Inhibition of CD73 expression or A2AR blockade reduces MRP1 expression and increases the sensitivity of cervical cancer cells to cisplatin.

Recently, a link between the biological activity of CD73 in solid tumors and multidrug resistance protein (MRP) has been proposed. Cisplatin (CP) is the most widely used anticancer agent to treat advanced and recurrent cervical cancer (CC). However, multidrug resistance protein-1 (MRP1) is overexpressed in approximately 85% of these tumors and has been strongly associated with cisplatin resistance (CPR). In this study, we examine the involvement of CD73 and the interaction of adenosine (ADO) with its receptors (ARs) in MRP1 expression in CC cells. We found that ADO positively modulates MRP1 expression in CC cells in a dose-dependent manner. The inhibition of CD73 expression with a CD73-targeted siRNA and A2AR blockade with the selective antagonist ZM241385 significantly decreased MRP1 expression and the extrusive capacity of CC cells, making them significantly more sensitive to CP treatment than cancer cells treated with MK-751, a specific MRP1 inhibitor. These results suggest CD73 inhibition or blocking ADO signaling through A2AR could be strategies to reverse CPR in patients with advanced or recurrent CC, which is characterized by very low response rates to CP (10%-20%).

Evidence that cervical cancer cells cultured as tumorspheres maintain high CD73 expression and increase their protumor characteristics through TGF-ß production.

Recently, a link between the biological activity of CD73 and tumorigenicity in solid tumors has been proposed. We previously reported that the generation of adenosine (Ado) by the activity of CD73 in cervical cancer (CC) cells induces transforming growth factor-beta 1 (TGF-ß1) production to maintain CD73 expression. In the present study, we analyzed the participation of TGF-ß1 in CD73 expression and the development of protumoral characteristics in CaSki CC cells cultured as tumorspheres (CaSki-T) and in monolayers (CaSki-M). Compared with those in CaSki-M cells, CD73 expression and Ado generation ability were significantly increased in CaSki-T cells. CaSki-T cells exhibited enrichment in the CSC-like phenotype due to increases in the expression levels of stem cell markers (CD49f, CK17, and P63; OCT4 and SOX2), greater sphere formation efficiency (SFE), and an increase in the percentage of side population (SP) cells. Interestingly, compared with CaSki-M cells, CaSki-T cells produced a greater amount of TGF-ß1 and presented a marked protumor phenotype characterized by a significant decrease in the expression of major histocompatibility complex class-I (MHC-I) molecules, an increase in the expression of multidrug resistance protein-I (MRP-I) and vimentin, and an increase in the protein expression levels of Snail-1 and Twist, which was strongly reversed with TGF-ß1 inhibition. These results suggest that the presence of TGF-ß1-CD73-Ado feedback loop can promote protumoral characteristics in the CC tumor microenvironment.

The relationship between physical activity, physical fitness and fatness in 3-6 years old boys and girls: a cross-sectional study.

Background: Physical activity (PA), fatness and fitness in children and teenagers have been associated with short and long-term health benefits. However, little research analyzing these variables focuses on the preschool education stage. Thus, the objective of this research is to study the relationship between PA, fatness and fitness in 3-6 years old boys and girls. Methods: This cross-sectional study includes 150 boys and girls at age between 3 and 6 years. Fatness and fitness were assessed using a PREFIT (FITness testing in PREschool children) battery as well as the sit and reach test. PA levels were measured using accelerometers for 7 days. Results: Higher PA levels were related to better fitness values. In addition, differences were found in the PA levels between boys and girls. However, PA subcomponents were not related to fatness. Furthermore, there were no significant differences in fitness tests between underweight, normal-weight and over-weight children, except in handgrip strength. Conclusions: The few studies that have analyzed the relationship between fatness, fitness and PA in preschool have revealed controversial results. However, our study is in accordance with the majority of studies which prove that PA is associated with better fitness performances in preschool children. Since fitness is an important indicator of health, schools and parents should encourage children to practice more daily PA, especially girls, who are less active than boys. However, the discrepancy about the relationship between PA and fatness between the results of the different research highlights the necessity of carrying out further studies that analyze the relationship between these 3 variables separately in each age group (3, 4, 5 and 6 years). This is due to the fact that associations were stronger in older children rather than in younger children.

Factores de riesgo ambientales y perinatales en pacientes pediátricos con Leucemia Linfoblástica aguda, de una población hospitalaria. Estudio de caso-control

RESUMEN Introducción: En la Leucemia linfoblástica aguda se han estudiado el rol de factores de riesgo ambientales y genéticos. Menos frecuentemente otros como los perinatales y parentales El objetivo del estudio fue analizar los factores de riesgo ambientales, parentales y perinatales de los niños con Leucemia linfoblástica aguda (LLA) en tratamiento en el servicio de oncología de un hospital pediátrico. Materiales y Métodos: estudio de caso-control, realizado en el departamento de oncohematología de un hospital pediátrico. Los casos fueron niños con diagnóstico de leucemia linfoblástica aguda y los controles niños con patología quirúrgica, previamente sanos pareados por edad. Se estudiaron variables ambientales, perinatales y parentales. Los análisis uni y multivariado fueron realizados en SPSS y los resultados se expresaron en OR con IC 95%. El protocolo fue aprobado por el comité de ética institucional. Resultados: se incluyó 66 casos y 132 controles. El 33,3 (22/66) vs el 8,3% (11/132) OR 5,5 (IC 95% 2,4 - 12,5 p=0,0001 de los casos y controles respectivamente, eran residentes desde el nacimiento de los departamentos con mayor área de cultivos. En el análisis multivariado el riesgo de proceder de departamentos con extensas áreas de cultivo fue 3,6 veces mayor, OR 3,6 (IC 95% 1,4 -9) p=0,008 ajustado por la edad materna, antecedente de hospitalización neonatal, ocupación paterna y exposición a rayos X. Conclusiones: La residencia en zonas con gran extensión de cultivos fue el factor de riesgo ambiental en los niños con LLA de una población hospitalaria.

ABSTRACT Introduction: The role of environmental and genetic risk factors has been studied in acute lymphoblastic leukemia, but other factors, such as perinatal and parental factors, less so. The objective of the study was to analyze the environmental, parental and perinatal risk factors of children with acute lymphoblastic leukemia (ALL) being treated in the oncology department of a pediatric hospital. Materials and methods: This was a case-control study, carried out in the oncohematology department of a pediatric hospital. The cases were children diagnosed with acute lymphoblastic leukemia and the controls were previously healthy children diagnosed with a surgical pathology, matched by age. Environmental, perinatal and parental variables were studied. Univariate and multivariate analysis were performed in SPSS and the results were expressed as OR with 95% CI. The protocol was approved by the institutional ethics committee. Results: We included 66 cases and 132 controls. 33.3% (22/66) vs. 8.3% (11/132) OR 5.5 (95% CI 2.4 - 12.5 p=0.0001) of the cases and controls, respectively, had been residents since birth of the departments with larger farmland crop areas. In the multivariate analysis, the risk of being from departments with extensive crop areas was 3.6 times higher, OR 3.6 (95% CI 1.4 -9, p=0.008) adjusted for maternal age, history of neonatal hospitalizations, paternal occupation, and exposure to X-rays. Conclusions: Residence in areas with a large area of crops was the environmental risk factor in children with ALL in a hospital population.

Violencia de género en mujeres confinadas durante la pandemia por SARS-CoV-2 / Gender-based violence in confined women during the SARS-CoV-2 pandemic

Resumen: Objetivo: Identificar la presencia de violencia de género en mujeres confinadas, debido a la pandemia por Covid-19 en la región Costa de Oaxaca. Materiales y métodos: Investigación cuantitativa, descriptiva, correlacional y de corte transversal en 50 mujeres mayores de 18 años, que permanecieron al menos 1 mes confinadas debido a la pandemia por Covid-19, a quienes aplicaron un cuestionario que empleó el Índice de Severidad de Violencia de Pareja, respetando las recomendaciones éticas pertinentes de la Ley General de Salud en Materia de Investigación para la Salud. Los datos fueron procesados en el programa estadístico SPSS versión 21 y se empleó estadística descriptiva y el coeficiente de correlación de Pearson. Resultados: Se encontró una prevalencia de violencia psicológica de 90%, 72% de las mujeres notificaron violencia física y 64% fueron víctimas de violencia sexual. Se observa correlación positiva entre la edad con la violencia física (r= 0.405, p=0.004), violencia psicológica (r= 0.416, p= 0.003) y la violencia sexual (r= 0.527, p=0.000); se observa correlación negativa en las variables escolaridad y violencia física (r= -0.538, p= 0.000), violencia psicológica (r= -0.488, p= 0.000), violencia sexual (r=-0.411, p= 0.003). Conclusiones: La violencia de género es un tema que ha tomado gran relevancia en los últimos años, y que en la actualidad sigue siendo preocupante. A pesar de que se ha difundido información, sigue existiendo violencia dentro de los hogares mexicanos, en la Costa de Oaxaca durante el confinamiento por Covid-19 la violencia de género ha sido altamente prevalente, por lo que se requiere implementar medidas tendentes a prevenir y tratar la violencia de género.

Abstract: Objective: To identify the presence of gender-based violence in women confined due to the Covid-19 pandemic in the Oaxaca Coast Region Materials and methods: Quantitative, descriptive, correlational and cross-sectional research in 50 women over 18 years of age who remained at least 1 month in confinement due to the Covid-19 pandemic, who applied a questionnaire using the Intimate Partner Violence Severity Index, respecting the pertinent ethical recommendations of the General Health Law on Health Research. The data were processed in the SPSS version 21 statistical program and descriptive statistics and Pearson´s correlation coefficient were used. Results: A prevalence of psychological violence was found to be 90%. 72% of the women reported physical violence and 64% were victims of sexual violence. A positive correlation was observed between age and physical violence (r= 0.405, p= 0.004), psychological violence (r= 0.416, p= 0.003) and sexual violence (r= 0.527, p=0.000); a negative correlation was observed in the variables schooling and physical violence (r= -0.538, p= 0.000), psychological violence (r= -0.488, p= 0.000), sexual violence (r= -0.411, p= 0.003). Conclusions: Gender-based violence is an issue that has taken great relevance in recent years, and that currently continues to be of concern. Despite the fact that information has been disseminated, violence continues to exist within mexican homes. In the Oaxaca Coast during the confinement by Covid-19, gender-based violence has been highly prevalent, which is why it is necessary to implement measures to prevent and treat gender-based violence.

High-Intensity Interval Training and Cardiometabolic Risk Factors in Children: A Meta-analysis.

CONTEXT: High-intensity interval training (HIIT) has been widely used to prevent and treat cardiovascular risk factors in adolescents and adults; nevertheless, the available evidence in children is scarce. OBJECTIVE: To synthesize evidence regarding the effectiveness of HIIT interventions on improving cardiovascular risk factors and cardiorespiratory fitness (CRF) in children from 5 to 12 years old. DATA SOURCES: We searched 5 databases, Medline, Embase, SPORTDiscus, the Cochrane Library, and Web of Science. STUDY SELECTION: Randomized controlled trials (RCTs) evaluating the effectiveness of HIIT interventions on cardiometabolic risk factors and CRF in children were included. DATA EXTRACTION: Meta-analyses were conducted to determine the effect of HIIT on body composition, cardiometabolic and CRF variables in comparison with nontraining control groups. RESULTS: A total of 11 RCTs and 512 participants were included. The results of the meta-analysis revealed a significant improvement in peak oxygen uptake (standardized mean difference [SMD] = 0.70, 95% confidence interval [CI] = 0.28 to 1.12; P = 0.001], in total cholesterol [SMD = -1.09, 95% CI = -1.88 to -0.30; P = 0.007], in low-density lipoprotein cholesterol [SMD = -1.28, 95% CI = -2.34 to -0.23; P = 0.017] and triglycerides [SMD = -0.71, 95% CI = -1.15 to -0.28; P = 0.001) levels. LIMITATIONS: Because of the small number of available RCTs, it was not possible to conduct a subgroup analysis or a linear meta-regression analysis. CONCLUSIONS: HIIT is a feasible and time-efficient approach for improving CRF, total cholesterol, low-density lipoprotein cholesterol, and triglycerides levels in children.

Homeostasis Model Assessment cut-off points related to metabolic syndrome in children and adolescents: a systematic review and meta-analysis.

The aim of this study was to perform a systematic review and meta-analysis of cut-off points of Homeostasis Model Assessment (HOMA-IR) to determine metabolic syndrome (MetS) in children and adolescents. A literature search was conducted in MEDLINE (via PubMed), EMBASE, Web of Science, Proquest, and Scopus databases from their inception to June 2018. Random effects models for the diagnostic odds ratio (dOR) value computed by Moses' constant for a linear model and 95% confidence intervals (CIs) were used to calculate the accuracy of the test. Hierarchical summary receiver operating characteristic curves (HSROC) were used to summarize the overall test performance. Six published studies were included in the meta-analysis that included 8732 children and adolescents. The region of HOMA-IR (i.e., dOR) associated with MetS range from 2.30 to 3.54. The pooled accuracy parameters from the studies that evaluated the diagnostic odds ratio of HOMA-IR ranged from 4.39 to 37.67.Conclusion: the HOMA-IR test may be useful for early evaluating children and adolescents with insulin resistance (IR). Furthermore, they present a good diagnostic accuracy independently of the definition of MetS used. According to the studies, the HOMA-IR cut point to avoid MetS risk ranged from 2.30 to 3.59.What is Known:• There is no consensus to define the optimal cut-off point of Homeostasis Model Assessment-Insulin Resistance in children and adolescents associated with Metabolic Syndrome.What is New:• The Homeostasis Model Assessment-Insulin Resistance test may be useful for early evaluations in children and adolescents with insulin resistance and presents a good diagnostic accuracy independently of the definition of Metabolic Syndrome used.• The Homeostasis Model Assessment-Insulin Resistance cut point to avoid Metabolic Syndrome risk ranged from 2.30 to 3.59.

Levels and Patterns of Objectively Assessed Physical Activity and Compliance with Different Public Health Guidelines in University Students.

BACKGROUND: Physical activity (PA) is associated with health enhancement. The aim of this study was to assess: 1) levels and patterns of PA in university students by using accelerometers; and 2) the percentage of fulfilment of PA recommendations for adults, according to different public health guidelines. METHODS: Observational cross-sectional study (Cuenca's Adults Study) involving 296 (206 women) healthy Spanish university students aged 18-25 years old. Participants wore the ActiGraph GT1M accelerometer for seven consecutive days. Total PA, steps and time spent in sedentary time, light, moderate, vigorous, and moderate to vigorous PA (MVPA) was assessed, and the prevalence of sufficient PA was calculated according to various public health guidelines. RESULTS: No sex differences in total PA were found. University students were more sedentary during weekend days than weekdays (p<0.05). Only 30.3% of participants accumulated 30 min/day at least five days a week of MVPA. A total of 5.4% of students met the recommendation of 150 min/week of MVPA or 75 min/week of vigorous PA, in PA bouts of at least 10 min. using the same definition, but on five or more days a week, only 0.5% students were found to meet the recommendation. In addition, only 0.5% of students met the recommendation of 30 min/day of MVPA, at least five days a week and in bouts of at least 10 min. Finally, 28.1% of the students met the recommendation of 10,000 steps/day. CONCLUSIONS: Our study shows a high incidence of sedentary time in university students. The number of students meeting PA recommendations significantly differed depending on the recommendation proposed. Specific strategies to promote PA in this population are necessary as well as an agreement as to which PA guidelines should be used.

Sonographic cervical length as a predictor of type of delivery after induced labor.

PURPOSE: This study was undertaken to evaluate the comparative value of sonographic cervical length and the Bishop score in predicting the type of delivery after induced labor. METHODS: The Bishop score was determined by digital examination and cervical length by transvaginal sonography in 177 women. RESULTS: The best cut-off points for predicting type of delivery found with ROC curves were 25.2 mm for cervical length and 5 for the Bishop score. The Bishop score was not predictive of type of delivery. Cervical length was related to type of delivery in women with Bishop score ≤5. A logistic regression model showed that only cervical length ≥25.2 mm, parity, and body mass index significantly predicted the likelihood of cesarean delivery. CONCLUSIONS: Our study suggests that both Bishop score and sonographic cervical length can contribute to predicting type of delivery after labor induction, but cervical length is a better predictor of the risk of cesarean delivery.

Reporting of methodologic information on trial registries for quality assessment: a study of trial records retrieved from the WHO search portal.

BACKGROUND: Although randomized clinical trials (RCTs) are considered the gold standard of evidence, their reporting is often suboptimal. Trial registries have the potential to contribute important methodologic information for critical appraisal of study results. METHODS AND FINDINGS: The objective of the study was to evaluate the reporting of key methodologic study characteristics in trial registries. We identified a random sample (n = 265) of actively recruiting RCTs using the World Health Organization International Clinical Trials Registry Platform (ICTRP) search portal in 2008. We assessed the reporting of relevant domains from the Cochrane Collaboration's 'Risk of bias' tool and other key methodological aspects. Our primary outcomes were the proportion of registry records with adequate reporting of random sequence generation, allocation concealment, blinding, and trial outcomes. Two reviewers independently assessed each record. Weighted overall proportions in the ICTRP search portal for adequate reporting of sequence generation, allocation concealment, blinding (including and excluding open label RCT) and primary outcomes were 5.7% (95% CI 3.0-8.4%), 1.4% (0-2.8%), 41% (35-47%), 8.4% (4.1-13%), and 66% (60-72%), respectively. The proportion of adequately reported RCTs was higher for registries that used specific methodological fields for describing methods of randomization and allocation concealment compared to registries that did not. Concerning other key methodological aspects, weighted overall proportions of RCTs with adequately reported items were as follows: eligibility criteria (81%), secondary outcomes (46%), harm (5%) follow-up duration (62%), description of the interventions (53%) and sample size calculation (1%). CONCLUSIONS: Trial registries currently contain limited methodologic information about registered RCTs. In order to permit adequate critical appraisal of trial results reported in journals and registries, trial registries should consider requesting details on key RCT methods to complement journal publications. Full protocols remain the most comprehensive source of methodologic information and should be made publicly available.

Actividad física y calidad de vida relacionada con la salud en escolares / Physical activity and quality of life in relation to the health in schoolars

Objetivo. Analizar la relación entre niveles de actividad física autorreferida y diferentes dimensionesde la Calidad de Vida Relacionada con la Salud (CVRS) en escolares.Diseño. Mediciones basales de un ensayo de campo aleatorizado por clusters.Emplazamiento. 22 colegios de la provincia de Cuenca.Sujetos: 1074 escolares de 4º y 5º curso de Educación Primaria.Mediciones principales. CHIP-CE, un cuestionario validado en castellano con 45 ítems en 5 dimensiones:satisfacción (satisfacción con la propia salud y la autoestima), bienestar (síntomas físicos y psicológicos y limitación de actividades), resistencia (factores protectores contra futuros problemas de salud), riesgos (conductas que potencialmente atentan contra salud del niño/a) y funciones (rendimiento académico e influencia positiva de los pares). Los ítems 13 (¿Cuántos días has hecho juegos de moverse mucho o deporte?) y 28 (¿Cuántos días has corrido mucho mientras jugabas o hacíasdeporte?) sirvieron para valorar los niveles de actividad física (AF) en las 4 semanas anteriores a laentrevista.Resultados. Mediante un modelo lineal multivariante – MANOVA - con las dimensiones de la CVRSdel CHIP-CE como variables dependientes, frecuencia en la práctica de actividad física autopercibida–sedentario, actividad media y activos- como factor fijo y la edad como co-variable, se observarondiferencias estadísticamente significativas (p<0,0001) en las dimensiones satisfacción, resistencia, riesgos y funciones. No se observaron diferencias estadísticamente significativas en la media de la dimensión bienestar por niveles de AF.Conclusiones. Los niños más activos no se diferencias de los menos activos en cuanto a los síntomas ni a las limitaciones que perciben, y sí en cuanto a su autoestima, en cuanto a cómo protegen su salud y evitan riesgos, y en cuanto a su rendimiento académico

Objective. To analyze the interrelationship between self-reported physical activity levels and differentdomains of health related to quality of life (HRQOL) for schoolchildren.Design. Basal measurement of a field trial randomized by clustersSetting. 22 schools from Cuenca Province (Spain).Subjects. 1074 primary schoolchildren aged from 8 to 11 years old.Main measurement. CHIP-CE: a validated Spanish questionnaire with 45 item belonging to five domainsof health status: Satisfaction (with self and health), Comfort (emotional and physical symptoms andlimitations), Resilience (positive activities that promote healthy habits), Risk Avoidance (risky behavioursthat influence future health), and Achievement (of social expectation in school and with peers). The 13th(How often did you play active games or sport?) and 28th (How often did you run hard to play or practicesports?) helped us to know the amount of physical exercise that students practiced in the 4 weeks priorto the interview.Results. By multivariate linear model –MANOVA- with HRQOL domains of the CHIP-CE as dependentvariables, physical activity levels–sedentary, average activity and active- as fixed factors and age asco-variables, significant statistical differences were observed in satisfaction, resilience, risk avoidanceand achievement, though no statistical significant differences were observed in comfort’s average forlevels of physical activity.Conclusions. Active children are no different to the less active in symptoms and limitation, but have adifferent perception in selfsteem, risk avoidance and health protection and academic performance