Gaining Insights into Inherited Bleeding Disorders of Complex Etiology in Pediatric Patients: Whole-Exome Sequencing as First-Line Investigation Tool.

INTRODUCTION: Investigation of the molecular basis of inherited bleeding disorders (IBD) is mostly performed with gene panel sequencing. However, the continuous discovery of new related genes underlies the limitation of this approach. This study aimed to identify genetic variants responsible for IBD in pediatric patients using whole-exome sequencing (WES), and to provide a detailed description and reclassification of candidate variants. MATERIAL AND METHODS: WES was performed for 18 pediatric patients, and variants were filtered using a first-line list of 290 genes. Variant prioritization was discussed in a multidisciplinary team based on genotype-phenotype correlation, and segregation studies were performed with available family members. RESULTS: The study identified 22 candidate variants in 17 out of 18 patients (94%). Eleven patients had complete genotype-phenotype correlation, resulting in a diagnostic yield of 61%, 5 (28%) were classified as partially solved, and 2 (11%) remained unsolved. Variants were identified in platelet (ACTN1, ANKRD26, CYCS, GATA1, GFI1B, ITGA2, NBEAL2, RUNX1, SRC, TUBB1), bleeding (APOLD1), and coagulation (F7, F8, F11, VWF) genes. Notably, 9 out of 22 (41%) variants were previously unreported. Variant pathogenicity was assessed according to the American College of Medical Genetics and Genomics guidelines and reclassification of three variants based on family segregation evidence, resulting in the identification of 10 pathogenic or likely pathogenic variants, 6 variants of uncertain significance, and 6 benign or likely benign variants. CONCLUSION: This study demonstrated the high potential of WES in identifying rare molecular defects causing IBD in pediatric patients, improving their management, prognosis, and treatment, particularly for patients at risk of malignancy and/or bleeding due to invasive procedures.

Presence of human papillomavirus in the buccal mucosa of blood donors / Presencia del virus del papiloma humano en la mucosa oral de donantes de sangre

Objective To determine the presence of human papillomavirus (HPV) in the oral mucosa of blood donors (BD) and risk factors associated with HPV and oral cancer. Materials and methods Prospective cross-sectional study, population matched to BD from the National Cancer Institute, Mexico for HPV identification in oral cytological samples using the CLART® Human Papillomavirus 2 Kit (35 genotypes) and risk factors. Results Of 352 BD with signed informed consent, 285 were selected by simple randomization. The prevalence of oral HPV was 17.5% (95% CI 13–21.9%), the genotype was identified in 13 cases, with a total of 16 genotypes (10 high-risk), the most common being 16 and 84. Five cases had multiple infections, three with at least one high-risk type. Associations were found for marital status (OR 3.3) and educational level (OR-1.9). Conclusions The percentage of HPV-positive cases in blood donors with no risk practices was similar to that found in Spanish-speaking population studies in which at least one risk practice was described. The presence of other genotypes with high oncogenic risk and multitype infection, described as a marker of persistence of HPV infection, is highlighted (AU)

Objetivo Identificar la presencia del virus del papiloma humano (VPH) en la mucosa oral de donantes de sangre (DS), así como los factores de riesgo relacionados con el VPH y el cáncer oral. Materiales y métodos Estudio transversal prospectivo. La población correspondió a los DS del Instituto Nacional de Cancerología, México, para la identificación de VPH en muestras citológicas orales con el kit CLART® Human Papillomavirus 2 (35 genotipos) y factores de riesgo. Resultados De 352 DS con firma de consentimiento informado, se seleccionaron 285 por aleatorización simple. La prevalencia de VPH oral fue del 17,5% (IC 95%: 13-21,9%); en 13 casos se identificó el genotipo, con un total de 16 genotipos (10 de alto riesgo), los más frecuentes el 16 y el 84. Cinco casos presentaron infección multitipo, 3 con al menos un tipo de alto riesgo. Las asociaciones encontradas fueron para el estado civil (OR 3,3) y el nivel de estudios (OR 1,9). Conclusiones El porcentaje de casos positivos para VPH en DS sin prácticas de riesgo fue similar a los hallazgos en estudios de población hispanohablante en los que se ha descrito al menos una práctica de riesgo. Se destaca la presencia de otros genotipos con alto riesgo oncogénico y la infección multitipo descrita como marcador de persistencia de la infección por VPH (AU)

DPPA3-HIF1α axis controls colorectal cancer chemoresistance by imposing a slow cell-cycle phenotype.

Tumor relapse is linked to rapid chemoresistance and represents a bottleneck for cancer therapy success. Engagement of a reduced proliferation state is a non-mutational mechanism exploited by cancer cells to bypass therapy-induced cell death. Through combining functional pulse-chase experiments in engineered cells and transcriptomic analyses, we identify DPPA3 as a master regulator of slow-cycling and chemoresistant phenotype in colorectal cancer (CRC). We find a vicious DPPA3-HIF1α feedback loop that downregulates FOXM1 expression via DNA methylation, thereby delaying cell-cycle progression. Moreover, downregulation of HIF1α partially restores a chemosensitive proliferative phenotype in DPPA3-overexpressing cancer cells. In cohorts of CRC patient samples, DPPA3 overexpression acts as a predictive biomarker of chemotherapeutic resistance that subsequently requires reduction in its expression to allow metastatic outgrowth. Our work demonstrates that slow-cycling cancer cells exploit a DPPA3/HIF1α axis to support tumor persistence under therapeutic stress and provides insights on the molecular regulation of disease progression.

Presence of human papillomavirus in the buccal mucosa of blood donors.

OBJECTIVE: To determine the presence of human papillomavirus (HPV) in the oral mucosa of blood donors (BD) and risk factors associated with HPV and oral cancer. MATERIALS AND METHODS: Prospective cross-sectional study, population matched to BD from the National Cancer Institute, Mexico for HPV identification in oral cytological samples using the CLART® Human Papillomavirus 2 Kit (35 genotypes) and risk factors. RESULTS: Of 352 BD with signed informed consent, 285 were selected by simple randomization. The prevalence of oral HPV was 17.5% (95% CI 13-21.9%), the genotype was identified in 13 cases, with a total of 16 genotypes (10 high-risk), the most common being 16 and 84. Five cases had multiple infections, three with at least one high-risk type. Associations were found for marital status (OR 3.3) and educational level (OR-1.9). CONCLUSIONS: The percentage of HPV-positive cases in blood donors with no risk practices was similar to that found in Spanish-speaking population studies in which at least one risk practice was described. The presence of other genotypes with high oncogenic risk and multitype infection, described as a marker of persistence of HPV infection, is highlighted.

Functional patient-derived organoid screenings identify MCLA-158 as a therapeutic EGFR × LGR5 bispecific antibody with efficacy in epithelial tumors.

Patient-derived organoids (PDOs) recapitulate tumor architecture, contain cancer stem cells and have predictive value supporting personalized medicine. Here we describe a large-scale functional screen of dual-targeting bispecific antibodies (bAbs) on a heterogeneous colorectal cancer PDO biobank and paired healthy colonic mucosa samples. More than 500 therapeutic bAbs generated against Wingless-related integration site (WNT) and receptor tyrosine kinase (RTK) targets were functionally evaluated by high-content imaging to capture the complexity of PDO responses. Our drug discovery strategy resulted in the generation of MCLA-158, a bAb that specifically triggers epidermal growth factor receptor degradation in leucine-rich repeat-containing G-protein-coupled receptor 5-positive (LGR5+) cancer stem cells but shows minimal toxicity toward healthy LGR5+ colon stem cells. MCLA-158 exhibits therapeutic properties such as growth inhibition of KRAS-mutant colorectal cancers, blockade of metastasis initiation and suppression of tumor outgrowth in preclinical models for several epithelial cancer types.

Wellbeing of School Communities in the Context of COVID-19 Pandemic: A Qualitative Study in Chilean Low-SES Schools.

The COVID-19 pandemic continues to impact schools and how education is conveyed to students. One of the aspects that has gained strength is supporting the wellbeing of educational communities. The purpose of this study was to describe and understand the construction of school wellbeing during the pandemic, based on the notion of collective and sustainable wellbeing. Through a qualitative design, we conducted a study in four Chilean low-SES schools in which a national school mental health program is implemented. A total of 41 in-depth interviews and one group interview were conducted with students, parents, teacher, teacher assistants, school principals, psychosocial professionals, and the school mental health officers during the second half of the 2020 school year. Thematic content analyses showed that, while facing the school closure challenges, schools strived to protect students' and teachers' wellbeing. However, participants highlighted necessary conditions for sustaining the school community's wellbeing and mental health in the context of the COVID-19 pandemic: assuring digital connectivity for all students; coordinated work with families and within the school; strengthening networks; curriculum adaptation and diversified pedagogical strategies; and emotional support toward teachers, families, and students. We discuss these findings and their implications for a sustainable and collective perspective of the wellbeing of school communities in low-SES schools, as well as for policy, practice, and research from the perspective of schools for social justice and health promotion.

Validación de un instrumento para evaluar consejería adolescente diferenciada en un centro de salud / Validation of an instrument for assessing adolescent counseling differentiated in a health center

RESUMEN La OMS/OPS admite que los patrones de conducta sexuales de los adolescentes y jóvenes han cambiado. Se afirma la consejería adolescente ha mostrado buenos resultados. Por ello el propósito de este estudio es evaluar un cuestionario que evaluará este tipo de intervención. Objetivos Establecer la validez de constructo y la confiabilidad de un instrumento para evaluar consejería en adolescentes asistentes al centro de salud Rucahueche. Métodos Estudio exploratorio con una muestra de 151 adolescentes entre 15 y 19 años, a los que se les aplicó un cuestionario autoadministrado. La validez de constructo y de consistencia interna fue evaluada por análisis factorial y el Alfa de Cronbach, respectivamente. Resultados El análisis factorial identificó en 3 dimensiones 10 constructos, los cuales explicaron el 62% - 67% de su variabilidad. A su vez, el análisis de consistencia interna obtuvo una puntuación de alfa de 0,934. Conclusiones El instrumento mostró evidencias de validez de constructo y de confiabilidad. Dichos análisis indican la factibilidad de aplicación del instrumento. Sin embargo, la validación del instrumento aún es un reto, debido a su relevancia para una mirada más profunda sobre la atención y la gestión en la atención de adolescentes. Por tanto, se considerará seguir haciendo estudios para explorar su dimensionalidad y validez de contenido.

ABSTRACT The WHO/PAHO admits that the sexual behavior patterns of adolescents and young people have changed. It is claimed adolescent counseling has shown good results. Therefore, the purpose of this study is to evaluate a questionnaire that will evaluate this type of intervention. Objectives To establish the construct validity and reliability of an instrument for assessing adolescent counseling attending the health center Rucahueche. Methods An exploratory study with a sample of 151 adolescents aged 15 to 19 years, who were applied a self-administered questionnaire. Construct validity and internal consistency was assessed by factor analysis and Cronbach's alpha, respectively. Results: Factor analysis identified three dimensions 10 constructs, which accounted for 62% -67% of its variability. In turn, analysis of internal consistency score was alpha of 0.934. Conclusions The instrument showed evidence of construct validity and reliability. These analyzes indícate the feasibility of the instrument. However, validation of the instrument is still a challenge, because of its relevance to a deeper look on the care and management in adolescent care. Therefore, it is deemed to continue doing studies to explore the dimensionality and content validity.

Common Genetic Variants in ABO and CLEC4M Modulate the Pharmacokinetics of Recombinant FVIII in Severe Hemophilia A Patients.

The pharmacokinetic (PK) response of severe hemophilia A (HA) patients to infused factor VIII (FVIII) shows substantial variability. Several environmental and genetic factors are associated with changes in FVIII plasma levels and infused FVIII PK. Based on the hypothesis that factors influencing endogenous FVIII can affect FVIII PK, the contribution of single-nucleotide variants (SNVs) in candidate genes was investigated in 51 severe HA patients. The effects of blood group, F8 variant type, von Willebrand factor antigen and activity levels, age, and weight were also explored. The myPKFiT device was used to estimate individual PK parameters, and SNVs and clinically reportable F8 variants were simultaneously analyzed in an Illumina MiSeq instrument, using the microfluidics-based Fluidigm Access Array system. The contribution of SNVs to FVIII half-life and clearance was addressed by robust regression modeling, taking into account other modulators. In line with previous studies, we provide robust evidence that age, body weight, and blood group, as well as SNVs in ABO and CLEC4M, participate in the variability of FVIII PK in HA patients. Main results: each copy of the rs7853989 (ABO) allele increases FVIII half-life by 1.4 hours (p = 0.0131) and decreases clearance by 0.5 mL/h/kg (p = 5.57E-03), whereas each additional rs868875 (CLEC4M) allele reduces FVIII half-life by 1.1 hours (p = 2.90E-05) and increases clearance by 0.3 mL/h/kg (p = 1.01E-03). These results contribute to advancing efforts to improve FVIII replacement therapies by adjusting to each patient's PK profile based on pharmacogenomic data. This personalized medicine will decrease the burden of treatment and maximize the benefits obtained.

Accumulation of heavy metals in native Andean plants: potential tools for soil phytoremediation in Ancash (Peru).

Metal contamination is a recurring problem in Peru, caused mainly by mine tailings from a past active mining activity. The Ancash region has the largest number of environmental liabilities, which mobilizes high levels of metals and acid drainages into soils and freshwater sources, posing a standing risk on human and environmental health. Native plant species spontaneously growing on naturally acidified soils and acid mine tailings show a unique tolerance to high metal concentrations and are thus potential candidates for soil phytoremediation. However, little is known about their propagation capacity and metal accumulation under controlled conditions. In this study, we aimed at characterizing nine native plant species, previously identified as potential hyperaccumulators, from areas impacted by mine tailings in the Ancash region. Plants were grown on mine soils under greenhouse conditions during 5 months, after which the concentration of Cd, Cu, Ni, Pb, and Zn was analyzed in roots, shoots, and soils. The bioaccumulation (BAF) and translocation factor (TF) were calculated to determine the amount of each metal accumulated in the roots and shoots and to identify which species could be better suited for phytoremediation purposes. Soil samples contained high Cd (6.50-49.80 mg/kg), Cu (159.50-1187.00 mg/kg), Ni (3.50-8.70 mg/kg), Pb (1707.00-4243.00 mg/kg), and Zn (909.00-7100.00 mg/kg) concentrations exceeding national environmental quality standards. After exposure to mine tailings, concentrations of metals in shoots were highest in Werneria nubigena (Cd, 16.68 mg/kg; Cu, 41.36 mg/kg; Ni, 26.85 mg/kg; Zn, 1691.03 mg/kg), Pennisetum clandestinum (Pb, 236.86 mg/kg), and Medicago lupulina (Zn, 1078.10 mg/kg). Metal concentrations in the roots were highest in Juncus bufonius (Cd, 34.34 mg/kg; Cu, 251.07 mg/kg; Ni, 6.60 mg/kg; Pb, 718.44 mg/kg) and M. lupulina (Zn, 2415.73 mg/kg). The greatest BAF was calculated for W. nubigena (Cd, 1.92; Cu, 1.20; Ni, 6.50; Zn, 3.50) and J. bufonius (Ni, 3.02; Zn, 1.30); BCF for Calamagrostis recta (Cd, 1.09; Cu, 1.80; Ni, 1.09), J. bufonius (Cd, 3.91; Cu, 1.79; Ni, 18.36), and Achyrocline alata (Ni, 137; Zn, 1.85); and TF for W. nubigena (Cd, 2.36; Cu, 1.70; Ni, 2.42; Pb, 1.17; Zn, 1.43), A. alata (Cd, 1.14; Pb, 1.94), J. bufonius (Ni, 2.72; Zn, 1.63), and P. clandestinum (Zn, 1.14). Our results suggest that these plant species have a great potential for soil phytoremediation, given their capability to accumulate and transfer metals and their tolerance to highly metal-polluted environments in the Andean region.

Novel Double Factor PGT strategy analyzing blastocyst stage embryos in a single NGS procedure.

In families at risk from monogenic diseases affected offspring, it is fundamental the development of a suitable Double Factor Preimplantation Genetic Testing (DF-PGT) method for both single-gene analysis and chromosome complement screening. Aneuploidy is not only a major issue in advanced-maternal-age patients and balanced translocation carriers, but also the aneuploidy rate is extremely high in patients undergoing in vitro fertilization (IVF), even in young donors. To adequate NGS technology to the DF-PGT strategy four different whole genome amplification systems (Sureplex, MALBAC, and two multiple displacement amplification systems-MDA) were tested using TruSight One panel on cell lines and blastocyst trophectoderm biopsies-TE. Embryo cytogenetic status was analyzed by Nexus software. Sureplex and MALBAC DNA products were considered not suitable for PGT diagnosis due to inconsistent and poor results on Trusight one (TSO) panel. Results obtained with both MDA based methods (GEH-MDA and RG-MDA) were appropriate for direct mutation detection by TSO NGS platform. Nevertheless, RG-MDA amplification products showed better coverage and lower ADO rates than GEH-MDA. The present work also demonstrates that the same TSO sequencing data is suitable not only for the direct mutation detection, but also for the indirect mutation detection by linkage analysis of informative SNPs. The present work also demonstrates that Nexus software is competent for the detection of CNV by using with TSO sequencing data from RG-MDA products, allowing for the whole cytogenetic characterization of the embryos. In conclusion, successfully development of an innovative and promising DF-PGT strategy using TSO-NGS technology in TE biopsies, performed in-house in a single laboratory experience, has been done in the present work. Additional studies should be performed before it could be used as a diagnostic alternative in order to validate this approach for the detection of chromosomal aneuploidies.

TET2 controls chemoresistant slow-cycling cancer cell survival and tumor recurrence.

Dormant or slow-cycling tumor cells can form a residual chemoresistant reservoir responsible for relapse in patients, years after curative surgery and adjuvant therapy. We have adapted the pulse-chase expression of H2BeGFP for labeling and isolating slow-cycling cancer cells (SCCCs). SCCCs showed cancer initiation potential and enhanced chemoresistance. Cells at this slow-cycling status presented a distinctive nongenetic and cell-autonomous gene expression profile shared across different tumor types. We identified TET2 epigenetic enzyme as a key factor controlling SCCC numbers, survival, and tumor recurrence. 5-Hydroxymethylcytosine (5hmC), generated by TET2 enzymatic activity, labeled the SCCC genome in carcinomas and was a predictive biomarker of relapse and survival in cancer patients. We have shown the enhanced chemoresistance of SCCCs and revealed 5hmC as a biomarker for their clinical identification and TET2 as a potential drug target for SCCC elimination that could extend patients' survival.

Colorectal Cancer Consensus Molecular Subtypes Translated to Preclinical Models Uncover Potentially Targetable Cancer Cell Dependencies.

Purpose: Response to standard oncologic treatment is limited in colorectal cancer. The gene expression-based consensus molecular subtypes (CMS) provide a new paradigm for stratified treatment and drug repurposing; however, drug discovery is currently limited by the lack of translation of CMS to preclinical models.Experimental Design: We analyzed CMS in primary colorectal cancers, cell lines, and patient-derived xenografts (PDX). For classification of preclinical models, we developed an optimized classifier enriched for cancer cell-intrinsic gene expression signals, and performed high-throughput in vitro drug screening (n = 459 drugs) to analyze subtype-specific drug sensitivities.Results: The distinct molecular and clinicopathologic characteristics of each CMS group were validated in a single-hospital series of 409 primary colorectal cancers. The new, cancer cell-adapted classifier was found to perform well in primary tumors, and applied to a panel of 148 cell lines and 32 PDXs, these colorectal cancer models were shown to recapitulate the biology of the CMS groups. Drug screening of 33 cell lines demonstrated subtype-dependent response profiles, confirming strong response to EGFR and HER2 inhibitors in the CMS2 epithelial/canonical group, and revealing strong sensitivity to HSP90 inhibitors in cells with the CMS1 microsatellite instability/immune and CMS4 mesenchymal phenotypes. This association was validated in vitro in additional CMS-predicted cell lines. Combination treatment with 5-fluorouracil and luminespib showed potential to alleviate chemoresistance in a CMS4 PDX model, an effect not seen in a chemosensitive CMS2 PDX model.Conclusions: We provide translation of CMS classification to preclinical models and uncover a potential for targeted treatment repurposing in the chemoresistant CMS4 group. Clin Cancer Res; 24(4); 794-806. ©2017 AACR.

Next generation sequencing to dissect the genetic architecture of KNG1 and F11 loci using factor XI levels as an intermediate phenotype of thrombosis.

Venous thromboembolism is a complex disease with a high heritability. There are significant associations among Factor XI (FXI) levels and SNPs in the KNG1 and F11 loci. Our aim was to identify the genetic variation of KNG1 and F11 that might account for the variability of FXI levels. The KNG1 and F11 loci were sequenced completely in 110 unrelated individuals from the GAIT-2 (Genetic Analysis of Idiopathic Thrombophilia 2) Project using Next Generation Sequencing on an Illumina MiSeq. The GAIT-2 Project is a study of 935 individuals in 35 extended Spanish families selected through a proband with idiopathic thrombophilia. Among the 110 individuals, a subset of 40 individuals was chosen as a discovery sample for identifying variants. A total of 762 genetic variants were detected. Several significant associations were established among common variants and low-frequency variants sets in KNG1 and F11 with FXI levels using the PLINK and SKAT packages. Among these associations, those of rs710446 and five low-frequency variant sets in KNG1 with FXI level variation were significant after multiple testing correction and permutation. Also, two putative pathogenic mutations related to high and low FXI levels were identified by data filtering and in silico predictions. This study of KNG1 and F11 loci should help to understand the connection between genotypic variation and variation in FXI levels. The functional genetic variants should be useful as markers of thromboembolic risk.

p38α regulates actin cytoskeleton and cytokinesis in hepatocytes during development and aging.

BACKGROUND: Hepatocyte poliploidization is an age-dependent process, being cytokinesis failure the main mechanism of polyploid hepatocyte formation. Our aim was to study the role of p38α MAPK in the regulation of actin cytoskeleton and cytokinesis in hepatocytes during development and aging. METHODS: Wild type and p38α liver-specific knock out mice at different ages (after weaning, adults and old) were used. RESULTS: We show that p38α MAPK deficiency induces actin disassembly upon aging and also cytokinesis failure leading to enhanced binucleation. Although the steady state levels of cyclin D1 in wild type and p38α knock out old livers remained unaffected, cyclin B1- a marker for G2/M transition- was significantly overexpressed in p38α knock out mice. Our findings suggest that hepatocytes do enter into S phase but they do not complete cell division upon p38α deficiency leading to cytokinesis failure and binucleation. Moreover, old liver-specific p38α MAPK knock out mice exhibited reduced F-actin polymerization and a dramatic loss of actin cytoskeleton. This was associated with abnormal hyperactivation of RhoA and Cdc42 GTPases. Long-term p38α deficiency drives to inactivation of HSP27, which seems to account for the impairment in actin cytoskeleton as Hsp27-silencing decreased the number and length of actin filaments in isolated hepatocytes. CONCLUSIONS: p38α MAPK is essential for actin dynamics with age in hepatocytes.

The Unravelling of the Genetic Architecture of Plasminogen Deficiency and its Relation to Thrombotic Disease.

Although plasminogen is a key protein in fibrinolysis and several mutations in the plasminogen gene (PLG) have been identified that result in plasminogen deficiency, there are conflicting reports to associate it with the risk of thrombosis. Our aim was to unravel the genetic architecture of PLG in families with plasminogen deficiency and its relationship with spontaneous thrombotic events in these families. A total of 13 individuals from 4 families were recruited. Their genetic risk profile of thromboembolism was characterized using the Thrombo inCode kit. Only one family presented genetic risk of thromboembolism (homozygous carrier of F12 rs1801020 and F13A1 rs5985). The whole PLG was tested using Next Generation Sequencing (NGS) and 5 putative pathogenic mutations were found (after in silico predictions) and associated with plasminogen deficiency. Although we can not find genetic risk factors of thrombosis in 3 of 4 families, even the mutations associated with plasminogen deficiency do not cosegregated with thrombosis, we can not exclude plasminogen deficiency as a susceptibility risk factor for thrombosis, since thrombosis is a multifactorial and complex disease where unknown genetic risk factors, in addition to plasminogen deficiency, within these families may explain the thrombotic tendency.

Efectividad de intervención preventiva y de limitación del daño por caries dental en la primera molar permanente en escolares de 7 a 8 años / Effectiveness of preventive intervention and limitation of damage due to dental caries in the first permanent molar in schoolchildren aged 7 to 8 years

Objetivo: Establecer la efectividad de intervención preventiva y limitación del daño por caries dental en la primera molar permanente, en escolares de 7 a 8 años; posterior a 3 y 6 meses de aplicada. Metodología: Esta investigación fue de tipo intervención cuasi experimental, dirigida a la prevención y limitación del daño por caries en las Primeras Molares Permanentes (PMP) de 150 escolares de centros educativos públicos. Fueron atendidas 568 PMP en total, en las que se aplicó 314 sellantes de fosas y fisuras preventivos, 124 sellantes curativos, 36 remineralizaciones con flúor barniz y 130 obturaciones. Posterior a 3 y 6 meses se efectuó la evaluación de caries y de la condición de los tratamientos (sellantes y obturaciones) para medir la efectividad. La prueba estadística utilizada para el análisis de los datos fue la de McNemar. Resultados: Posterior a 3 y 6 meses de aplicada la intervención, se encontraron respectivamente el 96.8% y 94.2% de molares sanas; en tanto que, en cuanto a supervivencia de tratamientos se encontró de 88% y 72.9% respectivamente. Conclusión: La intervención mostró a 3 y 6 meses, ser efectiva para prevenir y limitar el daño por caries dental en la primera molar permanente.

Objective: To establish the effectiveness of preventive intervention and limitation of damage by caries, in the first permanent molar (FPM), in scholar children from 7 to 8 years; after 3 and 6 months of being applied. Methodology: This research was a quasi-experimental dental intervention type, directed to the prevention and limitation of damage by caries in the first permanent molars of 150 scholar children, attending public schools. In total, 568 FPM were intervened; in which 314 preventive sealing of tooth cavities and fissures, were applied, as well as 124 healing sealants, 36 remineralization with varnish fluoride and 130 obturations (fillings). Afterwards to 3 and 6 months, the evaluation of caries and the condition of the treatments (sealants and obturations) was developed, to measure their effectiveness. The statistical test used for the analysis of the data was that of McNemar. Results: Afterwards to 3 and 6 months the dental intervention was applied; 96.8% and 94.2% of healthy molars was obtained, respectively; and, 88%; 72.9% permanence (survival) of treatments respectively. Conclusion: The intervention showed effectiveness to prevent and limit the damage by dental caries in first permanent molar; after 3 and 6 months of being done.