Open Access Journals at IU Indianapolis
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Abdominal Aortic Aneurysm Response to Interleukin-10 Hydrogel-Based “Bio-Ink” Therapy in Rodent Models
Get PDFAbdominal Aortic Aneurysms (AAA) are the pathological expansion of the aorta, which can rupture and cause significant mortality. Approximately 200,000 AAA cases occur annually in the US, with more than 15,000 cases resulting in death. Risk factors for AAA are similar to those of cardiovascular disease states, particularly cigarette smoking, and AAA patients are generally elderly, Caucasian males. Currently, no medical therapy exists for AAA outside of surgical intervention. We previously hypothesized that the early initiation and propagation of stages in AAA development are inflammatory driven. This process results in a weaker aortic wall, whichwe have evidenced through increased elastin breakdown products and inflammatory markers in AAA patients in comparison to matched controls. This project investigated the use of a novel anti-inflammatory hydrogel to ameliorate AAA progression.
Our study uses a gelatin-based biodegradable bio-ink containing the anti-inflammatory cytokine interleukin-10 (IL-10), which was applied to the aorta with a novel hydrogel extruding “BIOPENCIL” device. We used a previously described rodent model consisting of intra-luminal injection of elastase in the infrarenal aorta combined with topical application of calcium chloride; alternatively, topical calcium chloride was used alone for AAA development. The BIOPENCIL was used to deliver the hydrogel containing IL-10 or control at the time of AAA creation. The animals were euthanized 14 or 21 days post-procedure and evaluated for AAA volume, surface area, and diameter alongside molecular analyses to evaluate for immunological changes between control and treatment groups. We predict that the rodent groups treated with IL-10 will not have AAA expansion, while the control group will see AAA expansion. This is based onlongitudinal data from weekly ultrasounds and will be confirmed with microCT
Neutrophil-to-Lymphocyte Ratio (NLR) to Monitor Neuroinflammation Status During Long COVID
Get PDFBackground/Objective: 480 million people have been infected with COVID-19 worldwide. Roughly 10-15% of these patients will develop Long COVID which causes an array of symptoms including fatigue and “brain fog”. Currently, a reliable marker to monitor Long-COVID has not been established. NLR (neutrophil/lymphocyte ratio) has been shown to be an economical, reliable, and easily obtainable blood biomarker to monitor systemic inflammation. Our study aimed to use NLR to monitor Long COVID patients across pre-COVID to 24 months after acute COVID.
Methods: A retrospective patient chart review of 831 patients from a tertiary community hospital Post-COVID Clinic was completed to assess the changes in NLR. Symptoms and demographic information were collected.
Results: Our studies showed that at the time of acute COVID, NLR was elevated to 5.22+/-0.50 from the baseline pre-COVID NLR of 2.67+/-0.14. 4 to 6 months after the acute phase of COVID, the NLR was normalized to 2.61+/-0.20 which gradually re-elevated to 3.58+/-0.39 from 16-24 months after the acute COVID (p < .01) indicating a re-activation of systemic inflammation. At 16-24 months after the acute COVID, 66% of patients with elevated NLR were hospitalized during acute COVID, while 33% of patient with normal NLR were hospitalized (Chi Square=3.90; p<0.05).
Conclusion: Our findings support the potential connection between the sustained Long COVID symptoms with sustained elevation of NLR, a marker of systemic inflammation reactivation. Currently we are building a non-COVID control group with the expansion into a prospective study phase. If our findings can be validated with further studies, NLR may be a useful biomarker for future monitoring of disease progression and marker for treatment development
Association of Socio-Demographic Factors, Social Determinants of Health, and Weekly Physical Activity in an Urban Hospital in Northwest Indiana
Get PDFBackground: Engaging in regular physical activity has been proven to have beneficial health effects such as preventing chronic diseases and improving mental health. Recent studies have demonstrated correlations between socio-demographic factors and physical activity levels. This study determined the associations between socio-demographic factors, social determinants of health and the amount of weekly physical activity in patients occupying an urban underserved area.
Methods: This study retrospectively analyzed a dataset generated by St. Mary Medical Center from EPIC™ with demographic characteristics and physical activity levels partitioned by time per week for adult inpatient visits from January 2021 to March 2023. Patients were stratified into physical activity levels based upon published guidelines: inactive (no physical activity), insufficiently active (<150 minutes per week) or sufficiently active (≥150 minutes per week). Data analysis was conducted in SPSS 28.0 using tests of association including Kruskal Wallis H and multivariate ordinal regression model. This study was exempted by Indiana University Human Research Protection Program (IRB # 14040).
Results: The sample of individuals from the dataset who answered physical activity questions was comprised of 1498 patients. There was a statistically significant difference in physical activity level by age group (p<0.001), sex (p<0.05), insurance category (p<0.001), and social connections risk score (p<0.001); with race (p=0.057) and language (p=0.054) approaching significance. Multivariate analysis showed that age was the only significant factor when accounting for all variables, with higher age groups reporting lower proportions of physically active individuals.
Conclusion: Determining how socio-demographic factors influence physical activity levels will direct efforts to form and implement new interventions in the Northwest Indiana urban area and support community health initiatives. This data makes it possible to inform practitioners of the demographics that are at risk of being insufficiently active and having them direct those patients to programs in place to help bridge the lapse
Microplastic Identification and Quantification in Biological Samples
Get PDFBackground
The convenience and durability of plastics has made it a staple in the manufacturing industry, but without adequate recycling, these plastics are filling landfills at an alarming rate. This plastic waste is broken down into micro- and nano-plastics that have been found in both marine and terrestrial environments. The potential ramifications of accumulating plastic particles in the environment are of urgent attention as humans are exposed to these particles through ingestion, inhalation, and dermal exposure. Due to the lack of consensus of the effect microplastics have on the coagulation cascade, our aim was to form clots under various conditions so that a comparison can be drawn.
Methods
We utilized varying sizes (500-2,000 nm) and concentrations (25-250 µg/ml) of non-functionalized polystyrene (nPS) microplastics to characterize their effect on clot size, strength, and anatomy using ex-vivo shear flow clot formation of human whole blood via a Chandler loop apparatus. Additionally, we studied the effect of fluorescent Nile red dye (NR, ex/em: 545/625 nm) on clotting dynamics and visualization of microplastic particles via fluorescence microscopy.
Results
Ex-vivo clots were made (422 s-1 shear at increasing nanoplastic concentrations), sectioned, and utilized for quantification optimization in histological processing to preserve plastic integrity and fluorescent signal. NR-dyed microplastics were shown to produce sufficient fluorescent signal for imaging. Images were taken at various magnifications (4x-40x) and exposure times (100µs-500ms) using brightfield and fluorescent microscopy (Cy3 filter) on a Nikon Eclipse Ni microscope and a Nikon DS-Ri2 Microscope camera.
Potential Impacts
These results highlight the need for further analysis of the effects of microplastics on the coagulation cascade, as well as further optimization of techniques used to identify and quantify microplastics in complex biological samples.
 
Spatially Anchored Molecular Neighborhoods in Lupus Nephritis
Get PDFBackground:
Lupus nephritis (LN) affects 1 in 3 individuals with systemic lupus erythematosus. Suboptimal treatment precipitates irreversible kidney damage, leading to end stage renal disease. Kidney damage in lupus is characterized by immune cells injuring epithelial, endothelial, and stromal cells. We characterized molecular neighborhoods composed of immune cells interacting with resident cells of the kidney through spatial transcriptomics (ST).
Methods:
Visium ST experiments were conducted in 8 healthy controls (233 glomeruli) and 3 LN samples (48 glomeruli). Cell type labels from the Kidney Precision Medicine Project single cell RNA-seq atlas were transferred to deconvolute ST spots into specific cell types. Using histology and NPHS2 expression, glomeruli were selected as functional tissue units. Data were normalized, dimensionally reduced, and clustered with Seurat v4. Spatially anchored gene signatures of LN were identified. Glomeruli were re-clustered according to cell composition, to identify associated neighborhoods by fisher’s exact test. We characterized the cell composition, differentially expressed genes (DEGs), and pathways of relevant neighborhoods.
Results:
Between LN and control glomeruli, we identified HSPA8, PLEK, COL1A2 DEGs, associated with hypoxia, fibrosis, and immune response. We identified glomerular neighborhoods consistent with immune complex deposition, endothelial dysfunction (e.g. wire loop lesions), and mesangial cell expansion enriched in LN (p<0.05). Immune complex-mediated injury neighborhoods were characterized by interferon signaling, endothelial cell migration, and vascular genesis, consistent with DEGs BST2, CXCL12, and ENG. Endothelial dysfunction neighborhoods present cellular adhesion, immune cell signaling, and hypoxic pathways. DEGs included ITGB2, HLA-DPB1, and EGR1. Pathways enriched in mesangial expansion neighborhoods included matrix adhesion, podocyte development, and ERK1 and ERK2 cascade, aligned with ITGB3, NPHS1, and APOE DEGs.
Conclusion/ Clinical Impact and Implications:
Neighborhood characterization provides insight into cell-cell interactions that drive kidney disease progression. Future directions will change how kidney biopsy specimens drive treatment by delineating specific cell-cell interactions, linking molecular and histopathological signatures, and defining genes associated with therapeutic resistance
Comparison of Transfer Patterns by Emergency Medical Services in Trauma Patients in a Major U.S. City
Get PDFBackground:Trauma patients are often unable to communicate a preferred destination hospital to EMS due to their injuries and potentially decreased level of consciousness. The destination hospital is thus determined by the EMS team transporting the patient. This study focuses on trauma admissions between Eskenazi and IUH Methodist Hospitals in downtown Indianapolis, both of which are Level 1 trauma centers within one mile of each other. We are interested in identifying differentiating factors between patients that are admitted at these two hospitals, focusing on the injury type as well as the demographic information for each patient, to determine if there are differential transport patterns.
Methods:We performed a retrospective analysis of patient charts and transport documentation to determine basic demographic and admission data for each patient. We especially took note of the location of EMS pickup, the facility the patient was taken to, and the stated reasons for taking the patient to that specific facility. A simple Google Maps search allowed us to determine if the patient was taken to the facility closest to them, or not.
Results:We found that among the included patients that were not taken to the nearest Level 1 trauma center, a significant majority were taken to Eskenazi rather than Methodist. Among these patients, a majority were minorities, in contrast with demographic makeup of the patients that were admitted to the closest trauma center.
Conclusion:This study highlights how complex EMS transfer patterns are based upon diversion, traffic, individual driver preference, and other factors. There is a significant difference in transport patterns between the two hospitals that correlates with a difference in patient demographics.
Policy Implications:This data indicates a need to monitor these numbers closely going forward, paying special attention to all possible reasons that could impact to which facility a patient is admitted
An Introduction to Statistics for Librarians (Part Three): An Introduction to Statistical Tests
Get PDFIn the previous two columns, types of data, central tendency and distribution were discussed. This installment will build upon that content and explore various statistical tests. Three scenarios are introduced to illustrate how tests can be selected based on the type of data, the number of groups, and the distribution of the data. The column discusses interpreting test results, including challenges around establishing causation and the potential overreliance on p-values
The Outcomes and Experiences of Students in Course-based Undergraduate Research Experience (CURE)
Get PDFResearch is a pivotal element of music therapy education. Finding, interpreting, and integrating research into clinical practice are required in the professional competencies (American Music Therapy Association, 2013, 2021). Course-based undergraduate research experiences (CURE) have been identified by the National Science Foundation to increase access to underrepresented student populations in STEM programs. Fewer studies have been seen in humanities. To develop competency in a cohort of music therapy students, a CURE was developed with student research collaborating on all parts of the study. Elements of the CURE were guided by Dvorak and Hernandez-Ruiz (2019); one of the first publications in music therapy using this approach with students. However, in the present CURE each student developed their own research question within a larger project, modeled after a lab-based approach. Students who wished to present their research as a poster for the regional or national conference were prepared to do so. Significant improvements in were found (p<.0001) three categories on the Research Skill Development Questionnaire (RSDQ: Dvorak et al., 2021) including knowledge of research-related content, research skills, and research dispositions. Student reflections share a growth in comfort with and accessibility of conducting research as something “not just for scientists and doctors” but that was “a lot less stressful, and really fun!” Others reported a motivation to identify questions and conduct research in the future. The outcome was a fully immersive educational experience and functional a resource for members within the School of Music to educate on hearing loss prevention
