No abstract

Remote delivery of language and cognitive training is becoming increasingly prevalent within special education settings, and the recent COVID-19 pandemic has challenged many providers to pivot to telehealth models. This technical article outlines a procedure for developing computerized discrete-trial training programs using commonly available software, as well as a description of how to adapt this strategy to teach chained tasks remotely. Within this article, we describe how to establish unidirectional and bidirectional remote interfaces to work directly with learners. Finally, we conducted a field test of these approaches with programs adapted from two standardized curricula: PEAK and PRISM. We conclude the article by discussing barriers and potential solutions that we observed while field-testing these procedures within special education settings in response to the wide-scale emigration to remote teaching due to the COVID-19 pandemic. Supplementary Information The online version contains supplementary material available at 10.1007/s40617-020-00544-6.

Hidradenitis Suppurativa is a chronic inflammatory disease of which the pathogenesis is incompletely understood. Dermal fibroblasts have been previously identified as a major source of inflammatory cytokines, however information pertaining to the characteristics of subpopulations of fibroblasts in HS remains unexplored. Using in silico-deconvolution of whole-tissue RNAseq, Nanostring gene expression panels and confirmatory immunohistochemistry we identified fibroblast subpopulations in HS tissue and their relationship to disease severity and lesion morphology. Gene signatures of SFRP2+ fibroblast subsets were increased in lesional tissue, with gene signatures of SFRP1+ fibroblast subsets decreased. SFRP2+ and CXCL12+ fibroblast numbers, measured by IHC, were increased in HS tissue, with greater numbers associated with epithelialized tunnels and Hurley Stage 3 disease. Pro-inflammatory CXCL12+ fibroblasts were also increased, with reductions in SFRP1+ fibroblasts compared to healthy controls. Evidence of Epithelial Mesenchymal Transition was seen via altered gene expression of SNAI2 and altered protein expression of ZEB1, TWIST1, Snail/Slug, E-Cadherin and N-Cadherin in HS lesional tissue. The greatest dysregulation of EMT associated proteins was seen in biopsies containing epithelialized tunnels. The use of the oral Spleen tyrosine Kinase inhibitor Fostamatinib significantly reduced expression of genes associated with chronic inflammation, fibroblast proliferation and migration suggesting a potential role for targeting fibroblast activity in HS.

Hidradenitis suppurativa (HS) is a complex, heterogeneous inflammatory disease in need of novel therapies. 1 Currently, adalimumab is the sole licenced biologic therapy for HS, and only achieves clinical response (as measured by the hidradenitis suppurativa clinical response outcome measure) in 60% of patients. 2 Mechanistically, HS is associated with significant polarization of the Th17 immune axis with significant dysregulation of cytokines including IL-17A, 3 IL-17C, 4 IL-17F 3,[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] Agents targeting the Th17 immune axis have been explored in HS 6 including clinical trials, 7 but further development has been halted due to lack of positive results. 8 Two separate IL-23 antagonists (risankizumab and guselkumab) have been withdrawn from further development after a lack of positive results

Mast cells have traditionally been associated with allergic inflammatory responses; however they play important roles in cutaneous innate immunity and wound healing. The Hidradenitis Suppurativa tissue transcriptome is associated with alterations in innate immunity and wound healing associated pathways, however the role of Mast cells in the disease is unexplored. We demonstrate that Mast cell associated gene expression (using whole tissue RNAseq) is upregulated, and in-silico cellular deconvolution identifies activated mast cells upregulated and resting mast cells downregulated in lesional tissue. Tryptase/Chymase positive Mast cells (identified using IHC) localize adjacent to epithelialised tunnels, fibrotic regions of the dermis and at perivascular sites associated with Neutrophil Extracellular Trap formation and TNF-alpha production. Treatment with Spleen Tyrosine Kinase antagonist (Fostamatinib) reduces the expression of mast cell associated gene transcripts, associated biochemical pathways, and number of tryptase/chymase positive mast cells in lesional hidradenitis suppurativa tissue. This data indicates that although Mast cells are not the most abundant cell type in Hidradenitis Suppurativa tissue, the dysregulation of mast cells is associated with B cell/plasma cell inflammation, inflammatory epithelialized tunnels and epithelial budding. This provides an explanation as to the mixed inflammatory activation signature seen in HS, the correlation with dysregulated wound healing and potential pathways involved in the development of epithelialized tunnels.