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In this paper, methods and models for the design of educational interventions and usable systems are presented and synthesized. The purpose is to suplliment the design process with educational considerations and discern design principles for the development of serious STEM games. This synthesis can contribute to the design of the next generation of technologically enhanced learning environments.

In a cardiology department, there are some patients that require long-term antibiotics, such as those with infective endocarditis or infected prosthetic devices. We describe our experience with intravenous antibiotic therapy for patients with cardiology diagnoses who require a period of antibiotics in our outpatient service during the period of the COVID-19 pandemic. A total of 15 patients were selected to have outpatient antibiotic therapy (age range 36 to 97 years, 60% male). A total of nine patients had infective endocarditis, four patients had infected valve prosthesis or transcatheter aortic valve implantation (TAVI) endocarditis, one patient had infected pericardial effusion while another had infected pericarditis. For these 15 patients there was a total of 333 hospital bed-days, on average 22 days per patient. These patients also had a total of 312 days of outpatient antibiotic therapy, which was an average of 21 days per patient. The total cost, if patients were admitted for those days, assuming a night cost £400, was £124,800, which was on average £8,320 per patient. Three patients were readmitted within 30 days. One had ongoing endocarditis that was managed medically and another had pulmonary embolism. The last patient had a side effect related to daptomycin use. In conclusion, outpatient antibiotic therapy in selected patients with native or prosthetic infective endocarditis appears to be safe for a selected group of patients with associated cost savings.

O presente trabalho tem como objetivo contribuir com as reflexões sobre o pensamento gramsciano nas produções acadêmicas na área da educação brasileira por meio dos resultados obtidos na pesquisa intitulada Mapa Bibliográfico de Gramsci no Brasil. Mais especificamente, contribuir com reflexões acerca da relação entre educação, política e filosofia contidas no pensamento de Antonio Gramsci. A especificidade da filosofia da práxis delineada pelo filósofo italiano traz para o debate novas abordagens acerca da educação, por meio de uma construção teórico-prática, revolucionária, que visa a transformação do mundo a partir da criação de um novo projeto de sociedade. Recebido em 06 de outubro de 2019Aprovado em 15 de novembro de 2019Editado em 15 de dezembro de 2019

Objective To assess the safety and efficacy of lenabasum in diffuse cutaneous systemic sclerosis (dcSSc). Methods A randomized, double‐blind, placebo‐controlled, phase II study was conducted at 9 SSc clinics in the US. Adults with dcSSc of ≤6 years’ duration who were receiving stable standard‐of‐care treatment were randomized to receive lenabasum (n = 27) or placebo (n = 15). Lenabasum doses were 5 mg once daily, 20 mg once daily, or 20 mg twice daily for 4 weeks, followed by 20 mg twice daily for 8 weeks. Safety and efficacy were assessed at weeks 4, 8, 12, and 16. Results Adverse events (AEs) occurred in 63% of the lenabasum group and 60% of the placebo group, with no serious AEs related to lenabasum. Compared to placebo, lenabasum treatment was associated with greater improvement in the American College of Rheumatology Combined Response Index in diffuse cutaneous Systemic Sclerosis (CRISS) score and other efficacy outcome measures that assessed overall disease, skin involvement, and patient‐reported function. The median CRISS score increased in the lenabasum group during the study, reaching 0.33, versus 0.00 in the placebo group, at week 16 (P = 0.07 by 2‐sided mixed‐effects model repeated‐measures analysis). Gene expression in inflammation and fibrosis pathways was reduced, and inflammation and fibrosis were improved on histologic evaluation of skin biopsy specimens, in the lenabasum group compared to the placebo group (all P ≤ 0.05). Conclusion Despite a short trial duration in a small number of patients in this phase II study in dcSSc, our findings indicate that lenabasum improves efficacy outcomes and underlying disease pathology with a favorable safety profile.

Treatment options are limited for skin disease in dermatomyositis. Lenabasum is a cannabinoid receptor type 2 agonist that triggers the resolution of inflammation.The objective of this study was to evaluate the safety and efficacy of lenabasum in patients with refractory cutaneous dermatomyositis.This study was a single-center, double-blind, randomized, placebo-controlled phase 2 study conducted from July 2015 to August 2017.The population included subjects aged ≥18 years with at least moderately active dermatomyositis skin activity by Cutaneous Dermatomyositis Disease Area and Severity Index activity ≥ 14 and failure or intolerance to hydroxychloroquine.Participants received 20 mg lenabasum daily for 28 days and then 20 mg twice per day for 56 days or placebo.The primary outcome was a change in Cutaneous Dermatomyositis Disease Area and Severity Index activity. Safety and other secondary efficacy assessments were performed till day 113.A total of 22 subjects were randomized to lenabasum (n = 11) or placebo (n = 11). No serious or severe adverse events were related to lenabasum, and no participants discontinued the study. The adjusted least-squares mean for Cutaneous Dermatomyositis Disease Area and Severity Index activity decreased more for lenabasum, and the difference was significant on day 113 (least-squares mean [standard error] difference = ‒6.5 [3.1], P = 0.038). Numerically greater improvements were seen in multiple secondary efficacy outcomes and biomarkers with lenabasum.Lenabasum treatment was well tolerated and was associated with greater improvement in Cutaneous Dermatomyositis Disease Area and Severity Index activity and multiple efficacy outcomes.This study was registered at ClinicalTrials.gov, NCT02466243.

Background Lenabasum is a cannabinoid type 2 receptor (CB2R) reverse agonist that demonstrates anti-inflammatory effects in vivo and in vitro in dermatomyositis (DM) and is currently being investigated for therapeutic potential. The purpose of our study is to investigate CB2R distribution as well as the effects of lenabasum in DM. Methods Immunohistochemistry staining (IHC) was utilized to examine immune cell and cytokine production changes in lesional DM skin biopsies from lenabasum and placebo-treated patients. CB2R expression in various immune cell populations within DM skin was investigated with image mass cytometry (IMC), whereas flow cytometry elucidated CB2R expression in DM peripheral blood mononuclear cells (PBMCs) as well as cytokine production by CB2R-expressing cell populations. Results After 12 weeks of lenabasum treatment, IHC staining showed that CD4+ T cells, CB2R, IL-31, IFN-γ, and IFN-β cytokines were downregulated. IFN-γ and IFN-β mRNA decreased in lesional DM skin but not in PBMCs. IMC findings revealed that CB2R was upregulated in DM lesional skin compared to HC skin and DM PBMCs (pp Conclusion Our findings of differential CB2R expression based on location and cell type suggest modes by which lenabasum may exert anti-inflammatory effects in DM and highlights dendritic cells as potential therapeutic targets.

The Canadian Inflammatory Myopathy Study (CIMS) is a multicenter prospective cohort recruiting in 8 centers across Canada. One of the aims of CIMS is to conduct and participate in clinical trials in autoimmune inflammatory myopathies (AIM). Conducting clinical trials in rare diseases such as AIM presents challenges. During this symposium, experts in the field presented different solutions to successfully conduct clinical trials in AIM, including the importance of collaboration and careful trial design, as well as training and mentoring of young investigators.

Dermatomyositis pathogenesis remains incompletely understood; however, recent work suggests a predominant IFN-1 response. We explored dermatomyositis pathogenesis by quantifying the inflammatory cells in the skin, comparing myeloid with plasmacytoid dendritic cell release of IFN-β, and assessing myeloid dendritic cell (mDC) contribution to hydroxychloroquine refractoriness. Immunohistochemistry was performed to assess cell-type expression in lesional skin biopsies from 12 patients with moderate-to-severe cutaneous dermatomyositis. Immunofluorescence, laser-capture microdissection, and flow cytometry were used to assess mDC release of IFN-β in lesional skin biopsies and blood of patients with dermatomyositis. Immunohistochemistry was utilized to determine whether myeloid or plasmacytoid dendritic cells were increased in hydroxychloroquine nonresponders. CD4+, CD11c+, and CD69+ cells were more populous in lesional skin of patients with dermatomyositis. mDCs colocalized with IFN-β by immunofluorescence and laser-capture microdissection revealed increased IFN-β mRNA expression by mDCs in lesional skin of patients with dermatomyositis. In blood, both mDCs and plasmacytoid dendritic cells were major producers of IFN-β in patients with dermatomyositis, whereas plasmacytoid dendritic cells predominately released IFN-β in healthy controls (P0.01). mDCs were significantly increased in the skin of hydroxychloroquine nonresponders compared with that in the skin of responders (P0.05). mDCs cells appear to play an important role in dermatomyositis pathogenesis and IFN-β production.

BACKGROUND: Dermatomyositis (DM) is an autoimmune disease affecting skin, skeletal muscle, and lungs. Pathogenesis is considered largely driven by interferon-beta (IFN-beta) and involves CD4+ cells and dendritic cells (DCs). (I) Quantify inflammatory cells and IFN-beta in skin; correlate with Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) scores. (II) Identify DC type contributing to refractoriness to hydroxychloroquine (HCQ). (III) Compare IFN-beta production by mDCs vs. pDCs in DM. METHODS: (I) DM skin biopsies evaluated for cells and cytokines using IHC from 12 patients with moderate-severe skin disease at baseline and after 12 weeks of therapy. (II) IHC performed on skin biopsies to compare myeloid DC (mDC) and pDC expression in HCQ-responders vs. -nonresponders. (III) Flow cytometry performed on PBMCs from 5 healthy controls and 5 DM patients. RESULTS: (I) CD4+ cells, macrophages, mDCs, and TRM cells were the most populous in DM skin, followed by CD8+ cells, mast cells, and pDCs. Change in CD4+ and CD8+ cells/HPF significantly correlated with change in CDASI scores (r=0.82, P