The angiotensin II receptor 2 is expressed and mediates angiotensin II signaling in lung fibrosis

Idiopathic pulmonary fibrosis (IPF) is a severe interstitial lung disease unresponsive to currently available therapies. In IPF, initial alveolar epithelial cell damage leads to activation of fibroblast-(myo)fibroblasts, which deposit an increased amount of a collagen-rich extracellular matrix. Angiotensin II (ANGII) signaling, mediated via angiotensin II receptor type 1 (AGTR1) or type 2 (AGTR2), controls tissue remodeling in fibrosis, but the relevance of AGTR2 remains elusive. In the present study, we demonstrated increased expression of AGTR1 und AGTR2 in human and rodent lung tissues from patients with IPF and mice subjected to bleomycin-induced fibrosis, respectively. Both AGTR1 und AGTR2 localized to interstitial fibroblasts. Quantitative analysis of cell surface expression in primary mouse fibroblasts revealed a significant increase of AGTR2 surface expression in fibrotic fibroblasts, whereas AGTR1 surface expression levels remained similar. ANGII treatment of normal fibroblasts led to enhanced migration and proliferation, which was abrogated after pretreatment with losartan (LOS), an AGTR1 inhibitor. In contrast, in fibrotic fibroblasts, migration and proliferation was modified only by AGTR2, but not AGTR1 inhibition (using PD123319). ANGII-induced effects were mediated via phosphorylation of the mitogen-activated protein kinases p38 and p42/44, which was blocked via LOS and PD123319, respectively. Similar effects of AGTR1 and AGTR2 inhibition were observed using conditioned media of alveolar epithelial cells, a prominent source of ANGII in the lung in vivo. In summary, we conclude that ANGII signaling occurs primarily via AGTR1 in normal fibroblasts, while AGTR2-mediated effects are dominant on activated (myo)-fibroblasts, a receptor switch that may perturb epithelial-mesenchymal interaction, thereby further perpetuating fibrogenesis.     

Teaching individuals with autism spectrum disorder to ask questions: A systematic review

This review involved a systematic search and analysis of studies aimed at teaching individuals with autism spectrum disorder (ASD) to ask questions (i.e., teaching mands for information). A systematic search of databases, reference lists, and journals identified 21 studies that met predetermined inclusion criteria. Included studies were then summarized in terms of (a) participant characteristics, (b) dependent variables (e.g., types of question-asking skills that were taught), (c) intervention procedures, (d) research designs, and (e) outcomes. All 21 studies reported that participants acquired or improved in the targeted question-asking skills. The most common intervention components included (a) echoic prompts and systematic fading procedures (e.g., time delay), (b) positive reinforcement via provision of requested information and/or access to preferred items or activities, and (c) contriving situations to motivate specific questions (i.e., creating establishing operations). Implications for practitioners and directions for future research are discussed.     

Choosing a response topography for individuals with autism during functional communication training: A critically appraised topic

Abstract

A critically appraised topic (CAT) is one form of rapid review that can be particularly useful for informing practice. The purpose of this CAT was to examine the effects of mand preference on Functional Communication Training outcomes in individuals with autism spectrum disorder and to describe procedures used to assess preference for a mand topography. In addition to the methodology, the authors present and discuss the findings of this CAT. The authors propose an update to this CAT in September 2021.     

Effects of fibrin sealant on the fixation of porous titanium and pyrolytic carbon implants

The authors investigated the potential role the fibrin sealant system may portray in the fixation of osseous implants. The application of a layer of fibrin did not interfere with the fixation of osseous implants of either pyrolytic carbon or Biolite-coated porous titanium. A greater percentage of tissue ingrowth was observed in the porous titanium implants in the presence of the fibrin sealant system; however, no significant difference in the ultimate interfacial shear stress was observed.