ABSTRACT
RATIONALE: Severe viral respiratory infections are often characterised by extensive myeloid cell infiltration and activation and persistent lung tissue injury. However, the immunological mechanisms driving excessive inflammation in the lung remain poorly understood. OBJECTIVES: To identify the mechanisms that drive immune cell recruitment in the lung during viral respiratory infections and identify novel drug targets to reduce inflammation and disease severity. METHODS: Preclinical murine models of influenza virus and severe acute respiratory coronavirus 2 (SARS-CoV-2) infection. RESULTS: Oxidised cholesterols and the oxysterol-sensing receptor GPR183 were identified as drivers of monocyte-macrophage infiltration to the lung during influenza virus (IAV) and SARS-CoV-2 infection. Both IAV and SARS-CoV-2 infection upregulated the enzymes cholesterol 25-hydroxylase (CH25H) and cytochrome P450 family 7 subfamily member B1 (CYP7B1) in the lung, resulting in local production of the oxidised cholesterols 25-hydroxycholesterol (25-OHC) and 7α,25-dihydroxycholesterol (7α,25-OHC). Loss-of-function mutation of GPR183, or treatment with a GPR183 antagonist, reduced macrophage infiltration and inflammatory cytokine production in the lungs of IAV- or SARS-CoV-2-infected mice. The GPR183 antagonist significantly attenuated the severity of SARS-CoV-2 infection and viral loads. Analysis of single cell RNASeq data on bronchoalveolar lavage samples from healthy controls and COVID-19 patients with moderate and severe disease revealed that CH25H, CYP7B1 and GPR183 are significantly upregulated in macrophages during COVID-19. CONCLUSION: This study demonstrates that oxysterols drive inflammation in the lung via GPR183 and provides the first preclinical evidence for therapeutic benefit of targeting GPR183 during severe viral respiratory infections.
ABSTRACT
BACKGROUND: The majority of undergraduate anatomy learning has shifted online, or to a mixture of virtual and face-to-face teaching, due to the COVID-19 pandemic. Cadaveric shortages have also influenced the need for alternative methods of anatomical education. This study examines the current literature on the use of extended reality technologies (XR) such as Virtual reality (VR), Augmented reality (AR), and Mixed reality (MR) for anatomy teaching and explores its potential for implementation in medical education. METHODS: A literature review was performed of PubMed, ProQuest, Science Direct, and Springer databases. Included studies were assessed for user satisfaction, perceived effectiveness, cost, acceptability and side effects. RESULTS: The database search identified 1687 papers, of which 45 papers were included in this review. Both AR and VR had high rates of satisfaction and acceptability as a supplementary teaching aid amongst undergraduate participants. AR was found to have higher effectiveness than VR. VR is more expensive than AR. Results and comparisons were limited due to short length of study. CONCLUSIONS: VR is a popular choice with undergraduates as an aid to supplement teaching, in spite of the associated cost and side effects such as nausea. AR has shown the most potential for independent study. Larger and long-term studies are required to determine true effectiveness, and consideration of the clinical relevance of these technologies.