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BACKGROUND: Pharmacogenomic knowledge as a biomarker for cancer care has transformed clinical practice, however, as current guidelines are primarily derived from Eurocentric populations, this limits their application in Latin America, particularly among Hispanic or Latino groups. Despite advancements, systemic chemotherapy still poses challenges in drug toxicity and suboptimal response. This study explores pharmacogenetic markers related to anticancer drugs in a Chilean cohort, filling a gap in Latin American research. Notably, the influence of native South American Mapuche-Huilliche ancestry. METHODS: To explore pharmacogenetic markers related to anticancer drugs, we utilized an ethnically Admixed Chilean genome-wide association studies (GWAS) dataset of 1095 unrelated individuals. Pharmacogenomic markers were selected from PharmGKB, totaling 36 level 1 and 2 evidence single nucleotide polymorphisms (SNPs) and 571 level 3 SNPs. Comparative analyses involved assessing SNP frequencies across diverse populations from the 1000 Genomes Project. Haplotypes were estimated, and linkage disequilibrium was examined. Ancestry-based association analyses explored relationships between SNPs and Mapuche-Huilliche and European ancestries. Chi-square distribution with p ≤ 0.05 and Bonferroni's multiple adjustment tests determined statistical differences between allele frequencies. RESULTS: Our study reveals significant disparities in SNP frequency within the Chilean population. Notably, dihydropyrimidine dehydrogenase (DPYD) variants (rs75017182 and rs67376798), linked to an increased risk of severe fluoropyrimidine toxicity, exhibit an exceptionally low frequency (minor allele frequency (MAF) < 0.005). Nudix hydrolase 15 (NUDT15) rs116855232, associated with hematological mercaptopurine toxicity, is relatively common (MAF = 0.062), and is further linked to Mapuche-Huilliche ancestry. Thiopurine methyltransferase enzyme (TPMT), implicated in severe toxicity to mercaptopurines, SNPs rs1142345 and rs1800460 of TMPT gene demonstrate higher MAFs in Admixed Americans and the Chilean population (MAF range 0.031-0.057). Finally, the variant in the UDP-glucuronosyltransferase 1 gene (UGT1A1) rs4148323, correlated with irinotecan neutropenia, exhibits the highest MAF in East Asian (MAF = 0.136) and Chilean (MAF = 0.025) populations, distinguishing them from other investigated populations. CONCLUSIONS: This study provides the first comprehensive pharmacogenetic characterization of cancer therapy-related SNPs and highlights significant disparities in SNP frequencies within the Chilean population. Our findings underscore the necessity for inclusive research and personalized therapeutic strategies to ensure the equitable and effective application of precision medicine across diverse global communities.
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En el contexto de la pandemia de COVID 19 durante el año 2020 y hasta la fecha se diseñó un formato de evaluación para nuestros alumnos de pre y posgrado bajo el alero de los exámenes clínicos objetivos estructurados (ECOE) en un formato remoto. Se revisó la literatura al respecto y se diseñó un instrumento que diera cuenta en forma oportuna y estandarizada del desempeño de nuestros alumnos y residentes. Estas experiencias están siendo evaluadas en estudios con metodología mixta. Sin embargo, decidimos compartir esta experiencia, por su impacto en el desarrollo docente de las ciencias de la salud.
In the context of the COVID-19 pandemic during 2020 and to date, an evaluation format has been designed for our undergraduate and graduate students under the design of the objective structured clinical examinations (OSCE) in a remote format. The literature was reviewed, and an instrument was designed to account for the performance of our students and residents in a timely and standardized manner. These experiences are being evaluated in studies with mixed methodology. However, we wanted to convey this experience due to its impact on the educational development of health sciences.
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Environmental stressors, such as temperature, are relevant factors that could generate a negative effect on several tissues in fish. A key fish species for Chilean aquaculture diversification is the red cusk-eel (Genypterus chilensis), a native fish for which knowledge on environmental stressors effects is limited. This study evaluated the effects of high-temperature stress on the liver of red cusk-eel in control (14 °C) and high-temperature (19 °C) groups using multiple approaches: determination of plasmatic hepatic enzymes (ALT, AST, and AP), oxidative damage evaluation (AP sites, lipid peroxidation, and carbonylated proteins), and RNA-seq analysis. High-temperature stress generated a significant increase in hepatic enzyme activity in plasma. In the liver, a transcriptional regulation was observed, with 1239 down-regulated and 1339 up-regulated transcripts. Additionally, high-temperature stress generated oxidative stress in the liver, with oxidative damage and transcriptional modulation of the antioxidant response. Furthermore, an unfolded protein response was observed, with several pathways enriched, as well as a heat shock response, with several heat shock proteins up regulated, suggesting candidate biomarkers (i.e., serpinh1) for thermal stress evaluation in this species. The present study shows that high-temperature stress generated a major effect on the liver of red cusk-eel, knowledge to consider for the aquaculture and fisheries of this species.
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La percepción de padres ante los programas de vacunación de los niños para la prevención de enfermedades, así como las campañas de información y conocimiento sobre las vacunas, motiva el interés científico por conocer y evaluar los factores relacionados al grado de conocimiento, aptitudes y fuentes de información de la población sobre las vacunas, siendo la inmunización un método que permite adquirir inmunidad contra las enfermedades comunes y mortales y reduce gastos por tratamientos para la mejoría de la salud. Objetivo: Describir la percepción de los padres sobre la vacunación infantil. Metodología: Investigación cualitativa, a través del estudio de revisión de contenido relacionado con el descriptor vacunación, donde se recopila la información de interés según su aparición en la búsqueda. El estudio está basado en el paradigma positivista con observación y registro de información relevante con el tema. Resultados: La falta de información sobre los riesgos y beneficios de la vacunación es un factor que induce a la desconfianza e inseguridad respecto a las vacunas; gran parte de los padres considera útil la vacuna, necesaria y beneficiosa pero prevalece la idea que la inmunización puede ser algo peligroso y con efectos indeseables y secuelas graves por información mediática no bién conducida. Conclusiones: Diversos estudios señalan factores que impiden que los padres de los niños cumplan con los esquemas de vacunación, entre estos la falta de información y conocimiento sobre las vacunas, que evitan las enfermedades en los menores reforzando el sistema inmunológico, así como, otra de las razones es la falta de vacunas en los centros asistenciales, que genera desinterés y dificulta el cumplimiento de los programas de vacunación, además, servicios lentos y poca empatía del personal que presta atención en los centros de salud aumentan la percepción negativa sobre la vacunación(AU)
The perception of parents regarding the vaccination programs for children for the prevention of diseases, as well as the information and knowledge campaigns about vaccines, motivates the scientific interest in knowing and evaluating the factors related to the degree of knowledge, aptitudes and sources of information for the population about vaccines, immunization being a method that allows acquiring immunity against common and deadly diseases and reduces expenses for treatments to improve health. Objective: To describe the perception of parents about childhood vaccination. Materials and Methods Qualitative research, through a content review study related to the vaccination descriptor, where the information of interest is compiled according to its appearance in the search. The study is based on the positivist paradigm with observation and recording of information relevant to the subject. Results: The lack of information about the risks and benefits of vaccination is a factor that induces mistrust and insecurity regarding vaccines; A large part of the parents considers the vaccine useful, necessary and beneficial, but the idea prevails that immunization can be something dangerous and with undesirable effects and serious sequelae due to misguided media information. Conclusnios: Various studies point to factors that prevent parents of children from complying with vaccination schedules, including lack of information and knowledge about vaccines, which prevent diseases in minors by strengthening the immune system, as well as another of The reasons are the lack of vaccines in health centers, which generates disinterest and makes it difficult to comply with vaccination programs, in addition, slow services and little empathy of the personnel who provide care in health centers increase the negative perception about vaccination(AU)
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Pais , Percepção , Esquemas de Imunização , Vacinação , Centros de Saúde , Doença , Prevenção de DoençasRESUMO
Metabolic syndrome is a pre-diabetic state characterized by several biochemical and physiological alterations, including insulin resistance, visceral fat accumulation, and dyslipidemias, which increase the risk for developing cardiovascular disease. Metabolic syndrome is associated with augmented sympathetic tone, which could account for the etiology of pre-diabetic cardiomyopathy. This review summarizes the current knowledge of the pathophysiological consequences of enhanced and sustained ß-adrenergic response in pre-diabetes, focusing on cardiac dysfunction reported in diet-induced experimental models of pre-diabetic cardiomyopathy. The research reviewed indicates that both protein kinase A and Ca2+/calmodulin-dependent protein kinase II play important roles in functional responses mediated by ß1-adrenoceptors; therefore, alterations in the expression or function of these kinases can be deleterious. This review also outlines recent information on the role of protein kinase A and Ca2+/calmodulin-dependent protein kinase II in abnormal Ca2+ handling by cardiomyocytes from diet-induced models of pre-diabetic cardiomyopathy.
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Introducción: se realizó un análisis de la evidencia disponible sobre intervenciones orientadas a mejorar la adherencia al lavado de manos, para generar recomendaciones para los centros de atención en salud ambulatoria.Materiales y métodos: se realizó una búsqueda en Pubmed, Embase y Epistemonikos, y en las referencias de guías sobre el tema, seleccionando aquellos estudios no observacionales en que se realizaran intervenciones para aumentar la adherencia al lavado de manos en atención en salud. Se clasificaron las estrategias descritas según tipo de intervención, y se evaluaron según su efectividad en mejorar la adherencia al lavado de manos y el seguimiento en el tiempo.Resultados: se seleccionaron 34 estudios experimentales prospectivos, que se clasificaron en 10 grupos según el tipo de intervención realizada, y se evaluaron según efectividad y seguimiento en una escala del I al VII. 24 de 34 estudios mostraron un aumento estadísticamente significativo de la adherencia al lavado de manos mayor al 15% desde el basal o en comparación al grupo control, correspondiendo en su mayoría a estrategias multimodales y de feedback. Discusión: las intervenciones más efectivas para mejorar la adherencia al lavado de manos fueron las que incluían abordajes multimodales y las que incluían feedback. Se hace urgente generar mayor evidencia sobre esta temática en el contexto de atención ambulatoria.
Introduction: To analyze the available evidence on interventions aimed at improving adherence to handwashing, to generate re-commendations for outpatient health care centers. Methods: A search was made in Pubmed, Embase and Epistemonikos, and in the references of guides on the subject, selecting those non-observational studies in which interventions were carried out to increase adherence to handwashing in health care. The strategies described were classified according to the type of intervention, and evaluated according to their effectiveness in improving adherence to handwashing, and its follow-up time afterward. Results: 34 prospective experimental studies were selected, which were classified into 10 groups according to the type of intervention performed, and were evaluated according to effectiveness and follow-up on a scale from I to VII. 24 of 34 studies showed a statistically significant increase in handwashing adherence greater than 15% from baseline or compared to the control group, corresponding mostly to multimodal and feedback strategies. Discussion: The most effective interventions to improve adherence to handwashing were those that included multimodal approaches and the ones that included feedback. It is urgent to generate more evidence on the subject in the context of ambulatory care.
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INTRODUCTION: Robot-assisted Therapy (RAT) can improve the behavior of children with Autism Spectrum Disorder (ASD) in a spontaneous and entertaining way. There are no previous experiences of this type of inter vention in our country. OBJECTIVE: To describe a clinical experience of using RAT and its impact on the behaviors of a group of children with ASD, in a therapeutic context. PATIENTS AND METHOD: Quasi experimental clinical experience type study. 4 children with a clinical diagnosis of ASD were selected, supported by the ADOS-2 (Autism Diagnostic Observation Schedule); aged between 9 and 13 years, and normal IQ according to the WISC-III (Wechsler Intelligence Scale for Children). This study was approved by the Central Metropolitan Ethics Committee. Patients attended 10 structured robot-as sisted therapy sessions, working collaboratively in pairs. Workshop attendance and parent and child satisfaction were evaluated through surveys, the adaptive behavior with the Vineland scale, and so cial interaction with video coding guidelines. RESULTS: Patients presented a very good adherence and satisfaction with the activity. There was an improvement in socialization behaviors and social age. Video-coding showed an increase in social interaction and improvement in the behavior of the pa tients after attending workshops. CONCLUSIONS: We observed that the experience with RAT, adapted to the context of a Chilean public health center, was highly attractive and beneficial for patients with ASD, improving core symptoms such as difficulties in social interaction and behavioral problems.
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Transtorno do Espectro Autista , Transtorno Autístico , Comportamento Problema , Robótica , Transtorno do Espectro Autista/terapia , Humanos , PaisRESUMO
Objetivo: analisar as experiências de puérperas acerca das práticas profissionais desenvolvidas na atenção ao parto à luz do aporte teórico da humanização. Método: pesquisa qualitativa, com a participação de dez puérperas que vivenciaram parto vaginal, por meio de entrevista semiestruturada, desenvolvida entre setembro e novembro de 2019. Adotou-se a análise temática. Resultados: predominaram práticas que se distanciaram da humanização, como enema, restrição hídrica e alimentar, exames vaginais frequentes, episiotomia, manobras de Valsalva e de Kristeller. As práticas que se aproximaram da humanização foram a presença do acompanhante, utilização de métodos de alívio da dor no parto e contato cutâneo precoce entre mãe e bebê. Conclusão: as experiências das puérperas foram marcadas, principalmente, por condutas profissionais prejudiciais ou ineficazes, realizadas de forma inadequada e com poucas evidências científicas sobre a sua eficácia. Espera-se subsidiar a reflexão quanto à necessidade de revisão e atualização quanto às boas práticas de atenção ao parto.
Objective: to analyze the experiences of puerperal women about the professional practices developed in delivery care in the light of the theoretical contribution of humanization. Method: qualitative research, with the participation of ten puerperal women who experienced vaginal delivery, through semi-structured interviews, developed between September and November 2019. Thematic analysis was adopted. Results: practices that distanced themselves from humanization, such as enema, water and food restriction, frequent vaginal examinations, episiotomy, Valsalva and Kristeller maneuvers, predominated. The practices that approached humanization were the presence of the companion, use of methods of pain relief in the delivery and early skin contact between mother and baby. Conclusion: the experiences of the puerperal women were mainly marked by harmful or ineffective professional behaviors, performed inappropriately and with little scientific evidence about their efficacy. It is expected to support the reflection on the need for review and updating regarding good practices of delivery care.
Objetivo: analizar las experiencias de las mujeres puerperales sobre las prácticas profesionales desarrolladas en la atención del parto a la luz de la contribución teórica de la humanización. Método: investigación cualitativa, con la participación de diez mujeres puerperales que experimentaron el parto vaginal, a través de entrevistas semiestructuradas, desarrolladas entre septiembre y noviembre de 2019. Se adoptó un análisis temático. Resultados: predominaron las prácticas que se distanciaron de la humanización, como el enema, la restricción del agua y los alimentos, los exámenes vaginales frecuentes, la episiotomía, las maniobras de Valsalva y Kristeller. Las prácticas que se acercaron a la humanización fueron la presencia del compañero, el uso de métodos de alivio del dolor en el parto y el contacto temprano de la piel entre la madre y el bebé. Conclusión: las experiencias de las mujeres puerperales estuvieron marcadas principalmente por conductas profesionales dañinas o ineficaces, realizadas de manera inapropiada y con poca evidencia científica sobre su eficacia. Se espera que apoye la reflexión sobre la necesidad de revisar y actualizar las buenas prácticas de la atención al parto.
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Humanos , Saúde da Mulher , Enfermagem , Parto Humanizado , Parto , Humanização da AssistênciaRESUMO
The red cusk-eel (Genypterus chilensis) is a native species with strong potential to support Chilean aquaculture diversification. Environmental stressors, such as temperature, may generate important effects in fish physiology with negative impact. However, no information exists on the effects of thermal stress in Genypterus species or how this stressor affects the skeletal muscle. The present study evaluated for the first time the effect of high temperature stress in red cusk-eel juveniles to determine changes in plasmatic markers of stress (cortisol, glucose and lactate dehydrogenase (LDH)), the transcriptional effect in skeletal muscle genes related to (i) heat shock protein response (hsp60 and hsp70), (ii) muscle atrophy and growth (foxo1, foxo3, fbxo32, murf-1, myod1 and ddit4), and (iii) oxidative stress (cat, sod1 and gpx1), and evaluate the DNA damage (AP sites) and peroxidative damage (lipid peroxidation (HNE proteins)) in this tissue. Thermal stress generates a significant increase in plasmatic levels of cortisol, glucose and LDH activity and induced heat shock protein transcripts in muscle. We also observed an upregulation of atrophy-related genes (foxo1, foxo3 and fbxo32) and a significant modulation of growth-related genes (myod1 and ddit4). Thermal stress induced oxidative stress in skeletal muscle, as represented by the upregulation of antioxidant genes (cat and sod1) and a significant increase in DNA damage and lipid peroxidation. The present study provides the first physiological and molecular information of the effects of thermal stress on skeletal muscle in a Genypterus species, which should be considered in a climate change scenario.
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Enguias , Doenças dos Peixes , Transtornos de Estresse por Calor , Animais , Glicemia/análise , Dano ao DNA , Enguias/sangue , Enguias/genética , Enguias/fisiologia , Doenças dos Peixes/sangue , Doenças dos Peixes/genética , Doenças dos Peixes/metabolismo , Doenças dos Peixes/patologia , Proteínas de Peixes/genética , Transtornos de Estresse por Calor/sangue , Transtornos de Estresse por Calor/genética , Transtornos de Estresse por Calor/patologia , Transtornos de Estresse por Calor/veterinária , Hidrocortisona/sangue , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Atrofia Muscular , Estresse Oxidativo , TranscriptomaRESUMO
BACKGROUND: Skeletal muscle is one of the tissues most affected by stress conditions. The protein degradation in this tissue is vital for the supply of energy mediated by different proteolytic pathways such as the ubiquitin-proteasome (UPS), autophagy-lysosome (ALS) and the calpain/calpastatin system (CCS). Nevertheless, the regulation of this proteolytic axis under stress conditions is not yet completely clear. Chile is the main producer of rainbow trout (Oncorhynchus mykiss) in the world. This intensive fish farming has resulted in growing problems as crowding and stress are one of the major problems in the freshwater stage. In this context, we evaluated the crowding effect in juvenile rainbow trout kept in high stocking density (30 kg/m3) for 15, 45 and 60 days, using a control group of fish (10 kg/m3). RESULTS: Plasmatic cortisol and glucose were evaluated by enzyme immunoassay. The mRNA levels of stress-related genes (gr1, gr2, mr, hsp70, klf15 and redd1), markers of the UPS (atrogin1 and murf1) and CCS (capn1, capn1, cast-l and cast-s) were evaluated using qPCR. ALS (LC3-I/II and P62/SQSTM1) and growth markers (4E-BP1 and ERK) were measured by Western blot analysis. The cortisol levels increased concomitantly with weight loss at 45 days of crowding. The UPS alone was upregulated at 15 days of high stocking density, while ALS activation was observed at 60 days. However, the CCS was inactivated during the entire trial. CONCLUSION: All these data suggest that stress conditions, such as crowding, promote muscle degradation in a time-dependent manner through the upregulation of the UPS at early stages of chronic stress and activation of the ALS in long-term stress, while the CCS is strongly inhibited by stress conditions in the rainbow trout muscle farmed during freshwater stage. Our descriptive study will allow perform functional analysis to determine, in a more detailed way, the effect of stress on skeletal muscle physiology as well as in the animal welfare in rainbow trout. Moreover, it is the first step to elucidate the optimal crop density in the freshwater stage and improve the standards of Chilean aquaculture.
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Aglomeração , Músculo Esquelético/metabolismo , Oncorhynchus mykiss/metabolismo , Proteólise , Animais , Aquicultura/métodos , Autofagia , Peso Corporal , Proteínas de Ligação ao Cálcio/metabolismo , Calpaína/metabolismo , Hidrocortisona/sangue , Lisossomos/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , RNA Mensageiro , Estresse Fisiológico/genética , Ubiquitina/metabolismoRESUMO
BACKGROUND: Admission to the emergency department (ED) of patients with advanced or end-of-life (EoL) cancer saturates the services that provide active medical attention to the complications of anticancer therapy, and the lack of specific protocol limits proper handling. OBJECTIVE: The aim of this study was to describe the characteristics of patients with advanced cancer admitted to the ED at the EoL in a comprehensive cancer center in Mexico. PATIENTS AND METHODS: We conducted a retrospective analysis of patients admitted to ED of the National Cancer Institute of Mexico City, with 3 or less days before they died, between January 2011 and December 2018. The data collected included clinical and demographic characteristics, reason for admission to the ED, number of admissions to ED in the last month of life, and cancer treatment received. RESULTS: A total of 426 patients were included; 60.8% were female with a median age of 60 years; 71.6% patients were receiving some kind of disease-modifying treatment, although the oncologist had considered they could die within 6 months, and 16 of them were receiving concomitant PC. 8.9% of these patients had been admitted 3 or more times to the ED in the last month. The principal reasons for admission to ED were dyspnea, uncontrolled pain, 12 patients were admitted in active death and 94 died within hours of admission to ED. CONCLUSIONS: Palliative care approach in oncological patients admitted to ED is important to avoid unnecesary suffering at the EoL.
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Países em Desenvolvimento , Neoplasias , Morte , Serviço Hospitalar de Emergência , Feminino , Humanos , México/epidemiologia , Pessoa de Meia-Idade , National Cancer Institute (U.S.) , Neoplasias/epidemiologia , Neoplasias/terapia , Estudos Retrospectivos , Estados UnidosRESUMO
Antecedentes: La identificación de microorganismos como Streptococcus mutans(SM) y Lactobacillus sp. (LB) es un predictor del desarrollo de caries, sin embargo los métodos de identificación son de acceso limitado por su alto costo. Objetivo:determinar la correlación entre la biopelícula dental medida por el índice de placa bacteriana de (IPB) Silness y Löe modificado y el recuento de SM y LB en niños colombianos en edad preescolar. Este es un estudio descriptivo de corte transversal y correlacional. Materiales y métodos: Se tomaron 202 muestras de niños entre los 3 y 4 años de edad de tres jardines Infantiles de Cali, Colombia, pertenecientes al estrato socioeconómico 1 y 2, evaluados en cuatro tiempos (0, 3, 6 y 9 meses). Resultados: Hubo una correlación entre el IPB más alto y el mayor recuento de unidades formadoras de colonia de SMsólo a los 3 meses (p = 0,003*). Los recuentos de LB fueron homogéneos en todos los niños y no presentaron correlación con el IPB. Conclusión: Se observaron resultados mixtos sobre la relación entre IPB y los recuentos de SM presentes en la saliva, por lo cual se requiere un análisis de múltiples factores.
Background:The identification of microorganisms such as Streptococcus mutans(SM) and Lactobacillusspp. (LB) is a predictor of the development of caries, however the identification methods are of limited access due to their high cost. Aim:To determine the correlation between the dental biofilm measured by the modified Silness and Löe dental plaque index (DPI)) and the SM and LB count, in preschool children from Colombia. Materials and methods: This is a descriptive cross-sectional and correlational study. We took202 samples from children between 3 and 4 years of age from three kindergartens in Cali, Colombia, belonging to socioeconomic stratum 1 and 2, evaluated at four times (0, 3, 6 and 9 months). Results: We found a correlation between the highest IPB and thehighest count of SM colony forming units only at 3 months (p = 0.003*). LB counts were homogeneous in all children and there was no correlation with IPB. Conclusion: We observed mixed results on the relationship between IPB and the counts of SM present in the saliva, therefore an analysis of multiple factors is required.KEY WORDSDental plaque;Streptococcus mutans;Lactobacillus spp;dental caries.1
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The red cusk-eel (Genypterus chilensis) is a native Chilean species with a high-value market, with the potential to diversify Chilean aquaculture. The objective of this study was to develop a set of microsatellite markers, estimate genetic parameters, determine population differentiation, and identify the population structure of wild and commercial populations of G. chilensis. We discovered 6427 microsatellites markers from RNA-seq data, of which 54.9%, 20.2% and 16.8% were di-, tri-, and tetranucleotides, respectively. We used 12 of these markers to genotype two sets of broodstock, one group from commercial fish, and one group from wild fish from the Coquimbo Region of G. chilensis. We estimate the genetic parameters of the markers, selecting ten polymorphic markers (PIC > 0.5). We observed differences in the inbreeding coefficient among populations, with high values of inbreeding in one broodstock set and lower values in the other groups. The evaluation of population differentiation using Fst showed small (0.0195) to large (0.1888) genetic differentiation between the groups. The structure analysis showed that commercial and wild groups were formed by three clusters, without relevant evidence of admixture process, suggesting that groups evaluated in this study are formed of at least three subpopulations of G. chilensis, which could be explained by the low or lack of migration suggested for this species. This is the first study that identifies a high number of molecular markers in G. chilensis, providing relevant information of the genetic structure of commercial and wild population of this species.
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Peixes/genética , Repetições de Microssatélites/genética , Transcriptoma/genética , Animais , DNA/análise , DNA/genética , Pesqueiros , Variação GenéticaRESUMO
Hypercoagulable state is linked to cancer progression; however, the precise role of the coagulation cascade is poorly described. Herein, we examined the contribution of a hypercoagulative state through the administration of intravenous Coagulation Factor Xa (FXa), on the growth of solid human tumors and the experimental metastasis of the B16F10 melanoma in mouse models. FXa increased solid tumor volume and lung, liver, kidney and lymph node metastasis of tail-vein injected B16F10 cells. Concentrating on the metastasis model, upon coadministration of the anticoagulant Dalteparin, lung metastasis was significantly reduced, and no metastasis was observed in other organs. FXa did not directly alter proliferation, migration or invasion of cancer cells in vitro. Alternatively, FXa upon endothelial cells promoted cytoskeleton contraction, disrupted membrane VE-Cadherin pattern, heightened endothelial-hyperpermeability, increased inflammatory adhesion molecules and enhanced B16F10 adhesion under flow conditions. Microarray analysis of endothelial cells treated with FXa demonstrated elevated expression of inflammatory transcripts. Accordingly, FXa treatment increased immune cell infiltration in mouse lungs, an effect reduced by dalteparin. Taken together, our results suggest that FXa increases B16F10 metastasis via endothelial cell activation and enhanced cancer cell-endothelium adhesion advocating that the coagulation system is not merely a bystander in the process of cancer metastasis.
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Vasculogenic mimicry (VM) describes a process by which cancer cells establish an alternative perfusion pathway in an endothelial cell-free manner. Despite its strong correlation with reduced patient survival, controversy still surrounds the existence of an in vitro model of VM. Furthermore, many studies that claim to demonstrate VM fail to provide solid evidence of true hollow channels, raising concerns as to whether actual VM is actually being examined. Herein, we provide a standardized in vitro assay that recreates the formation of functional hollow channels using ovarian cancer cell lines, cancer spheres and primary cultures derived from ovarian cancer ascites. X-ray microtomography 3D-reconstruction, fluorescence confocal microscopy and dye microinjection conclusively confirm the existence of functional glycoprotein-rich lined tubular structures in vitro and demonstrate that many of structures reported in the literature may not represent VM. This assay may be useful to design and test future VM-blocking anticancer therapies.
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Modelos Biológicos , Neoplasias Ovarianas/patologia , Feminino , Humanos , Imageamento Tridimensional , Microscopia Confocal , Microscopia de Fluorescência , Técnicas de Cultura de Órgãos , Coloração e Rotulagem , Células Tumorais Cultivadas , Microtomografia por Raio-XRESUMO
Clinical studies have suggested a survival benefit in ovarian cancer patients with type 2 diabetes mellitus taking metformin, however the mechanism by which diabetic concentrations of metformin could deliver this effect is still poorly understood. Platelets not only represent an important reservoir of growth factors and angiogenic regulators, they are also known to participate in the tumor microenvironment implicated in tumor growth and dissemination. Herein, we investigated if diabetic concentrations of metformin could impinge upon the previously reported observation that platelet induces an increase in the tube forming capacity of endothelial cells (angiogenesis) and upon ovarian cancer cell aggressiveness. We demonstrate that metformin inhibits the increase in angiogenesis brought about by platelets in a mechanism that did not alter endothelial cell migration. In ovarian cancer cell lines and primary cultured cancer cells isolated from the ascitic fluid of ovarian cancer patients, we assessed the effect of combinations of platelets and metformin upon angiogenesis, migration, invasion and cancer sphere formation. The enhancement of each of these parameters by platelets was abrogated by the present of metformin in the vast majority of cancer cell cultures tested. Neither metformin nor platelets altered proliferation; however, metformin inhibited the increase in phosphorylation of focal adhesion kinase induced by platelets. We present the first evidence suggesting that concentrations of metformin present in diabetic patients may reduce the actions of platelets upon both endothelial cells and cancer cell survival and dissemination.
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Plaquetas , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Neovascularização Patológica/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Progressão da Doença , Feminino , Humanos , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/patologia , Células Tumorais CultivadasRESUMO
The vascular endothelium plays an essential role in the control of the blood flow. Pharmacological agents like quinone (menadione) at various doses modulate this process in a variety of ways. In this study, Q7, a 2-phenylamino-1,4-naphthoquinone derivative, significantly increased oxidative stress and induced vascular dysfunction at concentrations that were not cytotoxic to endothelial or vascular smooth muscle cells. Q7 reduced nitric oxide (NO) levels and endothelial vasodilation to acetylcholine in rat aorta. It also blunted the calcium release from intracellular stores by increasing the phenylephrine-induced vasoconstriction when CaCl2 was added to a calcium-free medium but did not affect the influx of calcium from extracellular space. Q7 increased the vasoconstriction to BaCl2 (10-3 M), an inward rectifying K+ channels blocker, and blocked the vasodilation to KCl (10-2 M) in aortic rings precontracted with BaCl2. This was recovered with sodium nitroprusside (10-8 M), a NO donor. In conclusion, Q7 induced vasoconstriction was through a modulation of cellular mechanisms involving calcium fluxes through K+ channels, and oxidative stress induced endothelium damage. These findings contribute to the characterization of new quinone derivatives with low cytotoxicity able to pharmacologically modulate vasodilation.
RESUMO
El diagnóstico de la infección cervical ocasionada por el virus del papiloma humano (VPH), se realiza básicamente a través de la biopsia y/o de métodos moleculares como la reacción en cadena de la polimerasa (PCR). Los resultados de estos estudios en ocasiones no coinciden. En este estudio se evalúa la posible influencia de diferentes factores asociados a resultados falsos positivos y a falsos negativos de ambas pruebas. Se analizaron 271 muestras de cuello uterino de pacientes que acudieron a la consulta ginecológica durante el período 1999-2009, a las cuales se les tomó biopsia por presentar hallazgos colposcópicos y/o citológicos sospechosos de infección por VPH. Tomando en consideración al resultado de PCR como prueba estándar de oro, la biopsia presentó 14% de falsos positivos y 16,6% de falsos negativos, el diagnóstico de VPH en biopsia y PCR presentó mayor concordancia cuando las muestras abarcan la zona de transformación endo-exocervical, así como la presencia de metaplasia escamosa en la muestra y el tamaño del fragmento mayor (>0,5 cm); mientras que el tiempo de fijación, el tipo e intensidad de la inflamación, la hemorragia y la erosión del epitelio no fueron significativos. En conclusión, a fin de disminuir la discrepancia de los resultados entre la biopsia y prueba de ADN, sería importante que la muestra de biopsia incluya la zona de transformación del cuello uterino y al menos un fragmento mayor de 0,5 cm.
The diagnosis of cervical infection caused by human papilloma virus (HPV) is made basically through the biopsy and/or molecular methods such as polymerase chain reaction (PCR). The results of these studies sometimes do not match. In this work is evaluated the possible influence of different factors associated with results false positive and false negative of both tests. Were analyzed 271 samples from uterin cervix of patients presenting to the gynecologist during the period 1999-2009, to which were taken biopsies due present findings colposcopics and/or cytological suspicious of HPV infection. Considering the result of PCR as gold standard test, biopsy showed 14% false positive and false negative 16.6%, the diagnostic of VPH in biopsy and PCR showed greater concordance when samples include endo-exocervical transformation zone, and the presence of squamous metaplasia in the sample and size of the largest fragment (>0.5 cm); while the fixation time, the type and intensity of inflammation, bleeding and erosion of the epithelium were not significant. In conclusion, in order to reduce the discrepancy between the results of the biopsy and test DNA, it is important that the biopsy sample includes the transformation zone of the uterin cervix and at least one fragment greater than 0.5 cm.
RESUMO
: Las cifras chilenas sobre abuso sexual (AS) y violencia al interior de las familias (VIF) son altísimas y transversales a todo estrato social. Un 25,9 por ciento de los niños ha sido víctima de violencia grave en sus hogares (patadas, puñetazos, mordeduras, quemaduras, agresiones con armas) y un 8,7 por ciento refiere haber experimentado AS. Un tercio de las chilenas ha sufrido VIF, cifra que se tradujo en 45 mujeres fallecidas el año 2015. Los médicos están en una posición única para identificar víctimas y romper el ciclo de violencia, sin embargo su formación al respecto es mínima. El Instituto de Medicina de Estados Unidos plantea que el medio más eficaz para mejorar la respuesta a VIF es la educación de los médicos, y ha llamado a que las facultades entreguen las competencias necesarias a sus estudiantes. Distintas Escuelas de Medicina de EEUU y Canadá ya lo están haciendo; en Chile esto aún no ocurre. Entre 2013 y 2014, mediante un Proyecto FONDEDOC revisamos la formación actual de los estudiantes de medicina en pesquisa y abordaje inicial de pacientes víctimas de VIFAS, y generamos una propuesta para fortalecer el desarrollo de competencias afines en el currículo de pregrado. Este artículo presenta los productos finales de ese proyecto. Se discute sobre la discordancia entre la magnitud del problema en Chile y la formación actual de nuestros médicos, se entrega un listado de competencias básicas para pesquisar y brindar una primera respuesta, y se ofrece una propuesta para fortalecer el currículo de pregrado en esta área. (AU)
The figures on sexual abuse and domestic violence are very high in Chile and they cut across the whole span of socioeconomic classes. 25.9 percent of children have suffered severe violence at home (kicks, punches, bites, burns, weapon agressions) and 8.7 percent refer having experimented sexual abuse. One third of Chilean women have suffered domestic violence, which translates in 45 women dying for this cause during 2015. Doctors are in a unique positoin to identify victims and to cut the violence cycle, however their training on this regard is scarce. The Institute of Medicine of the USA postulates the most effective way of improving the response to domestic violence is educating doctors, and has made a call to faculties to provide the competencies needed to their students. Several medical schools in USA and Canada are already doing so; in Chile this is not happening yet. Between 2013 and 2014 through a FONDEDOC project we reviewed the existing curriculum of Medical School in relation to identifying and to initially approach patients suffering domestic violence-sexual abuse, and we generated a proposal to strengthen the development of pertinent competencies in undergraduate curriculum. This article exposes the product of this project. The discrepancy between the magnitude of the problem in Chile and the current training of our doctors is discussed. A list of basic competencies to identify and deliver the first response is presented, and a proposal to strengthen undergraduate curriculum in this area is offered.(AU)
Assuntos
Humanos , Masculino , Feminino , Delitos Sexuais , Violência Doméstica , Currículo , Educação Médica , MedicinaRESUMO
BACKGROUND: An increase in circulating platelets, or thrombocytosis, is recognized as an independent risk factor of bad prognosis and metastasis in patients with ovarian cancer; however the complex role of platelets in tumor progression has not been fully elucidated. Platelet activation has been associated with an epithelial to mesenchymal transition (EMT), while Tissue Factor (TF) protein expression by cancer cells has been shown to correlate with hypercoagulable state and metastasis. The aim of this work was to determine the effect of platelet-cancer cell interaction on TF and "Metastasis Initiating Cell (MIC)" marker levels and migration in ovarian cancer cell lines and cancer cells isolated from the ascetic fluid of ovarian cancer patients. METHODS: With informed patient consent, ascitic fluid isolated ovarian cancer cells, cell lines and ovarian cancer spheres were co-cultivated with human platelets. TF, EMT and stem cell marker levels were determined by Western blotting, flow cytometry and RT-PCR. Cancer cell migration was determined by Boyden chambers and the scratch assay. RESULTS: The co-culture of patient-derived ovarian cancer cells with platelets causes: 1) a phenotypic change in cancer cells, 2) chemoattraction and cancer cell migration, 3) induced MIC markers (EMT/stemness), 3) increased sphere formation and 4) increased TF protein levels and activity. CONCLUSIONS: We present the first evidence that platelets act as chemoattractants to cancer cells. Furthermore, platelets promote the formation of ovarian cancer spheres that express MIC markers and the metastatic protein TF. Our results suggest that platelet-cancer cell interaction plays a role in the formation of metastatic foci.