The differential diagnosis of pilocytic astrocytoma with atypical features and malignant glioma: an analysis of 16 cases with emphasis on distinguishing molecular features

Rare pilocytic astrocytomas (PA) have atypical histologic and clinicoradiologic features that raise the differential diagnosis of glioblastoma. Whether ancillary studies can supplement histopathologic examination in placing these cases accurately on the spectrum of WHO Grade I PA to higher-grade glioma is not always clear, partly because these cases are not common. Here, ten PAs with atypical clinicoradiologic and histologic features and six pediatric glioblastoma multiforme (pGBMs) were analyzed for BRAF V600E, IDH1, IDH2, and TP53 mutations. Ki-67, p53, and p16 protein expression were also examined by immunohistochemistry. BRAF–KIAA1549 fusion status was assessed in the PA subgroup. The rate of BRAF–KIAA1549 fusion was high in these PAs (5/7 tumors) including four extracerebellar examples. A single BRAF V600E mutation was identified in the fusion-negative extracerebellar PA of a very young child who succumbed to the disease. TP53 mutations were present only in malignant gliomas, including three pGBMs and one case designated as PA with anaplastic features (with consultation opinion of pGBM). IDH1 and IDH2 were wild type in all cases, consistent with earlier findings that IDH mutations are not typical in high-grade gliomas of patients ≤14 years of age. Immunohistochemical studies showed substantial overlap in Ki-67 labeling indices, an imperfect correlation between p53 labeling and TP53 mutation status, and complete p16 loss in only two pGBMs but in no PAs. These results suggest that (a) BRAF–KIAA1549 fusion may be common in PAs with atypical clinicoradiologic and histologic features, including those at extracerebellar sites, (b) BRAF V600E mutation is uncommon in extracerebellar PAs, and (c) TP53 mutation analysis remains a valuable tool in identifying childhood gliomas that will likely behave in a malignant fashion.     

Central nervous system diseases related to pathological microglial phagocytosis

Microglia are important phagocytes of the central nervous system (CNS). They play an important role in protecting the CNS by clearing necrotic tissue and apoptotic cells in many CNS diseases. However, recent studies have found that microglia can phagocytose parts of neurons excessively, such as the neuronal cell body, synapse, or myelin sheaths, before or after the onset of CNS diseases, leading to aggravated injury and impaired tissue repair. Meanwhile, reduced phagocytosis of synapses and myelin results in abnormal circuit connections and inhibition of remyelination, respectively. Previous studies focused primarily on the positive effects of microglia phagocytosis, whereas only a few studies have focused on the negative effects. In this review, we use the term "pathological microglial phagocytosis" to refer to excessive or reduced phagocytosis by microglia that leads to structural or functional abnormalities in target cells and brain tissue. The classification of pathological microglial phagocytosis, the composition, and activation of related signaling pathways, as well as the process of pathological phagocytosis in various kinds of CNS diseases, are described in this review. We hypothesize that pathological microglial phagocytosis leads to aggravation of tissue damage and negative functional outcome. For example, excessive microglial phagocytosis of synapses can be observed in Alzheimer's disease and schizophrenia, leading to significant synapse loss and memory impairment. In Parkinson's disease, ischemic stroke, and traumatic brain injury, excessive microglial phagocytosis of neuronal cell bodies causes impaired gray matter recovery and sensory dysfunction. We therefore believe that more studies should focus on the mechanism of pathological microglial phagocytosis and activation to uncover potential targets of therapeutic intervention.     

The Effects of Sublethal Levels of 2,4-Dichlorophenoxyacetic Acid Herbicide (2,4-D) on Feeding Behaviors of the Crayfish O. rusticus

The widespread use of herbicides across the globe has increased the probability of synthetic chemicals entering freshwater habitats. On entering aquatic habitats, these chemicals target and disrupt both physiological and behavioral functioning in various aquatic organisms. Herbicides, such as 2,4-dichlorophenoxyacetic acid (2,4-D), can have negative impacts on chemoreception because these receptor cells are in direct contact with water-soluble chemicals in the environment. Studies focusing on lethal concentration (LC₅₀) levels may understate the impact of herbicides within aquatic habitats because damage to the chemoreceptors can result in modified behaviors or lack of appropriate responses to environmental or social cues. The purpose of this experiment was to determine whether exposure to sublethal levels of 2,4-D alters the foraging behaviors of crayfish Orconectes rusticus. We hypothesized that crayfish exposed to greater concentrations of 2,4-D would be less successful in locating food or on locating food would consume smaller amounts possibly due to an inability to recognize the food odors in the contaminated waters. Crayfish were exposed to three sublethal levels of 2,4-D for 96 h and placed into a Y-maze system with a fish gelatin food source placed randomly in the right or left arm. Average walking speed, average time spent in the correct arm, and percent consumption were analyzed. Our data show that crayfish were impaired in their ability to forage effectively. These inabilities to locate and consume adequate amounts of food could result in lower body weights and decreased fitness in populations of crayfish exposed to 2,4-D in natural habitats.     

First Evaluation of a Population-Based Screen to Detect Emotional-Behavior Disorders in Orphaned Children in Sub-Saharan Africa

Due to the HIV/AIDS pandemic which has left 12 million children orphaned in Sub-Saharan Africa, children are at increased risk for mental health problems. Currently, no validity data exist for any screening measure of emotional-behavior disorders in pre-adolescent children in Sub-Saharan Africa. The aims of the current study were to evaluate the construct validity of the caregiver-, teacher-, and self-report versions of the one-page Strengths and Difficulties Questionnaire (SDQ) in 466 orphans in South Africa between the ages of 7 and 11 (M _age = 9.23 years, SD = 1.33, 51.93 % female) and to provide, for the first time, clinical cut-offs for this population. Findings demonstrated support for the caregiver SDQ, but not the teacher and self-report versions. We provide clinical cut-offs, but caution their use before further research is conducted. There remains a critical need for further psychometric studies of the SDQ in the developing world.