Sex-specific effects of prenatal undernutrition on resting-state functional connectivity in the human brain at age 68.

Prenatal nutrition may significantly impact brain aging. Results from the Dutch Famine Birth Cohort indicated that prenatal undernutrition is negatively associated with cognition, brain volumes, perfusion and structural brain aging in late life, predominantly in men. This study investigates the association between prenatal undernutrition and late-life functional brain network connectivity. In an exploratory resting-state functional magnetic resonance imaging study of 112 participants from the Dutch Famine Birth Cohort, we investigated whether the within- and between-network functional connectivity of the default mode network, salience network and central executive network differ at age 68 in men (N = 49) and women (N = 63) either exposed or unexposed to undernutrition in early gestation. Additionally, we explored sex-specific effects. Compared to unexposed participants, exposed participants revealed multiple clusters of different functional connectivity within and between the three networks studied. Sex-specific analyses suggested a pattern of network desegregation fitting with brain aging in men and a more diffuse pattern of group differences in women. This study demonstrates that associations between prenatal undernutrition and brain network functional connectivity extend late into life.

Miswiring the brain: Human prenatal Δ9-tetrahydrocannabinol use associated with altered fetal hippocampal brain network connectivity.

Increasing evidence supports a link between maternal prenatal cannabis use and altered neural and physiological development of the child. However, whether cannabis use relates to altered human brain development prior to birth, and specifically, whether maternal prenatal cannabis use relates to connectivity of fetal functional brain systems, remains an open question. The major objective of this study was to identify whether maternal prenatal cannabis exposure (PCE) is associated with variation in human brain hippocampal functional connectivity prior to birth. Prenatal drug toxicology and fetal fMRI data were available in a sample of 115 fetuses [43 % female; mean age 32.2 weeks (SD = 4.3)]. Voxelwise hippocampal connectivity analysis in a subset of age and sex-matched fetuses revealed that PCE was associated with alterations in fetal dorsolateral, medial and superior frontal, insula, anterior temporal, and posterior cingulate connectivity. Classification of group differences by age 5 outcomes suggest that compared to the non-PCE group, the PCE group is more likely to have increased connectivity to regions associated with less favorable outcomes and to have decreased connectivity to regions associated with more favorable outcomes. This is preliminary evidence that altered fetal neural connectome may contribute to neurobehavioral vulnerability observed in children exposed to cannabis in utero.

Prenatal lead exposure impacts cross-hemispheric and long-range connectivity in the human fetal brain.

Lead represents a highly prevalent metal toxicant with potential to alter human biology in lasting ways. A population segment that is particularly vulnerable to the negative consequences of lead exposure is the human fetus, as exposure events occurring before birth are linked to varied and long-ranging negative health and behavioral outcomes. An area that has yet to be addressed is the potential that lead exposure during pregnancy alters brain development even before an individual is born. Here, we combine prenatal lead exposure information extracted from newborn bloodspots with the human fetal brain functional MRI data to assess whether neural network connectivity differs between lead-exposed and lead-naïve fetuses. We found that neural connectivity patterns differed in lead-exposed and comparison groups such that fetuses that were not exposed demonstrated stronger age-related increases in cross-hemispheric connectivity, while the lead-exposed group demonstrated stronger age-related increases in posterior cingulate cortex (PCC) to lateral prefrontal cortex (PFC) connectivity. These are the first results to demonstrate metal toxicant-related alterations in human fetal neural connectivity. Remarkably, the findings point to alterations in systems that support higher-order cognitive and regulatory functions. Objectives for future work are to replicate these results in larger samples and to test the possibility that these alterations may account for significant variation in future child cognitive and behavioral outcomes.

El uso de los agrotoxicos y su afectación al sistema inmune: un tema de interés actual / The use of pesticides and affectation on immune system: an issue of current interest

Actualmente se conoce que nos enfrentamos a una variedad de agentes químicos (agrotóxicos) como ser los plaguicidas, pesticidas, herbicidas, porque están presentes en el ambiente, en los alimentos, en el agua, en bajas concentraciones, pero que a la larga inducen efectos nocivos en la salud. Se utilizan estos agentes químicos en los programas públicos de salud, para la erradicación de criaderos de mosquitos transmisores de enfermedades como por ejemplo el vector de la malaria y se utilizan también en la agricultura, principalmente para el control de plagas, que afectan grandemente en la producción de productos alimenticios. La aplicación indiscriminada de estos agrotóxicos, ahora en países como el nuestro, está causando una grave contaminación ambiental, aumentando los potenciales riesgos para la salud, porque estos tóxicos se difunden rápidamente en el medio ambiente por lo que es necesario conocer los estudios realizados a nivel mundial de los potenciales riesgos para la salud humana. La mayoría de los estudios se han realizado en animales de experimentación. La inmunotoxicidad no es solo el resultado del contacto con grandes dosis de un agrotóxicos, sino también de la exposición crónica a bajas dosis, durante largos periodos de tiempo. Las investigaciones sobre la toxicidad de los plaguicidas se han centrado en observar: alteraciones enzimáticas, efectos patológicos, mutagénicos y cancerígenos en poblaciones humanas expuestas y solo recientemente se han estudiado los efectos de los plaguicidas sobre la respuesta inmune. Estos estudios no tienen conclusiones implícitas sobre la inmunotoxicidad, sin embargo, dejan claramente establecido que los efectos lentos o retrasados de los agrotóxicos sobre la salud y principalmente sobre el sistema inmune, a pesar de que son más difíciles de detectar, son los más importantes, porque dan lugar a diferentes tipos de alteraciones como la susceptibilidad a enfermedades, diagnosticadas tardíamente las cuales en muchos casos no tiene un pronóstico favorable.

Currently it is known that we face a variety of chemicals (pesticides) such as pesticides, pesticides, herbicides, because they are present in the environment, in food, in water, in low concentrations, but eventually induce effects harmful to health. These chemicals are used in public health programs for the eradication of breeding sites for mosquitoes transmitting diseases such as malaria vector and are also used in agriculture, mainly for pest control, which greatly affect the food production. The indiscriminate application of these pesticides, now in countries like ours, is causing severe environmental pollution, increasing the potential health risks because these toxic diffuse rapidly in the environment so it is necessary to know the level studies world of potential risks to human health. Most studies have been conducted in experimental animals. Immunotoxicity is not only the result of contact with large doses of pesticides, but chronic exposure to low doses over long periods of time.Researches on the toxicity of pesticides have focused on observing: enzyme abnormalities, pathological effects, mutagenic and carcinogenic in human populations exposed and only recently have studied the effects of pesticides on the immune response.These studies have implied conclusions on immunotoxicity, however, they leave it clear that the slow effects or delayed of pesticides on health and primarily on the immune system, although they are more difficult to detect, are the most important, because they give rise to different types of disturbances such as disease susceptibility, belatedly diagnosed which in many cases have a favorable prognosis.

Congenital hypothyroidism with neurological and respiratory alterations: a case detected using a variable diagnostic threshold for TSH.

We report a case of congenital hypothyroidism (CH) with neurological and respiratory alterations due to a heterozygotic c.374-1G > A mutation of TITF1/NKX2-1. The hypothyroidism was detected using a neonatal screening protocol in which the thyroid stimulating hormone (TSH) threshold is re-set each day on the basis of within-day variability and between-day variation. In this case, the threshold on the day of the initial analysis was 8.2 mIU/L, and the measured TSH level in heel-prick blood was 8.3 mIU/L.

Evolutionary analyses of entire genomes do not support the association of mtDNA mutations with Ras/MAPK pathway syndromes.

BACKGROUND: There are several known autosomal genes responsible for Ras/MAPK pathway syndromes, including Noonan syndrome (NS) and related disorders (such as LEOPARD, neurofibromatosis type 1), although mutations of these genes do not explain all cases. Due to the important role played by the mitochondrion in the energetic metabolism of cardiac muscle, it was recently proposed that variation in the mitochondrial DNA (mtDNA) genome could be a risk factor in the Noonan phenotype and in hypertrophic cardiomyopathy (HCM), which is a common clinical feature in Ras/MAPK pathway syndromes. In order to test these hypotheses, we sequenced entire mtDNA genomes in the largest series of patients suffering from Ras/MAPK pathway syndromes analyzed to date (n = 45), most of them classified as NS patients (n = 42). METHODS/PRINCIPAL FINDINGS: The results indicate that the observed mtDNA lineages were mostly of European ancestry, reproducing in a nutshell the expected haplogroup (hg) patterns of a typical Iberian dataset (including hgs H, T, J, and U). Three new branches of the mtDNA phylogeny (H1j1, U5b1e, and L2a5) are described for the first time, but none of these are likely to be related to NS or Ras/MAPK pathway syndromes when observed under an evolutionary perspective. Patterns of variation in tRNA and protein genes, as well as redundant, private and heteroplasmic variants, in the mtDNA genomes of patients were as expected when compared with the patterns inferred from a worldwide mtDNA phylogeny based on more than 8700 entire genomes. Moreover, most of the mtDNA variants found in patients had already been reported in healthy individuals and constitute common polymorphisms in human population groups. CONCLUSIONS/SIGNIFICANCE: As a whole, the observed mtDNA genome variation in the NS patients was difficult to reconcile with previous findings that indicated a pathogenic role of mtDNA variants in NS.