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Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants produced through the combustion of organic matter, with sources ranging from traffic pollution to diet. Although PAH exposure has been associated with adverse health effects, few studies have examined its impact on neurodevelopmental delay (NDD). Thus, our study aims to investigate the effect of prenatal PAH exposure on the odds of NDD. We measured 7 hydroxylated PAH metabolites in spot urine samples collected up to three times during pregnancy in the PROTECT birth cohort. NDD was identified using score cutoffs from the Ages and Stages Questionnaire, 3rd edition offered in Spanish, across five domains at 12, 24, 36, and 48 months. We utilized logistic regression and mixed effects logistic regression models to assess associations between prenatal PAH concentrations and NDD. Our results showed mostly lower odds of NDD with higher PAH exposure (p < 0.05). However, male children showed higher odds of NDD in relation to PAH exposure, particularly in the Fine Motor domain. For example, 1-hydroxypyrene was associated with 1.11 (1.01, 1.23) times odds of delay in fine motor function in male children versus 0.91 (0.82, 1.00) times odds in female children. Our preliminary sex-specific results suggest that PAH exposure may impact neurodevelopment in male children and prompt further investigation into the potential sex-specific mechanisms of PAHs on motor function.
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Contaminantes Ambientales , Hidrocarburos Policíclicos Aromáticos , Efectos Tardíos de la Exposición Prenatal , Humanos , Hidrocarburos Policíclicos Aromáticos/toxicidad , Hidrocarburos Policíclicos Aromáticos/orina , Femenino , Embarazo , Masculino , Contaminantes Ambientales/orina , Puerto Rico , Preescolar , Exposición Materna/estadística & datos numéricos , Lactante , Trastornos del Neurodesarrollo/epidemiología , Trastornos del Neurodesarrollo/inducido químicamente , Desarrollo Infantil/efectos de los fármacos , Exposición a Riesgos Ambientales/estadística & datos numéricos , AdultoRESUMEN
The aim of this study was to investigate the vertical transfer of microbiota from dams to the offspring. We studied a pair of 20 dams and its offspring. Maternal sources (colostrum, feces and vaginal secretion) and newborn fecal samples were analyzed using 16S rDNA amplicon sequencing on days 1, 3, 7, 14 and 28. Overall, newborns were maintained healthy and did not receive antimicrobial therapy. The Source Tracker analysis indicated that the newborn fecal microbiota was similar to colostrum and vaginal secretion from day 1 up to 7. However, an unknown source (probably from the environment) showed a gradual increase in its similarity with fecal samples from calves measured from day 3 to 28. The most abundant bacteria groups on meconium (day 1) and calf fecal samples on day 3 were Escherichia-Shigella and Clostridium, respectively. On day 7, the predominant genus were Bifidobacterium and Lactobacillus, while Fusobacterium was the most abundant genus on day 14, coinciding with the diarrhea peak. Faecalibacterium showed a gradual increase throughout the neonatal period. Maternal sources contribute to the neonatal microbiota, however other unknown sources (probably environment) had a strong influence on development of the gut microbiota later in the neonate period.
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Animales Recién Nacidos , Calostro , Heces , Microbioma Gastrointestinal , Animales , Microbioma Gastrointestinal/genética , Bovinos , Femenino , Heces/microbiología , Calostro/microbiología , ARN Ribosómico 16S/genética , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Embarazo , Vagina/microbiología , Meconio/microbiologíaRESUMEN
The developmental origins of healthy and disease (DOHaD) concept has demonstrated a higher rate of chronic diseases in the adult population of individuals whose mothers experienced severe maternal protein restriction (MPR). Using proteomic and in silico analyses, we investigated the lung proteomic profile of young and aged rats exposed to MPR during pregnancy and lactation. Our results demonstrated that MPR lead to structural and immune system pathways changes, and this outcome is coupled with a rise in the PI3k-AKT-mTOR signaling pathway, with increased MMP-2 activity, and CD8 expression in the early life, with long-term effects with aging. This led to the identification of commonly or inversely differentially expressed targets in early life and aging, revealing dysregulated pathways related to the immune system, stress, muscle contraction, tight junctions, and hemostasis. We identified three miRNAs (miR-378a-3p, miR-378a-5p, let-7a-5p) that regulate four proteins (ACTN4, PPIA, HSPA5, CALM1) as probable epigenetic lung marks generated by MPR. In conclusion, MPR impacts the lungs early in life, increasing the possibility of long-lasting negative outcomes for respiratory disorders in the offspring.
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Pulmón , MicroARNs , Proteómica , Animales , Femenino , Pulmón/metabolismo , Masculino , Proteómica/métodos , Embarazo , MicroARNs/genética , MicroARNs/metabolismo , Ratas , Efectos Tardíos de la Exposición Prenatal/metabolismo , Efectos Tardíos de la Exposición Prenatal/genética , Dieta con Restricción de Proteínas , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/genética , Longevidad/genética , Ratas Wistar , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteoma/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Envejecimiento/metabolismo , Envejecimiento/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 2 de la Matriz/genéticaRESUMEN
Rotavirus infection continues to be a significant public health problem in developing countries, despite the availability of several vaccines. The efficacy of oral rotavirus vaccines in young children may be affected by significant immunological differences between individuals in early life and adults. Therefore, understanding the dynamics of early-life systemic and mucosal immune responses and the factors that affect them is essential to improve the current rotavirus vaccines and develop the next generation of mucosal vaccines. This review focuses on the advances in T-cell development during early life in mice and humans, discussing how immune homeostasis and response to pathogens is established in this period compared to adults. Finally, the review explores how this knowledge of early-life T-cell immunity could be utilized to enhance current and novel rotavirus vaccines.
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Infecciones por Rotavirus , Vacunas contra Rotavirus , Rotavirus , Linfocitos T , Vacunas contra Rotavirus/inmunología , Vacunas contra Rotavirus/administración & dosificación , Humanos , Infecciones por Rotavirus/prevención & control , Infecciones por Rotavirus/inmunología , Animales , Rotavirus/inmunología , Linfocitos T/inmunología , Administración Oral , Inmunidad Mucosa , RatonesRESUMEN
Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis represents one of the most consistent pathophysiological findings in depressive disorders. Cortisol signaling is affected by proteins that mediate its cellular responses or alters its availability to mineralocorticoid and glucocorticoid receptors. In our study, we evaluated candidate genes that may influence the risk for depression and suicide due to its involvement in cortisol signaling. The aim of the study was to assess whether the genotypes of these genes are associated with the risk for depression, severity of depressive symptoms, suicidal ideation, and suicide attempts. And whether there is interaction between genes and early-life stress. In this study, 100 healthy controls and 140 individuals with depression were included. The subjects were clinically assessed using the 21-item GRID-Hamilton questionnaires (GRID-HAMD-21), Beck Scale for Suicidal Ideation (BSI), and the Childhood Trauma Questionnaire (CTQ). A robust multifactorial dimensionality reduction analysis was used to characterize the interactions between the genes HSD11B1, NR3C1, NR3C2, and MDR1 and early-life stress. It was found a significant association of the heterozygous genotype of the MDR1 gene rs1128503 polymorphism with reduced risk of at least one suicide attempt (OR: 0.08, p = 0.003*) and a reduction in the number of suicide attempts (ß = -0.79, p = 0.006*). Furthermore, it was found that the MDR1 rs1228503 and NR3C2 rs2070951 genes interact with early-life stress resulting in a strong association with depression (p = 0.001). Our findings suggest that polymorphisms in the MDR1 and NR3C2 genes and their interaction with childhood trauma may be important biomarkers for depression and suicidal behaviors.
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Epistasis Genética , Hidrocortisona , Receptores de Glucocorticoides , Receptores de Mineralocorticoides , Ideación Suicida , Intento de Suicidio , Humanos , Femenino , Masculino , Adulto , Receptores de Glucocorticoides/genética , Hidrocortisona/metabolismo , Receptores de Mineralocorticoides/genética , Experiencias Adversas de la Infancia , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Depresión/genética , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Adulto Joven , Estrés Psicológico/genética , Predisposición Genética a la EnfermedadRESUMEN
Environmental influences before and during pregnancy significantly impact offspring development. This study investigates open research questions regarding the associations between maternal early life stress (ELS), prenatal psychosocial stress, prenatal hair cortisol (HC), and birth outcomes in Argentinian women. Data on ELS, prenatal life events, HC (two samples representing first and second half of pregnancy), and birth outcomes were collected from middle-class Argentinian women (N = 69) upon delivery. Linear mixed models indicated that HC increased from the first half to the second half of pregnancy with considerable variability in the starting values and slopes between individuals. Mothers who experienced more ELS, were taller, or more educated, tended to show lower increases in HC. Older age was positively related to HC increases. Our data did not suggest an interaction between ELS and prenatal life events in relation to HC. We found that the change in HC was most likely negatively associated with birth weight. Our data are most compatible with either a weak or the absence of an association between ELS or prenatal life events and absolute values of HC. Mothers with stronger increases in hair cortisol tended to have newborns with slightly lower birth weight. Hence, ELS and birthweight may either have been related to changes in cortisol exposure during pregnancy or to factors that influence accumulation or retention of cortisol in hair.
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Peso al Nacer , Cabello , Hidrocortisona , Efectos Tardíos de la Exposición Prenatal , Estrés Psicológico , Humanos , Femenino , Embarazo , Hidrocortisona/metabolismo , Hidrocortisona/análisis , Estrés Psicológico/metabolismo , Adulto , Cabello/química , Argentina , Peso al Nacer/fisiología , Recién Nacido , Resultado del Embarazo , Adulto Joven , MadresRESUMEN
Abstract Objectives To verify the association between early-life nutrition and chronic adult diseases. Data Sources Medline, Embase, Cochrane Database, and Lilacs. Summary of finds The Developmental Origins of Health and Disease (DOHaD) hypothesis postulates that a mismatch between early-life circumstances and later-life situations may have an impact on chronic diseases. In this review, the authors emphasize the research supporting the impact of early nutrition on the origins of adult height, obesity and metabolic syndrome, type 2 diabetes mellitus, cardiovascular diseases, and reproductive outcomes. Conclusion Even though this is a new topic and there are still many research questions to be answered, there is strong evidence that both deficiency and excess nutrition in early life can cause epigenetic changes that have effects that last a lifetime and contribute to the development of chronic diseases. Public health efforts to protect adults from getting chronic diseases should focus on nutrition in the first 1000 days of life, from conception to the end of the second year of life.
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RESULTS: Hispanic children have higher odds of growth stunting than non-Hispanic White children. Native American children die younger and have higher odds of respiratory diseases and porous lesions than Hispanic and non-Hispanic Whites. Rural/urban location does not significantly impact age at death, but housing type does. Individuals who lived in trailers/mobile homes had earlier ages at death. When intersections between housing type and housing location are considered, children who were poor and from impoverished areas lived longer than those who were poor from relatively well-off areas. CONCLUSIONS: Children's health is shaped by factors outside their control. The children included in this study embodied experiences of social and ELS and did not survive to adulthood. They provide the most sobering example of the harm that social factors (structural racism/discrimination, socioeconomic, and political structures) can inflict.
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Mortalidad del Niño , Estado de Salud , Determinantes Sociales de la Salud , Factores Socioeconómicos , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Autopsia , Hispánicos o Latinos , Vivienda , México/epidemiología , BlancoRESUMEN
Brain disturbances during development can have a lasting impact on neural function and behavior. Seizures during this critical period are linked to significant long-term consequences such as neurodevelopmental disorders, cognitive impairments, and psychiatric symptoms, resulting in a complex spectrum of multimorbidity. The hippocampus-prefrontal cortex (HPC-PFC) circuit emerges as a potential common link between such disorders. However, the mechanisms underlying these outcomes and how they relate to specific behavioral alterations are unclear. We hypothesized that specific dysfunctions of hippocampal-cortical communication due to early-life seizure would be associated with distinct behavioral alterations observed in adulthood. Here, we performed a multilevel study to investigate behavioral, electrophysiological, histopathological, and neurochemical long-term consequences of early-life Status epilepticus in male rats. We show that adult animals submitted to early-life seizure (ELS) present working memory impairments and sensorimotor disturbances, such as hyperlocomotion, poor sensorimotor gating, and sensitivity to psychostimulants despite not exhibiting neuronal loss. Surprisingly, cognitive deficits were linked to an aberrant increase in the HPC-PFC long-term potentiation (LTP) in a U-shaped manner, while sensorimotor alterations were associated with heightened neuroinflammation, as verified by glial fibrillary acidic protein (GFAP) expression, and altered dopamine neurotransmission. Furthermore, ELS rats displayed impaired HPC-PFC theta-gamma coordination and an abnormal brain state during active behavior resembling rapid eye movement (REM) sleep oscillatory dynamics. Our results point to impaired HPC-PFC functional connectivity as a possible pathophysiological mechanism by which ELS can cause cognitive deficits and psychiatric-like manifestations even without neuronal loss, bearing translational implications for understanding the spectrum of multidimensional developmental disorders linked to early-life seizures.
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Hipocampo , Convulsiones , Ratas , Animales , Masculino , Hipocampo/patología , Encéfalo , Corteza Prefrontal/fisiología , Memoria a Corto Plazo/fisiologíaRESUMEN
Evidence shows that the gut microbiome in early life is an essential modulator of physiological processes related to healthy brain development, as well as mental and neurodegenerative disorders. Here, we conduct a systematic review of gut microbiome assessments on infants (both healthy and with conditions that affect brain development) during the first thousand days of life, associated with neurodevelopmental outcomes, with the aim of investigating key microbiome players and mechanisms through which the gut microbiome affects the brain. Bacteroides and Bifidobacterium were associated with non-social fear behavior, duration of orientation, cognitive and motricity development, and neurotypical brain development. Lachnospiraceae, Streptococcus, and Faecalibacterium showed variable levels of influence on behavior and brain development. Few studies described mechanistic insights related to NAD salvage, aspartate and asparagine biosynthesis, methanogenesis, pathways involved in bile acid transformation, short-chain fatty acids production, and microbial virulence genes. Further studies associating species to gene pathways and robustness in data analysis and integration are required to elucidate the functional mechanisms underlying the role of microbiome-gut-brain axis in early brain development.
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BACKGROUND: Different types of stress inflicted in early stages of life elevate the risk, among adult animals and humans, to develop disturbed emotional-associated behaviors, such as hyperphagia or depression. Early-life stressed (ELS) adults present hyperactivity of the hypothalamus-pituitary-adrenal (HPA) axis, which is a risk factor associated with mood disorders. However, the prevalence of hyperphagia (17%) and depression (50%) is variable among adults that experienced ELS, suggesting that the nature, intensity, and chronicity of the stress determines the specific behavioral alteration that those individuals develop. METHODS: We analyzed corticosterone serum levels, Crh, GR, Crhr1 genes expression in the hypothalamic paraventricular nucleus, amygdala, and hippocampus due to their regulatory role on HPA axis in adult rats that experienced maternal separation (MS) or limited nesting material (LNM) stress; as well as the serotonergic system activity in the same regions given its association with the corticotropin-releasing hormone (CRH) pathway functioning and with the hyperphagia and depression development. RESULTS: Alterations in dams' maternal care provoked an unresponsive or hyper-responsive HPA axis function to an acute stress in MS and LNM adults, respectively. The differential changes in amygdala and hippocampal CRH system seemed compensating alterations to the hypothalamic desensitized glucocorticoids receptor (GR) in MS or hypersensitive in LNM. However, both adult animals developed hyperphagia and depression-like behavior when subjected to the forced-swimming test, which helps to understand that both hypo and hypercortisolemic patients present those disorders. CONCLUSION: Different ELS types induce neuroendocrine, brain CRH and 5-hydroxytriptamine (5-HT) systems' alterations that may interact converging to develop similar maladaptive behaviors.
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Hormona Liberadora de Corticotropina , Serotonina , Humanos , Ratas , Animales , Hormona Liberadora de Corticotropina/genética , Hormona Liberadora de Corticotropina/metabolismo , Serotonina/metabolismo , Sistema Hipotálamo-Hipofisario/metabolismo , Depresión/etiología , Privación Materna , Sistema Hipófiso-Suprarrenal/metabolismo , Encéfalo/metabolismo , Hiperfagia/metabolismo , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Estrés PsicológicoRESUMEN
The early development of the freshwater fish Rhytiodus microlepis is characterized by the description of external morphological, meristic, and morphometric changes, as well as the growth patterns, thereby establishing a reference for the identification of its larvae and juveniles. Specimens were collected from the Amazon river channel and floodplain. Ninety-seven individuals were analysed with standard length varying between 4.31 and 79.23 mm. Rhytiodus microlepis larvae are altricial, with an elongated and fusiform body, anal opening reaching the middle region of the body, and simple nostrils becoming double and tubular during development. The pigments vary from one to two chromatophores in the dorsal region of the head in pre-flexion and flexion, but later the pigmentation pattern intensifies, transverse bands appear along the body, and a conspicuous spot appears in the basal region of the caudal fin. The total number of myomeres ranges from 49 to 50. During the transition from larval (post-flexion) to the juvenile periods, the most significant anatomical changes occur, such as the presence of all fins and increased body pigmentation. Integrated myomere count and pigmentation pattern are effective for the correct identification of the initial life stages of R. microlepis from the Amazon basin. Our results expand the knowledge about the early life history of Neotropical freshwater fish species.
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Characiformes , Larva , Pigmentación , Ríos , Animales , Characiformes/crecimiento & desarrollo , Characiformes/anatomía & histología , Brasil , Larva/crecimiento & desarrollo , Larva/anatomía & histología , Agua Dulce , Aletas de Animales/anatomía & histología , Aletas de Animales/crecimiento & desarrolloRESUMEN
Early life stress (ELS), characterized as abuse, neglect, and abandonment, can cause several adverse consequences in the lives of affected individuals. ELS experiences can affect an individual's development in variable ways, persisting in the long term and promoting lasting impacts, considering that early exposure to stressors can be biologically incorporated, as prolonged stimulation of stress response systems affects the development of the brain structure and other body systems, increasing the risk of diseases associated with stress and cognitive impairment. This type of stress increases the risk of developing major depressive disorder (MDD) in a severe form that does not respond adequately to traditional antidepressant treatments. Several alterations are studied as mechanisms that relate ELS with MDD, such as epigenetic alterations, neurotransmitters, and neuronal signaling. This review discusses research that brings evidence about the ELS mechanisms involved in synaptic impairments and MDD. The processes involved in epigenetic changes and the HPA axis are highlighted, as well as changes in neurotransmitters and neuronal signaling mechanisms.
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Trastorno Depresivo Mayor , Estrés Psicológico , Sinapsis , Humanos , Trastorno Depresivo Mayor/metabolismo , Estrés Psicológico/complicaciones , Animales , Sinapsis/metabolismo , Epigénesis Genética , Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipotálamo-Hipofisario/fisiopatología , Sistema Hipófiso-Suprarrenal/metabolismo , Sistema Hipófiso-Suprarrenal/fisiopatologíaRESUMEN
OBJECTIVES: To verify the association between early-life nutrition and chronic adult diseases. DATA SOURCES: Medline, Embase, Cochrane Database, and Lilacs. SUMMARY OF FINDS: The Developmental Origins of Health and Disease (DOHaD) hypothesis postulates that a mismatch between early-life circumstances and later-life situations may have an impact on chronic diseases. In this review, the authors emphasize the research supporting the impact of early nutrition on the origins of adult height, obesity and metabolic syndrome, type 2 diabetes mellitus, cardiovascular diseases, and reproductive outcomes. CONCLUSION: Even though this is a new topic and there are still many research questions to be answered, there is strong evidence that both deficiency and excess nutrition in early life can cause epigenetic changes that have effects that last a lifetime and contribute to the development of chronic diseases. Public health efforts to protect adults from getting chronic diseases should focus on nutrition in the first 1000 days of life, from conception to the end of the second year of life.
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Diabetes Mellitus Tipo 2 , Síndrome Metabólico , Adulto , Humanos , Diabetes Mellitus Tipo 2/etiología , Diabetes Mellitus Tipo 2/prevención & control , Estado Nutricional , Obesidad/complicaciones , Enfermedad CrónicaRESUMEN
BACKGROUND: Cocaine-use disorder (CUD) has been associated with early life adversity and activated cellular immune responses. Women are most vulnerable to complications from chronic substance disorders, generally presenting an intense feeling of abstinence and consuming significant drug amounts. Here, we investigated neutrophil functional activities in CUD, including the formation of neutrophil extracellular traps (NETs) and related intracellular signalling. We also investigated the role of early life stress in inflammatory profiles. METHODS: Blood samples, clinical data, and history of childhood abuse or neglect were collected at the onset of detoxification treatment of 41 female individuals with CUD and 31 healthy controls (HCs). Plasma cytokines, neutrophil phagocytosis, NETs, intracellular reactive oxygen species (ROS) generation, and phosphorylated protein kinase B (Akt) and mitogen-activated protein kinases (MAPK)s were assessed by flow cytometry. RESULTS: CUD subjects had higher scores of childhood trauma than controls. Increased plasma cytokines (TNF-α, IL-1ß, IL-6, IL-8, IL-12, and IL-10), neutrophil phagocytosis, and production of NETs were reported in CUD subjects as compared to HC. Neutrophils of CUD subjects also produced high levels of intracellular ROS and had more activated Akt and MAPKs (p38/ERK), which are essential signalling pathways involved in cell survival and NETs production. Childhood trauma scores were significantly associated with neutrophil activation and peripheral inflammation. CONCLUSION: Our study reinforces that smoked cocaine and early life stress activate neutrophils in an inflammatory environment.
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Maltrato a los Niños , Cocaína , Trastornos Relacionados con Sustancias , Humanos , Femenino , Niño , Neutrófilos/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Inflamación/metabolismo , Citocinas , Enfermedad Crónica , Cocaína/efectos adversos , Cocaína/metabolismoRESUMEN
BACKGROUND: Existing research on the impacts of adversity on young children's psychological well-being has largely focused on household-level risk factors using observational methods in high-income countries. This study leverages natural variation in the timing and location of community homicides to estimate their acute effects on the regulatory, behavioral, and developmental outcomes of Brazilian 3-year-olds. METHODS: We compared the outcomes of children who were assessed soon after a recent neighborhood homicide to those of children from the same residential neighborhoods who had not recently experienced community violence. Our sample included 3,241 3-year-olds (Mage = 41.05 months; 53% female; 45% caregiver education less than middle school; 26% receiving a public assistance program) from seven neighborhoods in São Paulo, Brazil. Child outcome measures included parent reports of effortful control and behavior problems as well as direct assessments of children's developmental (cognitive, language, and motor) skills. Community homicides were measured using police records. RESULTS: Recent exposure to community homicides was associated with lower effortful control, higher behavior problems, and lower overall developmental performance for children (d = .05-.20 standard deviations; p = ns - <.001). Effects were consistent across subgroups based on sociodemographic characteristics and environmental supports, but generally largest when community violence exposure was geographically proximal (within 600 m of home) and recent (within 2 weeks prior to assessment). CONCLUSIONS: Results highlight the pervasive effects that community violence can have on young children as well as the need to expand support to mitigate these effects and prevent inequities early in life.
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Pobreza , Violencia , Niño , Humanos , Femenino , Preescolar , Masculino , Brasil , Violencia/psicología , Destreza Motora , Factores de RiesgoRESUMEN
AIMS: The developmental Origins of Health and Disease (DOHaD) concept has provided the framework to assess how early life experiences can shape health and disease throughout the life course. Using a model of maternal exposure to a low protein diet (LPD; 6% protein) during the gestational and lactational periods, we demonstrated changes in the ventral prostate (VP) transcriptomic landscape in young rats exposed to maternal malnutrition. Male offspring Sprague Dawley rats were submitted to maternal malnutrition during gestation and lactation, and they were weighed, and distance anogenital was measured, followed were euthanized by an overdose of anesthesia at 21 postnatal days. Next, the blood and the ventral prostate (VP) were collected and processed by morphological analysis, biochemical and molecular analyses. RNA-seq analysis identified 411 differentially expressed genes (DEGs) in the VP of maternally malnourished offspring compared to the control group. The molecular pathways enriched by these DEGs are related to cellular development, differentiation, and tissue morphogenesis, all of them involved in both normal prostate development and carcinogenesis. Abcg1 was commonly deregulated in young and old maternally malnourished offspring rats, as well in rodent models of prostate cancer (PCa) and in PCa patients. Our results described ABCG1 as a potential DOHaD gene associated with perturbation of prostate developmental biology with long-lasting effects on carcinogenesis in old offspring rats. A better understanding of these mechanisms may help with the discussion of preventive strategies against early life origins of non-communicable chronic diseases.
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Desnutrición , Efectos Tardíos de la Exposición Prenatal , Animales , Femenino , Humanos , Masculino , Ratas , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 1/metabolismo , Carcinogénesis/genética , Carcinogénesis/metabolismo , Lactancia , Desnutrición/complicaciones , Efectos Tardíos de la Exposición Prenatal/genética , Efectos Tardíos de la Exposición Prenatal/metabolismo , Próstata/metabolismo , Ratas Sprague-DawleyRESUMEN
The relationship between events occurring during intrauterine development and later-life predisposition to long-term disease, has been described. The fetus responds to excess intrauterine exposure to high levels of corticosteroids, modifying their physiological development and stopping their growth. Fetal exposure to elevated levels of either endogenous (alterations in fetal hypothalamic-pituitary-adrenal axis) or synthetic corticosteroids, is one model of early-life adversity; to developing adult disease. At the molecular level, there are transcriptional changes in metabolic and growth pathways. Epigenetic mechanisms participate in transgenerational inheritance, not genomic. Exposures that change 11ß-hydroxysteroid dehydrogenase type 2 enzyme methylation status in the placenta can result in transcriptional repression of the gene, causing the fetus to be exposed to higher levels of cortisol. More precise diagnosis and management of antenatal corticosteroids for preterm birth, would potentially decrease the risk of long-term adverse outcomes. More studies are needed to understand the potential roles of factors to alter fetal corticosteroid exposure. Long-term infant follow-up is required to determine whether methylation changes in placenta may represent useful biomarkers of later disease risk. This review, summarize recent advances in the programming of fetal effects of corticosteroid exposure, the role of corticosteroids in epigenetic gene regulation of placental 11ß-hydroxysteroid dehydrogenase type 2 enzyme expression and transgenerational effects.
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Placenta , Nacimiento Prematuro , Adulto , Embarazo , Femenino , Recién Nacido , Humanos , Placenta/metabolismo , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 2/genética , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 2/metabolismo , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 2/farmacología , Sistema Hipotálamo-Hipofisario/fisiología , Sistema Hipófiso-Suprarrenal/fisiología , Nacimiento Prematuro/inducido químicamente , Feto , Glucocorticoides/efectos adversos , Epigénesis Genética , Desarrollo Fetal/fisiologíaRESUMEN
Infant formula intake is recommended to ensure comprehensive nutritional and caloric fulfillment when exclusive breastfeeding is not possible. However, similarly to breast milk, infant formulas may also contain pollutants capable of inducing endocrine-disrupting and neurotoxic effects. Thus, considering the sensitivity of their developing physiological systems and that infants have heightened susceptibility to environmental influences, this study was aimed at assessing the contents of essential elements, and inorganic and organic pollutants in infant formulas marketed in Brazil. Additionally, health risk assessments for selected contaminants were also performed. Measured contents of essential elements (Ca, Fe, Mg, Mn, Cu, Se, and Zn) were congruent with label information. Nevertheless, some toxic elements (Pb, Cd, As, Ni, and Al) were also detected. Notably, in the upper-bound scenario, Pb and Cd surpassed established threshold values when comparing the estimated daily intake (EDI) and tolerable daily intake (TDI - 3.57 and 0.36 µg/kg bw, respectively). Bisphenol P (BPP) and benzyl butyl phthalate (BBP) were frequently detected (84 % detection rate both) with elevated contents (BPP median = 4.28 ng/g and BBP median = 0.24 ng/g). Furthermore, a positive correlation (0.41) was observed between BPP and BBP, implying a potential co-occurrence within packaging materials. Methyl-paraben also correlated positively with BBP (0.57), showing a detection rate of 53 %. The cumulative PBDE contents ranged from 0.33 to 1.62 ng/g, with BDE-154 and BDE-47 the dominant congeners. When comparing EDI values with TDIs, all organic pollutants remained below the thresholds across all exposure scenarios. Moreover, non-carcinogenic risks were below the threshold (HQ > 1) when dividing the EDIs by the respective reference doses for chronic exposure. While the current findings may suggest that infant formula intake poses no immediate risk in terms of the evaluated chemicals, it remains imperative to conduct further research to safeguard the health of infants considering other chemicals, as well as their potential cumulative effects.
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Contaminantes Ambientales , Fórmulas Infantiles , Lactante , Femenino , Humanos , Fórmulas Infantiles/química , Contaminantes Ambientales/análisis , Cadmio , Brasil , Plomo/análisis , Leche Humana/químicaRESUMEN
IMPORTANCE: We investigated the presence and diversity of bacteria in the embryos of the viviparous lizard Sceloporus grammicus and their amniotic environment. We compared this diversity to that found in the maternal intestine, mouth, and cloaca. We detected bacterial DNA in the embryos, albeit with a lower bacterial species diversity than found in maternal tissues. Most of the bacterial species detected in the embryos were also found in the mother, although not all of them. Interestingly, we detected a high similarity in the composition of bacterial species among embryos from different mothers. These findings suggest that there may be a mechanism controlling the transmission of bacteria from the mother to the embryo. Our results highlight the possibility that the interaction between maternal bacteria and the embryo may affect the development of the lizards.