Severe early onset preeclampsia: short and long term clinical, psychosocial and biochemical aspects

Preeclampsia is a pregnancy specific disorder commonly defined as de novo hypertension and proteinuria after 20 weeks gestational age. It occurs in approximately 3-5% of pregnancies and it is still a major cause of both foetal and maternal morbidity and mortality worldwide1. As extensive research has not yet elucidated the aetiology of preeclampsia, there are no rational preventive or therapeutic interventions available. The only rational treatment is delivery, which benefits the mother but is not in the interest of the foetus, if remote from term. Early onset preeclampsia (<32 weeks’ gestational age) occurs in less than 1% of pregnancies. It is, however often associated with maternal morbidity as the risk of progression to severe maternal disease is inversely related with gestational age at onset2. Resulting prematurity is therefore the main cause of neonatal mortality and morbidity in patients with severe preeclampsia3. Although the discussion is ongoing, perinatal survival is suggested to be increased in patients with preterm preeclampsia by expectant, non-interventional management. This temporising treatment option to lengthen pregnancy includes the use of antihypertensive medication to control hypertension, magnesium sulphate to prevent eclampsia and corticosteroids to enhance foetal lung maturity4. With optimal maternal haemodynamic status and reassuring foetal condition this results on average in an extension of 2 weeks. Prolongation of these pregnancies is a great challenge for clinicians to balance between potential maternal risks on one the eve hand and possible foetal benefits on the other. Clinical controversies regarding prolongation of preterm preeclamptic pregnancies still exist – also taking into account that preeclampsia is the leading cause of maternal mortality in the Netherlands5 - a debate which is even more pronounced in very preterm pregnancies with questionable foetal viability6-9. Do maternal risks of prolongation of these very early pregnancies outweigh the chances of neonatal survival? Counselling of women with very early onset preeclampsia not only comprises of knowledge of the outcome of those particular pregnancies, but also knowledge of outcomes of future pregnancies of these women is of major clinical importance. This thesis opens with a review of the literature on identifiable risk factors of preeclampsia

Discutindo a educação ambiental no cotidiano escolar: desenvolvimento de projetos na escola formação inicial e continuada de professores

A presente pesquisa buscou discutir como a Educação Ambiental (EA) vem sendo trabalhada, no Ensino Fundamental e como os docentes desta escola compreendem e vem inserindo a EA no cotidiano escolar., em uma escola estadual do município de Tangará da Serra/MT, Brasil. Para tanto, realizou-se entrevistas com os professores que fazem parte de um projeto interdisciplinar de EA na escola pesquisada. Verificou-se que o projeto da escola não vem conseguindo alcançar os objetivos propostos por: desconhecimento do mesmo, pelos professores; formação deficiente dos professores, não entendimento da EA como processo de ensino-aprendizagem, falta de recursos didáticos, planejamento inadequado das atividades. A partir dessa constatação, procurou-se debater a impossibilidade de tratar do tema fora do trabalho interdisciplinar, bem como, e principalmente, a importância de um estudo mais aprofundado de EA, vinculando teoria e prática, tanto na formação docente, como em projetos escolares, a fim de fugir do tradicional vínculo “EA e ecologia, lixo e horta”.Facultad de Humanidades y Ciencias de la Educació

Plasticity in neurogenic competence of cortical progenitors in the developing mouse neocortex

La diversité de neurones à la base des fonctions corticales est générée au cours du développement embryonnaire par des progéniteurs. Leur capacité à répondre à des changements de signaux environnementaux pendant le développement, ainsi que leur restriction du potentiel reste mal connus. Nous avons examiné le devenir des neurones générés par des progéniteurs apicaux et intermédiaires après transplantations hétérochroniques. A l’inverse des progéniteurs intermédiaires qui perdent leur capacité de générer des neurones précoces, les progéniteurs apicaux conservent leur multipotencialité et restent en mesure d’inverser leur identité afin de produire des types neuronaux précoces. Ainsi, la progression temporelle de l’identité des progéniteurs apicaux qui sous-tend la génération de types neuronaux distincts au cours de temps ne fait pas l’objet de restriction au cours du développement. Ces résultats mettent en évidence les différences de plasticité de chaque type de progéniteurs, ceux-ci pouvant être exploités dans le cadre d’études de pathologies neurodégénératives

Principles of progenitor temporal patterning in the developing invertebrate and vertebrate nervous system

During the development of the central nervous system, progenitors successively generate distinct types of neurons which assemble into the circuits that underlie our ability to interact with the environment. Spatial and temporal patterning mechanisms are partially evolutionarily conserved processes that allow generation of neuronal diversity from a limited set of progenitors. Here, we review examples of temporal patterning in neuronal progenitors in the Drosophila ventral nerve cord and in the mammalian cerebral cortex. We discuss cell-autonomous mechanisms and environmental influences on the temporal transitions of neuronal progenitors. Identifying the principles controlling the temporal specification of progenitors across species, as highlighted here, may help understand the evolutionary constraints over brain circuit design and function. © 2019 Elsevier Lt

In vivo pulse labeling of isochronic cohorts of cells in the central nervous system using FlashTag

The tracing of neuronal cell lineages is critical to our understanding of cellular diversity in the CNS. This protocol describes a fluorescence birth-dating technique to label, track and isolate isochronic cohorts of newborn cells in the CNS in vivo in mouse embryos. Injection of carboxyfluorescein esters (CFSEs) into the cerebral ventricle allows pulse labeling of mitotic (M phase) ventricular zone (VZ) progenitors and their progeny across the CNS, a procedure we termed FlashTag. Specificity for M-phase apical progenitors is a result of the somata of these cells transiently contacting the ventricular wall during this cell-cycle phase, exposing them to CFSE injected into the cerebrospinal fluid. Using this approach, the developmental trajectory of progenitors and their daughter neurons can be tracked. Labeled cells can be imaged ex vivo or in fixed tissue, targeted for electrophysiological experiments or isolated using FACS for cell culture or (single-cell) RNA sequencing. Multiple embryos can be labeled within 30 min. The dye is retained for several weeks, allowing labeled cells to be identified postnatally. This protocol describes the labeling procedure using in utero injection, the isolation of live cells using FACS and the processing of labeled tissue for immunohistochemistry

Postnatal Sox6 Regulates Synaptic Function of Cortical Parvalbumin-Expressing Neurons

Cortical parvalbumin-expressing (Pvalb(+)) neurons provide robust inhibition to neighboring pyramidal neurons, crucial for the proper functioning of cortical networks. This class of inhibitory neurons undergoes extensive synaptic formation and maturation during the first weeks after birth and continue to dynamically maintain their synaptic output throughout adulthood. While several transcription factors, such as Nkx2-1, Lhx6, and Sox6, are known to be necessary for the differentiation of progenitors into Pvalb(+) neurons, which transcriptional programs underlie the postnatal maturation and maintenance of Pvalb(+) neurons' innervation and synaptic function remains largely unknown. Because Sox6 is continuously expressed in Pvalb(+) neurons until adulthood, we used conditional knock-out strategies to investigate its putative role in the postnatal maturation and synaptic function of cortical Pvalb(+) neurons in mice of both sexes. We found that early postnatal loss of Sox6 in Pvalb(+) neurons leads to failure of synaptic bouton growth, whereas later removal in mature Pvalb(+) neurons in the adult causes shrinkage of already established synaptic boutons. Paired recordings between Pvalb(+) neurons and pyramidal neurons revealed reduced release probability and increased failure rate of Pvalb(+) neurons' synaptic output. Furthermore, Pvalb(+) neurons lacking Sox6 display reduced expression of full-length tropomyosin-receptor kinase B (TrkB), a key modulator of GABAergic transmission. Once re-expressed in neurons lacking Sox6, TrkB was sufficient to rescue the morphologic synaptic phenotype. Finally, we showed that Sox6 mRNA levels were increased by motor training. Our data thus suggest a constitutive role for Sox6 in the maintenance of synaptic output from Pvalb(+) neurons into adulthood

Temporal plasticity of apical progenitors in the developing mouse neocortex

The diverse subtypes of excitatory neurons that populate the neocortex are born from apical progenitors located in the ventricular zone. During corticogenesis, apical progenitors sequentially generate deep-layer neurons followed by superficial-layer neurons directly or via the generation of intermediate progenitors. Whether neurogenic fate progression necessarily implies fate restriction in single progenitor types is unknown. Here we specifically isolated apical progenitors and intermediate progenitors, and fate-mapped their respective neuronal progeny following heterochronic transplantation into younger embryos. We find that apical progenitors are temporally plastic and can re-enter past molecular, electrophysiological and neurogenic states when exposed to an earlier-stage environment by sensing dynamic changes in extracellular Wnt. By contrast, intermediate progenitors are committed progenitors that lack such retrograde fate plasticity. These findings identify a diversity in the temporal plasticity of neocortical progenitors, revealing that some subtypes of cells can be untethered from their normal temporal progression to re-enter past developmental states

Search for narrow resonances using the dijet mass spectrum in pp collisions at s√=8 TeV

Results are presented of a search for the production of new particles decaying to pairs of partons (quarks, antiquarks, or gluons), in the dijet mass spectrum in proton-proton collisions at s√=8  TeV. The data sample corresponds to an integrated luminosity of 4.0  fb−1, collected with the CMS detector at the LHC in 2012. No significant evidence for narrow resonance production is observed. Upper limits are set at the 95% confidence level on the production cross section of hypothetical new particles decaying to quark-quark, quark-gluon, or gluon-gluon final states. These limits are then translated into lower limits on the masses of new resonances in specific scenarios of physics beyond the standard model. The limits reach up to 4.8 TeV, depending on the model, and extend previous exclusions from similar searches performed at lower collision energies. For the first time mass limits are set for the Randall–Sundrum graviton model in the dijet channel