Practical anatomy classes: An alternative to improve the learning of middle school students.

Anatomy is the branch discipline focused on studying organisms' physical structures and parts. Although technological advances are broadening the anatomy study, the practices of prosection and dissection of human cadavers and animals remain a primary teaching method. Despite the large body of research supporting its benefits, in some countries, cadaveric prosection and dissection of vertebrate animals in secondary education have been banned. In the current study, to prevent a lack of access to anatomical sciences education, the use of plastinated biological specimens was proposed for teaching practical biology in middle and high schools. The study was conducted in the 2014 academic year. Eighty-seven middle school students participated in the experiment. Groups consisted of: (i) theoretical classes only; (ii) theoretical class plus prosection with fresh specimens class; (iii) theoretical class plus expository with plastinated specimens classes. A post-test grade method was used to assess the impact of such tasks on the learning experience of each group. An ANOVA test and multiple regression model were used to analyze the effects of the variables of interest. Our study highlighted that students who underwent the plastination practical class had higher overall performance and a higher mean post-test grade than those in the pure theoretical group. A favorable effect of a positive self-knowledge assessment on the students' performance was found, supporting the self-efficacy model of human behavior. Thus, the current study provides further evidence to support the use of plastinated specimens as an effective teaching method in countries where dissection is not feasible.

O que é medicina de precisão e como ela pode impactar o setor de saúde? / Texto para Discussão (TD) 2557: O que é medicina de precisão e como ela pode impactar o setor de saúde? / Português

A medicina de precisão, ou medicina personalizada, é a customização de tratamento médico com base na capacidade de classificar indivíduos em subpopulações que diferem na susceptibilidade a uma determinada doença ou na resposta a um tratamento específico. Essa nova percepção sobre a forma de diagnóstico e tratamento vem ganhando espaço, dado o envelhecimento da população e a consequente transição epidemiológica, com ganho de evidência para as doenças crônico-degenerativas. As principais tecnologias incorporadas pela literatura no conceito de medicina de precisão são testes genéticos (diagnóstico); biossensores e wearables (monitoramento); e terapias celulares e gênicas (tratamento), sendo a maioria de recente implementação ou ainda em desenvolvimento. Os benefícios individuais do uso dessas tecnologias são claros, mas ainda há desafios para seu uso coletivo, tendo em vista, principalmente, seus custos. Este texto apresenta as tecnologias de medicina de precisão já existentes e discute sua eficácia e eficiência, bem como seus impactos nos custos e nos sistemas de saúde de forma geral. Além disso, são avaliados os desafios para o seu desenvolvimento e em que medida países como o Brasil podem atuar como usuários ou produtores dessas tecnologias.

Precision medicine or personalized medicine refers to the customization of medical treatment based on the ability to classify individuals into subpopulations that differ in susceptibility to a particular disease or in response to a specific treatment. This new perception about diagnosis and treatment is growing throughout the world, given the aging of the population and the consequent epidemiological transition, with gain of evidence for chronic-degenerative diseases. The main technologies incorporated by the literature in the concept of precision medicine are genetic tests (diagnosis), biosensors and wearables (monitoring), cellular and gene therapies (treatment), most of which have been recently implemented or are still under development. Individual benefits of precision medicine are clear, but there are still challenges for their collective use, given mainly its costs. This text presents the existing technologies and discusses their effectiveness and efficiency as well as their costs and impacts on the health system. In addition, we also discuss challenges to its development and to how countries such as Brazil could play a role as users or producers of these technologies.

Perinatal Asphyxia and Brain Development: Mitochondrial Damage Without Anatomical or Cellular Losses.

Perinatal asphyxia remains a significant cause of neonatal mortality and is associated with long-term neurodegenerative disorders. In the present study, we evaluated cellular and subcellular damages to brain development in a model of mild perinatal asphyxia. Survival rate in the experimental group was 67%. One hour after the insult, intraperitoneally injected Evans blue could be detected in the fetuses' brains, indicating disruption of the blood-brain barrier. Although brain mass and absolute cell numbers (neurons and non-neurons) were not reduced after perinatal asphyxia immediately and in late brain development, subcellular alterations were detected. Cortical oxygen consumption increased immediately after asphyxia, and remained high up to 7 days, returning to normal levels after 14 days. We observed an increased resistance to mitochondrial membrane permeability transition, and calcium buffering capacity in asphyxiated animals from birth to 14 days after the insult. In contrast to ex vivo data, mitochondrial oxygen consumption in primary cell cultures of neurons and astrocytes was not altered after 1% hypoxia. Taken together, our results demonstrate that although newborns were viable and apparently healthy, brain development is subcellularly altered by perinatal asphyxia. Our findings place the neonate brain mitochondria as a potential target for therapeutic protective interventions.

Impact of ethanol on the developing GABAergic system.

Alcohol intake during pregnancy has a tremendous impact on the developing brain. Embryonic and early postnatal alcohol exposures have been investigated experimentally to elucidate the fetal alcohol spectrum disorders' (FASD) milieu, and new data have emerged to support a devastating effect on the GABAergic system in the adult and developing nervous system. GABA is a predominantly inhibitory neurotransmitter that during development excites neurons and orchestrates several developmental processes such as proliferation, migration, differentiation, and synaptogenesis. This review summarizes and brings new data on neurodevelopmental aspects of the GABAergic system with FASD in experimental telencephalic models.

Neurologic birth defects after prenatal exposure to antiepileptic drugs.

Maternal epilepsy has a potential for fetal injury, either antiepileptic drug (AED)--induced or as a consequence of seizures per se. The intent of this article is to explore this relationship, discussing similar patterns of malformations seen with AEDs or different disease exposure during pregnancy, and the potential role of gap junctional intercellular communication in abnormal morphogenesis.

Ephrin-A5 promotes the formation of terminal thalamocortical arbors.

Ephrins-A5 are expressed in the cortical target layer of thalamic afferents at the time when these axons form terminal arbors. Previous in-vitro studies provided evidence that ephrin-A5 supports the branching of thalamic axons, but there is no direct in-vivo evidence for such a growth-promoting effect. Here we examined thalamocortical projections in ephrins-A5 deficient mice. Our results demonstrate that the laminar specificity of thalamic afferents in ephrin-A5 mutants remains preserved, but axonal arbor formation is greatly reduced. Thus, ephrin-A5 specifically regulates branch formation of thalamic axons, but does not affect target layer selection. Ephrin-A5-mutant mice are, therefore, a unique model to study the effects of reduced thalamic innervation on the assembly of cortical circuits and sensory processing.

Axons of callosal neurons bifurcate transiently at the white matter before consolidating an interhemispheric projection.

The main alternative output routes of adult cortical axons are the internal capsule and the corpus callosum. How do callosal axons choose their trajectories? We hypothesized that bifurcation followed by elimination of one branch is a developmental strategy for accomplishing this aim. Using embryonic and postnatal mice, we labelled cortical projecting neurons and quantified their axonal bifurcations in correlation with the mediolateral position of their somata. Bifurcating axons were numerous in the younger brains but declined during further development. Most bifurcating axons pertained to neurons located in the dorsolateral cortex. Moreover, callosal neurons bifurcate more often than subcortically projecting cells. We then quantified bifurcations formed by dissociated green fluorescent cells plated onto cortical slices. Cells grown over dorsolateral cortex bifurcated more often than those grown over medial cortex, irrespective of their positional origin in the donor. Removal of intermediate targets from the slices prevented bifurcation. We concluded that transient bifurcation and elimination of the lateral branch is a strategy employed by developing callosal axons in search of their targets. As cell body position and intermediate targets determine axon behaviour, we suggest that bifurcations are regulated by cues expressed in the environment.

Connecting thalamus and cortex: the role of ephrins.

The complex task of wiring up the brain during embryonic development is achieved by a multitude of guidance signals acting in complex combinations to drive growing axons to their proper targets. The somatosensory system provides an extensively studied model system featuring many universal mechanisms of neural development. In rodents, it constitutes an important model to study how precise topographic connections are achieved. Recent evidence suggests that the Eph/ephrin family of guidance molecules is of pivotal importance for the development of the somatosensory system. Members of Eph/ephrin family are thought to be involved in the global presorting of thalamic axons projecting to the cortex, in labeling specific cortical areas for innervation, in providing topographic cues within the target area, and in distinguishing cortical layers for intracortical wiring. The Eph/ephrin system also seems to contribute to the formation of specific corticothalamic feedback projections. So far, the functions of only a few members of the Eph/ephrin family have been examined, but expression analysis indicates complex combinatorial effects of these signaling molecules. Understanding the Eph/ephrin wiring code is expected to yield new insights into the development and plasticity of brain circuits involved in higher functions.

Blockade of gap junctions in vivo provides neuroprotection after perinatal global ischemia.

BACKGROUND AND PURPOSE: We investigated the contribution of gap junctions to brain damage and delayed neuronal death produced by oxygen-glucose deprivation (OGD). METHODS: Histopathology, molecular biology, and electrophysiological and fluorescence cell death assays in slice cultures after OGD and in developing rats after intrauterine hypoxia-ischemia (HI). RESULTS: OGD persistently increased gap junction coupling and strongly activated the apoptosis marker caspase-3 in slice cultures. The gap junction blocker carbenoxolone applied to hippocampal slice cultures before, during, or 60 minutes after OGD markedly reduced delayed neuronal death. Administration of carbenoxolone to ischemic pups immediately after intrauterine HI prevented caspase-3 activation and dramatically reduced long-term neuronal damage. CONCLUSIONS: Gap junction blockade may be a useful therapeutic tool to minimize brain damage produced by perinatal and early postnatal HI.

Cellular and molecular tunnels surrounding the forebrain commissures of human fetuses.

Glial cells and extracellular matrix (ECM) molecules surround developing fiber tracts and are implicated in axonal pathfinding. These and other molecules are produced by these strategically located glial cells and have been shown to influence axonal growth across the midline in rodents. We searched for similar cellular and molecular structures surrounding the telencephalic commissures of fetal human brains. Paraffin-embedded brain sections were immunostained for glial fibrillary acidic protein (GFAP) and vimentin (VN) to identify glial cells; for microtubule-associated protein-2 (MAP-2) and neuronal nuclear protein (NeuN) to document neurons; for neurofilament (NF) to identify axons; and for chondroitin sulfate (CS), tenascin (TN), and fibronectin (FN) to show the ECM. As in rodents, three cellular clusters surrounding the corpus callosum were identified by their expression of GFAP and VN (but not MAP-2 or NeuN) from 13 to at least 18 weeks postovulation (wpo): the glial wedge, the glia of the indusium griseum, and the midline sling. CS and TN (but not FN) were expressed pericellularly in these cell groups. The anterior commissure was surrounded by a GFAP+/VN+ glial tunnel from 12 wpo, with TN expression seen between the GFAP+ cell bodies. The fimbria showed GFAP+/VN+ cells at its lateral and medial borders from 12 wpo, with pericellular expression of CS. The fornix showed GFAP+ cells somewhat later (16 wpo). Because these structures are similar to those described for rodents, we concluded that the axon guiding mechanisms postulated for commissural formation in nonhuman mammals may also be operant in the developing human brain.

Multiple roles of ephrins during the formation of thalamocortical projections: maps and more.

The functional architecture of the cerebral cortex is based on intrinsic connections that precisely link neurons from distinct cortical laminae as well as layer-specific afferent and efferent projections. Experimental strategies using in vitro assays originally developed by Friedrich Bonhoeffer have suggested that positional cues confined to individual layers regulate the assembly of local cortical circuits and the formation of thalamocortical projections. One of these wiring molecules is ephrinA5, a ligand for Eph receptor tyrosine kinases. EphrinA5 and Eph receptors exhibit highly dynamic expression patterns in distinct regions of the cortex and thalamus during early and late stages of thalamocortical and cortical circuit formation. In vitro assays suggest that ephrinA5 is a multifunctional wiring molecule for different populations of cortical and thalamic axons. Additionally, the expression patterns of ephrinA5 during cortical development are consistent with this molecule regulating, in alternative ways, specific components of thalamic and cortical connectivity. To test this directly, the organization of thalamocortical projections was examined in mice lacking ephrinA5 gene expression. The anatomical studies in ephrinA5 knockout animals revealed a miswiring of limbic thalamic projections and changes in neocortical circuits that were predicted from the expression pattern and the in vitro analysis of ephrinA5 function.

Miswiring of limbic thalamocortical projections in the absence of ephrin-A5.

Axon guidance cues of the ephrin ligand family have been hypothesized to regulate the formation of thalamocortical connections, but in vivo evidence for such a role has not been examined directly. To test whether ephrin-mediated repulsive cues participate in sorting the projections originating from distinct thalamic nuclei, we analyzed the organization of somatosensory and anterior cingulate afferents postnatally in mice lacking ephrin-A5 gene expression. Projections from ventrobasal and laterodorsal nuclei to their respective sensory and limbic cortical areas developed normally. However, a portion of limbic thalamic neurons from the laterodorsal nucleus also formed additional projections to somatosensory cortical territories, thus maintaining inappropriate dual projections to multiple cortical regions. These results suggest that ephrin-A5 is not required for the formation of normal cortical projections from the appropriate thalamic nuclei, but rather acts as a guidance cue that restricts limbic thalamic axons from inappropriate neocortical regions.