Reconceptualizing Integrated Knowledge Translation goals: a case study on basic and clinical science investigating the causes and consequences of food allergy.

BACKGROUND: Integrated Knowledge Translation (IKT) and other forms of research co-production are increasingly recognized as valuable approaches to knowledge creation as a way to better facilitate the implementation of scientific findings. However, the nature of some scientific work can preclude direct knowledge to action as a likely outcome. Do IKT approaches have value in such cases? METHODS: This study used a qualitative case study approach to better understand the function of IKT in a non-traditional application: basic and clinical science investigating the causes and consequences of food allergy. Building off previous baseline findings, data were obtained through in-depth interviews with project scientists and steering committee members and complemented by researcher observation. Data were analyzed through an integrated approach to understand how well participants perceived the stipulated project IKT outcomes had been met and to better understand the relationship between different forms of IKT goals, outcomes, and impacts. RESULTS: We propose a conceptual model which builds temporal continuity into the IKT work and understands success beyond truncated timelines of any one project. The model proposes project IKT goals be conceptualized through three metaphorical tower blocks: foundational (changing the culture for both scientists and knowledge-users), laying the groundwork (building relationships, networks and sparking scientific inquiry), and putting scientific knowledge to action. Based on this model, this case study demonstrated notable success at the foundational and intermediate blocks, though did not turn basic and clinical research knowledge into actionable outcomes within the project timespan. CONCLUSIONS: We find that current IKT literature which situates success as filling a knowledge to action gap is conceptually inadequate for understanding the full contributions of IKT activities. This work highlights the need for building cultural and scientific familiarity with IKT in order to better enable knowledge to action translation. Improving understanding and communication of science and empowering knowledge-users to engage with the research agenda are long-term strategies to build towards knowledge implementation and lay the ground work for many future research projects.

Mast cells selectively produce inflammatory mediators and impact the early response to Chlamydia reproductive tract infection.

Introduction: Chlamydia trachomatis (C. trachomatis) is a Gram-negative obligate intracellular bacterium that causes reproductive tract complications in women, including ectopic pregnancies and tubal factor infertility. We hypothesized that mast cells, which are common at mucosal barriers, may contribute to responses to Chlamydia infection and aimed to define human mast cell responses to C. trachomatis. Methods: Human cord blood-derived mast cells (CBMCs) were exposed to C. trachomatis to assess bacterial uptake, mast cell degranulation, gene expression, and production of inflammatory mediators. The role of formyl peptide receptors and Toll-like receptor 2 (TLR2) were investigated using pharmacological inhibitors and soluble TLR2. Mast cell-deficient mice and littermate controls were used to examine the in vivo role of mast cells in influencing the immune response to Chlamydia infection in the female reproductive tract. Results: C. trachomatis bacteria were taken up by human mast cells but did not replicate efficiently inside CBMCs. C. trachomatis-activated mast cells did not degranulate but maintained viability and exhibited cellular activation with homotypic aggregation and upregulation of ICAM-1. However, they significantly enhanced the gene expression of IL1B, CCL3, NFKB1, CXCL8, and IL6. Inflammatory mediators were produced, including TNF, IL-1ß, IL-1RA, IL-6, GM-CSF, IL-23, CCL3, CCL5, and CXCL8. Endocytic blockade resulted in reduced gene expression of IL6, IL1B, and CCL3, suggesting C. trachomatis induced mast cell activation in both extracellular and intracellular locations. The IL-6 response to C. trachomatis was reduced when CBMCs were treated with C. trachomatis coated with soluble TLR2. Mast cells derived from TLR2-deficient mice also demonstrated a reduced IL-6 response to C. muridarum. Five days following C. muridarum infection, mast cell-deficient mice showed attenuated CXCL2 production and significantly reduced numbers of neutrophils, eosinophils, and B cells in the reproductive tract when compared with mast cell-containing littermates. Discussion: Taken together, these data demonstrate that mast cells are reactive to Chlamydia spp. through multiple mechanisms that include TLR2-dependent pathways. Mast cells also play an important role in shaping in vivo immune responses in Chlamydia reproductive tract infection through both effector cell recruitment and modification of the chemokine microenvironment.

From social determinants to social epigenetics: Health geographies of chronic disease.

Social epigenetics explores relationships between social factors and health inequities embodied at the molecular level. Through modulating gene expression, epigenetic changes resulting from human-environment interactions may play a role in shaping health trajectories. This paper applies a health geography lens to explore the potential and support for conducting social epigenetic studies of chronic diseases with complex and dynamic etiologies. In so doing, we argue that social epigenetics presents a novel space for investigations of health and disease that is transdisciplinary and builds upon new understandings of bodies and place-based experiences. Given gender disparities in chronic diseases, we adopt a feminist perspective that cogitates the transactive relationships between gender and health/ill-health as mediated by biosocial processes at a variety of scales. Looking forward to the practical undertaking of social epigenetic studies, we assess existing theoretical and methodological support as well as insights to be gained. Reflecting upon the central tenets of health geography, we propose a unique positionality for health geographers to drive this field forward.

Prevalence of lapine rotavirus, astrovirus, and hepatitis E virus in Canadian domestic rabbit populations.

Lapine rotavirus and astrovirus have been associated with disease in rabbits, and there is strong evidence of zoonotic transmission of lapine hepatitis E virus (HEV). Outbreaks of enteritis are common on commercial meat farms, resulting in poor welfare, high rabbit mortality, and significant financial losses for rabbit producers. Currently, none of these viruses are routinely tested by diagnostic laboratories. In this study, we assessed the prevalence of rotavirus, astrovirus, and HEV RNA in 205 pooled and individual fecal samples from healthy Canadian laboratory, companion, shelter and commercial meat rabbit populations. Viral RNA were extracted and amplified via RT-PCR using virus-specific primers. Positive samples from the first cohort of samples tested were sequenced and aligned to previously identified viruses to confirm the products. Almost 45% (13/29) of the surveyed commercial rabbit farms were astrovirus-positive. Three commercial meat rabbit samples were positive for rotavirus, and either astrovirus or HEV RNA was also detected. Three companion rabbit samples also tested positive for lapine HEV. Samples from specific pathogen-free laboratory animals were negative for all viruses. Sequencing results showed highest identity to rotavirus A strain 30-96, lapine astrovirus strain 2208 and lapine HEV strain CMC-1. These results permit a better understanding of the prevalence of rotavirus, astrovirus, and hepatitis E virus in Canadian domestic rabbit populations, and continued screening for viruses may help to reduce risk of zoonotic agent transmission as well as providing a better understanding of potential causative agents of rabbit enteritis.