Aspergillus fumigatus Supernatants Disrupt Bronchial Epithelial Monolayers: Potential Role for Enhanced Invasion in Cystic Fibrosis.

Aspergillus fumigatus is the most commonly isolated fungus in chronic lung diseases, with a prevalence of up to 60% in cystic fibrosis patients. Despite this, the impact of A. fumigatus colonisation on lung epithelia has not been thoroughly explored. We investigated the influence of A. fumigatus supernatants and the secondary metabolite, gliotoxin, on human bronchial epithelial cells (HBE) and CF bronchial epithelial (CFBE) cells. CFBE (F508del CFBE41o-) and HBE (16HBE14o-) trans-epithelial electrical resistance (TEER) was measured following exposure to A. fumigatus reference and clinical isolates, a gliotoxin-deficient mutant (ΔgliG) and pure gliotoxin. The impact on tight junction (TJ) proteins, zonula occludens-1 (ZO-1) and junctional adhesion molecule-A (JAM-A) were determined by western blot analysis and confocal microscopy. A. fumigatus conidia and supernatants caused significant disruption to CFBE and HBE TJs within 24 h. Supernatants from later cultures (72 h) caused the greatest disruption while ΔgliG mutant supernatants caused no disruption to TJ integrity. The ZO-1 and JAM-A distribution in epithelial monolayers were altered by A. fumigatus supernatants but not by ΔgliG supernatants, suggesting that gliotoxin is involved in this process. The fact that ΔgliG conidia were still capable of disrupting epithelial monolayers indicates that direct cell-cell contact also plays a role, independently of gliotoxin production. Gliotoxin is capable of disrupting TJ integrity which has the potential to contribute to airway damage, and enhance microbial invasion and sensitisation in CF.

Virtual clinics versus face-to-face review: Is the benefit the same for new orthopaedic patients?

BACKGROUND: COVID-19 shocked global healthcare systems, particularly the surgical services, resulting in a significant backlog of patients with waiting times not expected to return to pre-pandemic levels until 2025. The Royal College of Surgeons has recommended a wider use of virtual clinics to meet the increased demand. The efficacy of virtual follow up is well documented in the literature; however, there is very little evidence of the role of virtual clinics in the assessment of new elective patients. METHODS: Observational study comparing clinical outcomes of new patients electively referred to orthopaedic virtual clinics between January and February 2021 with face-to-face clinics in January and February 2020. RESULTS: Over the equivalent time frame, more patients were reviewed in virtual clinics compared to traditional face-to-face (821 vs 499). However, virtual clinics lead to significantly more patients being brought back for follow up (78.3% vs 37.3%) and fewer patients received outcomes that progressed their journey towards a definitive intervention or discharge. CONCLUSION: The overall benefit of virtual clinic appointments in the context of reviewing new patients remains to be proven. Despite increasing use of virtual clinics in the National Health Service, we have shown a potential delay to patients' clinical progression, ultimately delaying healthcare delivery. Potential methods to improve the benefit of virtual clinics are proposed.

Chemokine Regulation During Epidemic Coronavirus Infection.

SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus-2) is the third coronavirus to emerge as a cause of severe and frequently fatal pneumonia epidemics in humans, joining SARS-CoV and MERS-CoV (Middle East Respiratory Syndrome-coronavirus). As with many infectious diseases, the immune response to coronavirus infection may act as a double-edged sword: necessary for promoting antiviral host defense, but, if not appropriately regulated, also able to incite life-threatening immunopathology. Key immunoregulatory mediators include the chemokines, a large family of leukocyte chemoattractants that coordinate leukocyte infiltration, positioning and activation in infected tissue by acting at specific G protein-coupled receptors. Here, we compare the involvement of chemokines and chemokine receptors during infection with the three epidemic coronaviruses and discuss their potential value as biomarkers and targets for therapeutic development.