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Plan, Pivot, Proceed: A Multiphase Library Refresh Project
Get PDFOBJECTIVE: In 2019, Rowland Medical Library began a multiphase project to refresh the first floor and improve the overall environment for patrons. A major renovation was previously completed on the second floor in 2011. Consequently, there was a lack of design cohesiveness between floors.
METHODS: The project team consisted of faculty from the Access Services and the Research/Instruction divisions. Initial discussions around redesigning computer workstations for functionality and privacy eventually morphed into a more involved library endeavor encompassing projects on both levels of the library. The team met with the campus Planning, Construction and Design Department, Paint Department, and furniture vendors to determine options.
RESULTS: A new paint color scheme was selected, including dark accent walls for an art gallery look. The library’s substantial art collection was given new life by changing the location of many pieces. Furniture and shelving were rearranged to create open spaces and uncluttered sightlines. Dated signage was redesigned. An overabundance of trash receptacles were minimized and centralized. Some patron seating was reupholstered to coordinate with the new colors scheme. Custom workstations and task chairs were purchased to create private and comfortable workspaces for users.
CONCLUSIONS: The first phase of the project was completed in February 2020 – just before the coronavirus pandemic greatly impacted the campus. Changes to our recently improved furniture placement were required to comply with social distancing guidelines and reduce patron capacity. The second phase of the project is proceeding with revisions. There are aspects of this project that any type of library, with any budget or staffing level could replicate
Reimagining A to Z Database Descriptions to Improve User Experiences: A Database Description Project
Get PDFObjective: This poster examines how a Research and Instruction Librarian team at Rowland Medical Library updated and re-envisioned the library’s A to Z Database list. Methods: Two librarians worked to reimagine the format of the database descriptions provided on the A-Z Database page to include the relevant information users routinely requested. To this end, the librarians determined that each description should include alternative names, subjects, content categories, date range, icons, and vendor information. The reimagined descriptions removed extraneous vendor content that confused users and focused on information users could use to make quick determinations on which databases were best for their information needs. They worked systematically to correlate subjects and content with the educational, clinical, and research missions of the university. Results: The project team selected 20 subjects, 21 content categories, and four resource icons for possible assignment to each database. All categories went through review by the library director and all faculty librarians. The team created a Microsoft Form to collate all data for each database in one location and used the collated information to update descriptions. Decisions on database best bests and content experts, features of the Springshare platform, were made by consensus. Conclusion: The updated A to Z Database page will improve user access and experiences when using the library website and e-resources
The Characterization of Hematopoiesis in Murine Fetal Bone Marrow
Get PDFHematopoietic stem cells (HSCs) and their downstream progenitors are a heterogeneous population of cells that are indispensable for lifelong hematopoiesis and are often utilized in the clinic for the treatment of hematologic maladies via hematopoietic stem cell transplantation (HSCT). Over several decades, it has been discovered that HSCs arise in the dorsal aorta of the developing embryo, migrate to the fetal liver (FL), and undergo a large expansion before reaching their final resting place in the bone marrow (BM). Many resources have been invested in understanding the roles of the different niches HSCs encounter along their journey. A greater understanding of HSC niche regulation could provide clues for HSC maintenance and expansion in vitro. One critical niche during HSC ontogeny that has been greatly overlooked is the fetal BM (FBM), of which the hematopoietic and HSC niche compartments are poorly understood. For this reason, we meticulously characterized the hematopoietic progenitor compartment of the whole skeleton FBM from its colonization until after birth via competitive transplantation, immunophenotypic analysis of the hematopoietic stem and progenitor cell (HSPC) compartment, functional assessment of specific progenitor populations, and single-cell RNA-sequencing (scRNA-Seq) of the hematopoietic and stromal FBM environment. Here, we provide the first report of the presence of bona fide HSCs within the E15.5 FBM. We also found that HSCs were present in the all sources of BM, including the forelimbs, hindlimbs, and trunk of E15.5 embryos. We are also the first to assess the BM immunophenotypic HSPC compartment from initial seeding to adulthood and found that specific multipotent progenitor (MPP) cells (MPP2s) are the predominant HSPC population in the FBM, appearing to have the ability to migrate to and seed the FBM directly from the FL. Interestingly, immunophenotypic MPP2s are not functional in vitro or in vivo until birth (E18.5-P0), and display reduced repopulating capacity compared to adult BM and time-matched FL MPP2s. Also, the frequencies of the different FBM HSPCs shift around birth from an MPP2-dominant phenotype to the MPP3/MPP4-dominant phenotype seen in adult BM. To identify the intrinsic and extrinsic mechanisms controlling MPP2 functional maturation, we isolated stromal and hematopoietic progenitor (HP) populations from E16.5, E18.5, P0, and adult BM, and constructed the first known scRNA-Seq dataset spanning the HP and stromal compartment across BM ontogeny. Preliminary analysis of our scRNA-Seq datasets show that the FBM stroma and HP compartments are compositionally distinct from the adult BM compartments, and this disparity in composition is even more drastic at E16.5, suggesting that the reduced function of FBM MPP2s may be due to a semi-incompatible FBM niche. Our future studies will focus on identifying intrinsic differences between immunophenotypic HSPC populations across FBM ontogeny in our HP scRNA-Seq dataset, as well as defining putative niches for HSPCs in the FBM. We hope that these analyses will identify novel hematopoietic factors in the FBM niche that can be therapeutically exploited to enhance HSC expansion/function/differentiation in the clinic
Group Therapy Versus Individual Therapy for Older Adults with a Cerebrovascular Accident
Get PDFThe purpose of our critically appraised topic is to synthesize the best current evidence regarding the feasibility of group occupational therapy and outcomes related to ADL performance. The final portfolio contains a total of five research articles. Study designs include two pre-post single group designs, two case studies, and one non randomized pilot trial with a control group. All studies related directly to the PICO question and were used to determine best evidence for the feasibility of group therapy of the older adult population in a rehabilitation setting
Development of a New US Currency for the Post-Pandemic Remote Culture
Get PDFThe contemporary dollar currency was already under significant pressure prior to the emergence of the COVID-19 pandemic, but the economic pressures resulting from the national and world “lockdown” have very significantly exacerbated the vulnerabilities of those Federal Reserve Notes. The ostensible nationalization of the Federal Reserve by the United States federal government in April 2020 is a harbinger of a need to restructure the US currency. Today’s developing remote culture necessitates a new form of electronic currency. Herein is a conceptual blueprint for the development of such a restructured US currency that would function in the post-pandemic remote culture
Early Diagnosis of Alzheimer’s Disease in the Primary Care Setting
Get PDFThe burden of Alzheimer’s disease (AD) affects not just the individual but also families, providers, and society. Early recognition and diagnosis of AD may reduce cost by reducing interaction with the health care system, earlier initiation of treatment, and prolonging time to long- term care. Primary care providers, the first contact for diagnosis of patients with AD, are not fulfilling the potential of early diagnosis for a variety of reasons. Biomarkers of AD emerge on average 15 to 20 years before clinical diagnosis, yet currently established biomarkers are not easily available in the primary care setting. A growing body of literature is focused on identifying additional non-invasive early signs of AD. The aims of this program of research were to understand factors contributing to the AD diagnosis variability in primary care settings and methods to improve early diagnosis by primary care providers. Four studies were undertaken to achieve these aims. The first study reported the results of an integrated review estimating the prevalence of missed diagnosis in primary care when compared to trained raters’ diagnoses. The findings call to attention the difficulty primary care providers face to detect and diagnose AD at all levels of the healthcare system. This led to the second study. Chronic pain is a common comorbid ailment seen in those with AD and often is a driving factor of patients seeking medical care. In order to understand the pain experience in those with worsening cognition, the second study was a secondary analysis of a cross-sectional age- and sex-matched two group cohort study and found that the experience of pain differs between males and females as a measure of cognition worsened suggesting a possible role of pain as a tool to distinguish those at risk for AD. This finding led to the third study, which was a narrative review conducted to describe how alterations in senses have been associated with the diagnosis of AD. The results suggested differences in smell, taste, vision, hearing, and proprioception were associated with different levels of the AD continuum but points out an obvious gap in the literature concerning other senses. This led to the fourth study examining evidence that the ε4 allele of Apolipoprotein E modifies the experience of pain in those individuals carrying the allele such that greater temperatures are required to elicit pain and the experience of that pain is more unpleasant. Additional studies should expand on the results of this pilot study
Selective Targeting of CYP3A5 Through Chemical and Genetic Approaches
Get PDFCytochrome P450 enzymes function to catalyze a wide range of reactions important for various biological processes. In humans, the CYP3A subfamily is particularly critical for drug response. Within this family are CYP3A4 and CYP3A5, which collectively metabolize greater than half of all currently prescribed drugs. These promiscuous enzymes can bind a broad and structurally diverse array of compounds, in turn leading to an increased risk of their modulation via small molecules. In the case of CYP3A5, which is over-expressed in some cancers, this leads to chemoresistance. Such aberrant expression and corresponding drug resistance merit a need to selectively target CYP3A5. However, the significant overlap in sequence and structural identity with CYP3A4 as well as flexible and dynamic binding modes make development of a selective inhibitor challenging, and no progress has been made thus far. Moreover, the cancer-specific regulation of CYP3A5 remains unknown, removing the possibility of targeting a factor upstream of its transcription. While CYP3A4 regulation in liver is well-documented, these regulators don’t control CYP3A5 in extra-hepatic contexts. This warrants further investigation in order to understand the biological basis of CYP3A5 over-expression in disease models. Here we present discovery of the first isoform-selective CYP3A5 inhibitor. We used high-throughput technology to identify clobetasol propionate as capable of selectively inhibiting CYP3A5 enzymatic activity without conferring CYP3A4 inhibition. We further demonstrate the in vitro ability of the compound using a clinically relevant cell model with CYP3A5 overexpression and CRISPR/Cas9-mediated full genetic deletion. Additionally, we explore the mechanism of selectivity, employing computational and biophysical techniques to illustrate how subtle active site differences allow the compound to adopt a tight heme-ligand coordination exclusively in CYP3A5 and serving as the basis of its selective inhibition
Tobacco/HIV-1-Induced Myeloid Cell-Derived Extracellular Vesicles in HIV-1 Pathogenesis
Get PDFIntroduction. Smoking, which is highly prevalent in people living with HIV/AIDS, has been shown to exacerbate HIV-1 replication, in part via cytochrome P450 (CYP)-induced oxidative stress. CYP enzymes metabolize cigarette smoke condensate (CSC), causing oxidative stress and cytotoxicity. Our previous studies have demonstrated that CSC and specific CSC constituents, benzo(a)pyrene and nicotine, potentially induce CYPs, resulting in higher oxidative stress and subsequent exacerbation of HIV-1 replication in monocytes and macrophages. However, the exact mechanism behind tobacco-induced, oxidative stress-mediated enhancement of HIV-1 replication is still poorly understood. Extracellular vesicles (EVs) have recently gained attention for their unique nature as intercellular messengers which can package proteins, nucleic acids, lipids etc. EVs are known to alter HIV-1 pathogenesis through intercellular communication. Until now, the role of EVs in smoking-enhanced HIV-1 pathogenesis has been mostly unknown. In this study, we investigated the effect of CSC on the characteristics and differential packaging of monocyte- and macrophage-derived EVs, and their influence on HIV-1 replication. We hypothesized that CSC- and/or HIV-1-exposed monocyte and macrophage-derived EVs and their components, especially pro-oxidant factors, are key mediators of HIV-1 replication.
Methods. Two monocytic cell lines, U937 and HIV-1-infected U1 cells, and macrophages derived from these monocytes, as well as macrophages derived from primary human monocytes were used. Cells were treated with 10 μg/ml/day CSC. After treatment, the cells were harvested, and the supernatant was collected for isolating EVs by Total Exosome Isolation kit. The isolated EVs were characterized for their biophysical properties. Next, monocyte-derived macrophages were exposed to EVs, as well as subjected to downstream analysis (p24 ELISA, LDH cytotoxicity assay, DNA damage assay, rtPCR, western blot, cytokine analysis).
Results. Initially, we demonstrated that CSC reduced total protein and antioxidant capacity in EVs derived from HIV-1-infected and uninfected monocytes. The EVs from CSC-treated uninfected cells showed a protective effect against cytotoxicity and viral replication in HIV-1-infected macrophages. However, EVs derived from HIV-1-infected cells lost their protective capacity. The results suggested that the exosomal defense is likely to be more effective during the early phase of HIV-1 infection and diminishes at the latter phase.
Next, we investigated differential packaging of specific contents in EVs subjected to CSC and HIV-1 exposure. We observed CSC-induced upregulation of catalase in EVs from uninfected cells, with a decrease in the levels of catalase and PRDX6 in EVs from HIV-1-infected cells. We also observed higher expression of CYPs (1A1, 1B1, 3A4) and lower expression of antioxidant enzymes (SOD-1, catalase) in EVs from HIV-1-infected macrophages compared to those from uninfected macrophages. Together, they are expected to increase concentrations of oxidative stress factors in EVs derived from HIV-1-infected cells. Moreover, our results show that longer exposure to CSC increased the expression of cytokines in EVs from HIV-1-infected macrophages, when compared to the shorter exposure. Importantly, pro-inflammatory cytokines, especially IL-6, were highly packaged in EVs from HIV-1-infected macrophages upon both long and short-term CSC exposures. Anti-inflammatory cytokines, particularly IL-10, had high packaging in EVs, while packaging of chemokines was mostly increased in EVs upon CSC exposure in both HIV-1-infected and uninfected macrophages.
Conclusion. Taken together, our results suggest a potential role of CSC-exposure in modulating HIV-1-infected and uninfected cell-derived EVs, thereby affecting HIV-1 replication in recipient cells. Our study also suggests the packaging of increased levels of oxidative stress-inducing and inflammatory elements in EVs upon exposure to tobacco constituents and/or HIV-1, which would ultimately enhance HIV-1 replication in macrophages via cell-cell interactions
Rapid Response: Librarian Integration Into An Expedited Pandemic Medicine Elective
Get PDFObjective: Describe how two librarians contributed to a new graduate medical school elective course developed dynamically in the midst of the COVID-19 pandemic.
Methods: Shortly after the COVID-19 outbreak, the Assistant Director for Research & Education Services attended a clerkship curriculum committee meeting for the medical college where a four-week Pandemic Medicine elective was proposed. Clerkship rotations were canceled due to the pandemic, so the elective would provide opportunities for graduate medical students to participate in service learning and contribute to pandemic response efforts. The leaders and faculty members who proposed the elective suggested five areas of focus: information services; mental health and wellness; PPE taskforce; supporting medical education; and telemedicine. Immediately after the meeting the librarian contacted those organizing the elective and offered to contribute, particularly to the information services component.
Results: Both the Assistant Director for Research & Education Services and the Clinical Information Librarian were invited to serve as faculty advisors for the students leading the information services aspects of the elective. Much of the elective was student-driven, including daily COVID-19 and news updates, which were followed by lectures by faculty subject experts. The librarians attended weekly planning meetings with the information services group leaders, compiled lists of trustworthy resources for the students to consult, and performed literature searches. Within the information services area, the students chose to create relevant infographics in multiple languages, produce “mythbusters” information about COVID-19, develop a knowledge base from the literature using Zotero, and post a portal website. The website houses all the student-created content, along with local and national statistics about COVID-19. The website received recognition in the local press and university communication channels.
Conclusions: Librarians were successfully integrated into a medical school elective course developed in response to the COVID-19 outbreak
Clinical and Socioeconomic Predictors of Palliative Care Utilization
Get PDFINTRODUCTION: Palliative care continues to gain recognition among primary care providers, as patients suffering from chronic conditions may benefit from use of this growing service.
OBJECTIVES: This single-institution quality improvement study investigates the clinical characteristics and socioeconomic status (SES) of palliative care patients and identifies predictors of palliative care utilization.
METHODS: Retrospective chart review was used to compare clinical and SES parameters for three groups of patients: (1) palliative care patients who attended at least one visit since the inception of the University Clinical Health Palliative Care Clinic in Memphis, TN in October 2018 (n = 61), (2) palliative care patients who did not attend any appointments (n = 19), and (3) a randomized group of age-matched primary care patients seen by one provider from May 2018 to May 2019 (n = 36). A Poisson regression model with backward conditional variable selection was used to determine predictors of palliative care utilization.
RESULTS: Patients across the three care groups did not differ in demographic parameters. Compared to palliative care-referred non-users and primary care patients, palliative care patients tended to have lower health risk (p \u3c 0.001). Palliative care patients did not differ from primary care patients in socioeconomic status but did differ in comorbidity distribution, having a higher prevalence of cancer (2 = 14.648, df = 7, p = 0.041). Chance of 10-year survival did not differ across risk categories for palliative care patients but was significantly lower for very high-risk compared to moderate-risk primary care patients (30% vs. 78%, p = 0.019). Significant predictors of palliative care use and their corresponding incidence rate ratios (IRR) were hospital referral (IRR = 1.471; p = 0.039), higher number of prescribed medications (IRR = 1.045; p = 0.003), lower Charlson Comorbidity Index (IRR = 0.907; p = 0.003), and lower systolic blood pressure (IRR = 0.989; p = 0.004).
CONCLUSIONS: Patients who are expected to benefit from and of being high utilizers of palliative care may experience greater clinical benefit from earlier referral to this service