Faculty Bibliography

One means of stimulating the mammalian innate immune system is via Toll-like receptor 9 (TLR9) being exposed to unmethylated cytosine-phosphate-guanine (CpG) DNA, also known as pathogen-associated molecular patterns (PAMPs) of microbial origin. Synthetic CpG oligodeoxynucleotides (ODNs) with defined CpG motifs possess broad immunostimulatory properties that make CpG ODNs suitable as therapeutic interventions in a variety of human disease conditions, including Alzheimer's disease (AD). Rodent models are often used to preclinically test the effectiveness of CpG ODN therapeutic agents for AD and other disorders. However, the translatability of findings in such models is limited due to the significant difference of the expression of TLR9 between primates and rodents. The squirrel monkey (SQM), a New World non-human primate (NHP), is known to be phylogenetically proximate to humans, and develops extensive age-dependent cerebral amyloid angiopathy (CAA), a key pathological feature of AD. Hence, this model is currently being used to test AD therapeutics. In the present study, we conducted the first examination of Class C CpG ODN's immunomodulatory role in elderly SQMs. We documented the effectiveness of CpG ODN to trigger an immune response in an aged cohort whose immune system is senescent. The specific immune response patterns detected here closely resembled CpG ODN-induced immunostimulatory patterns observed in prior human studies. Overall, our findings provide critical data regarding the immunomodulatory potential of CpG ODN in this NHP model, allowing for future translational studies of innate immunity stimulation via TLR9 agonists for diverse indications, including AD therapeutics.

[This corrects the article DOI: 10.1186/s43058-020-00027-3.].

Background/UNASSIGNED:Implementation science (IS) has the potential to serve an important role in encouraging the successful uptake of evidence-based interventions. The current state of IS awareness and engagement among health researchers, however, is relatively unknown. Methods/UNASSIGNED:To determine IS awareness and engagement among health researchers, we performed an online survey of health researchers in the USA in 2018. Basic science researchers were excluded from the sample. Engagement in and awareness of IS were measured with multiple questionnaire items that both directly and indirectly ask about IS methods used. Unrecognized IS engagement was defined as participating in research using IS elements and not indicating IS as a research method used. We performed simple logistic regressions and tested multivariable logistic regression models of researcher characteristics as predictors of IS engagement. Results/UNASSIGNED:< 0.001). Conclusion/UNASSIGNED:Overall, awareness of IS is high among health researchers, yet there is also a high prevalence of unrecognized IS engagement. Efforts are needed to further disseminate what constitutes IS research and increase IS awareness among health researchers.