Tidy-Direct-to-MS: An Open-Source Data-Processing Pipeline for Direct Mass Spectrometry-Based Metabolomics Experiments.

Direct-to-Mass Spectrometry and ambient ionization techniques can be used for biochemical fingerprinting in a fast way. Data processing is typically accomplished with vendor-provided software tools. Here, a novel, open-source functionality, entitled Tidy-Direct-to-MS, was developed for data processing of direct-to-MS data sets. It allows for fast and user-friendly processing using different modules for optional sample position detection and separation, mass-to-charge ratio drift detection and correction, consensus spectra calculation, and bracketing across sample positions as well as feature abundance calculation. The tool also provides functionality for the automated comparison of different sets of parameters, thereby assisting the user in the complex task of finding an optimal combination to maximize the total number of detected features while also checking for the detection of user-provided reference features. In addition, Tidy-Direct-to-MS has the capability for data quality review and subsequent data analysis, thereby simplifying the workflow of untargeted ambient MS-based metabolomics studies. Tidy-Direct-to-MS is implemented in the Python programming language as part of the TidyMS library and can thus be easily extended. Capabilities of Tidy-Direct-to-MS are showcased in a data set acquired in a marine metabolomics study reported in MetaboLights (MTBLS1198) using a transmission mode Direct Analysis in Real Time-Mass Spectrometry (TM-DART-MS)-based method.

Especialización o diversificación en el desarrollo deportivo: Una revisión integrativa / Specialization or Diversification in Sports Development: An Integrative Review / Especialização ou diversificação no desenvolvimento esportivo: uma revisão integrativa

Resumen Objetivo: Explorar y discutir literatura científica teórica y práctica para comparar la diversificación y la especialización deportivas tempranas como un enfoque deportivo y educativo. Métodos: Se realizó una revisión sistemática siguiendo las pautas PRISMA, se incluyó un total de 61 estudios. Resultados: Entrenadores, padres e hijos consideran que la mejor forma de desarrollar el talento deportivo y alcanzar la élite en el deporte es participar en una sola disciplina y hacerlo lo antes posible para lograr la especialización y las máximas habilidades técnicas, físicas y psicológicas. Los caminos de especialización deportiva pueden conducir a una situación física, social y mental que comprometa su desarrollo integral. Conclusión: Se puede plantear, en primer lugar, la diversificación deportiva en edades tempranas y luego la especialización; una vez alcanzadas las bases de la fuerza, el acondicionamiento y el entrenamiento neuromuscular, así como una maduración psicomotora específica, para que su rendimiento deportivo y su salud no se vean comprometidos en el mediano o largo plazo. Es necesario considerar que pocos niños logran obtener un lugar en los deportes de élite, por lo que, para muchos de ellos, la educación en torno al deporte será la base para el ejercicio de su ciudadanía como personas activas.

Abstract Purpose: To explore and discuss theoretical and practical scientific literature to compare sports diversification and early sports specialization as a sport and educational approach. Methods: A systematic review was conducted following PRISMA guidelines, and 61 studies were included. Results: Coaches, parents, and children consider that the best way to develop sports talent and enter the elite in sports is to practice a single discipline as early as possible to achieve specialization and maximum technical skills and physical and psychological conditions. Sports specialization paths may lead to a physical, social, and mental state that compromises their integral development. Conclusion: Sports diversification should be considered first at an early age and, afterward, the specialization once the bases of strength, conditioning, neuromuscular training, and a specific psychomotor maturation have been achieved, so that sports performance and health are not compromised in the medium or long term. It is necessary to consider that few children enter elite sports, so for many of them, sports education will be the basis for exercising their citizenship as active people.

Resumo Objetivos: Explorar e discutir literatura científica teórica e prática para comparar a diversificação e especialização esportiva precoce como uma abordagem esportiva e educacional. Métodos: uma revisão sistemática foi realizada seguindo as diretrizes do PRISMA, um total de 61 estudos foram incluídos Resultados: Treinadores, pais e crianças acreditam que a melhor maneira de desenvolver talentos esportivos e ingressar na elite do esporte é participar de uma única disciplina e fazer o mais cedo possível para alcançar a especialização e o máximo de habilidades técnicas, físicas e psicológicas. Os caminhos da especialização esportiva podem levar a uma situação física, social e mental que comprometa seu desenvolvimento integral. Conclusão: Primeiro, a diversificação esportiva pode ser considerada em uma idade precoce e depois a especialização, uma vez que os princípios básicos de força, condicionamento e treinamento neuromuscular tenham sido alcançados, bem como a maturação psicomotora específica para que seu desempenho esportivo e saúde não sejam comprometidos a médio ou longo prazo. É necessário considerar que poucas crianças conseguem obter um lugar nos esportes de elite, de modo que, para muitas delas, a educação em torno do esporte será a base para o exercício de sua cidadania como pessoas ativas.

Aflatoxin Decontamination in Maize Steep Liquor Obtained from Bioethanol Production Using Laccases from Species within the Basidiomycota Phylum.

Maize (Zea mays L.) is an important crop in Argentina. Aspergillus section Flavi can infect this crop at the pre-harvest stage, and the harvested grains can be contaminated with aflatoxins (AFs). During the production of bioethanol from maize, AF levels can increase up to three times in the final co-products, known as, dry and wet distiller's grain with solubles (DDGS and WDGS), intended for animal feed. Fungal enzymes like laccases can be a useful tool for reducing AF contamination in the co-products obtained from this process. The aim of the present study was to evaluate the ability of laccase enzymes included in enzymatic extracts (EE) produced by different species in the Basidiomycota phylum to reduce AF (AFB1 and AFB2) accumulation under the conditions of in vitro assays. Four laccase activities (5, 10, 15, and 20 U/mL) exerted by nine isolates were evaluated in the absence and presence of vanillic acid (VA), serving as a laccase redox mediator for the degradation of total AFs. The enzymatic stability in maize steep liquor (MSL) was confirmed after a 60 h incubation period. The most effective EE in terms of reducing AF content in the buffer was selected for an additional assay carried out under the same conditions using maize steep liquor obtained after the saccharification stage during the bioethanol production process. The highest degradation percentages were observed at 20 U/mL of laccase enzymatic activity and 1 mM of VA, corresponding to 26% for AFB1 and 26.6% for AFB2. The present study provides valuable data for the development of an efficient tool based on fungal laccases for preventing AF accumulation in the co-products of bioethanol produced from maize used for animal feed.

UHPLC-HRMS-Based Analysis of S-Hydroxymethyl-Glutathione, GSH, and GSSG in Human Cells.

Glutathione (GSH) is one of the main antioxidant molecules present in cells. It harbors a thiol group responsible for sustaining cellular redox homeostasis. This moiety can react with cellular electrophiles such as formaldehyde yielding the compound S-hydroxymethyl-GSH (HSMGSH). HSMGSH is the substrate of the enzyme alcohol dehydrogenase 5 (ADH5) and thus a key intermediate in formaldehyde metabolism. In this work, we describe a method for the chemical synthesis of HSMGSH and a pipeline to identify this compound in complex cell extracts by means of ultra-high-performance liquid chromatography coupled to high-resolution spectrometry (UHPLC-HRMS). This method also allows determining GSH and oxidized disulfide (GSSG) in the same samples, thus providing broad information about formaldehyde-GSH metabolism.

S-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1) inhibits lung cancer tumorigenesis by regulating cell plasticity.

BACKGROUND: Lung cancer is one of the most frequently diagnosed cancers characterized by high mortality, metastatic potential, and recurrence. Deregulated gene expression of lung cancer, likewise in many other solid tumors, accounts for their cell heterogeneity and plasticity. S-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1), also known as Inositol triphosphate (IP(3)) receptor-binding protein released with IP(3) (IRBIT), plays roles in many cellular functions, including autophagy and apoptosis but AHCYL1 role in lung cancer is largely unknown. RESULTS: Here, we analyzed the expression of AHCYL1 in Non-Small Cell Lung Cancer (NSCLC) cells from RNA-seq public data and surgical specimens, which revealed that AHCYL1 expression is downregulated in tumors and inverse correlated to proliferation marker Ki67 and the stemness signature expression. AHCYL1-silenced NSCLC cells showed enhanced stem-like properties in vitro, which correlated with higher expression levels of stem markers POU5F1 and CD133. Also, the lack of AHCYL1 enhanced tumorigenicity and angiogenesis in mouse xenograft models highlighting stemness features. CONCLUSIONS: These findings indicate that AHCYL1 is a negative regulator in NSCLC tumorigenesis by modulating cell differentiation state and highlighting AHCYL1 as a potential prognostic biomarker for lung cancer.

Model-driven data curation pipeline for LC-MS-based untargeted metabolomics.

INTRODUCTION: There is still no community consensus regarding strategies for data quality review in liquid chromatography mass spectrometry (LC-MS)-based untargeted metabolomics. Assessing the analytical robustness of data, which is relevant for inter-laboratory comparisons and reproducibility, remains a challenge despite the wide variety of tools available for data processing. OBJECTIVES: The aim of this study was to provide a model to describe the sources of variation in LC-MS-based untargeted metabolomics measurements, to use it to build a comprehensive curation pipeline, and to provide quality assessment tools for data quality review. METHODS: Human serum samples (n=392) were analyzed by ultraperformance liquid chromatography coupled to high-resolution mass spectrometry (UPLC-HRMS) using an untargeted metabolomics approach. The pipeline and tools used to process this dataset were implemented as part of the open source, publicly available TidyMS Python-based package. RESULTS: The model was applied to understand data curation practices used by the metabolomics community. Sources of variation, which are often overlooked in untargeted metabolomic studies, were identified in the analysis. New tools were used to characterize certain types of variations. CONCLUSION: The developed pipeline allowed confirming data robustness by comparing the experimental results with expected values predicted by the model. New quality control practices were introduced to assess the analytical quality of data.

Postoperative Metabolic Phenoreversion in Clear Cell Renal Cell Carcinoma.

The ultimate goal of surgical treatment in cancer is to remove the tumor mass for restoring a healthy state. A 16-lipid panel that discriminated healthy controls from clear cell renal cell carcinoma (ccRCC) patients in a prior study was evaluated in the present work in paired-serum samples collected from patients (n = 41) before and after nephrectomy. Changes in the lipid and metabolite fingerprints from ccRCC patients were investigated and compared with fingerprints from healthy individuals obtained by means of ultra-performance liquid chromatography-high-resolution mass spectrometry. The lipid panel differentiated phenotypes associated with metabolic restoration after surgery, representing a serum signature of phenoreversion to a healthy metabolic state. In particular, PC 16:0/0:0, PC 18:2/18:2, and linoleic acid allowed discriminating serum samples from ccRCC patients with poor prognosis from those with an improved outcome during the follow-up period. Ratios of PC 16:0/0:0 and PC 18:2/18:2 with linoleic acid levels may contribute as prognostic tools to support decision-making during the patient follow-up care. The preliminary character of these results should be validated with larger cohorts, including subjects with different ethnicities, life style, and diets. MetaboLights study references: MTBLS1839, MTBLS3838, and MTBLS4629.

Endogenous formaldehyde scavenges cellular glutathione resulting in redox disruption and cytotoxicity.

Formaldehyde (FA) is a ubiquitous endogenous and environmental metabolite that is thought to exert cytotoxicity through DNA and DNA-protein crosslinking, likely contributing to the onset of the human DNA repair condition Fanconi Anaemia. Mutations in the genes coding for FA detoxifying enzymes underlie a human inherited bone marrow failure syndrome (IBMFS), even in the presence of functional DNA repair, raising the question of whether FA causes relevant cellular damage beyond genotoxicity. Here, we report that FA triggers cellular redox imbalance in human cells and in Caenorhabditis elegans. Mechanistically, FA reacts with the redox-active thiol group of glutathione (GSH), altering the GSH:GSSG ratio and causing oxidative stress. FA cytotoxicity is prevented by the enzyme alcohol dehydrogenase 5 (ADH5/GSNOR), which metabolizes FA-GSH products, lastly yielding reduced GSH. Furthermore, we show that GSH synthesis protects human cells from FA, indicating an active role of GSH in preventing FA toxicity. These findings might be relevant for patients carrying mutations in FA-detoxification systems and could suggest therapeutic benefits from thiol-rich antioxidants like N-acetyl-L-cysteine.

Investigation of Variables that Determine Levels of Self-Esteem in Central American Schoolchildren: A Binary Logistic Regression Model / Investigación de las variables que determinan los niveles de autoestima en los escolares centroamericanos: Un modelo de regresión logística binaria

Resumen El propósito de esta investigación fue examinar el enlace entre los hábitos de actividad física de los niños centroamericanos, su nivel de autoestima, edad y país de origen. Este fue un estudio correlacional de muestras probabilísticas aleatorias por conglomerados, que evaluó 5291 estudiantes matriculados en cuarto, quinto y sexto grado, de los cuales el 52.3 % corresponde a niñas y el 47.7 % a niños, pertenecientes a 74 escuelas en Guatemala, Honduras, El Salvador, Costa Rica, Nicaragua y Panamá, con una edad media de 10.90 ± 1.13. En todas las naciones, se utilizó el cuestionario LAWSEQ para medir el nivel de autoestima y se aplicó el de actividad física para la niñez (PAQ-C). Un análisis de regresión logística binaria fue ejecutado para estimar si las variables independientes podrían predecir el nivel de autoestima de los infantes. Los resultados mostraron que el 47 % de los estudiantes se percibió con un bajo nivel de actividad física y, con respecto a la autoestima, quienes poseen de 9 a 10 años tuvieron porcentajes más bajos, con 51.6 % y 47.7 %, respectivamente. En cuanto al país de origen, los niños de Costa Rica y Guatemala tienen un mejor nivel de autoestima que aquellos habitantes de El Salvador, Nicaragua, Honduras y Panamá. Además, se determinó que la edad, el nivel de actividad física y el país de origen predecían el 58 % del nivel de autoestima infantil centroamericana. Esto demuestra la importancia de promover la actividad física en dicho sector poblacional, para contribuir al desarrollo de su autoestima.

Abstract This research aimed to examine the relationships between the levels of self-esteem of Central American schoolchildren and their physical activity habits, ages, and countries of origin. This was a correlational study of random cluster probabilistic samples, which evaluated 5,291 students enrolled in fourth, fifth, and sixth grades, 52.3% of whom were girls and 47.7% boys, from 74 schools in Guatemala, Honduras, El Salvador, Costa Rica, Nicaragua, and Panama, with an average age of 10.90 ± 1.13 years. Lawrence's Self-Esteem Questionnaire (LAWSEQ) was used to measure levels of self-esteem, and the physical activity questionnaire for boys and girls (PAQ-C) was applied in all the countries. A binary logistic regression analysis was conducted to estimate the statistical probability that the independent variables (age, level of activity, and country of origin) could predict the level of self-esteem. The results of this investigation showed that 47% of the children under study perceive themselves to have a low level of physical activity and that children from 9 to 10 years had lower percentages of self-esteem with 51.6% and 47.7%, respectively. In terms of country of origin, children from Costa Rica and Guatemala have a better level of self-esteem than those living in El Salvador, Nicaragua, Honduras, and Panama. In addition, it was determined that age, level of physical activity, and country of origin predicted 58% of the level of self-esteem of Central American children. This situation shows the importance of promoting physical activity in childhood to contribute to the development of self-esteem.

Resumo O objetivo desta pesquisa foi examinar a ligação entre os hábitos de atividade física de crianças da América Central, seu nível de autoestima, idade e país de origem. Este foi um estudo correlacional de amostras probabilísticas aleatórias por conglomerados, que avaliou 5.291 estudantes matriculados na quarta, quinta e sexta séries do ensino fundamental, dos quais 52,3% correspondem a meninas e 47,7% a meninos, pertencentes a 74 escolas na Guatemala, Honduras, El Salvador, Costa Rica, Nicarágua e Panamá, com média de idade de 10,90 ± 1,13. Nesses países, o questionário LAWSEQ foi utilizado para medir o nível de autoestima e o questionário de atividade física para a infância (PAQ-C) foi aplicado. Uma análise de regressão logística binária foi realizada para estimar se as variáveis independentes poderiam predizer o nível de autoestima das crianças. Os resultados mostraram que 47% dos estudantes se perceberam com baixo nível de atividade física e, no que se refere à autoestima, aqueles com 9 a 10 anos apresentaram percentuais menores, com 51,6% e 47,7%, respectivamente. Quanto ao país de origem, as crianças da Costa Rica e da Guatemala apresentam um nível de autoestima superior as de El Salvador, Nicarágua, Honduras e Panamá. Além disso, determinou-se que a idade, o nível de atividade física e o país de origem previam os 58% do nível de autoestima da criança centro-americana. Isso mostra a importância da promoção da atividade física nesse setor populacional, de forma a contribuir para o desenvolvimento de sua autoestima.

Mass Spectrometry-Based Metabolic Fingerprinting Contributes to Unveil the Role of RSUME in Renal Cell Carcinoma Cell Metabolism.

Clear cell renal cell carcinoma (ccRCC) is a heterogeneous disease with 50-80% patients exhibiting mutations in the von Hippel-Lindau (VHL) gene. RSUME (RWD domain (termed after three major RWD-containing proteins: RING finger-containing proteins, WD-repeat-containing proteins, and yeast DEAD (DEXD)-like helicases)-containing protein small ubiquitin-related modifier (SUMO) enhancer) acts as a negative regulator of VHL function in normoxia. A discovery-based metabolomics approach was developed by means of ultraperformance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (MS) for fingerprinting the endometabolome of a human ccRCC cell line 786-O and three other transformed cell systems (n = 102) with different expressions of RSUME and VHL. Cross-validated orthogonal projection to latent structures discriminant analysis models were built on positive, negative, and a combination of positive- and negative-ion mode MS data sets. Discriminant feature panels selected by an iterative multivariate classification allowed differentiating cells with different expressions of RSUME and VHL. Fifteen identified discriminant metabolites with level 1, including glutathione, butyrylcarnitine, and acetylcarnitine, contributed to understand the role of RSUME in ccRCC. Altered pathways associated with the RSUME expression were validated by biological and bioinformatics analyses. Combined results showed that in the absence of VHL, RSUME is involved in the downregulation of the antioxidant defense system, whereas in the presence of VHL, it acts in rerouting energy-related pathways, negatively modulating the lipid utilization, and positively modulating the fatty acid synthesis, which may promote deposition in droplets.

Effect of fungicides commonly used for Fusarium head blight management on growth and fumonisin production by Fusarium proliferatum.

Fumonisin occurrence was reported in wheat grains and F. proliferatum has been suggested to be the main contributor to its presence in wheat. Thus, a survey was performed in order to study the impact of four commercial fungicides used in Argentina for controlling Fusarium head blight disease (epoxiconazole+metconazole, tebuconazole, pyraclostrobin+epoxiconazole, and prothioconazole) on growth and fumonisin production of two F. proliferatum strains in relation to water activity (aW; 0.99, 0.97, 0.95) and temperature (15°C and 25°C). Most fungicides reduced growth rates when compared to the control (reduction increased as fungicide concentration increased), and reduced fumonisin production when they were used at high doses; however, most fungicides enhanced fumonisin production at sublethal doses, with the exception of prothioconazole. Thus, fungicides used for FHB management could enhance fumonisin production by F. proliferatum strains present in wheat grains.

Coupled Mass-Spectrometry-Based Lipidomics Machine Learning Approach for Early Detection of Clear Cell Renal Cell Carcinoma.

A discovery-based lipid profiling study of serum samples from a cohort that included patients with clear cell renal cell carcinoma (ccRCC) stages I, II, III, and IV (n = 112) and controls (n = 52) was performed using ultraperformance liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry and machine learning techniques. Multivariate models based on support vector machines and the LASSO variable selection method yielded two discriminant lipid panels for ccRCC detection and early diagnosis. A 16-lipid panel allowed discriminating ccRCC patients from controls with 95.7% accuracy in a training set under cross-validation and 77.1% accuracy in an independent test set. A second model trained to discriminate early (I and II) from late (III and IV) stage ccRCC yielded a panel of 26 compounds that classified stage I patients from an independent test set with 82.1% accuracy. Thirteen species, including cholic acid, undecylenic acid, lauric acid, LPC(16:0/0:0), and PC(18:2/18:2), identified with level 1 exhibited significantly lower levels in samples from ccRCC patients compared to controls. Moreover, 3α-hydroxy-5α-androstan-17-one 3-sulfate, cis-5-dodecenoic acid, arachidonic acid, cis-13-docosenoic acid, PI(16:0/18:1), PC(16:0/18:2), and PC(O-16:0/20:4) contributed to discriminate early from late ccRCC stage patients. The results are auspicious for early ccRCC diagnosis after validation of the panels in larger and different cohorts.

A Python-Based Pipeline for Preprocessing LC-MS Data for Untargeted Metabolomics Workflows.

Preprocessing data in a reproducible and robust way is one of the current challenges in untargeted metabolomics workflows. Data curation in liquid chromatography-mass spectrometry (LC-MS) involves the removal of biologically non-relevant features (retention time, m/z pairs) to retain only high-quality data for subsequent analysis and interpretation. The present work introduces TidyMS, a package for the Python programming language for preprocessing LC-MS data for quality control (QC) procedures in untargeted metabolomics workflows. It is a versatile strategy that can be customized or fit for purpose according to the specific metabolomics application. It allows performing quality control procedures to ensure accuracy and reliability in LC-MS measurements, and it allows preprocessing metabolomics data to obtain cleaned matrices for subsequent statistical analysis. The capabilities of the package are shown with pipelines for an LC-MS system suitability check, system conditioning, signal drift evaluation, and data curation. These applications were implemented to preprocess data corresponding to a new suite of candidate plasma reference materials developed by the National Institute of Standards and Technology (NIST; hypertriglyceridemic, diabetic, and African-American plasma pools) to be used in untargeted metabolomics studies in addition to NIST SRM 1950 Metabolites in Frozen Human Plasma. The package offers a rapid and reproducible workflow that can be used in an automated or semi-automated fashion, and it is an open and free tool available to all users.

Reducción del riesgo cardiovascular en trabajadores de un instituto de salud especializado mediante un programa de prevención cardiovascular / Reduction of cardiovascular risk in professionals from a specialized health institute by a cardiovascular preventive program

RESUMEN Introducción. Los programas de rehabilitación cardiovascular (PRC) representan una estrategia médico-sanitaria multidisciplinaria eficaz en la prevención y control de los problemas cardiovasculares. Objetivos. Evaluar el impacto de un PRC realizado en el espacio de trabajo, en la reducción del riesgo cardiovascular absoluto en los trabajadores de INCOR. Métodos. Estudio experimental. Se incluyó a 41 trabajadores con diferentes niveles de riesgo cardiovascular, evaluados previa y posteriormente a su participación en el PRC sobre su capacidad funcional, sus factores de riesgo cardiovascular y niveles de estrés. El programa de intervención en el trabajo consistió en 36 sesiones de actividad física controlada, consejería nutricional, consejería psicológica y evaluación de laboratorio. Resultados. Se redujo el riesgo cardiovascular global al nivel bajo en el 100% medido mediante el índice de Framingham y en la medición con el score ASCVD 2013, se eliminó el nivel de riesgo alto y el nivel intermedio se redujo de 17,5% a 10%. La capacidad funcional mejoró, incrementándose la clase funcional I de 19,5% a 90%. Los niveles de VLDL, LDL, colesterol total y triglicéridos se redujeron significativamente en la post-intervención, mientras que para el HDL, la proporción de trabajadores con valores no recomendables se incrementó al final de la intervención. Se encontró disminución significativa del nivel de estrés. Conclusiones. Un PRC puede ser implementado en el mismo ámbito laboral y mostrar su comprobada eficacia para reducir el riesgo cardiovascular y el estrés.

ABSTRACT Introduction. The cardiovascular rehabilitation programs (CRP) represent an effective multidisciplinary medical-health strategy in prevention and control of cardiovascular problems. Objective. To assess the impact of a CRP carried out in the workplace, in reducing absolute cardiovascular risk in INCOR workers. Methods. An experimental study. 41 workers with different levels of cardiovascular risk were included and were evaluated before and after their participation in the CRP on their functional capacity, cardiovascular risk factors and stress levels. The work intervention program consisted of 36 sessions of controlled physical activity, nutritional counseling, psychological counseling and laboratory evaluation. Results. The intervention get a reduction of the overall cardiovascular risk to the low level in all workers (100%), measured by the Framingham index and when it was measured with the ASCVD 2013 score, the high-risk level was eliminated and the intermediate level was reduced from 17,5% to 10%. The functional capacity shows an improvement, with an increase of cardiovascular risk level I from 19,5% to 90%. Blood lipids levels as VLDL, LDL, total cholesterol and triglycerides were significantly reduced in the post-intervention. Contrarily, in the HDL levels, the proportion of workers with non-recommended values increased to the end of the intervention. Finally, the CRP showed effectiveness in reducing workers' stress. Conclusion. A CRP could to be implemented on workplace and it shows effectiveness in reducing cardiovascular risk and stress.

Efectos fetales y posnatales del tabaquismo durante el embarazo / Fetal and postnatal effects of smoking during pregnancy

Resumen La exposición al tabaco en el útero se asocia con un menor crecimiento fetal, una disminución en el peso al nacer y un incremento significativo de nacimientos con bajo peso. Por otra parte, diversos estudios han indicado que el tabaquismo materno puede provocar sobrepeso u obesidad y un aumento rápido de peso en la infancia, lo puede aumentar el riesgo de enfermedades cardiovasculares y diabetes tipo 2 en la adultez temprana. Los niños expuestos a humo de tabaco en la vida intrauterina, tienen un sistema autónomo hiperreactivo durante las primeras semanas de vida, un crecimiento desproporcionado entre el parénquima pulmonar y las vías aéreas (crecimiento disináptico pulmonar), una disminución en la función pulmonar, un riesgo aumentado de asma, bronquitis y sibilancias en el producto. Existen asociaciones entre el tabaquismo materno y la reducción de las capacidades psicomotoras infantiles, así como los problemas de conducta incluido el trastorno por déficit de atención/hiperactividad en la niñez. Se ha observado un aumento en el riesgo de neoplasias benignas en la infancia (hemangioma y quiste tiroideo), pero no de neoplasias malignas.

Abstract Exposure to tobacco in the uterus is associated with lower fetal growth, a decrease in birth weight and a significant increase in low birth weight births. On the other hand, several studies have indicated that maternal smoking can cause overweight or obesity and a rapid increase in weight in childhood, which can increase the risk of cardiovascular disease and type 2 diabetes in early adulthood. Children exposed to tobacco smoke in intrauterine life, have a hyperreactive autonomic system during the first weeks of life, a disproportionate growth in lung parenchyma and airways (pulmonary dysynaptic growth), a reduction in lung function, an Increased risk in asthma, bronchitis and wheezing in the product. There are associations between maternal smoking and the reduction of infant psychomotor abilities, as well as behavioral problems that include children attention-deficit/hyperactivity disorder. There has been an increase in the risk of benign neoplasms in childhood (hemangioma and thyroid cyst), but not malignant neoplasms.

Análisis de sobrepeso y obesidad, niveles de actividad física y autoestima en la niñez del II ciclo escolar del cantón central de Heredia, Costa Rica / Analysis of overweight and obesity, levels of physical activity and self-esteem in childhood of the II school cycle of the central canton of Heredia, Costa Rica

Resumen Objetivo: analizar la prevalencia de sobrepeso y obesidad, el nivel de actividad física y autoestima de la población escolar de II Ciclo del cantón central de Heredia Método: este fue un estudio descriptivo-comparativo transversal en el que se analizaron 442 niños, de cuarto, quinto y sexto grado escolar, de los cuales 234 fueron niños y 208 niñas con una edad entre los 9 y 13 años. Se realizó la medición del peso y la talla para el cálculo del índice de masa corporal, se aplicó el cuestionario de actividad física para niños mayores (PAQ-C) y el cuestionario LAWSEQ para la medición del nivel de autoestima. Resultados: los resultados mostraron un 20.6 % de infantes poseen sobrepeso y 13.6 % presentaron obesidad, en el nivel de actividad física un 29.4 % mostraron un nivel bajo y un 26.7 % baja autoestima. Además, los niños presentaron un nivel de actividad física más alto en comparación con las niñas (F (9) = 2.55; p=0.007). Conclusiones: en función del objetivo, la prevalencia de sobrepeso y obesidad en las niñas y en los niños fue de un 34.2 %. Un 30% presentó altos niveles de sedentarismo y un 27 % bajos niveles de autoestima. Estos datos indican la necesidad de generar opciones de intervención en los diferentes niveles educativos, fundamentalmente, trabajando en equipo con entes gubernamentales del país.

Abstract Objetive: analyze the prevalence of overweight and obesity, the level of physical activity and self-esteem of the school population of fourth, fifth and sixth grades of the Central District of Heredia. Method: The descriptive-comparative and transversal study analyzed 442 children, 234 boys and 208 girls between 9 and 13 years old. It was measured the weight and height to calculate the body mass index, the Physical Activity Questionnaire for Children (PAQ-C) and Lawrence's Self-Esteem Questionnaire (LAWSEQ). Results: the results suggest 20.6 % of infants with overweight and 13.6 % with obesity, 29.4 % indicated a low level of physical activity and 26.7 % with low self-esteem. In addition, boys report a higher level of physical activity compared to girls (F (9) =2.55; p=0.007). Conclusions: According to the objective, the prevalence of overweight and obesity in girls and boys was 34.2 %, 30 % presented high levels of sedentary lifestyle and 27 % low self-esteem. These information indicate the importance of generating intervention options is demonstrated in the different levels of education with the aim of palliate the results of this research, working as a team with government organization in the country.

De novo design approaches targeting an envelope protein pocket to identify small molecules against dengue virus.

Dengue fever is a mosquito-borne viral disease that has become a major public health concern worldwide. This disease presents with a wide range of clinical manifestations, from a mild cold-like illness to the more serious hemorrhagic dengue fever and dengue shock syndrome. Currently, neither an approved drug nor an effective vaccine for the treatment are available to fight the disease. The envelope protein (E) is a major component of the virion surface. This protein plays a key role during the viral entry process, constituting an attractive target for the development of antiviral drugs. The crystal structure of the E protein reveals the existence of a hydrophobic pocket occupied by the detergent n-octyl-ß-d-glucoside (ß-OG). This pocket lies at the hinge region between domains I and II and is important for the low pH-triggered conformational rearrangement required for the fusion of the virion with the host's cell. Aiming at the design of novel molecules which bind to E and act as virus entry inhibitors, we undertook a de novo design approach by "growing" molecules inside the hydrophobic site (ß-OG). From more than 240000 small-molecules generated, the 2,4 pyrimidine scaffold was selected as the best candidate, from which one synthesized compound displayed micromolar activity. Molecular dynamics-based optimization was performed on this hit, and thirty derivatives were designed in silico, synthesized and evaluated on their capacity to inhibit dengue virus entry into the host cell. Four compounds were found to be potent antiviral compounds in the low-micromolar range. The assessment of drug-like physicochemical and in vitro pharmacokinetic properties revealed that compounds 3e and 3h presented acceptable solubility values and were stable in mouse plasma, simulated gastric fluid, simulated intestinal fluid, and phosphate buffered saline solution.