ABSTRACT
PURPOSE: We attempted to evaluate the ability of 125 preschool and school children with autism spectrum disorder (ASD children) to understand the intentions of those speaking to them using prosody of the voice, by comparing it with that of 119 typically developing children (TDC) and 51 development-age-matched children with attention deficit hyperactivity disorder (ADHD children), and to explore, based on the results, a method for objective evaluation of children with ASD in the early and later periods of childhood. METHODS: Phrases routinely used by children were employed in the task administered to the children, with the prosody of the voice speaking these phrases changed to express the four emotions (acceptance, rejection, bluff and fooling). RESULTS: The percentage of children with ASD who could correctly identify the emotion of "fooling" was significantly lower than that of TDC, at each developmental age (corresponding to middle kindergarten class to sixth year of elementary school). On the other hand, in the children with ADHD, while the correct answer rate for identifying the emotion of "fooling" was significantly lower than that in the TDC and higher than that in the ASD children at development ages corresponding to the early years of elementary school, it did not differ significantly from that in the TDC and was higher than that ASD children at development ages corresponding to the later years of elementary school. CONCLUSION: These results indicate that children with ASD find it particularly difficult to understand the emotion of fooling by listening to speech with discrepancy between the meaning of the phrases and the emotion expressed by the voice, although the prosody of the voice may serve as a key to understanding the emotion of the speakers. This finding also suggests that the prosody of the voice expressing this emotion (fooling) may be used for objective evaluation of children with ASD.
Subject(s)
Autism Spectrum Disorder/diagnosis , Child Development Disorders, Pervasive/psychology , Attention Deficit Disorder with Hyperactivity/physiopathology , Auditory Perception/physiology , Autism Spectrum Disorder/physiopathology , Child , Child Development/physiology , Child, Preschool , Comprehension , Emotions , Female , Humans , Male , Neuropsychological Tests , Speech , Speech Perception/genetics , Speech Perception/physiologyABSTRACT
Differentiation of cancer stem cells (CSCs) into cancer cells causes increased sensitivity to chemotherapeutic agents. Although inhibition of mammalian target of rapamycin (mTOR) leads to CSC survival, the effect of branched chain amino acids (BCAAs), an mTOR complex 1 (mTORC1) activator remains unknown. In this study, we examined the effects of BCAA on hepatocellular carcinoma (HCC) cells expressing a hepatic CSC marker, EpCAM. We examined the effects of BCAA and/or 5-fluorouracil (FU) on expression of EpCAM and other CSC-related markers, as well as cell proliferation in HCC cells and in a xenograft mouse model. We also characterized CSC-related and mTOR signal-related molecule expression and tumorigenicity in HCC cells with knockdown of Rictor or Raptor, or overexpression of constitutively active rheb (caRheb). mTOR signal-related molecule expression was also examined in BCAA-treated HCC cells. In-vitro BCAA reduced the frequency of EpCAM-positive cells and improved sensitivity to the anti-proliferative effect of 5-FU. Combined 5-FU and BCAA provided better antitumor efficacy than 5-FU alone in the xenograft model. Stimulation with high doses of BCAA activated mTORC1. Knockdown and overexpression experiments revealed that inhibition of mTOR complex 2 (mTORC2) or activation of mTORC1 led to decreased EpCAM expression and little or no tumorigenicity. BCAA may enhance the sensitivity to chemotherapy by reducing the population of cscs via the mTOR pathway. This result suggests the utility of BCAA in liver cancer therapy.