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Early Biomarkers and Intervention Programs for the Infant Exposed to Prenatal Stress

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 Added by Marta Antonelli Dr.
 Publication date 2020
  fields Biology
and research's language is English




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Functional development of affective and reward circuits, cognition and response inhibition later in life exhibits vulnerability periods during gestation and early childhood. Extensive evidence supports the model that exposure to stressors in the gestational period and early postnatal life increases an individuals susceptibility to future impairments of functional development. Rece



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Three major biomarkers: beta-amyloid (A), pathologic tau (T), and neurodegeneration (N), are recognized as valid proxies for neuropathologic changes of Alzheimers disease. While there are extensive studies on cerebrospinal fluids biomarkers (amyloid, tau), the spatial propagation pattern across brain is missing and their interactive mechanisms with neurodegeneration are still unclear. To this end, we aim to analyze the spatiotemporal associations between ATN biomarkers using large-scale neuroimaging data. We first investigate the temporal appearances of amyloid plaques, tau tangles, and neuronal loss by modeling the longitudinal transition trajectories. Second, we propose linear mixed-effects models to quantify the pathological interactions and propagation of ATN biomarkers at each brain region. Our analysis of the current data shows that there exists a temporal latency in the build-up of amyloid to the onset of tau pathology and neurodegeneration. The propagation pattern of amyloid can be characterized by its diffusion along the topological brain network. Our models provide sufficient evidence that the progression of pathological tau and neurodegeneration share a strong regional association, which is different from amyloid.
What is the influence of chronic maternal prenatal stress (PS) on fetal iron homeostasis? In a prospective case-control study in 164 pregnant women, we show that cord blood transferrin saturation is lower in male stressed neonates. The total effect of PS exposure on fetal ferritin revealed a decrease of 15.4% compared with controls. Electrocardiogram-based Fetal Stress Index (FSI) identified affected fetuses non-invasively during the third trimester of gestation. FSI-based timely detection of fetuses affected by PS can support early individualized iron supplementation and neurodevelopmental follow-up to prevent long-term sequelae due to PS-exacerbated impairment of the iron homeostasis.
Neuroscientists are actively pursuing high-precision maps, or graphs, consisting of networks of neurons and connecting synapses in mammalian and non-mammalian brains. Such graphs, when coupled with physiological and behavioral data, are likely to facilitate greater understanding of how circuits in these networks give rise to complex information processing capabilities. Given that the automated or semi-automated methods required to achieve the acquisition of these graphs are still evolving, we develop a metric for measuring the performance of such methods by comparing their output with those generated by human annotators (ground truth data). Whereas classic metrics for comparing annotated neural tissue reconstructions generally do so at the voxel level, the metric proposed here measures the integrity of neurons based on the degree to which a collection of synaptic terminals belonging to a single neuron of the reconstruction can be matched to those of a single neuron in the ground truth data. The metric is largely insensitive to small errors in segmentation and more directly measures accuracy of the generated brain graph. It is our hope that use of the metric will facilitate the broader communitys efforts to improve upon existing methods for acquiring brain graphs. Herein we describe the metric in detail, provide demonstrative examples of the intuitive scores it generates, and apply it to a synthesized neural network with simulated reconstruction errors.
101 - Razvan V. Marinescu 2020
In order to find effective treatments for Alzheimers disease (AD), we need to identify subjects at risk of AD as early as possible. To this end, recently developed disease progression models can be used to perform early diagnosis, as well as predict the subjects disease stages and future evolution. However, these models have not yet been applied to rare neurodegenerative diseases, are not suitable to understand the complex dynamics of biomarkers, work only on large multimodal datasets, and their predictive performance has not been objectively validated. In this work I developed novel models of disease progression and applied them to estimate the progression of Alzheimers disease and Posterior Cortical atrophy, a rare neurodegenerative syndrome causing visual deficits. My first contribution is a study on the progression of Posterior Cortical Atrophy, using models already developed: the Event-based Model (EBM) and the Differential Equation Model (DEM). My second contribution is the development of DIVE, a novel spatio-temporal model of disease progression that estimates fine-grained spatial patterns of pathology, potentially enabling us to understand complex disease mechanisms relating to pathology propagation along brain networks. My third contribution is the development of Disease Knowledge Transfer (DKT), a novel disease progression model that estimates the multimodal progression of rare neurodegenerative diseases from limited, unimodal datasets, by transferring information from larger, multimodal datasets of typical neurodegenerative diseases. My fourth contribution is the development of novel extensions for the EBM and the DEM, and the development of novel measures for performance evaluation of such models. My last contribution is the organization of the TADPOLE challenge, a competition which aims to identify algorithms and features that best predict the evolution of AD.
For several decades optical tweezers have proven to be an invaluable tool in the study and analysis of a myriad biological responses and applications. However, as every tool, it can have undesirable or damaging effects upon the very sample it is helping to study. In this review the main negative effects of optical tweezers upon biostructures and living systems will be presented. Three are the main areas on which the review will focus: linear optical excitation within the tweezers, non-linear photonic effects, and thermal load upon the sampled volume. Additional information is provided on negative mechanical effects of optical traps on biological structures. Strategies to avoid or, in the least, minimize these negative effects will be introduced. Finally, all these effects, undesirable for the most, can have positive applications under the right conditions. Some hints in this direction will also be discussed.
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