Environmental Epigenetic Changes, as Risk Factors for the Development of Diseases in Children: A Systematic Review

Background: Children are susceptible to environmental contaminants and are at risk of developing diseases, more so if the exposure begins at an early age. Epidemiological studies have postulated the hypothesis of the fetal origin of disease, which is mediated by epigenetic changes. Epigenetic marks are inheritable; they modulate the gene expression and can affect human health due to the presence of environmental factors. Objective: This review focuses on DNA-methylation and its association with environmental-related diseases in children. Methods: A search for studies related to DNA-methylation in children by pre- or post-natal environmental exposures was conducted, and those studies with appropriate designs and statistical analyses and evaluations of the exposure were selected. Findings: Prenatal and early life environmental factors, from diet to exposure to pollutants, have been associated with epigenetic changes, specifically DNA-methylation. Thus, maternal nutrition and smoking and exposure to air particulate matter, polycyclic aromatic hydrocarbons, arsenic, heavy metals, persistent organic pollutants, and some endocrine disrupters during pregnancy have been associated with genomic and gene-specific newborns’ DNA-methylation changes that have shown in some cases sex-specific patterns. In addition, these maternal factors may deregulate the placental DNA-methylation balance and could induce a fetal reprogramming and later-in-life diseases. Conclusions: Exposure to environmental pollutants during prenatal and early life can trigger epigenetic imbalances and eventually the development of diseases in children. The integration of epigenetic data should be considered in future risk assessments

As "Ómicas" como ferramenta no estudo da Saúde Ambiental

Deaths caused by environmental pollution are agrowing public health issue. Most of the premature deaths related to pollution are caused by non communicable diseases such as chronic obstructive pulmonary disease, type-2 diabetes, cardiovascular disease and cancer. They are considered complex diseases because of their multicausality and the various mechanisms involved in their emergence and evolution.Knowledge of disease-causing mechanismsis increasing and the identification of disease-associated biomarkers improving thanks to technological progress, in particular that of the technologiesthat are applied to the measurement and interpretation of molecular components—the so-called “Omics” technologies. These technologies have allowed the cellular causes of some complex diseases to be identified: genetic variants of susceptibility or protection to pollutants (Genomics), as well as changes in the DNA (Epigenomics) and their effects on the process of transcription of specific genes for repair, on metabolism or on the non-coding RNA associated with diseases (Transcriptomics). In addition, Proteomics and Metabolomics do not cease to provide information on proteins and metabolites involved in disease processes. Bioinformatics has evolved parallel to the development of omics, which has allowed the results of the measurements of hundreds of molecules to be interpreted and organized into networks that show the relationships among them.Omics are mainly used to develop disease risk models based on population studies, but information on genomes, transcriptomes, epigenomes, microbiomes, proteomes and metabolomesis also used to decipher diseases in order to facilitate prognosis and guide patient treatment, thus contributing to personalized, precision medicine. However, their clinical application is still limited by their cost and their technical, regulatory and ethical implications.Las muertes provocadas por la contaminación ambiental son un problema de salud pública en incremento. La mayoría de las muertes prematuras provocadas por la contaminación son enfermedades no transmisibles, como enfermedad pulmonar obstructiva crónica, diabetes tipo 2, enfermedades cardiovasculares y cáncer. Estas son consideradas enfermedades complejas por su multicausalidad y los diversos mecanismos involucrados en su aparición y evolución. El conocimiento del mecanismo de producción de la enfermedad, y la identificación de biomarcadores asociados a enfermedad está avanzando gracias al avance de la tecnología, y específicamente de la tecnología aplicada a medición e interpretación de componentes moleculares: las tecnologías “ÓMICAS”. Estas han permitido identificar causas celulares de algunas enfermedades complejas: variantes genéticas de susceptibilidad o protección a agentes contaminantes (Genómica), así como cambios sobre el ADN (Epigenómica) y sus efectos en el proceso de transcripción de genes específicos de reparación, metabolismo o bien RNA no codificante asociado a enfermedades (Transcriptómica); además la Proteómica y la Metabolómica aportan constante información sobre las proteínas y metabolitos involucrados en los procesos de enfermedad. Paralelo al desarrollo de las tecnologías ómicas ha evolucionado la bioinformática, que ha permitido la interpretación de los resultados de mediciones de cientos de moléculas para organizarlos en redes que traducen las relaciones entre ellas. Las tecnologías ómicas se aplican principalmente para determinar modelos de riesgo de enfermedad en base a estudios poblacionales, pero también la información del genoma, transcriptoma, el epigenoma, el microbioma, el proteoma y el metaboloma se utilizarán para ayudar a descifrar la enfermedad a fin de facilitar el pronóstico y guiar el tratamiento de pacientes, ayudando a la medicina individualizada y medicina de precisión. Sin embargo, su aplicación clínica está aún limitada por el costo y las implicaciones técnicas, regulatorias y éticas.As mortes causadas pela poluição ambiental sãoum problema de saúde pública crescente. A maioria das mortes prematuras causadas por contaminação sãodoençasnãotransmissíveis, como doença pulmonar obstrutiva crónica, diabetes tipo 2, doenças cardiovasculares e cancro. Estas são consideradas doenças complexas pela sua multicausalidade e pelos vários mecanismos envolvidos no seu aparecimento e evolução. O conhecimento do mecanismo de produção da doença e a identificação de biomarcadores associados à doençaestá a avançar graçasao desenvolvimento da tecnologia e, especificamente, à tecnologia aplicada à medição e interpretação de componentes moleculares: as tecnologias “ÓMICAS”. Estas permitiram identificar as causas celulares de algumasdoenças complexas: variantes genéticas de suscetibilidade ouproteção a agentes contaminantes (Genómica), bem como alterações no DNA (Epigenética) e os seusefeitos no processo de transcrição de genes específicos de reparação, metabolismo ou RNAnão-codificanteassociado a doenças (Transcriptómica);acresce a Proteómica e a Metabolómica que fornecem informação sobre as proteínas e metabólitosenvolvidos nos processos de doença. Paralelamente ao desenvolvimento das novas técnicas biotecnológicas, geralmente denominadas por “Ómicas”, evoluiu a bioinformática, o que permitiu a interpretação dos resultados das análises de centenas de moléculas para organizá-las em redes que traduzem as relações entre elas. As tecnologias “Ómicas” aplicam-se principalmente para determinar modelos de risco de doença com base em estudos populacionais, mas igualmente a informação do genoma, do transcriptoma, do epigenoma, do microbioma, do proteoma e do metaboloma será usada para ajudar a decifrar a doença, a fim de facilitar o prognóstico e orientar o tratamento dos pacientes, auxiliado a medicina individualizada e a medicina de precisão. No entanto, a sua aplicação clínica ainda é limitada pelo custo e implicações técnicas, regulamentares e éticas

Omics as Environmental Health study tools

Deaths caused by environmental pollution are agrowing public health issue. Most of the premature deaths related to pollution are caused by non communicable diseases such as chronic obstructive pulmonary disease, type-2 diabetes, cardiovascular disease and cancer. They are considered complex diseases because of their multicausality and the various mechanisms involved in their emergence and evolution.Knowledge of disease-causing mechanismsis increasing and the identification of disease-associated biomarkers improving thanks to technological progress, in particular that of the technologiesthat are applied to the measurement and interpretation of molecular components—the so-called “Omics” technologies. These technologies have allowed the cellular causes of some complex diseases to be identified: genetic variants of susceptibility or protection to pollutants (Genomics), as well as changes in the DNA (Epigenomics) and their effects on the process of transcription of specific genes for repair, on metabolism or on the non-coding RNA associated with diseases (Transcriptomics). In addition, Proteomics and Metabolomics do not cease to provide information on proteins and metabolites involved in disease processes. Bioinformatics has evolved parallel to the development of omics, which has allowed the results of the measurements of hundreds of molecules to be interpreted and organized into networks that show the relationships among them.Omics are mainly used to develop disease risk models based on population studies, but information on genomes, transcriptomes, epigenomes, microbiomes, proteomes and metabolomesis also used to decipher diseases in order to facilitate prognosis and guide patient treatment, thus contributing to personalized, precision medicine. However, their clinical application is still limited by their cost and their technical, regulatory and ethical implications.</p

A hypoperfusion context may aid to interpret hyperlactatemia in sepsis-3 septic shock patients: a proof-of-concept study

__Background:__ Persistent hyperlactatemia is particularly difficult to interpret in septic shock. Besides hypoperfusion, adrenergic-driven lactate production and impaired lactate clearance are important contributors. However, clinical recognition of different sources of hyperlactatemia is unfortunately not a common practice and patients are treated with the same strategy despite the risk of over-resuscitation in some. Indeed, pursuing additional resuscitation in non-hypoperfusion-related cases might lead to the toxicity of fluid overload and vasoactive drugs. We hypothesized that two different clinical patterns can be recognized in septic shock patients through a multimodal perfusion monitoring. Hyperlactatemic patients with a hypoperfusion context probably represent a more severe acute circulatory dysfunction, and the absence of a hypoperfusion context is eventually associated with a good outcome. We performed a retrospective analysis of a database of septic shock patients with persistent hyperlactatemia after initial resuscitation. __Results:__ We defined hypoperfusion context by the presence of a ScvO2 < 70%, or a P(cv-a)CO2 ≥6 mmHg, or a CRT ≥4 s together with hyperlactatemia. Ninety patients were included, of whom seventy exhibited a hypoperfusion-related pattern and 20 did not. Although lactate values were comparable at baseline (4.8 ± 2.8 vs. 4.7 ± 3.7 mmol/L), patients with a hypoperfusion context exhibited a more severe circulatory dysfunction with higher vasopressor requirements, and a trend to longer mechanical ventilation days, ICU stay, and more rescue therapies. Only one of the 20 hyperlactatemic patients without a hypoperfusion context died (5%) compared to 11 of the 70 with hypoperfusion-related hyperlactatemia (16%). __Conclusions:__ Two different clinical patterns among hyperlactatemic septic shock patients may be identified according to hypoperfusion context. Patients with hyperlactatemia plus low ScvO2, or high P(cv-a)CO2, or high CRT values exhibited a more severe circulatory dysfunction. This provides a starting point to launch further prospective studies to confirm if this approach can lead to a more selective resuscitation strategy

Ruxolitinib in refractory acute and chronic graft-versus-host disease : a multicenter survey study

Graft-versus-host disease is the main cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. First-line treatment is based on the use of high doses of corticosteroids. Unfortunately, second-line treatment for both acute and chronic graft-versus-host disease, remains a challenge. Ruxolitinib has been shown as an effective and safe treatment option for these patients. Seventy-nine patients received ruxolitinib and were evaluated in this retrospective and multicenter study. Twenty-three patients received ruxolitinib for refractory acute graft-versus-host disease after a median of 3 (range 1-5) previous lines of therapy. Overall response rate was 69.5% (16/23) which was obtained after a median of 2 weeks of treatment, and 21.7% (5/23) reached complete remission. Fifty-six patients were evaluated for refractory chronic graft-versus-host disease. The median number of previous lines of therapy was 3 (range 1-10). Overall response rate was 57.1% (32/56) with 3.5% (2/56) obtaining complete remission after a median of 4 weeks. Tapering of corticosteroids was possible in both acute (17/23, 73%) and chronic graft-versus-host disease (32/56, 57.1%) groups. Overall survival was 47% (CI: 23-67%) at 6 months for patients with aGVHD (62 vs 28% in responders vs non-responders) and 81% (CI: 63-89%) at 1 year for patients with cGVHD (83 vs 76% in responders vs non-responders). Ruxolitinib in the real life setting is an effective and safe treatment option for GVHD, with an ORR of 69.5% and 57.1% for refractory acute and chronic graft-versus-host disease, respectively, in heavily pretreated patients

Association of Dietary Advanced Glycation End Products with Metabolic Syndrome in Young Mexican Adults

Background: Consumption of dietary advanced glycation end products is linked to metabolic syndrome. The objective was to describe the association between dietary advanced glycation end products intake and metabolic syndrome in young Mexican adults. Methods: The present was a cross-sectional study in 126 Mexican adults 18&#8315;35 years old evaluating metabolic syndrome through the harmonized criteria. Macronutrients and dietary advanced glycation end products intake were estimated through three 24-hour dietary recalls and food composition tables. Association between metabolic syndrome and high advanced glycation end products intake (&#8805;10,000 kU/day) was evaluated through three logistic regression models adjusted by sex, age, family history of cardiometabolic diseases and energy intake. Results: Subjects with a higher advanced glycation end products intake were more likely to have impaired fasting glucose (OR: 4.91, 95% CI 1.29&#8315;18.60, p &lt; 0.05) and metabolic syndrome (OR: 2.67, 95% CI 0.96&#8315;7.44, p = 0.059) than those participants with low consumption of these products after adjustment of sex, age, family history of cardiovascular disease and energy intake. Conclusions: High intake of dietary advanced glycation end products was significantly associated with impaired fasting glucose and marginally with metabolic syndrome in young Mexican adults regardless of sex, age, family history of cardiovascular disease and energy intake

Ruxolitinib in refractory acute and chronic graft-versus-host disease: a multicenter survey study.

Graft-versus-host disease is the main cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. First-line treatment is based on the use of high doses of corticosteroids. Unfortunately, second-line treatment for both acute and chronic graft-versus-host disease, remains a challenge. Ruxolitinib has been shown as an effective and safe treatment option for these patients. Seventy-nine patients received ruxolitinib and were evaluated in this retrospective and multicenter study. Twenty-three patients received ruxolitinib for refractory acute graft-versus-host disease after a median of 3 (range 1-5) previous lines of therapy. Overall response rate was 69.5% (16/23) which was obtained after a median of 2 weeks of treatment, and 21.7% (5/23) reached complete remission. Fifty-six patients were evaluated for refractory chronic graft-versus-host disease. The median number of previous lines of therapy was 3 (range 1-10). Overall response rate was 57.1% (32/56) with 3.5% (2/56) obtaining complete remission after a median of 4 weeks. Tapering of corticosteroids was possible in both acute (17/23, 73%) and chronic graft-versus-host disease (32/56, 57.1%) groups. Overall survival was 47% (CI: 23-67%) at 6 months for patients with aGVHD (62 vs 28% in responders vs non-responders) and 81% (CI: 63-89%) at 1 year for patients with cGVHD (83 vs 76% in responders vs non-responders). Ruxolitinib in the real life setting is an effective and safe treatment option for GVHD, with an ORR of 69.5% and 57.1% for refractory acute and chronic graft-versus-host disease, respectively, in heavily pretreated patients

Revista Temas Agrarios Volumen 26; Suplemento 1 de 2021

1st International and 2nd National Symposium of Agronomic Sciences: The rebirth of the scientific discussion space for the Colombian Agro.1 Simposio Intenacional y 2 Nacional de Ciencias Agronómicas: El renacer del espacio de discusión científica para el Agro colombiano