Prevention of measles virus infection by intranasal delivery of fusion inhibitor peptides.

UNLABELLED: Measles virus (MV) infection is undergoing resurgence and remains one of the leading causes of death among young children worldwide despite the availability of an effective measles vaccine. MV infects its target cells by coordinated action of the MV H and the fusion (F) envelope glycoprotein; upon receptor engagement by H, the prefusion F undergoes a structural transition, extending and inserting into the target cell membrane and then refolding into a postfusion structure that fuses the viral and cell membranes. By interfering with this structural transition of F, peptides derived from the heptad-repeat (HR) regions of F can potently inhibit MV infection at the entry stage. We show here that specific features of H's interaction with its receptors modulate the susceptibility of MV F to peptide fusion inhibitors. A higher concentration of inhibitory peptides is required to inhibit F-mediated fusion when H is engaged to its nectin-4 receptor than when H is engaged to its CD150 receptor. Peptide inhibition of F may be subverted by continued engagement of receptor by H, a finding that highlights the ongoing role of H-receptor interaction after F has been activated and that helps guide the design of more potent inhibitory peptides. Intranasal administration of these peptides results in peptide accumulation in the airway epithelium with minimal systemic levels of peptide and efficiently prevents MV infection in vivo in animal models. The results suggest an antiviral strategy for prophylaxis in vulnerable and/or immunocompromised hosts. IMPORTANCE: Measles virus (MV) infection causes an acute illness that may be associated with infection of the central nervous system (CNS) and severe neurological disease. No specific treatment is available. We have shown that parenterally delivered fusion-inhibitory peptides protect mice from lethal CNS MV disease. Here we show, using established small-animal models of MV infection, that fusion-inhibitory peptides delivered intranasally provide effective prophylaxis against MV infection. Since the fusion inhibitors are stable at room temperature, this intranasal strategy is feasible even outside health care settings, could be used to protect individuals and communities in case of MV outbreaks, and could complement global efforts to control measles.

Forming professional identities on the health care team: discursive constructions of the 'other' in the operating room.

BACKGROUND: Inter-professional health care teams represent the nucleus of both patient care and the clinical education of novices. Both activities depend upon the'talk' that team members use to interact with one another. This study explored team members' interpretations of tense team communications in the operating room (OR). METHODS: The study was conducted using 52 team members divided into 14 focus groups. Team members comprised 13 surgeons, 19 nurses, nine anaesthetists and 11 trainees. Both uni-disciplinary (n = 11) and multi-disciplinary (n = 3) formats were employed. All groups discussed three communication scenarios, derived from prior ethnographic research. Discussions were audio-recorded and transcribed. Using a grounded theory approach, three researchers individually analysed sample transcripts, after which group discussions were held to resolve discrepancies and confirm a coding structure. Using the confirmed code, the complete data set was coded using the 'NVivo' qualitative data analysis software program. RESULTS: There were substantial differences in surgeons', nurses', anaesthetists', and trainees' interpretations of the communication scenarios. Interpretations were accompanied by subjects' depictions of disciplinary roles on the team. Subjects' constructions of other professions' roles, values and motivations were often dissonant with those professions' constructions of themselves. CONCLUSIONS: Team members, particularly novices, tend to simplify and distort others' roles and motivations as they interpret tense communication. We suggest that such simplifications may be rhetorical, reflecting professional rivalries on the OR team. In addition, we theorise that novices' echoing of role simplification has implications for their professional identity formation.