Structural language impairment in Autism Spectrum Disorder versus Loss of Autism Diagnosis: Behavioral and neural characteristics.

This study probed for structural language impairment using behavioral and functional neuroimaging methods in individuals with Autism Spectrum Disorder (ASD) and those diagnosed with ASD in childhood who no longer meet criteria for ASD, referred to as Loss of Autism Diagnosis (LAD1). Participants were drawn from Fein et al. (2013): ASD (n = 35), LAD (n = 31), and Neurotypical (NT; n = 34). Criteria for structural language impairment were: Scores ≤ 82 on Clinical Evaluation of Language Fundamentals-4 (CELF) Core Language, an omnibus measure of language; and scores ≤ 7 on CELF Recalling Sentences, a clinical marker of structural language impairment. Task-based fMRI examined lateralization of significantly activated language-related brain regions in groups with structural language impairment (LI2) versus normal-range language (LN3), collapsed across ASD, LAD1, and NT status. Results showed no ASD versus LAD group differences in the proportion of participants with structural language impairment according to either metric (Recalling Sentences or Core Language). Functional MRI results indicated greater left hemisphere lateralization within significantly activated regions in the LI2 group. Structural language abilities were not meaningfully associated with either social abilities or lifetime ADHD symptoms in LI2 subgroups, further suggesting the presence of structural language impairment. Findings indicate the presence of persistent structural language difficulty even in the absence of ASD symptoms in some individuals within the LAD1 group and unique patterns of language-related neural specialization for language function in LI2 relative to LN3.

Parental Perceptions of Autism Spectrum Disorder in Latinx and Black Sociocultural Contexts: A Systematic Review.

Parents of children with autism spectrum disorder (ASD) face challenges in accessing diagnostic and treatment services; these challenges vary by race, ethnicity, and culture. This systematic review examines parental perceptions of ASD within Latinx and Black American communities. Findings indicate that interconnections with family and religious groups promoted positive coping and describe positive impacts of having a child with ASD. Relative to White families, community members reported reduced access to information and more inaccurate beliefs about ASD, higher levels of ASD-related stigma, and more negative experiences with healthcare providers, which serve to exacerbate healthcare disparities. Conclusions are limited by an underrepresentation of minority groups in research. We call for efforts to address the specific needs of racial and ethnic minorities.

Hypoxia regulates Notch-3 mRNA and receptor activation in prostate cancer cells.

The Notch-3 receptor is a recognized key regulator of vascular responses and is increasingly associated with tumorigenesis. Hypoxia-inducible factors activate specific signaling pathways such as Notch in a number of cellular models. This study aimed to evaluate the regulation of Notch-3 by hypoxia in prostate cancer cells. Notch-3 gene and protein expression was established in a panel of aerobic and hypoxic prostate cell lines in vitro, the CWR22 xenograft model and RNA extracted from low grade (Gleason score < = 6); high grade (Gleason score > = 7); non-hypoxic (low HIF, low VEGF); hypoxic (high HIF, high VEGF) patient FFPE specimens. NOTCH-3 was upregulated in PC3 (3-fold), 22Rv1 (4.1-fold) and DU145 (3.8-fold) but downregulated in LnCaP (12-fold) compared to the normal cell lines. NOTCH-3 expression was modified following hypoxic exposure in these cells. NOTCH-3 was upregulated (2.2-fold) in higher grade and hypoxic tumors, when compared to benign and aerobic pools. In the CWR22 xenograft model, Notch-3 expression was restored in castrate resistant tumors. Nuclear translocation of the Notch-3 intracellular domain was no longer detected following exposure of cells to hypoxia but not associated with a change in expression of HES-1. Our data further identifies Notch-3 as a potentially key hypoxic-responsive member of the Notch pathway in prostate tumorigenesis.

Hypoxia, notch signalling, and prostate cancer.

The notch signalling pathway is involved in differentiation, proliferation, angiogenesis, vascular remodelling, and apoptosis. Deregulated expression of notch receptors, ligands, and targets is observed in many solid tumours, including prostate cancer. Hypoxia is a common feature of prostate tumours, leading to increased gene instability, reduced treatment response, and increased tumour aggressiveness. The notch signalling pathway is known to regulate vascular cell fate and is responsive to hypoxia-inducible factors. Evidence to date suggests similar, therapeutically exploitable, behaviour of notch-activated and hypoxic prostate cancer cells.