Functional polymorphisms of DNA repair genes in Latin America reinforces the heterogeneity of Myelodysplastic Syndrome

Abstract Nucleotide excision repair pathway (NER) is an essential mechanism for single-strand breaks (SSB) repair while xeroderma pigmentosum family (XPA to XPG) is the most important system to NER. Myelodysplastic syndrome (MDS) is a heterogeneous hematological cancer characterized by cytopenias and risk of acute myeloid leukemia (AML) transformation. MDS pathogenesis has been associated with problems of DNA repair system. This report aimed to evaluate NER polymorphisms (XPA rs1800975, XPC rs2228000, XPD rs1799793 and XPF rs1800067) in 269 MDS patients of different populations in Latin America (173 Brazilian and 96 Argentinean). Genotypes were identified in DNA samples by RT-qPCR using TaqMan SNP Genotyping Assay. Regarding rs1799793 polymorphism of XPD for Brazilian population, the heterozygous genotype AG presented a high odds ratio (OR) to have a normal karyotype (p= 0.012, OR=3.000) and the mutant homozygous genotype AA was associated to a high OR of AML transformation (p= 0.034, OR=7.4). In Argentine population, the homozygous mutant AA genotype of rs1800975 polymorphism of XPA was associated with an increased odd to have hemoglobin levels below 8g/dL (p= 0.013, OR=10.000) while for the rs1799793 polymorphism of XPD, the heterozygous AG genotype decreased OR to be classified as good (p< 0.001, OR=9.05 × 10−10), and intermediate (p< 0.001, OR=3.08 × 10−10), according to Revised-International Prognostic Scoring System. Regarding the rs1800067 polymorphisms of XPF, the homozygous mutant AA genotype showed a decreased OR to be classified as good (p< 0.001, OR=4.03 × 10−13) and intermediate (p< 0.001, OR=2.54 × 10−13). Our report reinforces the heterogeneity of MDS and demonstrates the importance of ethnic differences and regional influences in pathogenesis and prognosis of MDS.

Validez de contenido de lineamientos de ejercicio físico para mujeres embarazadas / Content validity of guidelines for physical exercise for pregnant

Objetivo: determinar la validez de contenido del procedimiento ejercicio físico para mujeres embarazadas 2018. La prescripción del ejercicio físico en mujeres embarazadas es una de las actividades que mayores beneficios fisiológicos y psicosociales trae a la mujer y al niño. Materiales y métodos: estudio descriptivo. Valoración de contenido con la técnica de juicio de expertos. Resultados: se obtuvo un valor promedio de coeficientes kappa para la dimensión de examen de 0,64 y para la dimensión de intervención de 0,75. El índice kappa para el instrumento fue de 0,69 (acuerdo sustancial).Adicionalmente, para la dimensión de examen fisioterapéutico se obtuvieron valores de proporción de acuerdo medio (̅P a) que superan el umbral de concordancia sustancial, excepto la propiedad de claridad. En la dimensión de intervención los valores de (̅Pa) indican que todas las propiedades de la intervención fisioterapéutica superan el umbral de concordancia sustancial. Conclusiones: el ejercicio físico es una práctica fundamental durante el embarazo, su aplicación requiere de un examen riguroso que conlleve a una intervención individualizada donde se reconozcan los antecedentes de la mujer para así determinar la intensidad adecuada de la prescripción. A partir del procedimiento "lineamientos de ejercicio físico en mujeres embarazadas" los profesionales contarán con una herramienta basada en evidencia científica que incluye una fase de examen y una fase de intervención..Au

Objective: to determine the content validity of the procedure guidelines for physical exercise for pregnant women 2018. Prescribing physical exercise in pregnant women is one of the recommendations that brings the greatest physiological and psychosocial benefits to women and children. Materials and methods: descriptive study. Content validity with expert judgment technique. Results: an average value of kappa coefficients was obtained for the examination dimension of 0.64 and for the intervention dimension of 0.75. The Kappa index for the instrument was 0.69 (substantial agreement). Additionally, for the physiotherapeutic examination dimension, mean agreement ratio (̅P a) values were obtained that exceed the threshold of substantial agreement except the property of clarity. In the intervention dimension, the values of (̅Pa) indicate that all the properties of the physiotherapeutic intervention exceed the threshold of substantial agreement. Conclusions: physical exercise is a fundamental practice during pregnancy, its application requires a rigorous examination that leads to an individualized intervention where the woman's history is recognized in order to determine the appropriate intensity of the prescription. Starting with the procedure "Guidelines for physical exercise in pregnant women", professionals will have a tool based on scientific evidence that includes an examination phase and an intervention phase..Au