Assessment tool for visual perception deficits in cerebral visual impairment: development and normative data of typically developing children

Aim: To develop an assessment tool that measures a wide range of visual perceptual deficits common in cerebral visual impairment (CVI) and to provide normative data from typically developing children between 3 and 6 years of age. Method: Test development reflected cross‐talk between vision research and clinical relevance for CVI. The Children's Visual Impairment Test for 3‐ to 6‐year‐olds (CVIT 3–6) includes 14 subtests covering four domains of visual perception: Object Recognition, Degraded Object Recognition, Motion Perception, and Global–Local Processing. Normative data were collected from 301 typically developing children (mean age 4y 8mo [SD 9.7mo]; 148 females, 153 males). A questionnaire was administered to parents about pregnancy duration, birth, and developmental problems. Results: Average total CVIT 3–6 performance was 60.1 (SD 5.5) out of 70. The cut‐off score for normal visual perception (53) was set at the 10th centile of scores in typically developing children. Multiple regression indicated CVIT 3–6 visual perception scores increase with age for children born at 36 weeks’ gestational age or later (β=−18.03, 95% confidence interval −31.31 to −4.75). Interpretation: CVIT 3–6 is a tool to assess a wide range of visual perceptual deficits common in CVI. Age‐dependent normative data are available because we found performance increased with age. What the Paper Adds: - A test for visual perceptual deficits common in cerebral visual impairment. - Visual perceptual functions improve with age in full‐term typically developing children

Activation of the absent in melanoma 2 inflammasome in peripheral blood mononuclear cells from Idiopathic pulmonary fibrosis patients leads to the release of pro-fibrotic mediators

© 2018 Terlizzi, Molino, Colarusso, Donovan, Imitazione, Somma, Aquino, Hansbro, Pinto and Sorrentino. Idiopathic pulmonary fibrosis (IPF) is a chronic fibro-proliferative disease characterized by poor prognosis, with a mean survival of ~2-3 years after definite diagnosis. The cause of IPF is still unknown but it is a heterogeneous condition in which the aberrant deposition of extracellular matrix leads to extensive lung remodeling. This remodeling is a consequence of inflammatory responses, but the mechanisms involved are poorly understood. In this study, we first analyzed a bleomycin-induced mouse model, which showed that higher expression of IL-1β, but not IL-18, was correlated to pulmonary cell infiltration and fibrosis. Then, we found that peripheral blood mononuclear cells (PBMCs) from IPF patients released IL-1α and IL-18 in a NLRP3- and calpain-independent manner after LPS ± ATP stimulation. Instead, the activation of the absent in melanoma 2 (AIM2) inflammasome induced the release of IL-1α in a caspase-1-/caspase-8-independent manner; whereas IL-18 release was caspase-1 dependent. These effects correlated with the release of the pro-fibrotic TGF-β, which was induced by AIM2 activation in a caspase-1- and TLR4-independent manner, but dependent on IL-1α. In this context, the activation of AIM2 induced the release of caspase-4 from IPF-derived PBMCs, which correlated with the mRNA levels of this caspase that was higher in IPF than in healthy PBMCs. In conclusion, our findings identify a novel molecular mechanism whereby the activation of AIM2 could lead to the activation of the non-canonical inflammasome (caspase-4 dependent) that induces the release of IL-1α responsible for the release of TGF-β from PBMCs of IPF patients