de eventos arrítmicos agudos que pueden implicar situaciones con riesgo vital.

Objective: To confirm the clinical applicability of the diagnostic methodology based on the power law of cardiac dynamic systems, specifically for detecting arrhythmias, evaluating its concordance with respect to the Gold Standard, by means of the sensitivity, specificity, and Kappa coefficient. Methods: Forty Holter were studied, of which 10 corresponded to normal subjects and 30 to patients diagnosed with different types of arrhythmias. A theoretical simulation of all cardiac frequencies (of at least 21 hours) was performed from the maximum and minimum frequency values registered, to build the cardiac dynamics attractor and its fractal dimension was calculated; the spatial occupation of each one of them was quantified in the generalized Box-Counting space. Finally, the mathematical parameters to differentiate normality of acute cardiac disease and of the evolution toward disease were applied. Results: There were six cases with mathematically-diagnosed acute arrhythmias, 24 cases were between 73 and 200 occupied ranges for the Kp grid that correspond to cases of evolution toward disease. This physical-mathematical diagnosis was compared with the Gold Standard and yielded a sensitivity and specificity of 100% and a Kappa coefficient of 1. Conclusions: The application of this method to the study of chaotic cardiac dynamics evidences its usefulness as a tool of diagnostic aid for the prediction of acute arrhythmic events which may imply situations of vital risk.

Objetivo: confirmar a aplicabilidade clínica da lei exponencial de ajuda diagnóstica especificamente em arritmias e avaliar a concordância diagnóstica do mesmo com respeito ao Gold Estándar, por meio do cálculo da sensibilidade, especificidade e o coeficiente Kappa. Metodologia: se realizou um estudo de 40 Holter, 10 correspondem a sujeitos normais e 30 diagnosticados com diferentes tipos de arritmias. Se realizou una simulação teórica de todas as frequências cardíacas de mínimo 21 horas a partir dos valores máximos e mínimos de frequências registrados, para construir o atractor da dinâmica cardíaca. Seguidamente se calculou a dimensão fractal do atractor e se quantificou a ocupação espacial de cada um deles no espaço generalizado de Box-counting. Finalmente, se aplicaram os parâmetros matemáticos que diferenciam dinâmicas cardíacas normais de doentes e agudas, assim como em evolução para a doença. Resultados: os casos com arritmias diagnosticados matematicamente com dinâmica aguda foram seis, se encontraram 24 casos entre as faixas de 73 e 200 de ocupação da grade Kp, que correspondem a casos de evolução para o agravamento da dinâmica. O diagnóstico físico-matemático, depois de ser comparado com o Gold Estándar, apresentou uma sensibilidade e especificidade de 100% e um coeficiente Kappa de um. Conclusões: a aplicação desta metodologia ao estudo da dinâmica cardíaca caótica, evidência sua utilidade como ferramenta de ajuda diagnóstica para a predição e prevenção de eventos arrítmicos agudos que possam implicar situações com risco vital.

Establishment and characterization of a new cell line (SSP-9) derived from Atlantic salmon Salmo salar that expresses type I ifn.

In the present work, the establishment and biological characterization of a new cell line, SSP-9, derived from the pronephros of the Atlantic salmon Salmo salar, are reported. These cells grew well in Leibovitz's (L15) medium supplemented with 10% foetal calf serum at temperatures from 15 to 25° C, and they have been sub-cultured over 100 passages to produce a continuous cell line with an epithelial-like morphology. The SSP-9 cells attached and spread efficiently at different plating densities, retaining 80% of cell viability after storage in liquid nitrogen. When karyotyped, the cells had 40-52 chromosomes, with a modal number of 48. Viral susceptibility tests showed that SSP-9 cells were susceptible to infectious pancreatic necrosis virus and infectious haematopoietic necrosis virus, producing infectious virus and regular cytopathic effects. Moreover, these cells could be stimulated by poly I:C, showing significant up-regulation in the expression of the genes that regulate immune responses, such as ifn and mx-1. SSP-9 cells constitutively express genes characteristic of macrophages, such as major histocompatibility complex (mhc-II) and interleukin 12b (il-12b), and flow cytometry assays confirmed that SSP-9 cells can be permanently transfected with plasmids expressing a reporter gene. Accordingly, this new cell line is apparently suitable for transgenic manipulation, and to study host cell-virus interactions and immune processes.

Elsevier Trophoblast Research Award Lecture: origin, evolution and future of placenta miRNAs.

MicroRNAs (miRNAs) regulate the expression of a large number of genes in plants and animals. Placental miRNAs appeared late in evolution and can be found only in mammals. Nevertheless, these miRNAs are constantly under evolutionary pressure. As a consequence, miRNA sequences and their mRNA targets may differ between species, and some miRNAs can only be found in humans. Their expression can be tissue- or cell-specific and can vary time-dependently. Human placenta tissue exhibits a specific miRNA expression pattern that dynamically changes during pregnancy and is reflected in the maternal plasma. Some placental miRNAs are involved in or associated with major pregnancy disorders, such as preeclampsia, intrauterine growth restriction or preterm delivery and, therefore, have a strong potential for usage as sensitive and specific biomarkers. In this review we summarize current knowledge on the origin of placental miRNAs, their expression in humans with special regard to trophoblast cells, interspecies differences, and their future as biomarkers. It can be concluded that animal models for human reproduction have a different panel of miRNAs and targets, and can only partly reflect or predict the situation in humans.

Methicillin-resistant Staphylococcus aureus ST30-SCCmec IVc clone as the major cause of community-acquired invasive infections in Argentina.

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections have become a major concern worldwide. We conducted a prospective multicenter study of invasive CA-MRSA to evaluate clinical features and genotype of strains causing invasive infections in Argentina. A total of 55 patients with invasive CA-MRSA infections were included. Most patients (60%) had bloodstream infections, 42% required admission to intensive care unit and 16% died. No CA-MRSA isolates were multiresistant (resistant ⩾3 classes of antibiotics). All isolates carried Panton-Valentine leukocidin (PVL) genes and staphylococcal cassette chromosome (SCCmec) type IV. The majority CA-MRSA strains belonged to ST30 and had identical pulsed-field gel electrophoresis (PFGE) patterns, qualifying as a clonal dissemination of a highly transmissible strain. The main clone recovered from patients with CA-MRSA invasive infections was genotyped as pulsed-field gel electrophoresis type C-ST30, SCCmec type IVc-spa type 019, PVL positive. It has become predominant and replaced the previously described CA-MRSA clone (PFGE type A, ST5, SCCmec type IV, spa type 311).

Antiviral activity of casein and αs2 casein hydrolysates against the infectious haematopoietic necrosis virus, a rhabdovirus from salmonid fish.

Salmonid fish viruses, such as infectious haematopoietic necrosis virus (IHNV), are responsible for serious losses in the rainbow trout and salmon-farming industries, and they have been the subject of intense research in the field of aquaculture. Thus, the aim of this work is to study the antiviral effect of milk-derived proteins as bovine caseins or casein-derived peptides at different stages during the course of IHNV infection. The results indicate that the 3-h fraction of casein and α(S2) -casein hydrolysates reduced the yield of infectious IHNV in a dose-dependent manner and impaired the production of IHNV-specific antigens. Hydrolysates of total casein and α(S2) -casein target the initial and later stages of viral infection, as demonstrated by the reduction in the infective titre observed throughout multiple stages and cycles. In vivo, more than 50% protection was observed in the casein-treated fish, and the kidney sections exhibited none of the histopathological characteristics of IHNV infection. The active fractions from casein were identified, as well as one of the individual IHNV-inhibiting peptides. Further studies will be required to determine which other peptides possess this activity. These findings provide a basis for future investigations on the efficacy of these compounds in treating other viral diseases in farmed fish and to elucidate the underlying molecular mechanisms of action. However, the present results provide convincing evidence in support of a role for several milk casein fractions as suitable candidates to prevent and treat some fish viral infections.

Predicción de unión de péptidos de Plasmodium falciparum al HLA clase II. Probabilidad, combinatoria y entropía aplicadas a las proteínas MSP-5 y MSP-6 / Plasmodium falciparum binding peptides prediction to HLA class II. Probability, combinatory and entropy applied to MSP-5 and MSP-6 proteins

Las proteínas de superficie del merozoíto (MSP) son de importancia en la invasión parasitaria al glóbulo rojo. La proteína MSP-5, encontrada en merozoítos libres, tiene un papel en la inmunización de ratones al P. falciparum y P. yoelii, pese a lo cual algunos estudios cuestionan su rol en la invasión. La proteína MSP-6 forma junto con MSP-1 y MSP-7 un complejo en la superficie del merozoíto, liberado del parásito cerca del momento de la invasión al glóbulo rojo. Con el fin de predecir el fenómeno de unión de péptidos de las proteínas de superficie MSP-5 y MSP-6, se aplicó una teoría de unión al HLA clase II, a la totalidad de secuencias de 20 aminoácidos de tales moléculas. Se calcularon los valores de probabilidad, combinatoria y entropía de 168 secuencias nonámeras sobrelapadas de la proteína MSP-5 y 228 de MSP-6. Por último se aplicó la teoría de unión a todos los péptidos nonámeros de tres proteínas construidas computacionalmente, cada una con una longitud de 500 aminoácidos. Para la proteína MSP-5 se predijo un total de 31 secuencias asociadas al macroestado de unión y 137 al de no unión, mientras que se predijo la existencia de 35 secuencias asociadas al macroestado de unión para MSP-6 y 193 al de no unión. Se encontraron respectivamente 100, 111 y 91 secuencias predichas de unión para las tres proteínas teóricas construidas. La predicción teórica de unión de péptidos es útil para facilitar el desarrollo de vacunas, al evidenciar el orden físico-matemático subyacente al fenómeno.(AU)

Calprotectin: a novel biomarker for the diagnosis of pleural effusion.

BACKGROUND: Novel non-invasive biomarkers for the precise diagnosis of malignancy in pleural effusion (PE) are needed. The aim of this study was to determine the diagnostic accuracy of calprotectin for predicting malignancy in patients with exudative PE. METHODS: Calprotectin concentration was measured in 156 individuals diagnosed with exudative PE (67 malignant and 89 benign). Calprotectin accuracy for discriminating between malignant and benign PE was evaluated using receiver operating characteristic (ROC) curves. Univariate and multivariate logistic regression were performed to test the association between calprotectin levels and malignant PE. RESULTS: Calprotectin levels were significantly lower in malignant pleural fluid (257.2 ng ml(-1), range: 90.7-736.4) than benign effusions (2627.1 ng ml(-1), range: 21-9530.1). The area under the curve was 0.963. A cutoff point of ≤ 736.4 ng ml(-1) rendered a sensitivity of 100%, with a specificity of 83.15%, which could prove useful to delimit those patients with negative cytology tests that should be referred for more invasive diagnostic procedures. Logistic regression demonstrated a strong association between calprotectin and malignancy (adjusted OR 663.14). CONCLUSION: Calprotectin predicts malignancy in pleural fluid with high accuracy and could be a good complement to cytological methods.

Terapia ocupacional precoz e intensiva en la prevención del delirium en adultos mayores ingresados a unidades de paciente crítico: ensayo clínico randomizado: resultados preliminares / Early and intensive occupational therapy in prevention of delirium in older adults admitted to critical patient unit: randomized clinical trial: prelimary results

Objetivo: comparar la eficacia de la prevención no farmacológica estándar (PnFE) versus la prevención no farmacológica reforzada (PnFR), consistente en prevención no farmacológica estándar más terapia ocupacional (TO) precoz e intensiva, en la incidencia del delirium en adultos mayores (AM) ingresados a unidad de pacientes críticos (UPC). Diseño: ensayo clínico randomizado, en UPC del Hospital Clínico de la Universidad de Chile (HCUCH). Sujetos: 70 pacientes de edad igual o superior a 60 años, ingresados al HCUCH entre abril y octubre del 2011, con necesidad de ingreso a UPC para monitorización, hospitalización por enfermedad aguda/crónica descompensada, con consentimiento del paciente o familiar y sin presencia de delirium al ingreso ni deterioro cognitivo previo al estudio. Materiales y métodos: PnFE (grupo control) consiste en: reorientación, movilización precoz, corrección de déficit sensoriales, manejo ambiental, protocolo de sueño y reducción de fármacos anticolinérgicos, versus PnFR (grupo experimental), que considera las siguientes áreas de intervención de TO: estimulación polisensorial, posicionamiento, estimulación cognitiva, entrenamiento en actividades de la vida diaria básica, estimulación motora de extremidades superiores y participación familiar; durante 5 días, dos veces al día. Se evaluó la presencia del delirium, con el CAM dos veces al día durante 5 días, y la severidad de éste con DRS; previo al alta se evaluó, independencia funcional con FIM, estado cognitivo con MMSE y fuerza de garra con dinamómetro de Jamar. Resultados: la PnFR de TO se asocia a menor incidencia de delirium, afectando al 16,1 por ciento del grupo con prevención no farmacológica estándar versus un 3,1 por ciento del con prevención no farmacológica reforzada, así como a menos días de hospitalización (20,6 días versus 10,4 p=.009). La independencia funcional al alta se mantiene en aspectos cognitivos (32,5 versus 32,9) mientras que en aspectos motores aumenta...

Objective: to compare the efficacy of standard non pharmacological prevention of delirium versus intensified prevention of delirium (standard prevention plus early and intensive occupational therapy) in the incidence of delirium in older adults (OA) admitted to critical patient unit (CPU). Desing: randomized control trial, blinded to outcome evaluator, in the CPU of Hospital Clínico Universidad de Chile. Subjects: 70 patients aged 60 years or older, admitted to CPU between April and October of 2011, with need for admission to CPU for monitoring, acute or decompensated chronic illness, without cognitive impairment and consent by patient or family member. Materials and methods: standard prevention group consisted in: reorienting, early mobilization, correction of sensory deficit, environmental management, protocol of sleep and reduction of drugs, and intensified prevention based on standard measured plus early and intensive Occupational therapy: multisensory stimulation, positioning, cognitive stimulation, training in activities of daily living, motor stimulation of the upper extremities and family participation, twice a day for 5 days. Delirium was evaluated (twice a day for 5 days) with CAM and severity with DRS. Primary outcome was delirium incidence, and secondarily were functional independence (FIM), cognitive status (MMSE) and strength of grip with jamar dynamometer at leaving. Results: early intervention and intensive occupational therapy is associated with lower incidence of delirium, affecting 16.1 percent of non-pharmacological standard prevention group and 3.1 percent of intensified prevention group, as well as fewer days of hospitalization (20, 6 days versus 10,4, p= 0,009). The functional independence at leaving keeps in cognitive (32.5 versus 32.9) and is increases significantly in motor aspects (46.5 versus 58.3 l, P =. 03). Conclusion: standard prevention plus early intensive intervention of occupational therapy is effective in...

MicroRNA expression profiles of trophoblastic cells.

BACKGROUND: MicroRNAs (miRNAs) are small single-stranded RNA molecules working as post-transcriptional modulators of gene expression. Trophoblast cells are a heterogenous group of fetal cells forming the feto-maternal interface and displaying a wide spectrum of functions. The regulation of their behavior may partly underly the control through miRNAs. Therefore, we aimed to compare the miRNA profile of primary first and third trimester trophoblast cells with that of different trophoblastic cell lines. MATERIAL AND METHODS: Total RNA was obtained from isolated cytotrophoblast cells from healthy term and first trimester placentae and the cell lines HTR-8/SVneo (immortalized trophoblast cells), JEG-3 (choriocarcinoma), ACH-3P and AC1-M59, which are choriocarcinoma cells fused with first and third trimester trophoblast cells, respectively. The expression level of 762 different miRNAs was quantitatively analyzed by using a TaqMan Human MicroRNA Array. For testing the reproducibility of the array technique, the expression of 9 selected miRNAs has been re-analyzed by individual qPCR. RESULTS: The analyzed cell types share many similar patterns of miRNAs, but are significantly distinct in the expression of three miRNA clusters: chromosome 19 miRNA cluster (C19MC; containing 54 different miRNAs), C14MC (34 miRNAs) and a minor cluster (miRNA-371 to miRNA-373 cluster), also located on chromosome 19. Expression of miRNAs within C19MC increases significantly from first to third trimester trophoblast while that of C14MC members decreases. MiRNAs within the miR-371-3 cluster augment slightly. C19MC and the miR-371-3 cluster are not expressed by HTR-8/SVneo cells whilst C14MC is almost not detectable in the choriocarcinoma-derived cell lines complete array data available at NCBI Gene Expression Omnibus accession number GSE32346: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE32346). Beside the miRNAs within the mentioned clusters, further 27 miRNAs are differentially expressed (>100 fold) between term and first trimester trophoblast cells. The placenta-specific miRNAs miR-141 and miR-21 as well as let-7g are expressed in all tested cells with the highest expression in primary trophoblast cells. CONCLUSION: Primary first trimester and term trophoblast cells and trophoblastic cell lines display major differences in their miRNA fingerprints which may be involved in their different behavior and characteristics.

Secreted clusterin in colon tumor cell models and its potential as diagnostic marker for colorectal cancer.

We studied the specific changes of the secreted protein clusterin and its cytoplasmic precursor regarding colorectal tumorigenesis, using in vitro differentiation of Caco-2 cells. In tumor-like stage, we observed an overexpression of both precursor and secreted clusterin, corroborated in the cell line SW-480. Noticeably, SW-620 cells (from a tumoral node, thus with metastatic capacity) did not show overexpression of either precursor or secreted clusterin, suggesting a downregulation related to local metastasis. We further investigated clusterin in serum, finding a significant increase in colorectal cancer patients, with 81% sensitivity, 79% specificity, and an area under the ROC curve of 0.85.

Immune responses elicited in rainbow trout through the administration of infectious pancreatic necrosis virus-like particles.

Virus like particles (VLPs) against viral pathogens not only constitute a novel approach for the development of antiviral vaccines for an specific virus, but also for the creation of multivalent vaccines in which antigens from other pathogens may be expressed on the surface of these VLPs. Despite positive results on protection for many of these VLPs in both fish and mammals, not many studies have focused on the immune response triggered by these particles; studies that may provide hints for the identification of immune mechanisms responsible for antiviral protection, which are mostly unknown in fish. In the current work, we have studied the levels of transcription of several immune genes in the spleen of rainbow trout (Oncorhynchus mykiss) intraperitoneally injected with VLPs from infectious pancreatic necrosis virus (IPNV) focusing on the chemokine response as well as the response of genes related to interferon (IFN) production. Surprisingly, the capacity of VLPs to induce chemokines differed from that of live IPNV, suggesting a direct effect of viral replication on the chemokine response in this organ. While VLPs up-regulated the transcription of CK3, CK10 and CXCd and down-modulated CK5B, CK6 and CK9 transcription, a previous study in which the transcription of γIP, CXCd, CK1, CK3, CK5B, CK6, CK7A, CK9 and CK12 had been studied demonstrated that IPNV only significantly up-regulated CK6 and down-modulated CK3 in the spleen. On the other hand, the administration of VLPs produced a strong mobilization to the peritoneum of CD4(+), IgM(+), IgT(+) and CD83(+) leukocytes similar to that induced by the live viral infection. In both cases, this leukocyte recruitment seemed to be greatly mediated through CK3, CK5B, CK9 and CK10 chemokine production. These results together with the fact that VLPs strongly induced non-specific lymphocyte proliferation and specific anti-IPNV antibody production point to VLPs as excellent candidates for vaccine development.