RESUMEN
Over a century of bacteriophage research has uncovered a plethora of fundamental aspects of their biology, ecology, and evolution. Furthermore, the introduction of community-level studies through metagenomics has revealed unprecedented insights on the impact that phages have on a range of ecological and physiological processes. It was not until the introduction of viral metagenomics that we began to grasp the astonishing breadth of genetic diversity encompassed by phage genomes. Novel phage genomes have been reported from a diverse range of biomes at an increasing rate, which has prompted the development of computational tools that support the multilevel characterization of these novel phages based solely on their genome sequences. The impact of these technologies has been so large that, together with MAGs (Metagenomic Assembled Genomes), we now have UViGs (Uncultivated Viral Genomes), which are now officially recognized by the International Committee for the Taxonomy of Viruses (ICTV), and new taxonomic groups can now be created based exclusively on genomic sequence information. Even though the available tools have immensely contributed to our knowledge of phage diversity and ecology, the ongoing surge in software programs makes it challenging to keep up with them and the purpose each one is designed for. Therefore, in this review, we describe a comprehensive set of currently available computational tools designed for the characterization of phage genome sequences, focusing on five specific analyses: (i) assembly and identification of phage and prophage sequences, (ii) phage genome annotation, (iii) phage taxonomic classification, (iv) phage-host interaction analysis, and (v) phage microdiversity.
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Bacteriófagos , Bacteriófagos/genética , Genoma Viral/genética , Genómica , Metagenómica , FilogeniaRESUMEN
OBJECTIVE: To provide guidance for the management of RAS wild-type (wt) metastatic colorectal cancer (mCRC) in daily practice. METHODS: Nominal group and Delphi techniques were used. A steering committee of seven experts analyzed the current management of RAS wt mCRC, through which they identified controversies, critically analyzed the available evidence, and formulated several guiding statements for clinicians. Subsequently, a group of 30 experts (the expert panel) was selected to test agreement with the statements, through two Delphi rounds. The following response categories were established in both rounds: 1 = totally agree, 2 = basically agree, 3 = basically disagree, 4 = totally disagree. Agreement was defined if ≥ 75% of answers were in categories 1 and 2 (consensus with the agreement) or 3 and 4 (consensus with the disagreement). RESULTS: Overall, 71 statements were proposed, which incorporated the following areas: (1) overarching principles; (2) tumor location; (3) triplets; (4) maintenance; (5) second-line and beyond treatments; (6) Rechallenge and liquid biopsy. After the two Delphi rounds, only six statements maintained a lack of clear consensus. CONCLUSIONS: This document aims to describe the expert's attitude when dealing with several common clinical questions regarding patients with RAS wt mCRC.
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Comités Consultivos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Consenso , Técnica Delphi , Genes ras/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab/uso terapéutico , Camptotecina/análogos & derivados , Camptotecina/uso terapéutico , Colon Ascendente/patología , Colon Transverso/patología , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/genética , Neoplasias del Colon/patología , Neoplasias Colorrectales/patología , Receptores ErbB/antagonistas & inhibidores , Fluorouracilo/uso terapéutico , Genotipo , Humanos , Leucovorina/uso terapéutico , Biopsia Líquida , Quimioterapia de Mantención/métodos , Compuestos Organoplatinos/uso terapéutico , Proteínas Proto-Oncogénicas B-raf/genética , RetratamientoRESUMEN
Gastric cancer (GC) is the fifth most common cancer worldwide with a varied geographic distribution and an aggressive behavior. In Spain, it represents the sixth cause of cancer death. In Western countries, the incidence is decreasing slightly, with an increase in gastroesophageal junction adenocarcinoma (GEJA), a different entity that we separate specifically in the guideline. Molecular biology advances have been done recently, but do not yet lead to the choice in treatment approach except in advanced disease with overexpression of HER2. Endoscopic resection in very early stage, perioperative chemotherapy in locally advanced tumors and preliminary immune therapy resulting in advanced disease are the main treatment innovations in the GC/GEJA treatment. We describe the different evidences and recommendations following the statements of the American College of Physicians.
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Adenocarcinoma/diagnóstico , Adenocarcinoma/terapia , Ensayos Clínicos como Asunto/normas , Unión Esofagogástrica/patología , Guías de Práctica Clínica como Asunto/normas , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/terapia , Humanos , Oncología Médica , Sociedades MédicasRESUMEN
BACKGROUND: The optimal duration of first-line chemotherapy for patients with advanced gastric cancer is unknown. Diverse clinical trials have proposed different strategies including limited treatment, maintenance of some drugs, or treatment until progression. METHOD: The sample comprises patients from the AGAMENON multicenter registry without progression after second evaluation of response. The objective was to explore the optimal duration of first-line chemotherapy. A frailty multi-state model was conducted. RESULTS: 415 patients were divided into three strata: discontinuation of platinum and maintenance with fluoropyrimidine until progression (30%, n = 123), complete treatment withdrawal prior to progression (52%, n = 216), and full treatment until progression (18%, n = 76). The hazard of tumor progression decreased by 19% per month with the full treatment regimen. However, we found no evidence that fluoropyrimidine maintenance (hazard ratio [HR] 1.07, confidence interval [CI] 95%, 0.69-1.65) worsened progression-free survival (PFS) with respect to treatment until progression. Predictive factors for PFS were ECOG performance status, ≥ 3 metastatic sites, prior tumor response, and bone metastases. Toxicity grade 3/4 was more common in those who continued the full treatment until progression vs fluoropyrimidine maintenance (16% vs 6%). CONCLUSION: The longer duration of the full initial regimen exerted a protective effect on the patients of this registry. Platinum discontinuation followed by fluoropyrimidine maintenance yields comparable efficacy to treatment up to PD, with a lower rate of serious adverse events.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Sistema de Registros , Neoplasias Gástricas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Toma de Decisiones Clínicas , Femenino , Humanos , Quimioterapia de Mantención , Masculino , Persona de Mediana Edad , Platino (Metal)/administración & dosificación , Platino (Metal)/efectos adversos , Supervivencia sin Progresión , Pirimidinas/administración & dosificación , Pirimidinas/efectos adversos , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Tasa de Supervivencia , Factores de Tiempo , Adulto JovenRESUMEN
The order Herpesvirales encompasses a wide variety of important and broadly distributed human pathogens. During the last decades, similarities in the viral cycle and the structure of some of their proteins with those of the order Caudovirales, the tailed bacterial viruses, have brought speculation regarding the existence of an evolutionary relationship between these clades. To evaluate such hypothesis, we used over 600 Herpesvirales and 2000 Caudovirales complete genomes to search for the presence or absence of clusters of orthologous protein domains and constructed a dendrogram based on their compositional similarities. The results obtained strongly suggest an evolutionary relationship between the two orders. Furthermore, they allowed to propose a core genome for the Herpesvirales, composed of 4 proteins, including the ATPase subunit of the DNA-packaging terminase, the only protein with previously verified conservation. Accordingly, a phylogenetic tree constructed with sequences derived from the clusters associated to these proteins grouped the Herpesvirales strains accordingly to the established families and subfamilies. Overall, this work provides results supporting the hypothesis that the two orders are evolutionarily related and contributes to the understanding of the history of the Herpesvirales.
Asunto(s)
Caudovirales/genética , Genoma Viral , Herpesviridae/genética , Evolución Molecular , Infecciones por Herpesviridae/virología , Humanos , Filogenia , Proteínas Virales/genéticaRESUMEN
Colorectal cancer (CRC) is the second cause of cancer death in Spain, the objective of this guide published by the Spanish Society of Medical Oncology is to develop a consensus for the diagnosis and management of metastatic disease. The optimal treatment strategy for patients with metastatic CRC should be discussed in a multidisciplinary expert team to select the most appropriate treatment, and integrate systemic treatment and other options such as surgery and ablative techniques depending on the characteristics of the tumour, the patient and the location of the disease and metastases.
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Neoplasias Colorrectales/terapia , Neoplasias Hepáticas/terapia , Guías de Práctica Clínica como Asunto/normas , Ensayos Clínicos como Asunto , Neoplasias Colorrectales/patología , Terapia Combinada , Manejo de la Enfermedad , Humanos , Neoplasias Hepáticas/secundario , Pronóstico , Sociedades MédicasRESUMEN
BACKGROUND: The choice of chemotherapy in HER2-negative gastric cancer is based on centre's preferences and adverse effects profile. No schedule is currently accepted as standard, nor are there any factors to predict response, other than HER2 status. We seek to evaluate whether Lauren type influences the efficacy of various chemotherapies and on patient overall survival (OS). METHODS: We have conducted a multicenter study in 31 hospitals. The eligibility criteria include diagnosis of stomach or gastroesophageal junction adenocarcinoma, HER2 negativity, and chemotherapy containing 2-3 drugs. Cox proportional hazards regression adjusted for confounding factors, with tests of 'treatment-by-histology' interaction, was used to estimate treatment effect. RESULTS: Our registry contains 1303 tumours analysable for OS end points and 730 evaluable for overall response rate (ORR). A decrease in ORR was detected in the presence of a diffuse component: odds ratio 0.719 (95% confidence interval (CI), 0.525-0.987), P=0.039. Anthracycline- or docetaxel-containing schedules increased ORR only in the intestinal type. The diffuse type displayed increased mortality with hazard ratio (HR) of 1.201 (95% CI, 1.054-1.368), P=0.0056. Patients receiving chemotherapy with docetaxel exhibited increased OS limited to the intestinal type: HR 0.65 (95% CI, 0.49-0.87), P=0.024, with no increment in OS for the subset having a diffuse component. With respect to progression-free survival (PFS), a significant interaction was seen in the effect of docetaxel-containing schedules, with better PFS limited to the intestinal type subgroup, in the comparison against any other schedule: HR 0.65 (95% CI, 0.50-0.85), P=0.015, and against anthracycline-based regimens: HR 0.64 (95% CI, 0.46-0.88), P=0.046. CONCLUSIONS: As a conclusion, in this registry, Lauren classification tumour subtypes predicted survival and responded differently to chemotherapy. Future clinical trials should stratify effect estimations based on histology.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Sistema de Registros , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Antraciclinas/administración & dosificación , Chile , Cisplatino/administración & dosificación , Supervivencia sin Enfermedad , Docetaxel , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Receptor ErbB-2 , España , Neoplasias Gástricas/clasificación , Taxoides/administración & dosificación , Resultado del TratamientoRESUMEN
Pancreatic ductal adenocarcinoma (PDAC) is currently the third most frequent form of malignancy. The role of biomarkers in the diagnostic and therapeutic strategy of cancer is constantly expanding. Translational research is already changing paradigms in tumours encompassing from early diagnosis to precision medicine in advanced disease. Nomenclature for molecular subtypes of tumours is gradually gaining acceptance and there are growing expectations it will further go from the bench to the bedside. However, the clinical relevance of biomarkers in PDAC is still far behind the relevance of biomarkers in other solid tumours. This article is part of a wider project (GALLgo) involving over forty specialists devoted to the multidisciplinary management of PDAC which concluded in recommendations based on scientific evidence. The aim of the present article is to review the diagnostic, prognostic and predictive biomarkers, either in localised or advanced disease, which have been lately subjected to study and analysis and others currently available for PDAC in order to give strength-graded recommendations linked to quality of evidence that can be used as guidelines in routine clinical practice.
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Adenocarcinoma/diagnóstico , Biomarcadores de Tumor/metabolismo , Carcinoma Ductal Pancreático/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Adenocarcinoma/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Humanos , Neoplasias Pancreáticas/metabolismo , Medicina de Precisión , Neoplasias PancreáticasRESUMEN
The management of patients with pancreatic cancer has advanced over the last few years. We convey a multidisciplinary group of experts in an attempt to stablish practical guidelines for the diagnoses, staging and management of these patients. This paper summarizes the main conclusions of the working group. Patients with suspected pancreatic ductal adenocarcinoma should be rapidly evaluated and referred to high-volume centers. Multidisciplinary supervision is critical for proper diagnoses, staging and to frame a treatment plan. Surgical resection together with chemotherapy offers the highest chance for cure in early stage disease. Patients with advanced disease should be classified in treatment groups to guide systemic treatment. New chemotherapeutic regimens have resulted in improved survival. Symptomatic management is critical in this disease. Enrollment in a clinical trial is, in general, recommended.
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Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/terapia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia , Estudios de Seguimiento , Humanos , Guías de Práctica Clínica como Asunto , EspañaRESUMEN
Colombian creole cattle have important adaptation traits related to heat tolerance and reproductive and productive efficiency. Romosinuano (ROMO) and Blanco Orejinegro (BON) are the most common breeds used by Colombian cattle breeders. Growth traits are of prime importance in these animals, which are mainly raised for beef production. Genes encoding growth hormone, growth hormone receptor, homeobox protein, insulin growth factor binding protein 3, leptin, and myostatin have been associated with physiological growth pathways in cattle and other species. We therefore aimed to identify single nucleotide polymorphisms (SNPs) within these genes in ROMO, BON, and Zebu cattle. DNA regions of these genes were sequenced in 386 animals; 47 new SNPs were found, of which 14 were located in the exonic regions, thereby changing the protein sequence. An association of SNPs with weaning weight (WW), daily weight gain at weaning (DWG), and weight at 16 months (W16M) traits was deduced. The genetic analysis revealed several SNPs related to these traits. The SNP GhRE06.2 had a significant association with WW and the SNP Lep03.4 was highly associated with DWG and W16M. Other polymorphisms were significantly associated with WW and DWG, although they did not surpass the Bonferroni significance threshold. The new mutations identified may indicate important points of genetic control in the DNA that could be responsible for changes in the expression of the analyzed traits. These SNPs might be used in future breeding programs to improve the productive performance of cattle in beef farms.
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Bovinos/crecimiento & desarrollo , Bovinos/genética , Animales , Secuencia de Bases , Biometría , Peso Corporal/genética , Colombia , Hormona del Crecimiento/genética , Fenotipo , Polimorfismo de Nucleótido Simple , Receptores de Somatotropina/genética , Selección ArtificialRESUMEN
Biliary tract cancer (BTC) is an uncommon and highly fatal malignancy. It is composed of three main different entities; Gall bladder carcinoma (GBC), intrahepatic cholangiocarcinoma (iCC) and extrahepatic cholangiocarcinoma (eCC) sharing different genetic, risk factors and clinical presentation. Multidetector-row computed tomography (MDCT) and magnetic resonance cholangio-pancreatography (MRCP) are the more important diagnostic techniques. Surgery is the only potentially curative therapy but disease recurrence is frequent. Treatment with chemotherapy, radiotherapy or both has not demonstrated survival benefit in the adjuvant setting. Cisplatin plus gemcitabine constitutes the gold standard in metastatic disease. New ongoing studies mainly in the adjuvant and neoadjuvant setting along with molecular research will hopefully help to improve survival and quality of life of this disease.
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Neoplasias del Sistema Biliar/diagnóstico , Neoplasias del Sistema Biliar/terapia , Guías de Práctica Clínica como Asunto/normas , Ensayos Clínicos como Asunto , Terapia Combinada , Manejo de la Enfermedad , Detección Precoz del Cáncer , Humanos , Oncología Médica , Estadificación de Neoplasias , Pronóstico , Calidad de Vida , Sociedades MédicasRESUMEN
In environmental geochemistry studies it is common practice to normalize element concentrations in order to remove the effect of grain size. Linear regression with respect to a particular grain size or conservative element is a widely used method of normalization. In this paper, the utility of functional linear regression, in which the grain-size curve is the independent variable and the concentration of pollutant the dependent variable, is analyzed and applied to detrital sediment. After implementing functional linear regression and classical linear regression models to normalize and calculate enrichment factors, we concluded that the former regression technique has some advantages over the latter. First, functional linear regression directly considers the grain-size distribution of the samples as the explanatory variable. Second, as the regression coefficients are not constant values but functions depending on the grain size, it is easier to comprehend the relationship between grain size and pollutant concentration. Third, regularization can be introduced into the model in order to establish equilibrium between reliability of the data and smoothness of the solutions.
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Química/métodos , Interpretación Estadística de Datos , Ecología/métodos , Contaminación Ambiental/análisis , Modelos Lineales , Modelos Teóricos , Contaminantes del Suelo/análisis , Reproducibilidad de los Resultados , EspañaRESUMEN
Sediment quality has been assessed within the Avilés estuary, an important industrial area in the NW of Spain. The study started with a geochemical characterization of the superficial sediments that revealed some anomalous metal(oid)s concentrations in sensitive areas such as beaches or dunes. These data were studied by means of multivariate statistical techniques and enrichment factors calculation to evaluate the correlations and geochemical origin within the different elements. A novel approach using the combination of enrichment factors with a sequential application of factor analysis, clustering and kriging was essential to identify the possible sources of pollution. The collected information suggested that Cd (strongly correlated with Zn and Pb) was the potentially toxic element most widely distributed and problematic. Furthermore, particulate emissions from Zn metallurgy, as well as dust generated by the mineral loading and stockpile activities in the port were identified as the most important sources of pollution.
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Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente/métodos , Estuarios , Sedimentos Geológicos/química , Metales/análisis , Algoritmos , Cadmio/análisis , Análisis por Conglomerados , Análisis Discriminante , Contaminantes Ambientales/análisis , Geografía , Plomo/análisis , Metalurgia , Análisis Multivariante , España , Emisiones de Vehículos , Zinc/análisisRESUMEN
Las enfermedades cardiovasculares son la principal causa de mortalidad en el mundo, por lo que el desarrollo de algoritmos que detecten arritmias cardíacas en tiempo real se ha convertido en un campo de investigación importante. El desarrollo de estos algoritmos ha conllevado a la mejora de dispositivos cardiacos portátiles. Este artículo presenta el desempeño de dos algoritmos basados en aprendizaje de máquina no supervisado para la detección de latidos de contracción ventricular prematura en la señal ECG. Los latidos se extraen de las bases de datos del MIT-BIH, los cuales fueron pre-procesados y segmentados por el grupo de investigación de Dinámica Cardiovascular de la UPB. La Transformada Wavelet Discreta, el Análisis de Componentes Principales y un método híbrido propuesto son implementados para la extracción de características y reducción de dimensiones, a partir de los cuales se generan 8 espacios de características para la evaluación de los algoritmos. Kmeans y Mapas auto-organizados son desarrollados y comparados en términos de precisión y costo computacional. Se logró una especificidad del 96.22 % y una sensibilidad del 95.04 % con un tiempo de ejecución de 79.41µs por latido. Los resultados permiten concluir que estos métodos pueden implementarse en aplicaciones de detección de arritmias en tiempo real debido a su bajo costo computacional.
Cardiovascular diseases are the principal cause of mortality in the world, so that the development of algorithms that detect cardiac arrhythmias in real time has become an important field of research. The development of these algorithms has led to the improvement of wearable cardiac devices. This paper presents the performance of two algorithms based in unsupervised learning methods for the detection of Premature Ventricular Contraction in the ECG signal. The beats are extracted from MIT-BIH databases, which were preprocessed and segmented by the UPB’s Dynamic Cardiovascular research group. The Discrete Wavelet Transform (DWT), Principal Component Analysis (PCA) and a proposed hybrid method are implemented for the feature extraction and dimension reduction, from which 8 feature spaces are generated and tested. Kmeans and Self Organizing Maps are developed and compared in terms of accuracy and computational cost. Specificity of 96.22 % and sensitivity of 95.94% with 79.41µs per beat are accomplished. The results show that these methods can be implemented in applications of real time arrhythmia detection because of their low computational cost.
A doença cardiovascular é a principal causa de morte em todo o mundo, de modo que o desenvolvimento de algoritmos para detectar arritmias cardíacas, em tempo real, tornou-se um importante campo de pesquisa. O desenvolvimento desses algoritmos tem levado a melhores dispositivos cardíacos portáteis. Este artigo apresenta o desempenho dos dois com base na aprendizagem de máquina sem supervisão para detecção de batidas de contração ventriculares prematuras nos algoritmos de sinais de ECG. As batidas são extraídos das bases de dados do MIT-BIH, que foram pré-processados e segmentado pelo grupo da UPB Cardiovasculares Dynamics pesquisa. A Transformada Wavelet Discreta, Análise de Componentes Principais e uma abordagem híbrida proposta são implementadas para extração de características e redução de dimensão, a partir do qual 8 espaços de recursos para a avaliação dos algoritmos são gerados. Kmeans e mapas de auto-organização são desenvolvidos e comparados em termos de precisão e custo computacional. A especificidade de 96,22% e uma sensibilidade de 95,04% com um tempo de execução de 79.41µs por batida foi alcançado. Os resultados mostram que estes métodos podem ser implementados em aplicações de detecção de arritmia em tempo real, devido ao seu baixo custo computacional.
RESUMEN
Exocrine pancreatic cancer (PC) is a very aggressive and heterogeneous tumor with several cellular signaling pathways implicated in its pathogenesis and maintenance. Several risk factors increase the risk of developing PC. Therapeutic strategies used are dictated by the extent of disease. Supportive treatment is critical because of the high frequency of symptoms. For localized disease, surgery followed by adjuvant gemcitabine is the standard. Neoadjuvant and new adjuvant chemotherapy regimens are being evaluated. Locally advanced disease should respond best guided by a multidisciplinary team. Various treatment options are appropriate such as chemotherapy alone or chemoradiotherapy with integration of rescue surgery if the tumor becomes resectable. In metastatic disease, chemotherapy should be reserved for patients with ECOG 0-1 using Folfirinox or gemcitabine plus nab-paclitaxel as the most recommended options. Several therapeutic strategies targeting unregulated pathways are under evaluation with an unmet need for biomarkers to guide management.
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Carcinoma Ductal Pancreático/terapia , Cistadenocarcinoma/terapia , Neoplasias Pancreáticas/terapia , Guías de Práctica Clínica como Asunto , Adenocarcinoma/diagnóstico , Adenocarcinoma/terapia , Carcinoma Ductal Pancreático/diagnóstico , Cistadenocarcinoma/diagnóstico , Humanos , Páncreas Exocrino , Neoplasias Pancreáticas/diagnósticoRESUMEN
The relevance of reactive oxygen species (ROS) production relies on the dual role shown by these molecules in aerobes. ROS are known to modulate several physiological phenomena, such as immune response and cell growth and differentiation; on the other hand, uncontrolled ROS production may cause important tissue and cell damage, such as deoxyribonucleic acid oxidation, lipid peroxidation, and protein carbonylation. The manganese superoxide dismutase (MnSOD) antioxidant enzyme affords the major defense against ROS within the mitochondria, which is considered the main ROS production locus in aerobes. Structural and/or functional single nucleotide polymorphisms (SNP) within the MnSOD encoding gene may be relevant for ROS detoxification. Specifically, the MnSOD Ala16Val SNP has been shown to alter the enzyme localization and mitochondrial transportation, affecting the redox status balance. Oxidative stress may contribute to the development of type 2 diabetes, cardiovascular diseases, various inflammatory conditions, or cancer. The Ala16Val MnSOD SNP has been associated with these and other chronic diseases; however, inconsistent findings between studies have made difficult drawing definitive conclusions. Environmental factors, such as dietary antioxidant intake and exercise have been shown to affect ROS metabolism through antioxidant enzyme regulation and may contribute to explain inconsistencies in the literature. Nevertheless, whether environmental factors may be associated to the Ala16Val genotypes in human diseases still needs to be clarified.
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Antioxidantes/metabolismo , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Animales , Exposición a Riesgos Ambientales , Humanos , Estrés Oxidativo , Polimorfismo de Nucleótido Simple , Especies Reactivas de Oxígeno/metabolismoRESUMEN
PURPOSE: To evaluate the efficacy and safety profile of the combination of panitumumab and irinotecan every 3 weeks in a phase II trial as second-line treatment in patients with advanced wild-type (WT) K-RAS colorectal cancer (CRC). METHODS: Fifty-three patients received 9 mg/kg of panitumumab followed by 350 mg/m(2) of irinotecan every 21 days until disease progression, unacceptable toxicity or consent withdrawal. RESULTS: Median age of patients included was 67 years. All patients had previously received 5-fluorouracil, 84 % oxaliplatin and 8 % irinotecan as first-line treatment. Patients received a median of five infusions of panitumumab and irinotecan. On an intention-to-treat analysis, 12 patients (23 %) achieved partial responses and 22 patients (41 %) achieved disease stabilization. Median progression-free survival and overall survival were 4.5 and 15.1 months, respectively. The most frequent treatment-related severe toxicities per patient were diarrhoea (35.8 %), followed by skin rash (32.1 %), asthenia (18.9 %) and neutropenia (13.2 %). A significant association between clinical response and incidence and grade of skin toxicity was observed (p = 0.0032). CONCLUSION: This study shows that the administration of panitumumab plus irinotecan every 3 weeks is safe, active and feasible as second-line treatment in patients with advanced WT K-RAS CRC.
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Anticuerpos Monoclonales/administración & dosificación , Camptotecina/análogos & derivados , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Proteínas ras/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Antineoplásicos Fitogénicos/administración & dosificación , Camptotecina/administración & dosificación , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Genes ras , Humanos , Irinotecán , Masculino , Persona de Mediana Edad , Panitumumab , Estudios Prospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
AIMS: The aim of this study was to evaluate the potential protective effects of ad libitum black grape (Vitis labrusca) juice against liver oxidative damage in whole-body acute X-irradiated rats. MAIN METHODS: Animals were fed ad libitum and drank voluntarily black grape juice or placebo (isocaloric glucose and fructose solution) for 6 days before and 15 days following a 6 Gy X-irradiation from a 200 kV machine. KEY FINDINGS: Irradiated animals receiving placebo showed a significant increase in the concentration of thiobarbituric acid-reactive substances (TBARS), a marker of lipid peroxidation, as well as a significant decrease in both Cu/Zn superoxide dismutase (Cu/ZnSOD) and glutathione peroxidase (GPx) activity and reduced glutathione concentration (GSH). Black grape juice supplementation resulted in a reversal of lipid peroxidation, Cu/ZnSOD activity, and GSH concentration, towards values not significantly differing from those in non-irradiated, placebo-supplemented rats. Poly(ADP-ribose) polymerase (PARP-1) and Cu/ZnSOD changes in protein expression were observed for irradiated rats. No change in p53 expression or DNA fragmentation was found. SIGNIFICANCE: Ad libitum black grape juice intake is able to restore the liver primary antioxidant system against adverse effects due to whole-body acute X-irradiation in rats after 15 days post-irradiation. The results support using antioxidant supplements as a preventive tool against radiation-induced harm.
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Bebidas , Hígado/diagnóstico por imagen , Estrés Oxidativo , Vitis , Irradiación Corporal Total , Animales , Western Blotting , Fragmentación del ADN , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Peroxidación de Lípido , Hígado/enzimología , Hígado/metabolismo , Hígado/patología , Masculino , Placebos , Radiografía , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Rayos XRESUMEN
The genetic structure of 4 Colombian Creole cattle breeds, namely, Costeño con Cuernos, Blanco Orejinegro (BON), Romosinuano (ROMO), and Sanmartinero (SM), was studied with an analysis of the available pedigree data. The comparison between the effective number of founders (f(e)) and the effective number of ancestors (f(a)) revealed a decrease in the genetic variation that was rather important for the ROMO and San Martinero breeds, which had the lowest f(a)/f(e) ratios (0.34 and 0.53, respectively). All breeds showed similar values for the number of equivalent generations traced, ranging from 3.1 in BON to 4.8 in ROMO. These 2 populations also had the lowest and the highest population sizes, respectively. The lowest average inbreeding coefficient considering the whole pedigree was obtained by BON (0.18%), whereas the highest was attained by ROMO (1.22%). Finally, the percentage of individuals with an inbreeding level greater than 6.25% in the reference population was high, indicating that the existing conservation management strategies could be improved to successfully maintain the genetic variability of these populations.
Asunto(s)
Bovinos/genética , Conservación de los Recursos Naturales , Variación Genética , Genética de Población , Animales , Colombia , Femenino , Pool de Genes , Endogamia , Masculino , Modelos Genéticos , Linaje , Factores de TiempoRESUMEN
Objetivo: Comparar la percepción del dolor-temor durante el trabajo de parto y parto, y el grado de dificultad-satisfacción con la experiencia de parto, en un grupo de adolescentes acompañadas por doula y otro con atención habitual. Método: El grupo estudio comprendió 80 adolescentes del "Programa Emprende Mamá" que controlaron sus embarazos en centros de salud de la comuna de La Florida y con parto en el hospital Dr. Sótero del Río, acompañadas por una mujer familiar o amiga, elegida por la joven, con capacitación previa de 2 horas. El grupo control estuvo formado por 80 adolescentes no participantes del programa, que controlaron sus embarazos en los mismos centros de salud, con parto en el mismo período. Resultados: El grupo estudio refirió menor percepción de dolor durante el trabajo de parto y parto, menor temor durante el parto y lo percibió como más fácil. No se encontraron diferencias significativas en el nivel de satisfacción respecto de la experiencia total. Sin embargo, las adolescentes con doula señalaron estar satisfechas por aspectos positivos de la vivencia, mientras que el grupo control centra su satisfacción en la ausencia de expectativas negativas temidas. Conclusión: El acompañamiento por doula en el parto de la embarazada adolescente, es una intervención de bajo costo que permite mejorar cualitativamente su vivencia de parto.
Objective: To compare the effects of continuous doula support and standard hospital care on pain and fear perception, during labor and delivery, as well as perception of difficulty and satisfaction with the birth experience, in a sample of pregnant teenagers. Method: The study group was conformed by eighty pregnant teenagers participants in "Emprende Mama Program" attended in the outpatient clinics of La Florida county for their prenatal care and delivery at a public hospital. They received emotional support during labor by a 2 hour trained female relative or friend, previously chosen by them. The control group was conformed by eighty non participants teenagers attended at the same outpatient clinics and delivery in the same period. Results: Teenagers with doula support reported less pain and fear during labor and delivery and perceived their birth experience as less difficult. No significant differences were reported in relation to satisfaction with birth experience. Although teenagers with doula support reported satisfaction due to positive aspects with birth experience, meanwhile the control group felt mostly satisfied due the absence of negative feared expectations. Conclusion: Labor support given by doula, is a low cost intervention which improves quality perception of birth experience in the adolescent pregnant.