The Human Tissue-Biomaterial Interface : A Role for PPARγ-Dependent Glucocorticoid Receptor Activation in Regulating the CD163(+) M2 Macrophage Phenotype

In vivo studies of implanted acellular biological scaffolds in experimental animals have shown constructive remodeling mediated by anti-inflammatory macrophages. Little is known about the human macrophage response to such biomaterials, or the nature of the signaling mechanisms that govern the macrophage phenotype in this environment. The cellular events at the interface of a tissue and implanted decellularized biomaterial were examined by establishing a novel ex vivo tissue culture model in which surgically excised human urinary tract tissue was combined with porcine acellular bladder matrix (PABM). Evaluation of the tissue-biomaterial interface showed a time-dependent infiltration of the biomaterial by CD68(+) CD80(-) macrophages. The migration of CD68(+) cells from the tissue to the interface was accompanied by maturation to a CD163(hi) phenotype, suggesting that factor(s) associated with the biomaterial or the wound edge was/were responsible for the active recruitment and polarization of local macrophages. Glucocorticoid receptor (GR) and peroxisome proliferator activated receptor gamma (PPARγ) signaling was investigated as candidate pathways for integrating inflammatory responses; both showed intense nuclear labeling in interface macrophages. GR and PPARγ activation polarized peripheral blood-derived macrophages from a default M1 (CD80(+)) toward an M2 (CD163(+)) phenotype, but PPARγ signaling predominated, as its antagonism blocked any GR-mediated effect. Seeding on PABM was effective at polarizing peripheral blood-derived macrophages from a default CD80(+) phenotype on glass to a CD80(-) phenotype, with intense nuclear localization of PPARγ. These results endorse in vivo observations that the infiltration of decellularized biological scaffolds, exemplified here by PABM, is pioneered by macrophages. Thus, it appears that natural factors present in PABM are involved in the active recruitment and polarization of macrophages to a CD163(+) phenotype, with activation of PPARγ identified as the candidate pathway. The harnessing of these natural matrix-associated factors may be useful in enhancing the integration of synthetic and other natural biomaterials by polarizing macrophage activation toward an M2 regulatory phenotype

Using a Search Strategy Tool To Teach Search Strategy Development

Objective: To demonstrate how use of a search strategy form together with a health science librarian consult improved student understanding of search strategy. Methods: Two embedded librarians for pharmacy and public health had separately designed assignments to teach advanced search techniques for their respective students but felt the outcomes were unsatisfactory. To address this, the pharmacy librarian created an exercise for students that would facilitate understanding of the search development process. Students completed a form that walked through the steps of the development process prior to meeting with a research librarian. Students then integrated librarian feedback into the final search strategy to complete the assignment. The public health librarian adopted a modified version of the pharmacy form. These students participated in a librarian led hands-on searching exercise and were encouraged to meet individually with the librarian as they progressed with their own projects. Results: Both librarians noticed better developed and more robust search strategies and greater understanding of controlled vocabulary. Instead of vague searches, multiple poorly-developed searches, and haphazard article selection, students found additional on-target results more effectively. For the pharmacy cohort, the mandatory librarian session involved more of the students in the search while overall assignment grades improved. For the public health doctoral students, the step-by-step process resulted in an improved understanding of the search process and better designed search strategies. One limitation is that we did not obtain IRB approval in advance of collecting data so cannot report on specifics. Conclusions: Breaking down the search process into separate steps using the search form seems to have increased the students’ knowledge about using controlled vocabulary and designing robust search strategies. Students that worked with a librarian were more engaged and showed greater understanding. The search form along with hands-on time with a librarian is a winning combination

Accounting for Work from Home in the Time of COVID

Objective: As our university moved to a work from home model in response to the COVID-19 pandemic, our research unit needed to reconsider how we accounted for our daily work. Our objective was to consolidate and standardize our data collection to meet requirements for a variety of different time-, project-, or college/program-based reports. Methods: We started by reviewing all the data elements that we might be asked to provide for internal and external reporting. Using the categories in our university activity report as the foundation, we discussed the level of granularity required and assigned activities to each group. We established common reportable elements, with the ability to add individual- or project-specific elements. We tested the categories using our real activities, regrouped to discuss challenges, and made changes as needed. Results: With the start of the new fiscal year, we incorporated these categories into Timeneye and now use them to track our activities. We export these data on a regular basis as our timesheet for the university to meet its work from home requirements. So far, this system also has been effective for creating time-, project-, or college/program-based reports. Conclusions: This project streamlined the process of tracking our time and facilitated the creation of ad hoc reports. It has made it easier for us to track our time across the unit and it will also make it easier for new hires to account for their time in a logical manner

Using a Reflexive Process to Investigate Organizational Change: The Use of the Research Spider Matrix

The primary objective was to assess the research competencies (knowledge, experience, and skills) of librarians at an academic health sciences library using the Research Spider matrix (Smith et al., 2002). This was motivated by the shift from a traditional reference model to a research-centric paradigm

Tumor-associated changes in intestinal epithelial cells cause local accumulation of KLRG1(+) GATA3(+) regulatory T cells in mice

CD4(+) Foxp3(+) regulatory T cells (Treg) include differentiated populations of effector Treg characterized by the expression of specific transcription factors. Tumors, including intestinal malignancies, often present with local accumulation of Treg that can prevent tumor clearance, but how tumor progression leads to Treg accumulation is incompletely understood. Here using genetically modified mouse models we show that ablation of E-cadherin, a process associated with epithelial to mesenchymal transition (EMT) and tumor progression, promotes the accumulation of intestinal Treg by the specific accumulation of the KLRG1(+) GATA3(+) Treg subset. Epithelial E-cadherin ablation activates the β-catenin pathway, and we find that increasing β-catenin signals in intestinal epithelial cells also boosts Treg frequencies through local accumulation of KLRG1(+) GATA3(+) Treg. Both E-cadherin ablation and increased β-catenin signals resulted in epithelial cells with higher levels of IL-33, a cytokine that preferentially expands KLRG1(+) GATA3(+) Treg. Tumors often present reduced E-cadherin expression and increased β-catenin signaling and IL-33 production. Accordingly, Treg accumulation in intestinal tumors from APC(min/+) mice was exclusively due to the increase in KLRG1(+) GATA3(+) Treg. Our data identify a novel axis through which epithelial cells control local Treg cell subsets, which may be activated during intestinal tumorigenesis

Building Responsive Research Capacity: A Survey of Academic Health Faculty

The objective of this study was to evaluate the use of and satisfaction with the University of South Florida Health Libraries (USFHL) research support services (RSS). A secondary objective was to understand the research skills of academic health faculty. The data will help inform future service offerings. The mixed methods study is comprised of two phases: a survey followed by focus groups. The survey assessed 1) knowledge of and satisfaction with specific RSS, 2) faculty confidence in performing 10 specific research tasks, and 3) preference for potential class topics. Open-ended fields allowed for additional comments and suggestions. Respondents self-identified if they were willing to participate in subsequent focus groups. The survey was emailed to all Health faculty, with two reminders. Basic demographics broke out respondents by their college, department, or school; years of conducting and publishing research, and writing grants. Preliminary analyses of the 105 respondents indicated most were extremely/satisfied with USFHL RSS, which were defined as consultations with the librarians, library classes/workshops, LibGuides, and research databases. Less than half of faculty reported confidence in using qualitative research methods and applying for research funding. Potential class topics identified were the 1) scholarly publishing topics, 2) conduct of types of literature reviews, 3) research metrics, 4) research tool recommendations, and 5) effective search strategies. A third of participants volunteered to participate in future focus groups. The qualitative data centered around issues with access and tools; requests for additional trainings, and praise for librarians, resources, & services. Based on initial findings, we plan to add more grants workshops and develop a series on finding, critically reviewing, and writing qualitative studies

A Visual Approach to Query Formulation for Systematic Search

Knowledge workers (such as healthcare information professionals, patent agents and legal researchers) need to create and execute search strategies that are accurate, repeatable and transparent. The traditional solution offered by most database vendors is to use proprietary line-by-line'query builders'. However, these offer limited support for error checking or query optimisation, and their output can often be compromised by errors and inefficiencies. Using the healthcare domain for context, we demonstrate a new approach to search strategy formulation in which concepts are expressed as objects on a two-dimensional canvas, and relationships are articulated using direct manipulation. This approach eliminates many sources of syntactic error, makes the query semantics more transparent, and offers new ways to optimise, save and share search strategies and best practice

Alpha kinase 1 controls intestinal inflammation by suppressing the IL-12/Th1 axis

Inflammatory bowel disease (IBD) are heterogenous disorders of the gastrointestinal tract caused by a spectrum of genetic and environmental factors. In mice, overlapping regions of chromosome 3 have been associated with susceptibility to IBD-like pathology, including a locus called Hiccs. However, the specific gene that controls disease susceptibility remains unknown. Here we identify a Hiccs locus gene, Alpk1 (encoding alpha kinase 1), as a potent regulator of intestinal inflammation. In response to infection with the commensal pathobiont Helicobacter hepaticus (Hh), Alpk1-deficient mice display exacerbated interleukin (IL)-12/IL-23 dependent colitis characterized by an enhanced Th1/interferon(IFN)-γ response. Alpk1 controls intestinal immunity via the hematopoietic system and is highly expressed by mononuclear phagocytes. In response to Hh, Alpk1−/− macrophages produce abnormally high amounts of IL-12, but not IL-23. This study demonstrates that Alpk1 promotes intestinal homoeostasis by regulating the balance of type 1/type 17 immunity following microbial challenge