Macrosomía fetal: estudio de factores predictores y complicaciones asociadas.

Introducción. Se define como macrosoma aquel feto con peso >4000 o 4500 g, independientemente de la edad gestacional. La macrosomía (MC) conlleva un aumento del riesgo de complicaciones maternas, fetales, perinatales y neonatales. Dichas complicaciones aumentan de manera abrupta con pesos > 4500 gramos. La MC fetal se relaciona con obesidad y diabetes materna. Dado que nuestra comunidad autónoma tiene una alta prevalencia de dichas patologías, planteamos este trabajo. El objetivo principal fue describir los antecedentes maternos y gestacionales y las complicaciones de los neonatos macrosómicos. Métodos. Estudio observacional, descriptivo y analítico, retrospectivo de tipo casos y controles en el que se estudiaron los embarazos atendidos en el HUNSC de recién nacidos con peso igual o superior a 4500 gramos entre 2014 y 2019. Se tomó un control por cada caso. Se recogieron variables clínicas de madres y recién nacidos. Resultados. En ese periodo hubo 17349 recién nacidos, 115 de ellos con peso > 4500 g (0.6%). Los principales factores de riesgo relacionados con la MC fueron: edad materna avanzada, obesidad, multiparidad y diabetes mellitus. Los fetos MC se asociaron significativamente con edades gestacionales más prolongadas, mayor número de cesáreas y de infección intraamniótica. También sufrieron más hipoglucemias y distocias de hombros. Además, las ecografías a término han demostrado tener una buena capacidad predictiva del peso fetal. Conclusiones: El control de los factores de riesgo maternos: estado óptimo de peso y control glucémico podrían disminuir la incidencia de macrosomía y sus complicaciones. De igual modo, la predicción mediante de ecografía de esta condición mostró una fiabilidad óptima.Background: Fetal macrosomia is defined as birth weight >4000-4500g regardless of gestational age. Macrosomy is related to a higher risk of maternal, perinatal and neonatal complications, especially on weight >4500g. As the prevalence of obesity and diabetes is very high in our community and being two of the main risk factors for macrosomia, we propose this study. The purpose was to describe the maternal and gestational history and complications of macrosomic neonates. Methods: An observational, descriptive, analytic, case-control study was performed on 115 neonates weighing more than 4500g (and their controls) born in the Hospital Universitario Nuestra Señora de la Candelaria from 2014 to 2019.A control was chosen for each case. Clinical variables were collected from mothers and newborns. Results: The incidence of macrosomia was 0.6%. The main risk factors associated with macrosomia were: advanced age, obesity, multiparity, and diabetes. Macrosomia was related to long gestational age, cesarean section and intraamniotic infection Macrosomic infants were more likely to suffer hypoglycemia and shoulder dystocia. Furthermore, ultrasound measurement has been shown to have an optimum reliability for prediction of fetal weight. Conclusions: It is important to control mother risk factors such as weight, blood glucose and to plan pregnancy in order to avoid these macrosomia complications. Also, ultrasound is a reliable method for newborn birth weight predictio

Super-rough dynamics on tumor growth

The growth of a cultivated typical brain tumor is studied in this work. The tumor is analyzed both dynamically and morphologically. We have measured its fractal dimension to be d(f) = 1.21 +/- 0.05. From its dynamical behavior we determine the scaling critical exponents of this circular symmetry system which are compatible with the linear molecular beam epitaxy universality class. A very important feature of tumor profiles is that they are super-rough, which constitutes the first (1 + 1)-dimensional experiment in literature with super-roughness. The results obtained from the dynamics study make manifest two very surprising features of tumor growth: Its dynamics is mainly due to contour cells and the tendency of an interface cell to duplicate is a function of the local curvature. [S0031-9007(98)07545-0]

A new microfluidic method enabling the generation of multi-layered tissues-on-chips using skin cells as a proof of concept

Microfluidic-based tissues-on-chips (TOCs) have thus far been restricted to modelling simple epithelia as a single cell layer, but likely due to technical difficulties, no TOCs have been reported to include both an epithelial and a stromal component despite the biological importance of the stroma for the structure and function of human tissues. We present, for the first time, a novel approach to generate 3D multilayer tissue models in microfluidic platforms. As a proof of concept, we modelled skin, including a dermal and an epidermal compartment. To accomplish this, we developed a parallel flow method enabling the deposition of bilayer tissue in the upper chamber, which was subsequently maintained under dynamic nutrient flow conditions through the lower chamber, mimicking the function of a blood vessel. We also designed and built an inexpensive, easy-to-implement, versatile, and robust vinyl-based device that overcomes some of the drawbacks present in PDMS-based chips. Preliminary tests indicate that this biochip will allow the development and maintenance of multilayer tissues, which opens the possibility of better modelling of the complex cell–cell and cell–matrix interactions that exist in and between the epithelium and mesenchyme, allowing for better-grounded tissue modelling and drug screening.This work was supported by the "Programa de Actividades de I+D entre Grupos de Investigación de la Comunidad de Madrid" project S2018/BAA-4480, Biopieltec-CM and the Cátedra Fundación Ramón Areces

Random positions of dendritic spines in human cerebral cortex

Dendritic spines establish most excitatory synapses in the brain and are located in Purkinje cell’s dendrites along helical paths, perhaps maximizing the probability to contact different axons. To test whether spine helixes also occur in neocortex, we reconstructed >500 dendritic segments from adult human cortex obtained from autopsies. With Fourier analysis and spatial statistics, we analyzed spine position along apical and basal dendrites of layer 3 pyramidal neurons from frontal, temporal, and cingulate cortex. Although we occasionally detected helical positioning, for the great majority of dendrites we could not reject the null hypothesis of spatial randomness in spine locations, either in apical or basal dendrites, in neurons of different cortical areas or among spines of different volumes and lengths. We conclude that in adult human neocortex spine positions are mostly random. We discuss the relevance of these results for spine formation and plasticity and their functional impact for cortical circuits

Rat-strain dependent changes of dendritic and spine morphology in the hippocampus after cocaine self-administration

We previously showed that cocaine self-administration increases spine density in CA1 hippocampal neurons in Lewis (LEW) but not in Fischer 344 (F344) rats. Dendritic spine morphology is intimately related to its function. Thus, we conducted a 3D morphological analysis of CA1 dendrites and dendritic spines in these two strains of rats. Strain-specific differences were observed prior to cocaine self-administration: LEW rats had significantly larger dendritic diameters but lower spine density than the F344 strain. After cocaine self-administration, proximal dendritic volume, dendritic surface area and spine density were increased in LEW rats, where a higher percentage of larger spines were also observed. In addition, we found a strong positive correlation between dendritic volume and spine morphology, and a moderate correlation between dendritic volume and spine density in cocaine self-administered LEW rats, an effect that was not evident in any other condition. By contrast, after cocaine self-administration, F334 rats showed decreased spine head volumes. Our findings suggest that genetic differences could play a key role in the structural plasticity induced by cocaine in CA1 pyramidal neurons. These cocaine-induced alterations could be related to differences in the memory processing of drug reward cues that could potentially explain differential individual vulnerability to cocaine addiction

Reelin regulates the maturation of dendritic spines, synaptogenesis and glial ensheathment of newborn granule cells

The Reelin pathway is essential for both neural migration and for the development and maturation of synaptic connections. However, its role in adult synaptic formation and remodeling is still being investigated. Here, we investigated the impact of the Reelin/Dab1 pathway on the synaptogenesis of newborn granule cells (GCs) in the young-adult mouse hippocampus. We show that neither Reelin overexpression nor the inactivation of its intracellular adapter, Dab1, substantially alters dendritic spine numbers in these neurons. In contrast, 3D-electron microscopy (focused ion beam milling/scanning electron microscope) revealed that dysregulation of the Reelin/Dab1 pathway leads to both transient and permanent changes in the types and morphology of dendritic spines, mainly altering mushroom, filopodial, and branched GC spines. We also found that the Reelin/Dab1 pathway controls synaptic configuration of presynaptic boutons in the dentate gyrus, with its dysregulation leading to a substantial decrease in multi-synaptic bouton innervation. Lastly, we show that the Reelin/Dab1 pathway controls astroglial ensheathment of synapses. Thus, the Reelin pathway is a key regulator of adult-generated GC integration, by controlling dendritic spine types and shapes, their synaptic innervation patterns, and glial ensheathment. These findings may help to better understanding of hippocampal circuit alterations in neurological disorders in which the Reelin pathway is implicated. Significance Statement: The extracellular protein Reelin has an important role in neurological diseases, including epilepsy, Alzheimer's disease and psychiatric diseases, targeting hippocampal circuits. Here we address the role of Reelin in the development of synaptic contacts in adult-generated granule cells (GCs), a neuronal population that is crucial for learning and memory and implicated in neurological and psychiatric diseases. We found that the Reelin pathway controls the shapes, sizes, and types of dendritic spines, the complexity of multisynaptic innervations and the degree of the perisynaptic astroglial ensheathment that controls synaptic homeostasis. These findings show a pivotal role of Reelin in GC synaptogenesis and provide a foundation for structural circuit alterations caused by Reelin deregulation that may occur in neurological and psychiatric disorders

A univocal definition of the neuronal soma morphology using Gaussian mixture models

The definition of the soma is fuzzy, as there is no clear line demarcating the soma of the labeled neurons and the origin of the dendrites and axon. Thus, the morphometric analysis of the neuronal soma is highly subjective. In this paper, we provide a mathematical definition and an automatic segmentation method to delimit the neuronal soma. We applied this method to the characterization of pyramidal cells, which are the most abundant neurons in the cerebral cortex. Since there are no benchmarks with which to compare the proposed procedure, we validated the goodness of this automatic segmentation method against manual segmentation by neuroanatomists to set up a framework for comparison. We concluded that there were no significant differences between automatically and manually segmented somata, i.e., the proposed procedure segments the neurons similarly to how a neuroanatomist does. It also provides univocal, justifiable and objective cutoffs. Thus, this study is a means of characterizing pyramidal neurons in order to objectively compare the morphometry of the somata of these neurons in different cortical areas and species

FIB/SEM technology and high-throughput 3D reconstruction of dendritic spines and synapses in GFP-labeled adult-generated neurons

The fine analysis of synaptic contacts is usually performed using transmission electron microscopy (TEM) and its combination with neuronal labeling techniques. However, the complex 3D architecture of neuronal samples calls for their reconstruction from serial sections. Here we show that focused ion beam/scanning electron microscopy (FIB/SEM) allows efficient, complete, and automatic 3D reconstruction of identified dendrites, including their spines and synapses, from GFP/DAB-labeled neurons, with a resolution comparable to that of TEM. We applied this technology to analyze the synaptogenesis of labeled adult-generated granule cells (GCs) in mice. 3D reconstruction of dendritic spines in GCs aged 3-4 and 8-9 weeks revealed two different stages of dendritic spine development and unexpected features of synapse formation, including vacant and branched dendritic spines and presynaptic terminals establishing synapses with up to 10 dendritic spines. Given the reliability, efficiency, and high resolution of FIB/SEM technology and the wide use of DAB in conventional EM, we consider FIB/SEM fundamental for the detailed characterization of identified synaptic contacts in neurons in a high-throughput manner

A Unified Framework for Neuroscience Morphological Data Visualization

The complexity of the human brain makes its understanding one of the biggest challenges that science is currently confronting. Due to its complexity, the brain has been studied at many different levels and from many disciplines and points of view, using a diversity of techniques for getting meaningful data at each specific level and perspective, producing sometimes data that are difficult to integrate. In order to advance understanding of the brain, scientists need new tools that can speed up this analysis process and that can facilitate integrating research results from different disciplines and techniques. Visualization has proved to be useful in the analysis of complex data, and this paper focuses on the design of visualization solutions adapted to the specific problems posed by brain research. In this paper, we propose a unified framework that allows the integration of specific tools to work together in a coordinated manner in a multiview environment, displaying information at different levels of abstraction and combining schematic and realistic representations. The two use cases presented here illustrate the capability of this approach for providing a visual environment that supports the exploration of the brain at all its organizational levels

Reelin Regulates the Maturation of Dendritic Spines, Synaptogenesis and Glial Ensheathment of Newborn Granule Cells

The extracellular protein Reelin has an important role in neurological diseases, including epilepsy, Alzheimer's disease and psychiatric diseases, targeting hippocampal circuits. Here we address the role of Reelin in the development of synaptic contacts in adult-generated granule cells (GCs), a neuronal population that is crucial for learning and memory and implicated in neurological and psychiatric diseases. We found that the Reelin pathway controls the shapes, sizes, and types of dendritic spines, the complexity of multisynaptic innervations and the degree of the perisynaptic astroglial ensheathment that controls synaptic homeostasis. These findings show a pivotal role of Reelin in GC synaptogenesis and provide a foundation for structural circuit alterations caused by Reelin deregulation that may occur in neurological and psychiatric disorders