Plasmidmediated catabolism for the elimination of xenobiotics from the surroundings

Although pediatric stroke is associated with higher survival rates compared with adult stroke, a substantial body of evidence indicates significant neuropsychologic morbidity in pediatric stroke survivors. Neuroplasticity does not guarantee good outcome in children. The general trends observed in the literature are reviewed as is the profile observed in common causes of pediatric stroke congenital heart disease, moyamoya disease, and sickle cell disease. The neuropsychologic profile of pediatric stroke patients is heterogeneous due to the multiplicity of associated causes. Stroke in early infancy and large strokes are associated with cognitive impairment while more limited disorders, such as phasic deficit, are observed in childhood stroke. Executive dysfunction is common in pediatric stroke, but social interaction skills are usually preserved. Congenital heart disease and sickle cell disease are associated with global neuropsychologic dysfunction while cognition is usually preserved in moyamoya. Executive dysregulation is instead more frequently reported in this population. Further study of maladaptive processes after pediatric stroke will allow identification of predictors of functional and neuropsychologic outcomes and permit personalization of care.Childhood traumatic brain injury (TBI) commonly occurs during brain development and can have direct, immediately observable neurologic, cognitive, and behavioral consequences. However, it can also disrupt subsequent brain development, and long-term outcomes are a combination of preinjury development and abilities, consequences of brain injury, as well as delayed impaired development of skills that were immature at the time of injury. There is a growing number of studies on mild TBI/sport-related concussions, describing initial symptoms and their evolution over time and providing guidelines for effective management of symptoms and return to activity/school/sports. Mild TBI usually does not lead to long-term cognitive or academic consequences, despite reports of behavioral/psychologic issues postinjury. Regarding moderate to severe TBI, injury to the brain is more severe, with evidence of a number of detrimental consequences in various domains. Patients can display neurologic impairments (e.g., motor deficits, to rehabilitation and care). Interventions should identify and target these specific factors, given their major role in postinjury outcomes. Abusive head trauma (AHT) occurs in very young children (most often less then 6 months) and is a form of severe TBI, usually associated with delay before appropriate care is sought. Outcomes are systematically worse following AHT than following accidental TBI, even when controlling for age at injury and injury severity. Children with moderate to severe TBI and AHT usually require specific, coordinated, multidisciplinary, and long-term rehabilitation interventions and school adaptations, until transition to adult services. Interventions should be patient- and family-centered, focusing on specific goals, comprising education about TBI, and promoting optimal parenting, communication, and collaborative problem-solving.This chapter focuses on new concepts and new paradigms shedding light on the complex issue of socioenvironmental factors that affect the psychologic development of the child. Longitudinal controlled studies have sorted out "what leads to what under which circumstances," adding to the heuristic value of the addition of risks and of the Bronfenbrenner's ecologic model of development and disentangling the socioeconomic status (SES) from poverty. We emphasize the importance of taking attachment styles and attachment disorganization into account for a better understanding of both normal development and early psychopathology. Intervention studies demonstrate the real life effect of the gene-environment interaction with or without epigenetic processes. Thus, this chapter deals with paradigmatic situations as ADS, Prader-Willi, or prematurity as they allow us to learn more about early development and epigenetic influences.Optimal brain function critically hinges on the remarkably precise interconnections made among millions of neurons. These specialized interconnected neuronal junctions, termed synapses, are used for neuronal communication, whence the presynaptic neurons releases a specific neurotransmitter, which then binds to the appropriate protein receptor on the membrane of the postsynaptic neuron, activating and eliciting a response in this connected neuron. In this chapter, we discuss how synapses form and are modified as the brain matures. Genetic programs control most of the wiring in the brain, from allowing axons to choose where to target their synapses, to determining synapse identity. However, the final map of neuronal connectivity in the brain crucially relies on incoming sensory information during early childhood to strengthen and refine the preexisting synapses thus allowing both nature and nurture to shape the final structure and function of the nervous system (Fig. 5.1). Finally, we discuss how advances in the knowledge of basic mechanisms governing synapse formation and plasticity can shed light on the pathophysiology of neurodevelopmental disorders.Exposure to environmental toxicants can have deleterious effects on the development of physical, cognitive, and mental health. Extensive laboratory and clinical studies have demonstrated how the developing brain is uniquely sensitive to toxic agents. This chapter focuses on the main neurologic impairments linked to prenatal and postnatal exposure to lead, methylmercury, and polychlorinated biphenyls, three legacy environmental contaminants whose neurotoxic effects have been extensively studied with respect to cognitive and behavioral development. The main cognitive, emotion regulation, sensory, and motor impairments in association with these contaminants are briefly reviewed, including the underlying neural mechanisms such as neuropathologic damages, brain neurotransmission, and endocrine system alterations. https://www.selleckchem.com/products/bay-11-7085.html The use of neuroimaging as a novel tool to better understand how the brain is affected by exposure to environmental contaminants is also discussed.Congenital infections are infections transmitted from mother to child during pregnancy (transplacentally) or delivery (peripartum). They have the potential to adversely affect fetal development and long-term neurodevelopmental outcome through inflammatory, destructive, developmental, or teratogenic lesions of the brain. Because the fetal/neonatal brain has a limited capacity to respond to injury, early inflammatory changes may be difficult to visualize and only manifest as neurocognitive disability later in life. Teratogenic effects, which may include aberrations of neuronal proliferation and migration, are more easily visible on imaging, but may be equally difficult to use to predict long-term neurocognitive outcomes. This chapter reviews the general pathophysiology of congenital infection and describes the epidemiology, the antenatal and postnatal diagnosis, and the treatment of congenital infections as well as the long-term neurodevelopmental outcomes.Substance use during pregnancy and the short- and long-term impacts of different substances on maternal, fetal, and longer-term health outcomes of individuals prenatally exposed have been the subject of much investigation. Alcohol has been recognized as harmful during pregnancy and has been clearly recognized as a neurobehavioral teratogen, and the pattern of effects has been termed fetal alcohol spectrum disorder. More recently, the effects of prenatal cannabis exposure have been vigorously explored as a priority research area following decriminalization/legalization of cannabis in Canada and the United States. As the data become more and more robust, we are learning that cannabis during pregnancy can have negative effects on maternal and fetal outcomes and on longer-term neurodevelopmental and cognitive functions.Since the historical scandal of thalidomide in the 1960s, practitioners and future mothers are fearful of drugs during pregnancy. In-uterine exposure to drugs can induce major malformation of the fetus or even intrauterine fetal death. Prescribing drugs to a pregnant woman requires particular attention, and it is necessary to consider both the maternal needs and the proven and potential fetal risks. In this chapter, we review the mechanisms for medication transfer from mother to fetus, fetal risk according to pregnancy timeline, and the main dangerous drugs during pregnancy. We also focus on three prescription debates, which are relevant for neurodevelopmental disorder, because they each point to a paradigmatic situation-diethylstilbestrol, which shows transgenerational adversary effects; valproate, which impacts neurodevelopment as a whole; and antidepressants for which the adverse impact on neurodevelopment is still controversial given the impact of depression itself. Finally, we consider the implications for practice and toxicologic research to promote risk prevention.The consequences of prematurity on brain functional development are numerous and diverse, and impact all brain functions at different levels. Prematurity occurs between 22 and 36 weeks of gestation. This period is marked by extreme dynamics in the physiologic maturation, structural, and functional processes. These different processes appear sequentially or simultaneously. They are dependent on genetic and/or environmental factors. Disturbance of these processes or of the fine-tuning between them, when caring for premature children, is likely to induce disturbances in the structural and functional development of the immature neural networks. These will appear as impairments in learning skills progress and are likely to have a lasting impact on the development of children born prematurely. The level of severity depends on the initial alteration, whether structural or functional. In this chapter, after having briefly reviewed the neurodevelopmental, structural, and functional processes, we describe, in a nonexhaustive manner, the impact of prematurity on the different brain, motor, sensory, and cognitive functions.Neurodevelopmental disorders occur more frequently in boys than in girls and often differ in presentation between the sexes. The sex differences in prevalence and presentation of autism spectrum disorder, intellectual disability, communication disorders, specific learning disabilities, attention deficit/hyperactivity disorder, Tourette's syndrome, and epilepsy are discussed, as well as sex differences in the patterns of comorbidities between these disorders. Prominent theories have been proposed to explain sex biases. These include genetic factors, sex hormones, sociological factors, cognitive differences between the sexes, and environmental insult. Despite the large body of research reviewed in this chapter, many aspects of sex-related effects in neurodevelopmental disorders remain poorly understood.Neurodevelopmental disorders encompass a broad range of conditions, which include autism, epilepsy, and intellectual disability. These disorders are relatively common and have associated clinical and genetic heterogeneity. Technology has driven much of our understanding of these diseases and their genetic underlying mechanisms, particularly highlighted by the study of large cohorts with comparative genomic hybridization and the more recent implementation of next-generation sequencing (NGS). The mapping of copy number variants throughout the genome has highlighted the recurrent, highly penetrant, de novo variation in syndromic forms of neurodevelopmental disease. NGS of affected individuals and their parents led to a dramatic shift in our understanding as these studies showed that a significant proportion of affected individuals carry rare, de novo variants within single genes that explain their disease presentation. Deep sequencing studies further implicate mosaicism as another mechanism of disease. However, it has also become clear that while rare variants explain a significant proportion of sporadic neurodevelopmental disease, rare variation still does not fully account for the familial clustering and high heritability observed.