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Kari Palonen’s work has remained an inspiration for conceptual and intellectual historians as well as for political theorists over the years. His career and contributions make him an ideal interlocutor for a conversation on the joint practice of conceptual history and the study of political thought. This interview, conducted by Rosario López and José María Rosales, took place as one of the sessions of the online seminar On the Joint Practice of Conceptual History and the Study of Political Thought, organized by Concepta: Research Seminars in Conceptual History and Political Thought on 8 and 9 January 2024.

Abstract Background Several studies describe an inverse statistical relationship between the presence of an allergy and development of cancer. However, the immunological mechanism involved in the relationship between these two degenerative diseases has not been explored. Aims The main objective of this study was to explore the possibility that the lymphocyte T helper (Th) 2 response, a characteristic of allergy, induces recognition of tumor antigens. Methods and results Patients with a clinical diagnosis of breast ductal carcinoma were included. Histopathological markers related to proliferation of tumor cells were determined (Her‐2‐neu, Ki‐67, estrogen receptor, and progesterone receptor). IHC was performed using IgE antibodies purified from an allergy patient and from each biopsy donor patient. Serum concentrations of cytokines representative of Th1 and Th2 inflammatory responses were determined. A total of 14 patients with a confirmed diagnosis of breast ductal carcinoma were included. IHC performed on biopsies showed a weak response when using purified IgE antibodies from an allergy patient; however, IHC using the IgE of each patient as the primary antibody showed an intense and highly specific signal. Serum concentrations of cytokines of the Th2 response, that is, IL‐4 (130.5 pg/mL (116–135 pg/mL)), IL‐5 (202 pg/mL (191–213 pg/mL)), and IL‐13 (105.5 pg/mL (98–117 pg/mL)), were significantly higher than those of the Th1 response, that is, IL‐6 (86 pg/mL (79–90 pg/mL)) and INF‐γ (93 pg/mL (79–99 pg/mL)). Conclusion Purified IgE antibodies specifically recognize tumor cells in breast ductal carcinoma.

This paper offers an analysis of Sheri Tepper’s novel, The Gate to Women’s Country, through the lenses of Classical Reception and feminist reinterpretation, aligning with Hardwick’s theoretical framework and drawing upon the specific conceptual propositions of Ostriker, Keen and Durand. Tepper’s narrative comprises both utopian and dystopian elements. In her utopian projection, a Greek tragedy is reimagined as Iphigenia in Ilium, wherein she introduces a dialogue with the deceased to underscore the inherent violence of men and its consequences for women and children. In the dystopian projection, she indirectly utilises the myth of Persephone and Demeter, with a notable emphasis on the catabatis motif, implicitly employed to depict the harrowing and violent experiences faced by the central character, Stavia. This portrayal of Hades, transposed to Tepper’s envisioned society, serves as a cautionary tale highlighting the perils that women encounter when they lack control, influence or a voice.

Reseña de Las mil naves, de Natalie Haynes.

Abstract Rare variants affecting host defense against pathogens could be involved in COVID-19 severity and may help explain fatal outcomes in young and middle-aged patients. Our aim was to report the presence of rare genetic variants in certain genes, by using whole exome sequencing, in a selected group of COVID-19 patients under 65 years who required intubation or resulting in death (n = 44). To this end, different etiopathogenic mechanisms were explored using gene prioritization-based analysis in which genes involved in immune response, immunodeficiencies or blood coagulation were studied. We detected 44 different variants of interest, in 29 different patients (66%). Some of these variants were previously described as pathogenic and were located in genes mainly involved in immune response. A network analysis, including the 42 genes with candidate variants, showed three main components, consisting of 25 highly interconnected genes related to immune response and two additional networks composed by genes enriched in carbohydrate metabolism and in DNA metabolism and repair processes. In conclusion, we have detected candidate variants that may potentially influence COVID-19 outcome in our cohort of patients. Further studies are needed to confirm the ultimate role of the genetic variants described in the present study on COVID-19 severity.

Resumen: Introducción: Existe consenso en cuanto a la eficacia y seguridad de las pautas de rehidratación intravenosa rápida (RIR) en niños con deshidratación secundaria a gastroenteritis aguda (GEA), pero también una gran variabilidad en su uso en la práctica clínica. Objetivo: Elaborar un documento de recomendaciones sobre la RIR en población pediátrica basadas en la evidencia científica. Metodología: Se diseñó un proyecto basado en metodología GRADE, siguiendo el siguiente esquema de trabajo: formación del grupo de trabajo; formulación de preguntas de investigación y definición de «desenlaces de interés»; puntuación y selección de ítems; revisión bibliográfica; evaluación y síntesis de la evidencia (GRADE); revisión, discusión y formulación de recomendaciones. Se incluyeron 10 preguntas clínicas y 15 desenlaces de interés (siete de eficacia y ocho de seguridad). Resultados: Se establecieron 16 recomendaciones, destacando como principales: 1) la RIR es segura en niños con deshidratación leve-moderada secundaria a GEA, salvo contraindicación expresa o comorbilidad aguda grave (recomendación fuerte, evidencia moderada); 2) se recomienda su uso en este contexto cuando la rehidratación oral haya fracasado o esté contraindicada (fuerte, alta); 3) se recomienda utilizar sueros isotónicos (fuerte, alta), sugiriendo como primera opción el suero fisiológico (débil, baja), añadiendo glucosa (2,5%) en pacientes con glucemia normal y cetosis (fuerte, moderada); 4) se recomienda un ritmo de infusión de 20 mL/kg/hora (fuerte, alta), durante una a cuatro horas (fuerte, moderada). Conclusiones: En este documento se establecen recomendaciones de consenso, basadas en la evidencia científica disponible, que podrían contribuir a homogeneizar el uso de la RIR en nuestro medio. Abstract: Introduction: The efficacy and safety of the rapid intravenous rehydration (RIR) guidelines in children affected by dehydration secondary to acute gastroenteritis is supported by current scientific evidence, but there is also great variability in its use in clinical practice. Objective: To prepare a document with evidence-based recommendations about RIR in paediatric population. Methods: The project was developed based on GRADE methodology, according to the following work schedule: Working Group training; creation of a catalogue of questions about research and definition of «relevant outcomes»; score and selection criteria for each item; bibliographic review; scientific evidence evaluation and synthesis (GRADE); review, discussion and creation of recommendations. 10 clinical questions and 15 relevant outcomes were created (7 about efficacy and 8 about security). Results: Sixteen recommendations were set up, from which we can highlight as the main ones: (1) RIR is safe for children affected by mild-moderate dehydration secondary to acute gastroenteritis, unless expressly contraindicated or acute severe comorbidity (strong recommendation and moderate evidence). (2) Its use is recommended in this situation when oral rehydration has failed or due to contraindication (strong and high). (3) Isotonic fluids are recommended (strong and high), suggesting saline fluid as the first option (light and low), supplemented by glucose (2.5%) in those patients showing normoglycemia and ketosis (strong and moderate). (4) A rhythm of 20 cc/kg/h is recommended (strong and high) during 1–4 h (strong and moderate). Conclusions: This document establishes consensus recommendations, based on the available scientific evidence, which could contribute to the standardisation of the use of RIR in our setting.

Introduction: The efficacy and safety of the Rapid Intravenous Rehydration (RIR) guidelines in children affected by dehydration secondary to acute gastroenteritis is supported by current scientific evidence, but there is also great variability in its use in clinical practice. Objective: To prepare a document with evidence-based recommendations about RIR in paediatric population. Methods: The project was developed based on GRADE methodology, according to the following work schedule: Working Group training; creation of a catalogue of questions about research and definition of “relevant outcomes”; score and selection criteria for each item; bibliographic review; scientific evidence evaluation and synthesis (GRADE); review, discussion and creation of recommendations. 10 clinical questions and 15 relevant outcomes were created (7 about efficacy and 8 about security). Results: 16 recommendations were set up, from which we can highlight as the main ones: 1) RIR is safe for children affected by mild-moderate dehydration secondary to acute gastroenteritis, unless expressly contraindicated or acute severe comorbidity (strong recommendation, moderate evidence). 2) Its use is recommended in this situation when oral rehydration has failed or due to contraindication (strong, high). 3) Isotonic fluids are recommended (strong, high), suggesting saline fluid as the first option (light, low), supplemented by glucose (2.5%) in those patients showing normoglycemia and ketosis (strong, moderate). 4) A rhythm of 20cc/kg/h is recommended (strong, high) during 1−4 h (strong, moderate). Conclusions: This document establishes consensus recommendations, based on the available scientific evidence, which could contribute to the standardisation of the use of RIR in our setting. Resumen: Introducción: Existe consenso en cuanto a la eficacia y seguridad de las pautas de rehidratación intravenosa rápida (RIR) en niños con deshidratación secundaria a gastroenteritis aguda (GEA), pero también una gran variabilidad en su uso en la práctica clínica. Objetivo: elaborar un documento de recomendaciones sobre la RIR en población pediátrica basadas en la evidencia científica. Metodología: Se diseñó un proyecto basado en metodología GRADE, siguiendo el siguiente esquema de trabajo: Formación del Grupo de Trabajo; formulación de preguntas de investigación y definición de “desenlaces de interés”; puntuación y selección de ítems; revisión bibliográfica; evaluación y síntesis de la evidencia (GRADE); revisión, discusión y formulación de recomendaciones. Se incluyeron 10 preguntas clínicas y 15 desenlaces de interés (7 de eficacia y 8 de seguridad). Resultados: Se establecieron 16 recomendaciones, destacando como principales: 1) La RIR es segura en niños con deshidratación leve-moderada secundaria a GEA, salvo contraindicación expresa o comorbilidad aguda grave (recomendación fuerte, evidencia moderada); 2)Se recomienda su uso en este contexto cuando la rehidratación oral haya fracasado o esté contraindicada (fuerte, alta); 3)Se recomienda utilizar sueros isotónicos (fuerte, alta), sugiriendo como primera opción el suero fisiológico (débil, baja), añadiendo glucosa (2,5%) en pacientes con glucemia normal y cetosis (fuerte, moderada). 4)Se recomienda un ritmo de infusión de 20 mL/kg/hora (fuerte, alta), durante una a cuatro horas (fuerte, moderada). Conclusiones: En este documento se establecen recomendaciones de consenso, basadas en la evidencia científica disponible, que podrían contribuir a homogeneizar el uso de la RIR en nuestro medio.

Las habilidades del siglo XXI corresponden a un conjunto de habilidades y aptitudes que son necesarias para desenvolverse y desarrollarse en el mundo actual, el que, gracias a las tecnologías de la información y el proceso de globalización, ha generado nuevas dinámicas sociales que confluyeron en la formación de lo que conocemos como “sociedad de la información”, rápidamente cambiante debido al acelerado progreso de las propias tecnologías. Entre las habilidades del siglo XXI se encuentran las que se refieren al pensamiento crítico, la comunicación, el trabajo en equipo, la colaboración y la creatividad, entre otras. Todas ellas son necesarias para que las personas se desarrollen en un mundo en constante cambio. Por tal razón, el Ministerio de Educación de Chile y los organismos supranacionales e intergubernamentales las fomentan en los contextos de aprendizaje escolar. Este artículo tiene como objetivo mostrar cómo se abordan y fomentan estas habilidades en las Bases Curriculares de Religión Católica (2020), asumiendo que dichas habilidades son esenciales para el desarrollo integral de las personas y la formación de ciudadanos críticos aptos para desenvolverse adecuadamente en la sociedad actual. Además, se señala la vinculación de estas habilidades con el desarrollo y la formación propia del creyente y con el estímulo del ámbito espiritual y religioso de los estudiantes.

The present study reports the development and application of a rapid, low-cost in-situ method for the quantification of tartrazine in carbonated beverages using a smartphone-based colorimetric device with molecularly imprinted polymer (MIP). The MIP was synthesized using the free radical precipitation method with acrylamide (AC) as the functional monomer, N,N′-methylenebisacrylamide (NMBA) as the cross linker, and potassium persulfate (KPS) as radical initiator. The smartphone (RadesPhone)-operated rapid analysis device proposed in this study has dimensions of 10 × 10 × 15 cm and is illuminated internally by light emitting diode (LED) lights with intensity of 170 lux. The analytical methodology involved the use of a smartphone camera to capture images of MIP at various tartrazine concentrations, and the subsequent application of the Image-J software to calculate the red, green, blue (RGB) color values and hue, saturation, value (HSV) values from these images. A multivariate calibration analysis of tartrazine in the range of 0 to 30 mg/L was performed, and the optimum working range was determined to be 0 to 20 mg/L using five principal components and a limit of detection (LOD) of 1.2 mg/L was obtained. Repeatability analysis of tartrazine solutions with concentrations of 4, 8, and 15 mg/L (n = 10) showed a coefficient of variation (% RSD) of less than 6%. The proposed technique was applied to the analysis of five Peruvian soda drinks and the results were compared with the UHPLC reference method. The proposed technique showed a relative error between 6% and 16% and % RSD lower than 6.3%. The results of this study demonstrate that the smartphone-based device is a suitable analytical tool that offers an on-site, cost-effective, and rapid alternative for the quantification of tartrazine in soda drinks. This color analysis device can be used in other molecularly imprinted polymer systems and offers a wide range of possibilities for the detection and quantification of compounds in various industrial and environmental matrices that generate a color change in the MIP matrix.

Resumen: Introducción: SARS-CoV-2, responsable de la enfermedad por coronavirus 2019 (COVID-19), fue detectado por primera vez en España el 31 de enero de 2020. El 14 de marzo fue declarado el estado de alarma con el objetivo de controlar la pandemia. El objetivo de este estudio es analizar las consecuencias de esta crisis sanitaria sobre el patrón de demanda asistencial, así como el manejo y las características de los pacientes con sospecha de COVID-19 en el Servicio de Urgencias Pediátricas. Pacientes y métodos: Estudio retrospectivo observacional en niños y adolescentes menores de 18 años, atendidos en nuestro Servicio de Urgencias Pediátricas durante el periodo comprendido desde el 14 de marzo hasta el 17 de abril de 2020. Resultados: Durante el periodo de estudio se atendieron 1.666 pacientes, un 65,4% menos que en el mismo periodo de 2019. La edad media fue de 5,4 años y el 51,2% eran varones. El 39,9% fueron clasificados con niveles de alta prioridad, un 6,5% más que en 2019. Los principales motivos de consulta fueron fiebre (26,5%), síntomas respiratorios (16,1%) y traumatismos (15,2%). Un total de 218 pacientes (13%) fueron diagnosticados de posible COVID-19, confirmándose la infección en el 18,4%. El 44% (96/218) fueron diagnosticados de infección respiratoria inferior y el 33,9% (74/218), superior. El 23,8% (52/218) fueron hospitalizados. Conclusiones: Durante el brote epidémico SARS-CoV-2 disminuyó la demanda de asistencia pediátrica urgente, aumentando la proporción de casos con niveles de triaje de alta prioridad. La mayoría de los pacientes con sospecha o confirmación microbiológica de COVID-19 cursaron con clínica respiratoria leve. Abstract: Introduction: SARS-CoV-2, coronavirus that causes coronavirus disease 2019 (COVID-19), was first detected in Spain on 31 January 2020. On 14 March 2020, a state of emergency was declared in Spain in a bid to control the spread of the COVID-19 pandemic in the country. The aim of our study is to analyse the impact on emergency medicine attendance after the national lockdown, as well as the clinical presentation and the management of patients with suspected COVID-19 in the Paediatric Emergency Department. Patients and methods: This retrospective observational study included children and adolescents under the age of 18, attended in our Paediatric Emergency Department during the period March 14 to April 17, 2020. Results: A total of 1,666 patients were attended during the study period, 65.4% less than in the same period of 2019. Just over half (51.2%) were males, and mean age was 5.4 years. In triage, 39.9% were high priority levels, 6.5% more than 2019. Most frequent reasons for consultation at the Paediatric Emergency Department were fever (26.5%), respiratory symptoms (16.1%), and trauma (15.2%). A total of 218 patients (13%) received a diagnosis of possible COVID-19, with SARS-CoV-2 infection confirmed in 18.4%, and 23.8% (52/218) were hospitalised. At discharge, 44% (96/218) were diagnosed with lower, and 33.9% (74/218) with upper respiratory infection. Conclusions: During the SARS-CoV-2 outbreak, the demand for urgent paediatric care decreased, with the proportion of cases with high priority triage levels increasing. Most of the patients with suspected or microbiological confirmation of COVID-19 had mild respiratory symptoms.

Introduction: SARS-CoV-2, coronavirus that causes coronavirus disease 2019 (COVID-19), was first detected in Spain on 31 January 2020. On 14 March 2020, a state of emergency was declared in Spain in a bid to control the spread of the COVID-19 pandemic in the country. The aim of our study is to analyze the impact on emergency medicine attendance after the national lockdown, as well as the clinical presentation and the management of patients with suspected COVID-19 in the Paediatric Emergency Department. Patients and methods: This retrospective observational study included children and adolescents under the age of 18, attended in our Paediatric Emergency Department during the period March 14 to April 17, 2020. Results: A total of 1666 patients were attended during the study period, 65.4% less than in the same period of 2019. Just over half (51.2%) were males, and mean age was 5.4 years. In triage, 39.9% were high priority levels, 6.5% more than 2019. Most frequent reasons for consultation at the Paediatric Emergency Department were fever (26.5%), respiratory symptoms (16.1%), and trauma (15.2%). A total of 218 patients (13%) received a diagnosis of possible COVID-19, with SARS-CoV-2 infection confirmed in 18.4%, and 23.8% (52/218) were hospitalised. At discharge, 44% (96/218) were diagnosed with lower, and 33.9% (74/218) with upper respiratory infection. Conclusions: During the SARS-CoV-2 outbreak, the demand for urgent paediatric care decreased, with the proportion of cases with high priority triage levels increasing. Most of the patients with suspected or microbiological confirmation of COVID-19 had mild respiratory symptoms. Resumen: Introducción: SARS-CoV-2, responsable de la enfermedad por coronavirus 2019 (COVID-19), fue detectado por primera vez en España el 31 de enero de 2020. El 14 de marzo fue declarado el estado de alarma con el objetivo de controlar la pandemia. El objetivo de este estudio es analizar las consecuencias de esta crisis sanitaria sobre el patrón de demanda asistencial, así como el manejo y las características de los pacientes con sospecha de COVID-19 en el Servicio de Urgencias Pediátricas. Pacientes y métodos: Estudio retrospectivo observacional en niños y adolescentes menores de 18 años, atendidos en nuestro Servicio de Urgencias Pediátricas durante el periodo comprendido desde el 14 de marzo hasta el 17 de abril de 2020. Resultados: Durante el periodo de estudio se atendieron 1.666 pacientes, un 65,4% menos que en el mismo periodo de 2019. La edad media fue de 5,4 años y el 51,2% eran varones. El 39,9% fueron clasificados con niveles de alta prioridad, un 6,5% más que en 2019. Los principales motivos de consulta fueron fiebre (26,5%), síntomas respiratorios (16,1%) y traumatismos (15,2%). Un total de 218 pacientes (13%) fueron diagnosticados de posible COVID-19, confirmándose la infección en el 18,4%. El 44% (96/218) fueron diagnosticados de infección respiratoria inferior y el 33,9% (74/218), superior. El 23,8% (52/218) fueron hospitalizados. Conclusiones: Durante el brote epidémico SARS-CoV-2 disminuyó la demanda de asistencia pediátrica urgente, aumentando la proporción de casos con niveles de triaje de alta prioridad. La mayoría de los pacientes con sospecha o confirmación microbiológica de COVID-19 cursaron con clínica respiratoria leve.

ABSTRACT Mutant spectra of RNA viruses are important to understand viral pathogenesis and response to selective pressures. There is a need to characterize the complexity of mutant spectra in coronaviruses sampled from infected patients. In particular, the possible relationship between SARS-CoV-2 mutant spectrum complexity and disease associations has not been established. In the present study, we report an ultradeep sequencing (UDS) analysis of the mutant spectrum of amplicons from the nsp12 (polymerase)- and spike (S)-coding regions of 30 nasopharyngeal isolates (diagnostic samples) of SARS-CoV-2 of the first COVID-19 pandemic wave (Madrid, Spain, April 2020) classified according to the severity of ensuing COVID-19. Low-frequency mutations and deletions, counted relative to the consensus sequence of the corresponding isolate, were overwhelmingly abundant. We show that the average number of different point mutations, mutations per haplotype, and several diversity indices was significantly higher in SARS-CoV-2 isolated from patients who developed mild disease than in those associated with moderate or severe disease (exitus). No such bias was observed with RNA deletions. Location of amino acid substitutions in the three-dimensional structures of nsp12 (polymerase) and S suggest significant structural or functional effects. Thus, patients who develop mild symptoms may be a richer source of genetic variants of SARS-CoV-2 than patients with moderate or severe COVID-19. IMPORTANCE The study shows that mutant spectra of SARS-CoV-2 from diagnostic samples differ in point mutation abundance and complexity and that significantly larger values were observed in virus from patients who developed mild COVID-19 symptoms. Mutant spectrum complexity is not a uniform trait among isolates. The nature and location of low-frequency amino acid substitutions present in mutant spectra anticipate great potential for phenotypic diversification of SARS-CoV-2.

Amoxicillin (AMX) is an antibiotic frequently used for the treatment of bacterial disorders and respiratory problems in both humans and animals. This work aims to synthesize a molecularly imprinted superparamagnetic polymer (SP-MIP) with a core-shell structure for the selective detection of AMX in real samples. Magnetite superparamagnetic nanoparticles (SNP) were prepared by the polyol method, coated with silica, and functionalized with silane groups. The polymerization process was executed using the free-radical precipitation method. Thermogravimetric analysis (TGA) was used to evaluate the thermal stability of the synthesized materials. The results obtained from N2 adsorption and desorption analyses showed that the surface area of SP-MIP (19.8 m2/g) was higher than that of the non-molecularly imprinted superparamagnetic polymer (SP-NIP—9.24 m2/g). The optimized adsorption analysis showed that both SP-MIP and SP-NIP followed SIP-type behavior, with adsorption constant KS 0.01176, 1/n 1.73. The selectivity tests showed that SP-MIP is highly selective for AMX in the presence of other molecules. Finally, for the recovery analysis, the application of SP-MIP for determining AMX in samples of tap water, river water, and drugs using HPLC yielded a mean recovery value of 94.3%.

Background: Ideal cardiovascular health (CVH) sought to reduce cardiovascular (CV) morbidity and mortality. In Chile, CV mortality in women is high. The study's main aim was to determine the prevalence of ideal CVH, and the factors and behaviors associated with ideal CVH in women from Santiago de Chile. Methods: Cross-sectional study in women between 35 - 70 years old who were selected through a probabilistic, multistage, and geographically stratified sampling. The study included a survey on demographic and CV risk factors and anthropometric, blood pressure, and biochemical measurements. Three categories were used to characterize low (0-2), intermediate (3-4), and high (5-7) levels of AHA's Ideal CVH index. We assessed the prevalence of ideal CVH by age, education level, and socioeconomic status and determined the independent associations of different variables with ideal CVH. Findings: 620 women, mean age 51± 4 years old, were recruited. Ideal CVH prevalence was 14.3%; none of the women presented an ideal healthy diet, and only 22.6% reached an ideal BMI. The best predictors of ideal CVH were a high education level (OR= 2.85; 1.43 to 5.92; p < 0.01), having less than two alcoholic drinks per day (OR= 4.09; 1.60 to 13.77; p< 0.01), and having a pregnancy history without preeclampsia and/or gestational diabetes (OR=1.94; 1.07 to 3.71; p=0.04). Interpretation: This study demonstrates a low ideal CVH prevalence in Chilean women. Education level was a significant factor associated with ideal CVH. But also, women-specific risk factors, such as a history of preeclampsia/gestational diabetes, and alcohol consumption, were important factors related to CVH. Funding: This study was supported by grants from Fundación SOCHICAR de la Sociedad Chilena de Cardiología y Cirugía Cardiovascular, the American Heart Association and an unrestricted grant by TEVA Pharmaceuticals.

This work describes an electrochemical sensor for the selective recognition and quantification of amoxicillin and a β-lactam antibiotic in real samples. This sensor consists of a carbon paste electrode (CPE) modified with mag-MIP (magnetic molecularly imprinted polymer), which was prepared by precipitation method via free radical using acrylamide (AAm) as functional monomer, N,N′-methylenebisacrylamide (MBAA) as a crosslinker, and potassium persulfate (KPS) as initiator, to functionalized magnetic nanoparticles. The magnetic non-imprinted polymers (mag-NIP) were prepared using the same experimental procedure without analyte and used for the preparation of a CPE for comparative studies. The morphological, structural, and electrochemical characteristics of the nanostructured material were evaluated using Field emission gun scanning electron microscopy (FEG-SEM), Transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), Vibrating sample magnetometry (VSM), X-ray diffraction (XRD), and voltammetric technique. Electrochemical experiments performed by square wave voltammetry show that the mag-MIP/CPE sensor had a better signal response compared to the non-imprinted polymer-modified electrode (mag-NIP/CPE). The sensor showed a linear range from 2.5 to 57 μmol L−1 of amoxicillin (r2 = 0.9964), with a limit of detection and a limit of quantification of 0.75 and 2.48 μmol L−1, respectively. No significant interference in the electrochemical signal of amoxicillin was observed during the testing experiments in real samples (skimmed milk and river water). The proposed mag-MIP/CPE sensor could be used as a good alternative method to confront other techniques to determine amoxicillin in different samples.

Populations of RNA viruses are composed of complex and dynamic mixtures of variant genomes that are termed mutant spectra or mutant clouds. This applies also to SARS-CoV-2, and mutations that are detected at low frequency in an infected individual can be dominant (represented in the consensus sequence) in subsequent variants of interest or variants of concern. Here we briefly review the main conclusions of our work on mutant spectrum characterization of hepatitis C virus (HCV) and SARS-CoV-2 at the nucleotide and amino acid levels and address the following two new questions derived from previous results: (i) how is the SARS-CoV-2 mutant and deletion spectrum composition in diagnostic samples, when examined at progressively lower cut-off mutant frequency values in ultra-deep sequencing; (ii) how the frequency distribution of minority amino acid substitutions in SARS-CoV-2 compares with that of HCV sampled also from infected patients. The main conclusions are the following: (i) the number of different mutations found at low frequency in SARS-CoV-2 mutant spectra increases dramatically (50- to 100-fold) as the cut-off frequency for mutation detection is lowered from 0.5% to 0.1%, and (ii) that, contrary to HCV, SARS-CoV-2 mutant spectra exhibit a deficit of intermediate frequency amino acid substitutions. The possible origin and implications of mutant spectrum differences among RNA viruses are discussed.

BackgroundBoth chronic hypoxia (CH) and long-term chronic intermittent hypoxia (CIH) exposure lead to right ventricular hypertrophy (RVH). Weight loss is an effective intervention to improve cardiac function and energy metabolism in cardiac hypertrophy. Likewise, caloric restriction (CR) also plays an important role in this cardioprotection through AMPK activation. We aimed to determine the influence of body weight (BW) on RVH, AMPK and related variables by comparing rats exposed to both hypoxic conditions.MethodsSixty male adult rats were separated into two groups (n = 30 per group) according to their previous diet: a caloric restriction (CR) group and an ad libitum (AL) group. Rats in both groups were randomly assigned to 3 groups: a normoxic group (NX, n = 10), a CIH group (2 days hypoxia/2 days normoxia; n = 10) and a CH group (n = 10). The CR group was previously fed 10 g daily, and the other was fed ad libitum. Rats were exposed to simulated hypobaric hypoxia in a hypobaric chamber set to 428 Torr (the equivalent pressure to that at an altitude of 4,600 m above sea level) for 30 days. Measurements included body weight; hematocrit; serum insulin; glycemia; the degree of RVH (Fulton’s index and histology); and AMPK, mTOR, and PP2C expression levels in the right ventricle determined by western blotting.ResultsA lower degree of RVH, higher AMPK activation, and no activation of mTOR were found in the CR groups exposed to hypobaric hypoxia compared to the AL groups (p < 0.05). Additionally, decreased glycemia and serum insulin levels were observed. Interestingly, PP2C expression showed an increase in the AL groups but not in the CR groups (p < 0.05).ConclusionMaintaining a low weight before and during exposure to high-altitude hypoxia, during either CH or CIH, could prevent a major degree of RVH. This cardioprotection would likely be due to the activation of AMPK. Thus, body weight is a factor that might contribute to RVH at high altitudes.

Abstract About 70 genetic studies have already addressed the need of biomarkers to predict the response of patients with rheumatoid arthritis (RA) to methotrexate (MTX) treatment. However, no genetic biomarker has yet been sufficiently validated. Here, we aimed to replicate a selection of 25 SNPs in the largest collection of patients up to date, which consisted of 915 patients treated with MTX. The change in disease activity (measured as ΔDAS28) from baseline was considered the primary outcome. In addition, response according to widely used criteria (EULAR) was taken as secondary outcome. We considered consistency between outcomes, P values accounting for the number of SNPs, and independence from potential confounders for interpretation of the results. Only the rs1801394 SNP in MTRR fulfilled the high association standards. Its minor allele was associated with less improvement than the major allele according to ΔDAS28 (p = 0.0016), and EULAR response (p = 0.004), with independence of sex, age, baseline DAS28, smoking, seropositivity, concomitant corticosteroid use or previous treatments. In addition, previous evidence suggests the association of this SNP with response to MTX in another autoimmune disease, juvenile idiopathic arthritis, and with high intracellular folate levels, which could contribute to poor response.

Amoebiasis in humans is caused by the protozoan parasite Entamoeba histolytica, which cytotoxic activity has been demonstrated on a wide variety of target cells. The process involves the adherence of the parasite to the cell, and such adherence is mediated by an amoebic surface lectin, known as Gal/GalNAc lectin. It is composed of heavy, intermediate, and light subunits. The carbohydrate recognition domain (CRD) has been identified within a cysteine-rich region in the lectin heavy subunit and has an amino acid sequence identity to the receptor-binding domain of hepatocyte growth factor (HGF). Recombinant CRD has been previously shown to compete with HGF for binding to the c-Met receptor IgG fusion protein. In the present study, we searched for evidence of interaction between the Gal/GalNAc lectin at the surface of trophozoites with the c-Met receptor expressed at the surface of HepG2 in coculture assays. Immunoprecipitation of the coculture lysate indicated interaction of the c-Met with a 60 kDa peptide recognized by antiamoebic lectin antibody. Colocalization of both molecules was detected by fluorescence confocal microscopy. Incubation of HepG2 cells with HGF before coculture with trophozoites prevents the cytotoxic effect caused by the parasites but not their adherence to the cells. Our results point to Gal/GalNAc lectin as a ligand of the c-Met receptor at the surface of HepG2 cells.

Este trabajo pretende determinar en qué ámbitos es posible identificar la influencia de las máscaras de la farsa atellana en la comedia latina palliata. También se discute en qué medida los rasgos específicos de la atellana, unidos a los personajes fijos de la comedia nueva griega, la Néa, explican la singularidad de la palliata y el éxito de Plauto ante el difícil público de Roma, habituado a una comicidad ligada a los sentidos. This paper discusses where one can identify the influence of the masks of the Atellan farce on palliata Latin comedy. I also discuss to what extent the specific characteristics of the atellana, together with the fixed character types of Greek new comedy (Néa), explain the singularity of the palliata and the success of Plautus in front of the difficult Roman public, which was used to a comicality linked to the senses.

This paper explores Richard Cobden’s parliamentary career, political thinking, and activism as illustrating the role of debate and the value of dissent in nineteenthcentury British political culture. Cobden was unusual among British politicians of the time; he was a self-made man, experienced traveller, and middle-class hero, yet managed to retain a seat in Parliament between 1841 and 1865 (with a two-year interval outside Parliament between 1857–59). One of my aims is to reassess Cobden’s significance as a politician. I ask in what ways he was seen by contemporaries as an ambivalent figure who represented both radical, democratic activism as the leader of the anti-Corn Law League and a moderate cosmopolitanism as a professional politician, and the role that public speaking played in fostering his profile. My reading may challenge some contemporary interpretations, providing a balanced portrait of Cobden as an activist and politician genuinely concerned with the general welfare of all European countries rather than exclusively the interests of Great Britain (Gott, 1988: 90–101). Focusing on Cobden and the success of the anti-Corn Law League is also a way of exploring how material culture and public speaking were linked in Victorian Britain. Cobden’s popularity can be explained as a result of his eminence as a public speaker, yet discussing his popularity cannot be reduced to his rhetorical abilities. Representations of Cobden’s image and the different anti-Corn Law League symbols in a variety of objects constitute an opportunity to explore the role of nonverbal aspects in the political culture at the time. This paper takes on board Joseph Meisel’s claim that historians have neglected nineteenth-century public speaking culture, while it suggests that, at least when considering Cobden as a study case, verbal and nonverbal communication converge (Meisel, 2001: 2).

Gene expression is generally regulated by recruitment of transcription factors and RNA polymerase II (RNAP II) to specific sequences in the gene promoter region. The Integrator complex mediates processing of small nuclear RNAs (snRNAs) as well as the initiation and release of paused RNAP II at specific genes in response to growth factors. Here we show that in C. elegans, disruption of the Integrator complex leads to transcription of genes located downstream of the snRNA loci via a non-conventional transcription mechanism based on the lack of processing of the snRNAs. RNAP II read-through generates long chimeric RNAs containing snRNA, the intergenic region and the mature mRNA of the downstream gene located in sense. These chimeric sn-mRNAs remain as untranslated long non-coding RNAs, in the case of U1- and U2-derived sn-mRNAs, but can be translated to proteins in the case of SL-derived sn-mRNAs. The transcriptional effect caused by disruption of the Integrator complex is not restricted to genes located downstream of the snRNA loci but also affects key regulators of signal transduction such as kinases and phosphatases. Our findings highlight that these transcriptional alterations may be behind the correlation between mutations in the Integrator complex and tumor transformation.

Este trabajo compara dos reescrituras de la Odisea, planteadas desde la perspectiva de Penélope, que, sin viajar, se ve obligada a crear sus propias estrategias de supervivencia. Se trata de la obra de Margaret Atwood, Penélope y las doce criadas, y la obra de la gallega Begoña Caamaño, Circe o el placer del azul, novelas con finalidad subversiva, narradas desde una posición femenina o incluso feminista, que cuestionan la verdad del relato homérico. A pesar de las coincidencias, ambas reescrituras articulan procedimientos muy distintos, el humor o la sublimación, entre otros, para dar voz a Penélope.

Background: Living at high altitude or with chronic hypoxia implies functional and morphological changes in the right ventricle and pulmonary vasculature with a 10% prevalence of high-altitude pulmonary hypertension (HAPH). The implications of working intermittently (day shifts) at high altitude (hypobaric hypoxia) over the long term are still not well-defined. The aim of this study was to evaluate the right cardiac circuit status along with potentially contributory metabolic variables and distinctive responses after long exposure to the latter condition.Methods: A cross-sectional study of 120 healthy miners working at an altitude of 4,400–4,800 m for over 5 years in 7-day commuting shifts was designed. Echocardiography was performed on day 2 at sea level. Additionally, biomedical and biochemical variables, Lake Louise scores (LLSs), sleep disturbances and physiological variables were measured at altitude and at sea level.Results: The population was 41.8 ± 0.7 years old, with an average of 14 ± 0.5 (range 5–29) years spent at altitude. Most subjects still suffered from mild to moderate symptoms of acute mountain sickness (mild was an LLS of 3–5 points, including cephalea; moderate was LLS of 6–10 points) (38.3%) at the end of day 1 of the shift. Echocardiography showed a 23% mean pulmonary artery pressure (mPAP) >25 mmHg, 9% HAPH (≥30 mmHg), 85% mild increase in right ventricle wall thickness (≥5 mm), 64% mild right ventricle dilation, low pulmonary vascular resistance (PVR) and fairly good ventricle performance. Asymmetric dimethylarginine (ADMA) (OR 8.84 (1.18–66.39); p < 0.05) and insulin (OR: 1.11 (1.02–1.20); p < 0.05) were associated with elevated mPAP and were defined as a cut-off. Interestingly, the correspondence analysis identified association patterns of several other variables (metabolic, labor, and biomedical) with higher mPAP.Conclusions: Working intermittently at high altitude involves a distinctive pattern. The most relevant and novel characteristics are a greater prevalence of elevated mPAP and HAPH than previously reported at chronic intermittent hypobaric hypoxia (CIHH), which is accompanied by subsequent morphological characteristics. These findings are associated with cardiometabolic factors (insulin and ADMA). However, the functional repercussions seem to be minor or negligible. This research contributes to our understanding and surveillance of this unique model of chronic intermittent high-altitude exposure.

Numerosos trabajos llevados a cabo en docencia de la contabilidad, que relacionan metodologías de participación activa con desarrollo de competencias técnicas y no técnicas, utilizan cuestionarios para sustentar los hallazgos obtenidos en los mismos. Sin embargo, no se ha llevado a cabo un proceso de validación de los cuestionarios utilizados que garantice la validez y la fiabilidad de cada uno de los ítems que forman parte de los mismos. El objetivo del trabajo ha sido el diseño y validación de un cuestionario que sirva para medir la efectividad de las metodologías de participación activa, en concreto en Aprendizaje Basado en Proyectos (ABPrj). La muestra utilizada está compuesta por alumnos de Administración y Dirección de Empresas que cursaron Contabilidad Avanzada y Análisis Contable, y el periodo de observación es de cuatro cursos (años) académicos. El trabajo examinó la estructura factorial del Cuestionario de Efectividad del Uso de Metodologías de Participación Activa (CEMPA) a través de un Análisis Factorial Exploratorio y Confirmatorio. Los resultados obtenidos revelaron que la estructura del cuestionario es válida y adecuada para medir la percepción que tienen los alumnos sobre las habilidades y capacidades adquiridas a través de la metodología de participación activa ABPr

This paper describes an Educational Change Project carried out within the branch of the Initial Training Program for Teachers at the Autónoma University of Madrid. The main porpoise of that Project was to introduce some innovations in the methodology and evaluation of the course “The Transmission of Classical Heritage”, part of the “Master's Degree in Education Training for Secondary Teachers”. The paper deals with the training needs of the university teacher in the EHEA (European Higher education Area) and the implementation of innovative teaching methods and principles. It also explains the changes introduced in a course aimed at the training of Secondary teachers and it assesses the results of this experience.

Entamoeba histolytica is the causative agent of amebiasis in humans and is responsible for 100,000 deaths annually, making it the third leading cause of death due to a protozoan parasite. Pathogenesis appears to result from the potent cytotoxic activity of the parasite, which kills host cells within minutes. Although the mechanism is unknown, it is well established to be contact-dependent. The life cycle of the parasite alternates with two forms: the resistant cyst and the invasive trophozoite. The adhesive interactions between the parasite and surface glycoconjugates of host cells, as well as those lining the epithelia, are determinants for invasion of human tissues, for its cytotoxic activity, and finally for the outcome of the disease. In this review we present an overview of the information available on the amebic lectins and adhesins that are responsible of those adhesive interactions and we also refer to their effect on the host immune response. Finally, we present some concluding remarks and perspectives in the field.

El propósito de este artículo es estudiar, desde la perspectiva del alumnado con discapacidad, cómo el profesorado a través de sus actitudes, proyectos docentes, adaptaciones curriculares, desarrollo de la acción tutorial y formación puede contribuir o no, a la inclusión del alumnado en la Universidad. Los resultados de este trabajo se enmarcan dentro de un Proyecto de Investigación más amplio que se está desarrollando en la Universidad de Sevilla[1]. El objetivo global de dicho proyecto es analizar las barreras y ayudas que los estudiantes identifican en su acceso, trayectoria y resultados en la Universidad. Aunque en el estudio se tiene en cuenta tanto la perspectiva institucional como de aula, en este trabajo tan solo nos centramos en la figura del docente universitario, en cuanto a barreras y ayudas identificadas en la respuesta al alumnado con discapacidad. La metodología empleada para el desarrollo del estudio ha sido la biográfico-narrativa, obteniéndose los datos a través de diversas técnicas de recogida de información: grupos de discusión, entrevistas en profundidad, observaciones en las aulas, fotografías, biogramas, etc. Los principales resultados obtenidos se dividen en los siguientes bloques: (1) Actitudes del profesor frente al alumnado con discapacidad (2) Prácticas de inclusión y de exclusión dentro del aula (3) adaptaciones curriculares (4) Tutorías y (5) Formación del profesorado. Dentro de las conclusiones del artículo destaca la idea de que el avance en la respuesta inclusiva al alumnado con discapacidad implica una oportunidad para mejorar las instituciones universitarias, por ello, las Universidades deberían proporcionar respuestas proactivas y no reactivas. ABSTRACTUniversity teachers facing students with disabilities: Building bridges or erecting barriers?The purpose of this article is to study, from the perspective of disabled students, how teachers may or may not contribute towards the integration of students at University through teacher’s attitudes, teaching projects, curricular adaptations and development of tutorial action and training. The results of this work are part of a broader research project that is being carried out at the University of Seville[1]. The overall goal of this project is to analyse the barriers and supports that students identify in their access, experience and results at University. Although the study takes into account both the institutional and the classroom perspective, in this article we only consider the figure of the university teacher, as far as identified barriers and supports in responding to disabled students are concerned.The biographical-narrative methodology has been applied for the development of this study, obtaining data through different techniques of information collection: groups of discussion, in-depth interviews, observations in the classrooms, photographs, biograms, etc. The main obtained results are divided into the following blocks: (1) Attitudes of the teacher towards disabled students, (2) Inclusion and exclusion practices in the classroom, (3) curricular adaptations, (4) tutorials and (5) teacher training. The progress in the inclusive response to disabled students as a chance to improve university institutions is a highlighted idea among the conclusions of the article; thus universities should provide proactive answers rather than reactive ones. [1] “Barriers and Supports that Disabled Students identify in the University”. Project funded by the Spanish Ministry of Science and Innovation (EDU 2010- 16264) [1] Barreras y ayudas que los estudiantes con discapacidad identifican en la Universidad. Proyecto financiado por el MICINN, I+D+I (EDU 2010-16264)

The purpose of this article is to study, from the perspective of disabled students, how teachers may or may not contribute towards the integration of students at University through teacher’s attitudes, teaching projects, curricular adaptations and development of tutorial action and training. The results of this work are part of a broader research project that is being carried out at the University of Seville2 . The overall goal of this project is to analyse the barriers and supports that students identify in their access, experience and results at University. Although the study takes into account both the institutional and the classroom perspective, in this article we only consider the figure of the university teacher, as far as identified barriers and supports in responding to disabled students are concerned.The biographical-narrative methodology has been applied for the development of this study, obtaining data through different techniques of information collection: groups of discussion, indepth interviews, observations in the classrooms, photographs, biograms, etc. The main obtained results are divided into the following blocks: (1) Attitudes of the teacher towards disabled students, (2) Inclusion and exclusion practices in the classroom, (3) curricular adaptations, (4) tutorials and (5) teacher training. The progress in the inclusive response to disabled students as a chance to improve university institutions is a highlighted idea among the conclusions of the article; thus universities should provide proactive answers rather than reactive ones.

INTRODUCTION:Chronic hepatitis C (CHC) is a major cause of liver disease worldwide which often leads to progressive liver inflammation, fibrosis, cirrhosis and hepatocellular carcinoma (HCC). CHC displays heterogeneous progression depending on a broad set of factors, some of them intrinsic to each individual such as the patient's genetic profile. This study aims to evaluate the contribution of certain genetic variants of crucial interferon alpha and lambda signaling pathways to the hepatic necroinflammatory activity (NIA) grade of CHC patients. METHODS:NIA was evaluated in 119 CHC patients by METAVIR scale and classified as low (NIA = 0-2, n = 80) or high grade (NIA = 3, n = 39). In a candidate gene approach, 64 SNPs located in 30 different genes related to interferon pathways (IL-28B, IFNAR1-2, JAK-STAT and OAS1-3, among others) were genotyped using the Illumina GoldenGate® Genotyping Assay. Statistical association was determined by logistic regression and expressed as OR and 95% CI. Those SNPs significantly associated were further adjusted by other covariates. RESULTS:Seven SNPs located in IL-28B (rs12979860), JAK1 (rs11576173 and rs1497056), TYK2 (rs280519), OAS1 (rs2057778), SOCS1 (rs33932899) and RNASEL (rs3738579) genes were significantly related to severe NIA grade (p40 IU/L (p40 IU/L), TYK2 rs280519 (G allele) and RNASEL rs3738579 (G allele) were factors independently associated with elevated NIA (p

Este trabajo ofrece un análisis comparativo de las características propias de la comedia palliata de Plauto (comediógrafo romano del siglo II a.C.) y de los elementos definitorios de la sitcom, género televisivo de gran aceptación popular. A través de este planteamiento, los autores pretenden poner de manifiesto la existencia de una tradición cómica que, de forma continua, ha ido transmitiendo una serie de rasgos sin conciencia de su origen remoto. Desde esta perspectiva, la sitcom permite explicar con un enfoque contemporáneo el rotundo éxito que en su momento gozó la comedia plautina y, a la inversa, ciertos patrones compositivos del teatro antiguo dan la pauta para entender la gran influencia del fenómeno televisivo que supone la sitcom.Palabras clave: Plauto, comedia palliata, cultura popular, sitcom, recepción, cultura clásica.AbstractThis paper offers a comparative analysis of the features of fabula togata by Plautus, a Roman writer of comedies of the 2nd century, and the defining characteristics of the successful TV genre, the sitcom. Using this approach, the authors aim to demonstrate the existence of a continuous tradition through which several comical features have been transmitted, without consciousness of their distant origin. Thus, the sitcom offers us an explanation, from a contemporary point of view, for the resounding success of the Plautinian comedy. Conversely, several composite elements of ancient theatre provide us with the key to understanding the reasons behind the great influence of the sitcom as a TV phenomenon.Keywords: Plautus, palliata, popular culture, sitcom, reception, classical culture.

El objetivo de este trabajo es analizar mediante un estudio empírico multivariante el posicionamiento de profesores y auditores sobre los aspectos legales que regulan la realización de otras actividades distintas a la auditoría de cuentas anuales. A través de la opinión manifestada por los dos colectivos anteriormente indicados, se puede identificar en ellos tres grupos en función del nivel de prohibición global de las incompatibilidades analizadas y del nivel de importancia asignada a las prohibiciones sobre los que se han denominado “servicios relacionados directa/indirectamente con la información financiera sometida a auditoría”: auditores consolidados, auditores no consolidados y profesores. Los profesores manifiestan un alto nivel de prohibición global, mientras que los auditores, tanto consolidados como no consolidados, se muestran en sentido contrario. Por otro lado, los profesores y los auditores no consolidados dan mayor importancia a las prohibiciones sobre los servicios “relacionados directamente con la información financiera sometida a auditoría”, que a las prohibiciones sobre los “relacionados indirectamente”, mientras que los auditores consolidados invierten el sentido de la importancia de esas prohibiciones.

La presente investigación analiza si realmente las medidas relacionadas con la imposición de publicación de honorarios en España contribuyen intrínsecamente a paliar, en cierta medida, los conflictos de independencia que la profesión auditora tiene actualmente. En relación con la evidencia obtenida del cuestionario utilizado en la investigación, es interesante subrayar que los profesores universitarios se inclinan, en general, a favor de la existencia de este tipo de medidas de transparencia informativa, sin embargo, los auditores se muestran contrarios a la misma. No obstante, a pesar de este posicionamiento inicial discrepante, la evidencia indica que dentro de la categoría de auditores es preciso diferenciar dos grupos: los profesionales consolidados y los profesionales no consolidados. De esta forma, los resultados indican que estos últimos muestran una opinión intermedia cercana, en algunos puntos, a la indicada por los profesores universitarios.

Response to treatment of rheumatoid arthritis shows large inter-individual variability. This heterogeneity is observed with all the anti-rheumatic drugs, including the commonly used TNF inhibitors. It seems that drug-specific and target-specific factors lead individual patients to respond or not to a given drug, although this point has been challenged. The search of biomarkers distinguishing responders from non-responders has included shotgun proteomics of serum, as a previous study of response to infliximab, an anti-TNF antibody. Here, we have used the same study design and technology to search biomarkers of response to a different anti-TNF antibody, adalimumab, and we have compared the results obtained for the two anti-TNF drugs. Search of biomarkers of response to adalimumab included depletion of the most abundant serum proteins, 8-plex isobaric tag for relative and absolute quantitation (iTRAQ) labeling, two-dimensional liquid chromatography fractionation and relative quantification with a hybrid Orbitrap mass spectrometer. With this approach, 264 proteins were identified in all the samples with at least 2 peptides and 95% confidence. Nine proteins showed differences between non-responders and responders (P < 0.05), representing putative biomarkers of response to adalimumab. These results were compared with the previous study of infliximab. Surprisingly, the non-responder/responder differences in the two studies were not correlated (rs = 0.07; P = 0.40). This overall independence with all the proteins showed two identifiable components. On one side, the putative biomarkers of response to either adalimumab or infliximab, which were not shared and showed an inverse correlation (rs = -0.69; P = 0.0023). On the other, eight proteins showing significant non-responder/responder differences in the analysis combining data of response to the two drugs. These results identify new putative biomarkers of response to treatment of rheumatoid arthritis and indicate that they are notably drug-specific.

Se presentan los resultados de un análisis de la evolución de la demanda asistencial en un ESMD para la población general desde su creación en 1981 hasta 2001, analizando variables sociodemográficas, clínicas y psicoterapéuticas de 200 historias clínicas

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The aim of this study was to analyse the distribution of KIR haplotypes and the KIR2DL2/3 alleles in chronic HCV-infected patients in order to establish the influence on the response to pegylated interferon plus ribavirin classical treatment. The alleles study of previously associated KIR2DL2/3 showed that KIR2DL2*001 was more frequent in non-SVR (NSVR) (42.2% vs. 27.5%, p

BACKGROUND: Hepatitis C virus (HCV) infection is a major cause of chronic liver disease (CLD) and is frequently linked to intrahepatic microvascular disorders. Activation of hepatic stellate cells (HSC) is a central event in liver damage, due to their contribution to hepatic renewal and to the development of fibrosis and hepatocarcinoma. During the progression of CLDs, HSC attempt to restore injured tissue by stimulating repair processes, such as fibrosis and angiogenesis. Because HSC express the key vascular receptor Tie2, among other angiogenic receptors and mediators, we analyzed its involvement in the development of CLD. METHODS: Tie2 expression was monitored in HSC cultures that were exposed to media from HCV-expressing cells (replicons). The effects of Tie2 blockade on HSC activation by either neutralizing antibody or specific signaling inhibitors were also examined. RESULTS: Media from HCV-replicons enhanced HSC activation and invasion and upregulated Tie2 expression. Notably, the blockade of Tie2 receptor (by a specific neutralizing antibody) or signaling (by selective AKT and MAPK inhibitors) significantly reduced alpha-smooth muscle actin (α-SMA) expression and the invasive potential of HCV-conditioned HSC. CONCLUSIONS: These findings ascribe a novel profibrogenic function to Tie2 receptor in the progression of chronic hepatitis C, highlighting the significance of its dysregulation in the evolution of CLDs and its potential as a novel therapeutic target.