Self-assembling peptide for co-delivery of HIV-1 CD8+ T cells epitope and Toll-like receptor 7/8 agonists R848 to induce maturation of monocyte derived dendritic cell and augment polyfunctional cytotoxic T lymphocyte (CTL) response.

Peptide based vaccine that incorporates one or several highly conserved CD8+ T cells epitopes to induce potent cytotoxic T lymphocyte (CTL) response is desirable for some infectious diseases, such as HIV-1 (human immunodeficiency virus-1), and cancers. However, the CD8+ T cells epitope is often weakly immunogenic, and thus requires a specific adjuvant or delivery system to enhance the efficiency. Here we investigated the use of self-assembling peptide EAK16-II based platform to achieve the co-delivery of CD8+ T cells epitope and TLR7/8 agonists (R848 or R837) for augmenting DCs maturation and HIV-1 specific CTL response. HIV-1 CTL epitope SL9 was conjugated with EAK16-II to obtain SL9-EAK16-II, which further spontaneously co-assembled with R848 or R837 in aqueous solution, forming co-assembled nanofibers. Fluorescence spectra and calorimetrical titration revealed the interaction between SL9-EAK16-II assemblies and R848 or R837 via hydrogen bonding and hydrophobic interaction, with the binding affinity (dissociation constant Kd) of 0.62µM or 0.53µM, respectively. Ex vivo generated DCs from HIV-1+ patients pulsed with the SL9-EAK16-II/R848 nanofibers stimulated significantly more polyfunctional SL9 specific CTLs, compared to the DCs pulsed with SL9 alone or the mixture of SL9 and TLR agonist. Furthermore, the nanofibers elicited stronger SL9 specific CTL response in vaccinated mice. Our findings suggest the self-assembling peptide EAK16-II might be used as a new delivery system for peptide based vaccines.

Health of patients on the waiting list: Opportunity to improve health in Canada?

INTRODUCTION: A number of countries have healthcare systems where access to elective surgery is constrained. The inevitable outcome is wait lists for surgery. The objective of this study is to report cross-sectional health data collected from a broad sample of patients awaiting elective surgery and shed light on potential non-surgical treatments to improve health. RESEARCH DESIGN: Prospective cross-sectional survey of patients newly enrolled on the surgical wait list in the Vancouver Coastal Health region. Multivariate regression models were used to estimate the associations between patient characteristics and health, pain and depression. MEASURES: Health status instruments were used to measure study participants' general health, pain, and depression immediately after they were enrolled on the wait list for one of the targeted elective surgeries. RESULTS: A majority of patients reported some problems with pain or discomfort, and a large portion reported problems associated with anxiety or depression. Orthopedic patients were significantly more likely to report problems with mobility, usual activities and pain/discomfort. Neurosurgery patients were the most likely to report significant and severe depression. CONCLUSIONS: The high rates of pain and depression not only have implications for patients' immediate health, but may also affect long-term surgical outcomes. This study draws attention to recognizing a wider array of morbidity, some potentially requiring non-surgical interventions, while patients wait for elective surgery. Policy options include re-examining the surgical triage system and expanding surgical capacity to match self-reported health.

Improving hospital quality through payment reforms: A policy impact analysis in British Columbia.

Among the most devastating and costly consequences of fragmented care is unplanned readmissions. This study adapts Medicare's incentive program and applies the policy to hospitals in British Columbia. The financial implications for hospitals affected by these policies would be small and it is questionable whether the disincentive is worth the trade-offs.