DNA damage and its association with early-life exposome: Gene-environment analysis in Colombian children under five years old.

Environmental exposures and gene-exposure interactions are the major causes of some diseases. Early-life exposome studies are needed to elucidate the role of environmental exposures and their complex interactions with biological mechanisms involved in childhood health. This study aimed to determine the contribution of early-life exposome to DNA damage and the modifying effect of genetic polymorphisms involved in air pollutants metabolism, antioxidant defense, and DNA repair. We conducted a cohort study in 416 Colombian children under five years. Blood samples at baseline were collected to measure DNA damage by the Comet assay and to determine GSTT1, GSTM1, CYP1A1, H2AX, OGG1, and SOD2 genetic polymorphisms. The exposome was estimated using geographic information systems, remote sensing, LUR models, and questionnaires. The association exposome-DNA damage was estimated using the Elastic Net linear regression with log link. Our results suggest that exposure to PM2.5 one year before the blood draw (BBD) (0.83, 95 %CI: 0.76; 0.91), soft drinks consumption (0.94, 0.89; 0.98), and GSTM1 null genotype (0.05, 0.01; 0.36) diminished the DNA damage, whereas exposure to PM2.5 one-week BBD (1.18, 1.06; 1.32), NO2 lag-5 days BBD (1.27, 1.18; 1.36), in-house cockroaches (1.10, 1.00; 1.21) at the recruitment, crowding at home (1.34, 1.08; 1.67) at the recruitment, cereal consumption (1.11, 1.04; 1.19) and H2AX (AG/GG vs. AA) (1.44, 1.11; 1.88) increased the DNA damage. The interactions between H2AX (AG/GG vs. AA) genotypes with crowding and PM2.5 one week BBD, GSTM1 (null vs. present) with humidity at the first year of life, and OGG1 (SC/CC vs. SS) with walkability at the first year of life were significant. The early-life exposome contributes to elucidating the effect of environmental exposures on DNA damage in Colombian children under five years old. The exposome-DNA damage effect appears to be modulated by genetic variants in DNA repair and antioxidant defense enzymes.

Early-life external exposome in children 2-5 years old in Colombia.

Exposome studies are advancing in high-income countries to understand how multiple environmental exposures impact health. However, there is a significant research gap in low- and middle-income and tropical countries. We aimed to describe the spatiotemporal variation of the external exposome, its correlation structure between and within exposure groups, and its dimensionality. A one-year follow-up cohort study of 506 children under 5 in two cities in Colombia was conducted to evaluate asthma, acute respiratory infections, and DNA damage. We examined 48 environmental exposures during pregnancy and 168 during childhood in eight exposure groups, including atmospheric pollutants, natural spaces, meteorology, built environment, traffic, indoor exposure, and socioeconomic capital. The exposome was estimated using geographic information systems, remote sensing, spatiotemporal modeling, and questionnaires. The median age of children at study entry was 3.7 years (interquartile range: 2.9-4.3). Air pollution and natural spaces exposure decreased from pregnancy to childhood, while socioeconomic capital increased. The highest median correlations within exposure groups were observed in meteorology (r = 0.85), traffic (r = 0.83), and atmospheric pollutants (r = 0.64). Important correlations between variables from different exposure groups were found, such as atmospheric pollutants and meteorology (r = 0.76), natural spaces (r = -0.34), and the built environment (r = 0.53). Twenty principal components explained 70%, and 57 explained 95% of the total variance in the childhood exposome. Our findings show that there is an important spatiotemporal variation in the exposome of children under 5. This is the first characterization of the external exposome in urban areas of Latin America and highlights its complexity, but also the need to better characterize and understand the exposome in order to optimize its analysis and applications in local interventions aimed at improving the health conditions and well-being of the child population and contributing to environmental health decision-making.

Characterization of the external exposome and its contribution to the clinical respiratory and early biological effects in children: The PROMESA cohort study protocol.

BACKGROUND: Air pollution contains a mixture of different pollutants from multiple sources. However, the interaction of these pollutants with other environmental exposures, as well as their harmful effects on children under five in tropical countries, is not well known. OBJECTIVE: This study aims to characterize the external exposome (ambient and indoor exposures) and its contribution to clinical respiratory and early biological effects in children. MATERIALS AND METHODS: A cohort study will be conducted on children under five (n = 500) with a one-year follow-up. Enrolled children will be followed monthly (phone call) and at months 6 and 12 (in person) post-enrolment with upper and lower Acute Respiratory Infections (ARI) examinations, asthma development, asthma control, and genotoxic damage. The asthma diagnosis will be pediatric pulmonologist-based and a standardized protocol will be used. Exposure, effect, and susceptibility biomarkers will be measured on buccal cells samples. For environmental exposures PM2.5 will be sampled, and questionnaires, geographic information, dispersion models and Land Use Regression models for PM2.5 and NO2 will be used. Different statistical methods that include Bayesian and machine learning techniques will be used for the ambient and indoor exposures-and outcomes. This study was approved by the ethics committee at Universidad Pontificia Bolivariana. EXPECTED STUDY OUTCOMES/FINDINGS: To estimate i) The toxic effect of particulate matter transcending the approach based on pollutant concentration levels; ii) The risk of developing an upper and lower ARI, based on different exposure windows; iii) A baseline of early biological damage in children under five, and describe its progression after a one-year follow-up; and iv) How physical and chemical PM2.5 characteristics influence toxicity and children's health.

Genetic and Bioinformatic Strategies to Improve Diagnosis in Three Inherited Bleeding Disorders in Bogotá, Colombia.

Inherited bleeding disorders (IBDs) are the most frequent congenital diseases in the Colombian population; three of them are hemophilia A (HA), hemophilia B (HB), and von Willebrand Disease (VWD). Currently, diagnosis relies on multiple clinical laboratory assays to assign a phenotype. Due to the lack of accessibility to these tests, patients can receive an incomplete diagnosis. In these cases, genetic studies reinforce the clinical diagnosis. The present study characterized the molecular genetic basis of 11 HA, three HB, and five VWD patients by sequencing the F8, F9, or the VWF gene. Twelve variations were found in HA patients, four in HB patients, and 19 in WVD patients. From these variations a total of 25 novel variations were found. Disease-causing variations were used as positive controls for validation of the high-resolution melting (HRM) variant-scanning technique. This approach is a low-cost genetic diagnostic method proposed to be incorporated in developing countries. For the data analysis, we developed an accessible open-source code in Python that improves HRM data analysis with better sensitivity of 95% and without bias when using different HRM equipment and software. Analysis of amplicons with a length greater than 300 bp can be performed by implementing an analysis by denaturation domains.

Novel complexes with ONNO tetradentate coumarin schiff-base donor ligands: x-ray structures, DFT calculations, molecular dynamics and potential anticarcinogenic activity.

The synthesis of eight novel Zn(II), Co(II), Cu(II), Ni(II) and Pt(II) complexes (2-9) derived from the ONNO tetradentate coumarin Schiff-Base donor ligands, L1 and the novel L2, was performed. All compounds were characterized by analytical, spectrometry and spectroscopy techniques. Complexes 2-4 were also characterized by DFT calculations and the structures of 5 and 6 were determined by single-crystal X-ray diffraction analysis. A cytotoxicity study was carried out through an MTT assay in the carcinogenic cell line HeLa and the noncarcinogenic cell lines HFF-1 and HaCaT. The results indicated that among all the evaluated compounds, 2 and 6 presented the best anticarcinogenic potential against HeLa cells with an IC50 of 3.5 and 4.1 µM, respectively. In addition, classical molecular dynamics simulations were performed on the synthesized coordination compounds bound to G4 DNA architectures in the scope of shedding light on their inhibition mode and the most conserved interactions that may lead to the biological activity of the compounds.

Efficacy and Molecular Effects of a Reduced Graphene Oxide/Fe3O4 Nanocomposite in Photothermal Therapy Against Cancer.

PURPOSE: Expanded research on the biomedical applications of graphene has shown promising results, although interactions between cells and graphene are still unclear. The current study aims to dissect the cellular and molecular effects of graphene nanocomposite in photothermal therapy against cancer, and to evaluate its efficacy. METHODS: In this study, a reduced graphene oxide and iron oxide (rGO-Fe3O4) nanocomposite was obtained by chemical synthesis. The nanocomposite was fully characterized by Raman spectroscopy, TEM, VSM and thermal profiling. Cell-nanocomposite interaction was evaluated by confocal microscopy and viability assays on cancer cell line HeLa. The efficacy of the thermal therapy and changes in gene expression of Bcl-2 and Hsp70 was assessed. RESULTS: The resulting rGO-Fe3O4 nanocomposite exhibited superparamagnetic properties and the capacity to increase the surrounding temperature by 18-20°C with respect to the initial temperature. The studies of cell-nanocomposite interaction showed that rGO-Fe3O4 attaches to cell membrane but there is a range of concentration at which the nanomaterial preserves cell viability. Photothermal therapy reduced cell viability to 32.6% and 23.7% with 50 and 100 µg/mL of nanomaterial, respectively. The effect of treatment on the molecular mechanism of cell death demonstrated an overexpression of anti-apoptotic proteins Hsp70 and Bcl-2 as an initial response to the therapy and depending on the aggressiveness of the treatment. CONCLUSION: The results of this study contribute to understanding the interactions between cell and graphene and support its application in photothermal therapy against cancer due to its promising results.

Tridimensional alginate disks of tunable topologies for mammalian cell encapsulation.

We have developed a protocol to produce three-dimensional matrices based on alginate hydrogels for mammalian cell encapsulation. Based on the gelation properties of this polysaccharide, we implemented a calcium ion-based diffusion method where the designed hydrogels can be obtained with well-defined mechanical properties and replicable 3D topologies. The developed protocol can be extended to different types of alginates and an ample range of concentrations. This makes it very attractive for various biomedical applications where strict control over structure-function relationships is desirable.

Novel BUF2-magnetite nanobioconjugates with cell-penetrating abilities.

INTRODUCTION: One of the major challenges of modern pharmacology is the development of systems for the delivery of therapeutic molecules in a controlled and localized manner. One strategy is to use nanostructured supports, which are well suited to carry a large number of molecules on a per mass basis. A major challenge for these supports is, however, their limited ability to bypass the cell membrane. Recent studies propose that to overcome this issue, potent translocating cell-penetrating peptides (CPPs) can be conjugated to their surfaces. METHODS: Here, we conjugated the antimicrobial CPP buforin II (BUF2) to the surface of magnetite nanoparticles to enhance their cell penetration. Conjugates were characterized via Fourier transform infrared spectroscopy, dynamic light scattering, and thermogravimetric analysis, and their biocompatibility was corroborated. The conjugates were delivered in both bacterial and mammalian cells demonstrating the intracellular inclusion in THP-1 cells for the first time. RESULTS: Despite the promising outcome, our studies showed that the obtained conjugates failed to maintain the native antimicrobial activity of BUF2. We hypothesize that to overcome this issue, a flexible linker can be inserted prior to conjugation. CONCLUSION: Our study highlights the potential of BUF2-magnetite conjugates as cell-penetrating vehicles for the targeted delivery of pharmacological agents. This provides support for the idea of a promising combined drug delivery and antimicrobial peptide therapy.

Evaluación de la exposición al polvo de carbón y de sílice en sitios de minería subterránea en tres departamentos de Colombia / Evaluation of the exposure to coal dust and prevalence of pneumoconiosis in underground mining in three Colombian departments

Introducción. La neumoconiosis de mineros del carbón es una enfermedad crónica e irreversible que se considera un problema de salud pública. Objetivo. Estimar la prevalencia de neumoconiosis y sus factores asociados en mineros de carbón de Boyacá, Cundinamarca y Norte de Santander. Materiales y métodos. Se hizo un estudio de corte transversal en 476 mineros. Se les hizo valoración médica, se tomaron radiografías de tórax siguiendo los criterios de la Organización Internacional del Trabajo, así como espirometrías, y se identificaron los polimorfismos de la glutatión S-transferasa y de las enzimas de reparación. Las asociaciones entre las condiciones ocupacionales y de la empresa con la neumoconiosis, se estudiaron usando modelos de regresión de Cox. Resultados. En 31 empresas se hicieron 479 monitorizaciones ambientales y se evaluaron 476 trabajadores cuyo tiempo de trabajo fluctuaba entre 10 y 57 años. La prevalencia de la neumoconiosis fue de 33,8 % (IC95% 27,0-41,3). En el modelo de regresión multivariado de Cox, con tiempo de riesgo constante para la neumoconiosis, esta se asoció significativamente con el trabajo en empresas medianas (razón de prevalencias, RP=2,00; IC95% 0,995- 2,690; p=0,052), con un nivel alto de exposición al polvo de carbón según el índice de exposición (RP=2,055; IC95% 1,043-4,048; p=0,038), y una antigüedad de 25 años o más (para 25,0 a 29,9 años: RP=2,199; IC95% 1,449-3,338; p=0,001). Conclusiones. La prevalencia de la neumoconiosis fue muy alta y se asoció a la exposición a altos niveles de polvo de carbón, a una exposición laboral mayor o igual a 25 años y al trabajo en empresas medianas.

Introduction: Coal workers' pneumoconiosis is a chronic and irreversible disease representing a public health problem. Objective: To estimate the prevalence of pneumoconiosis and its associated factors among underground coal miners in the Colombian departments of Boyacá, Cundinamarca and Norte de Santander. Materials and methods: We conducted a cross-sectional study of 476 miners to measure the prevalence of pneumoconiosis and its associated factors such as coal dust and silica levels, as well as the occupational conditions. The medical assessment and a chest x-ray were performed according to the International Labor Organization criteria, along with spirometry and the identification of glutathione S-transferase and repair enzyme polymorphisms. The associations were explored using Cox regression models. Results: We performed a total of 479 environmental monitoring sessions in 31 companies and we evaluated 476 workers with 10 to 57 years of mining work experience. The prevalence of pneumoconiosis was 33.8% (95% CI: 27.0 - 41.3%). In the Cox multivariate regression model with a constant risk time, pneumoconiosis was significantly associated with working in medium-sized companies (PR=2.00, 95% CI: 0.995 - 2.690; p=0.052), the level of severe exposure to coal dust (PR=2.055, 95% CI: 1.043 - 4.048; p=0.038), and working in underground mining for 25 years or more (for those with 25.0-29.9 years: PR=2.199, 95% CI: 1.449 - 3.338; p=0.001). Conclusions: The prevalence of pneumoconiosis was very high and was found to be associated with severe exposure to coal dust, work exposure for 25 years or more and working in medium-sized enterprises.

Unveiling the Multifaceted Mechanisms of Antibacterial Activity of Buforin II and Frenatin 2.3S Peptides from Skin Micro-Organs of the Orinoco Lime Treefrog (Sphaenorhynchus lacteus).

Amphibian skin is a rich source of natural compounds with diverse antimicrobial and immune defense properties. Our previous studies showed that the frog skin secretions obtained by skin micro-organs from various species of Colombian anurans have antimicrobial activities against bacteria and viruses. We purified for the first time two antimicrobial peptides from the skin micro-organs of the Orinoco lime treefrog (Sphaenorhynchus lacteus) that correspond to Buforin II (BF2) and Frenatin 2.3S (F2.3S). Here, we have synthesized the two peptides and tested them against Gram-negative and Gram-positive bacteria, observing an effective bactericidal activity at micromolar concentrations. Evaluation of BF2 and F2.3S membrane destabilization activity on bacterial cell cultures and synthetic lipid bilayers reveals a distinct membrane interaction mechanism. BF2 agglutinates E. coli cells and synthetic vesicles, whereas F2.3S shows a high depolarization and membrane destabilization activities. Interestingly, we found that F2.3S is able to internalize within bacterial cells and can bind nucleic acids, as previously reported for BF2. Moreover, bacterial exposure to both peptides alters the expression profile of genes related to stress and resistance response. Overall, these results show the multifaceted mechanism of action of both antimicrobial peptides that can provide alternative tools in the fight against bacterial resistance.

Evaluation of the exposure to coal dust and prevalence of pneumoconiosis in underground mining in three Colombian departments / Evaluación de la exposición al polvo de carbón y de sílice en sitios de minería subterránea en tres departamentos de Colombia

Introduction: Coal workers' pneumoconiosis is a chronic and irreversible disease representing a public health problem. Objective: To estimate the prevalence of pneumoconiosis and its associated factors among underground coal miners in the Colombian departments of Boyacá, Cundinamarca and Norte de Santander. Materials and methods: We conducted a cross-sectional study of 476 miners to measure the prevalence of pneumoconiosis and its associated factors such as coal dust and silica levels, as well as the occupational conditions. The medical assessment and a chest x-ray were performed according to the International Labor Organization criteria, along with spirometry and the identification of glutathione S-transferase and repair enzyme polymorphisms.The associations were explored using Cox regression models. Results: We performed a total of 479 environmental monitoring sessions in 31 companies and we evaluated 476 workers with 10 to 57 years of mining work experience. The prevalence of pneumoconiosis was 33.8% (95% CI: 27.0 - 41.3%). In the Cox multivariate regression model with a constant risk time, pneumoconiosis was significantly associated with working in medium-sized companies (PR=2.00, 95% CI: 0.995 - 2.690; p=0.052), the level of severe exposure to coal dust (PR=2.055, 95% CI: 1.043 - 4.048; p=0.038), and working in underground mining for 25 years or more (for those with 25.0-29.9 years: PR=2.199, 95% CI: 1.449 - 3.338; p=0.001). Conclusions: The prevalence of pneumoconiosis was very high and was found to be associated with severe exposure to coal dust, work exposure for 25 years or more and working in medium-sized enterprises

Introducción. La neumoconiosis de mineros del carbón es una enfermedad crónica e irreversible que se considera un problema de salud pública. Objetivo. Estimar la prevalencia de neumoconiosis y sus factores asociados en mineros de carbón de Boyacá, Cundinamarca y Norte de Santander. Materiales y métodos. Se hizo un estudio de corte transversal en 476 mineros. Se les hizo valoración médica, se tomaron radiografías de tórax siguiendo los criterios de la Organización Internacional del Trabajo, así como espirometrías, y se identificaron los polimorfismos de la glutatión S-transferasa y de las enzimas de reparación. Las asociaciones entre las condiciones ocupacionales y de la empresa con la neumoconiosis, se estudiaron usando modelos de regresión de Cox. Resultados. En 31 empresas se hicieron 479 monitorizaciones ambientales y se evaluaron 476 trabajadores cuyo tiempo de trabajo fluctuaba entre 10 y 57 años. La prevalencia de la neumoconiosis fue de 33,8 % (IC95% 27,0-41,3). En el modelo de regresión multivariado de Cox, con tiempo de riesgo constante para la neumoconiosis, esta se asoció significativamente con el trabajo en empresas medianas (razón de prevalencias, RP=2,00; IC95% 0,995- 2,690; p=0,052), con un nivel alto de exposición al polvo de carbón según el índice de exposición (RP=2,055; IC95% 1,043-4,048; p=0,038), y una antigüedad de 25 años o más (para 25,0 a 29,9 años: RP=2,199; IC95% 1,449-3,338; p=0,001). Conclusiones. La prevalencia de la neumoconiosis fue muy alta y se asoció a la exposición a altos niveles de polvo de carbón, a una exposición laboral mayor o igual a 25 años y al trabajo en empresas medianas.

Effect of diabetes status and hyperglycemia on global DNA methylation and hydroxymethylation.

Type 2 diabetes mellitus (T2DM) is characterized by oxidative stress that could lead to chronic micro- and macrovascular complications. We hypothesized that some of the target organ damage is mediated by oxidative alterations in epigenetic mechanisms involving DNA methylation (5mC) and DNA hydroxymethylation (5hmC). We analyzed global DNA methylation and hydroxymethylation in peripheral blood cells in well-controlled and poorly controlled patients with T2DM and compared them with healthy controls. We also analyzed microarrays of DNA methylation and gene expression of other important tissues in the context of diabetes from the GEO database repository and then compared these results with our experimental gene expression data. DNA methylation and, more importantly, DNA hydroxymethylation levels were increased in poorly controlled patients compared to well-controlled and healthy individuals. Both 5mC and 5hmC measurements were correlated with the percentage of glycated hemoglobin, indicating a direct impact of hyperglycemia on changes over the epigenome. The analysis of methylation microarrays was concordant, and 5mC levels were increased in the peripheral blood of T2DM patients. However, the DNA methylation levels were the opposite of those in other tissues, such as the pancreas, adipose tissue and skeletal muscle. We hypothesize that a process of DNA oxidation associated with hyperglycemia may explain the DNA demethylation in which the activity of ten-eleven translocation (TET) proteins is not sufficient to complete the process. High levels of glucose lead to cellular oxidation, which triggers the process of DNA demethylation aided by TET enzymes, resulting in epigenetic dysregulation of the damaged tissues.

Oxidative stress and repetitive element methylation changes in artisanal gold miners occupationally exposed to mercury.

Mercury (Hg) exposure is a public health concern due to its persistence in the environment and its high toxicity. Such toxicity has been associated with the generation of oxidative stress in occupationally exposed subjects, such as artisanal gold miners. In this study, we characterize occupational exposure to Hg by measuring blood, urine and hair levels, and investigate oxidative stress and DNA methylation associated with gold mining. To do this, samples from 53 miners and 36 controls were assessed. We show higher levels of oxidative stress marker 8-OHdG in the miners. Differences in LINE1 and Alu(Yb8) DNA methylation between gold miners and control group are present in peripheral blood leukocytes. LINE1 methylation is positively correlated with 8-OHdG levels, while XRCC1 and LINE1 methylation are positively correlated with Hg levels. These results suggest an effect of Hg on oxidative stress and DNA methylation in gold miners that may have an impact on miners' health.

[Real-time quantification to analyze historical Colombian samples detecting a short fragment of hypervariable region II of mitochondrial DNA].

INTRODUCTION: Unlike other molecular biology studies, the analysis of ancient DNA (aDNA) requires special infrastructure and methodological conditions to guarantee the quality of the results. One of the main authenticity criteria is DNA quantification, where quantitative real-time PCR is often used given its sensitivity and specificity. Nevertheless, the implementation of these conditions and methodologies to fulfill authenticity criteria imply higher costs. Objective: To develop a simple and less costly method for mitochondrial DNA quantification suitable for highly degraded samples. Materials and methods: The proposed method is based on the use of mini-primers for the specific amplification of short fragments of mitochondrial DNA. The subsequent purification of these amplified fragments allows a standard curve to be constructed with concentrations in accordance to the state of degradation of the samples. Results: The proposed method successfully detected DNA from ancient samples including bone remains and mummified tissue. DNA inhibitory substances were also detected. Conclusion: The proposed method represents a simpler and cost-effective way to detect low amounts of aDNA, and a tool to differentiate DNA-free samples from samples with inhibitory substances.

Outlining the Ancestry Landscape of Colombian Admixed Populations.

The ancestry of the Colombian population comprises a large number of well differentiated Native communities belonging to diverse linguistic groups. In the late fifteenth century, a process of admixture was initiated with the arrival of the Europeans, and several years later, Africans also became part of the Colombian population. Therefore, the genepool of the current Colombian population results from the admixture of Native Americans, Europeans and Africans. This admixture occurred differently in each region of the country, producing a clearly stratified population. Considering the importance of population substructure in both clinical and forensic genetics, we sought to investigate and compare patterns of genetic ancestry in Colombia by studying samples from Native and non-Native populations living in its 5 continental regions: the Andes, Caribe, Amazonia, Orinoquía, and Pacific regions. For this purpose, 46 AIM-Indels were genotyped in 761 non-related individuals from current populations. Previously published genotype data from 214 Colombian Natives from five communities were used for population comparisons. Significant differences were observed between Native and non-Native populations, among non-Native populations from different regions and among Native populations from different ethnic groups. The Pacific was the region with the highest African ancestry, Amazonia harboured the highest Native ancestry and the Andean and Orinoquían regions showed the highest proportion of European ancestry. The Andean region was further sub-divided into 6 sub-regions: North East, Central West, Central East, West, South West and South East. Among these regions, the South West region showed a significantly lower European admixture than the other regions. Hardy-Weinberg equilibrium and variance values of ancestry among individuals within populations showed a potential stratification of the Pacific population.

Determinantes sociales de la intoxicación por plaguicidas entre cultivadores de arroz en Colombia / Determining social factors related to pesticide poisoning among rice farmers in Colombia

Objetivo Caracterizar la forma en que los agricultores se exponen a los plaguicidas y se presenta la intoxicación. Materiales y Métodos Estudio multi-métodos y multinivel (individuo y comunidad), que incluyó métodos etnográficos, encuesta y medición de plaguicidas en agua y muestras humanas. Resultados Se describió el proceso productivo y se conocieron los principales factores de riesgo. Los plaguicidas son considerados el mayor peligro en el trabajo y en sus viviendas. Los trabajadores tienen precarias condiciones laborales y no están protegidos por el sistema de riesgos laborales. En las muestras de agua se encontraron azinfos-metil, endosulfán, b-BHC, bromofos-metil, bromofos-etil y 2,4-DDT. En la encuesta participaron 381 trabajadores de los cuales 12,9, 68 y 5,5 % tuvieron intoxicaciones leves, moderadas y severas, respectivamente. Los casos severos tenían menores niveles de escolaridad, menor nivel de afiliación al régimen contributivo del sistema de seguridad social y un mayor número tenía enfermedad cardiovascular, diabetes, herpes u otras infecciones virales. Conclusión Existen precarias condiciones laborales que favorecen la exposición a plaguicidas caracterizadas por la exclusión del sistema de riesgos laborales, pobreza y baja educación. Es urgente la inclusión de estos trabajadores al sistema de riesgos laborales y la mejora de las condiciones de vida. De esa manera se podrán disminuir las prácticas inseguras en el manejo de plaguicidas.(AU)

Objective Large quantities of pesticides are used in rice crops. The aim of this study is to characterize how farmers are exposed to pesticides and subsequent poisoning. Materials and Methods A multilevel (individual and community) multi-method study, which included ethnographic and survey methods, as well as measurement of pesticides in water and human samples, was performed. Results The production process is described and the main risk factors are presented. Pesticides are considered the greatest danger at work and at their homes. Workers have poor working conditions and are not protected by the system of occupational risks. Azinphos-methyl, endosulfan, β-BHC, bromophos-methyl, bromophos-ethyl and 2,4- DDT were found in water samples. The survey included 381 workers with mild (12.86 %), moderate (67.98 %) and severe (5.51 %) poisonings respectively. Severe cases presented lower levels of education, lower levels of health care access to the contributory regimen of the Colombian social security system and higher incidence of cardiovascular disease, diabetes, herpes or other viral infections. Conclusion There are precarious working conditions that favor exposure to pesticides correlated to the exclusion of farmers from the occupational risk system, to poverty and to poor education. It is urgent to include these workers to the system of occupational risk system and to improve their living conditions, thus reducing unsafe practices when handling pesticides.(AU)

Frog skin cultures secrete anti-yellow fever compounds.

There is an urgent need to develop novel antimicrobial substances. Antimicrobial peptides (AMPs) are considered as promising candidates for future therapeutic use. Because of the re-emergence of the Flavivirus infection, and particularly the yellow fever virus (YFV), we have compared the antiviral activities from skin secretions of seven different frog species against YFV (strain 17D). Secretions from Sphaenorhynchus lacteus, Cryptobatrachus boulongeri and Leptodactylus fuscus displayed the more powerful activities. S. lacteus was found to inhibit viral lysis of Vero E6 cells even at the highest viral concentration evaluated of 10 LD50. We also report the identification of a novel frenatin-related peptide from S. lacteus and found that this peptide-on its own-can lead to 35% protection against YVF, while displaying no cytotoxicity against somatic cells even at fivefold higher concentrations. These results are attractive and support the need for continued exploration of new sources of AMPs from frog skin secretions such as those described here in the development of new compounds for the treatment of infectious diseases in general and specific viral infections in particular.

[Determining social factors related to pesticide poisoning among rice farmers in Colombia]. / Determinantes sociales de la intoxicación por plaguicidas entre cultivadores de arroz en Colombia.

Objective Large quantities of pesticides are used in rice crops. The aim of this study is to characterize how farmers are exposed to pesticides and subsequent poisoning. Materials and Methods A multilevel (individual and community) multi-method study, which included ethnographic and survey methods, as well as measurement of pesticides in water and human samples, was performed. Results The production process is described and the main risk factors are presented. Pesticides are considered the greatest danger at work and at their homes. Workers have poor working conditions and are not protected by the system of occupational risks. Azinphos-methyl, endosulfan, ß-BHC, bromophos-methyl, bromophos-ethyl and 2,4- DDT were found in water samples. The survey included 381 workers with mild (12.86 %), moderate (67.98 %) and severe (5.51 %) poisonings respectively. Severe cases presented lower levels of education, lower levels of health care access to the contributory regimen of the Colombian social security system and higher incidence of cardiovascular disease, diabetes, herpes or other viral infections. Conclusion There are precarious working conditions that favor exposure to pesticides correlated to the exclusion of farmers from the occupational risk system, to poverty and to poor education. It is urgent to include these workers to the system of occupational risk system and to improve their living conditions, thus reducing unsafe practices when handling pesticides.

Sexual Dysfunctions in Men and Women with Inflammatory Bowel Disease: The Influence of IBD-Related Clinical Factors and Depression on Sexual Function.

INTRODUCTION: Inflammatory bowel disease (IBD) is likely to have an impact on sexual function because of its symptoms, like diarrhea, fatigue, and abdominal pain. Depression is commonly reported in IBD and is also related to impaired sexual function. This study aimed to evaluate sexual function and its association with depression among patients with IBD compared with controls. METHODS: IBD patients registered at two hospitals participated. The control group consisted of a general practitioner practice population. The web-based questionnaire included the Female Sexual Function Index (FSFI) for women and the International Index of Erectile Function (IIEF) for men. Other variables evaluated were depression, disease activity, IBD-related quality of life, body image, and fatigue. RESULTS: In total, 168 female and 119 male patients were available for analysis (response rate 24%). Overall, patients with IBD did not significantly differ in prevalence of sexual dysfunctions from controls: female patients 52%, female controls 44%, male patients and male controls both 25%. However, men and women with an active disease scored significantly lower than patients in remission and controls, indicating impaired sexual functioning during disease activity. Significant associations were found between active disease, fatigue, depressive mood, quality of life, and sexual function for both male and female patients. The association between disease activity and sexual function was totally mediated by depression. CONCLUSION: Male and female IBD patients with an active disease show impaired sexual function relative to patients in remission and controls. Depression is the most important determinant for impaired sexual function in IBD.

The combined expression patterns of Ikaros isoforms characterize different hematological tumor subtypes.

A variety of genetic alterations are considered hallmarks of cancer development and progression. The Ikaros gene family, encoding for key transcription factors in hematopoietic development, provides several examples as genetic defects in these genes are associated with the development of different types of leukemia. However, the complex patterns of expression of isoforms in Ikaros family genes has prevented their use as clinical markers. In this study, we propose the use of the expression profiles of the Ikaros isoforms to classify various hematological tumor diseases. We have standardized a quantitative PCR protocol to estimate the expression levels of the Ikaros gene exons. Our analysis reveals that these levels are associated with specific types of leukemia and we have found differences in the levels of expression relative to five interexonic Ikaros regions for all diseases studied. In conclusion, our method has allowed us to precisely discriminate between B-ALL, CLL and MM cases. Differences between the groups of lymphoid and myeloid pathologies were also identified in the same way.