In various types of cancers including glioblastoma, accumulating evidence show the existence of cancer stem‐like cells (CSCs), characterized by stem cell marker expression, capability of differentiation and self‐renewal, and high potential for tumor propagation in vivo. LGR5, whose expression is positively regulated by the Wnt signaling pathway, is a stem cell marker in intestinal mucosa and hair follicle in the skin. As Wnt signaling is also involved in brain development, the function of LGR5 in the maintenance of brain CSCs is to be assessed. Our study showed that the LGR5 transcript level was increased in CSCs. Co‐immunofluorescence staining demonstrated the co‐localization of CD133‐ and LGR5‐positive cells in glioblastoma tissue sections. Functionally, silencing of LGR5 by lentiviral shRNA‐mediated knockdown induced apoptosis in brain CSCs. Moreover, LGR5 depletion led to a downregulation of L1 cell adhesion molecule expression. In line with an important function in glioma tumorigenesis, LGR5 expression increased with glioma progression and correlated with an adverse outcome. Our findings suggest that LGR5 plays a role in maintenance and/or survival of brain CSCs.
7 May 2019 in Archives of Clinical Neuropsychology
Objective: Verbal fluency (VF) tasks are widely used to investigate children’s lexical knowledge and executive functions skills. Consistency of measurement of the strategic retrieval components is still an issue and performance of Brazilian–Portuguese speaking children are currently not available. A cross-sectional study investigated the effects of age, school type (public × private) and the influence of language, memory and inhibitory control on VF. Method: We assessed 414 Brazilian children, aged 6–12, in the number of words produced and both clustering and switching components, with two measures of VF: letter (LVF) and semantic (SVF). Results: Analysis of the number of words produced showed a significant increase between 6–8-year-olds, 9–10-year-olds and 11–12-year-olds in SVF, while in LVF, the differences were significant only in the later age group. In SVF, the numbers of clusters and switches increased with age, whereas in LVF, the number of switches increased in all age groups, but clusters increased only in the older group. Structural equation model analyses showed that oral and written language, verbal memory and inhibitory control are associated with VF performance and IQ, while age mediated VF performance. Conclusions: The results indicate a different development pattern between LVF and SVF in the number of words produced and in clustering and switching, with the latter predicting VF performance in words produced. VF development is shown to depend on language, memory and inhibitory control. Our results have important implications to clinical neuropsychology.
1 June 2020 in Trends in Psychiatry and Psychotherapy
Introduction Children with anxiety disorders have been suggested to possess deficits in verbal fluency, shifting and attention, with inconsistent results regarding working memory and its subcomponents. This study extends previous findings by analyzing the performance of children with anxiety disorders in a wide range of neuropsychological functions. Methods We evaluated 54 children with a primary diagnosis of an anxiety disorder according to diagnostic criteria from the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) using subtests of a neuropsychological battery. The severity of anxiety disorders was assessed using the Pediatric Anxiety Rating Scale (PARS). We calculated the frequency of neuropsychological impairments (-1.5 standard deviation of the normative sample). Comparisons between groups were performed based on the severity of anxiety symptoms, as well as in the presence of one vs. more diagnoses of anxiety disorder. Results We found higher impairment in visuospatial working memory (23.1%), semantic memory (27.8%), oral language (35.4%) and word writing (44.4%) in anxious children. Moreover, children with higher anxiety severity presented lower performance in visuospatial working memory, inferential processing, word reading, writing comprehension, copied writing, and semantic verbal fluency (d = 0.49 to 0.96 [Cohen’s d]). The higher the number of anxiety diagnoses, the lower the performance in episodic memory and oral and written language (d = 0.56 to 0.77). Conclusion Our data suggested the presence of memory (visuospatial working memory and semantic memory) and language deficits (oral and writing) in some children with an anxiety disorder. Severity and number of anxiety diagnoses were associated with lower performance in memory and language domains in childhood.
The objective of this study was to describe an adaptation to Brazilian Portuguese of the methodological criteria for analysis of clustering and switching in semantic verbal fluency (SVF) and phonemic verbal fluency (PVF) tasks. The adaptation process consisted of six steps, including the selection of the clustering and switching variables based on data from a sample of 419 children and the analysis of inter-rater reliability (six raters). The following variables were scored: the total number of words generated the raw number of clusters, the mean cluster size, and the raw number of switches. There was a significant association between raters (intra-class correlation coefficients between 0.95 and 0.99), showing that the analytical method was reliable. Our study provides an evaluation of SVF and PVF tasks that goes beyond the overall score, making it possible to investigate the cognitive processes underlying this neuropsychological function.
1 March 2017 in Trends in Psychiatry and Psychotherapy
Objective: The aim of the present study was to assess children and adolescents with mild and severe anxiety disorders for their performance in attention, verbal episodic memory, working memory, visuoconstructive skills, executive functions, and cognitive global functioning and conduct comparative analyses with the performance of children free from anxiety disorders. Methods: Our sample comprised 68 children and adolescents aged 10 to 17 years (41 with current diagnoses of anxiety disorders and 27 controls) selected from a larger cross-sectional community sample of adolescents. Children and adolescents with anxiety disorders were categorized into two groups on the basis of anxiety severity (mild or severe). All participants underwent a neuropsychological assessment battery to evaluate attention, verbal episodic memory, working memory, visuoconstructive skills, and executive and cognitive functions. Results: No differences were found in any neuropsychological tests, with the single exception that the group with mild anxiety had better performance on the Digit Span backward test compared to subjects with severe anxiety and to controls (p = 0.041; η2 = 0.11). Conclusions: Not only might anxiety disorders spare main cognitive functions during adolescence, they may even enhance certain working memory processes.
What is Dissemination and Implementation Science? The field of Implementation Science studies how intentional actions promote the incorporation of evidence-based intervention into usual care, while Dissemination Science examines how to intentionally share information about evidence-based intervention. It is important to clarify that scientific research results are understood as effective interventions or innovations (e.g., practices, programs, policies, procedures, products, medications, etc.) that are evidence-based.() To implement and disseminate an intervention in usual care, one of the models of D&I proposes the [...] What is Dissemination and Implementation Science? The field of Implementation Science studies how intentional actions promote the incorporation of evidence-based intervention into usual care, while Dissemination Science examines how to intentionally share information about evidence-based intervention. It is important to clarify that scientific research results are understood as effective interventions or innovations (e.g., practices, programs, policies, procedures, products, medications, etc.) that are evidence-based.() To implement and disseminate an intervention in usual care, one of the models of D&I proposes the