Open Access Journals at IU Indianapolis
Not a member yet
23580 research outputs found
Sort by
Analysis of the Binding Partners of Clusterin in their Role in Increased Intraocular Pressure in Glaucoma
Get PDFBackground and Objective:Elevated intraocular pressure (IOP) is a risk factor for primary open-angle glaucoma (POAG). Clusterin (CLU) is a secretory chaperone protein found in trabecular meshwork tissue that is implicated with POAG risk. In this study, we aimed at understanding the role of CLU and its binding partners in IOP homeostasis and POAG pathology.
Methods:Normal trabecular meshwork (NTM) cell lines were used. Half of the NTM cell lines were transfected with adenovirus empty (AdMT) while the other half of the NTM cell lines were transfected with adenovirus clusterin with histidine tag (AdCLUHIS). AdCLUHIS allows for the overexpression of CLU HIS in the NTM cells. After 72 hours of transfection, the media and cell lysate were collected. As CLU is a secretory chaperone protein, the media was analyzed. Immunoprecipitation (IP) was conducted to isolate CLU HIS and all the proteins bound to it. Western blot analysis was conducted to confirmed IP worked successfully. Once it was confirmed that CLU HIS with all its binding partners was isolated successfully using IP, the media samples were sent to proteomics to determine all the specific proteins that are bound directly to CLU.
Results:Western blot analysis confirmed that the overexpression of CLU HIS was successfully accomplished through adenovirus transfection. In addition, Western blot analysis confirmed that IP worked successfully. At the current moment, results of proteomics are still being developed, so the specific binding partners of CLU are still unknown at the time.
Conclusions and Potential Impact:Our preliminary study suggests that CLU can be overexpressed via adenovirus and analyzed via IP. Understanding this allows for the purification of the protein and its attached binding partners. Identifying these binding partners can be novel targets for improving aqueous humor outflow through trabecular meshwork to decrease IOP and decrease one’s risk for POAG
Efficacy of Novel Bracing for Treating Sciatica and Cadaveric Dissection to Examine Excursion of the Sciatic Nerve
Get PDFBackground/Objective:Sciatica affects nearly half of all Americans and can often become debilitating, leading to severe pain that can limit performing activities of daily living. Brace application has not been tried for alleviation of pain. In this study, we seek to find if a novel brace can decrease pain and decrease bothersome level of symptoms for those suffering from sciatica. In addition, this study utilizes a cadaveric dissection to understand how the sciatic nerve stretches and tensions upon lower limb manipulation.
Methods:Fourteen patients self-reported pain, functionality, and bothersome levels pre- and post-bracing. Excel’s data analysis tool was utilized to run statistical tests. One cadaver (2 lower limbs) was dissected, revealing the sciatic nerve at the hip and knee, while tibial nerve at the ankle. Excursion was measured utilizing a fixed pin and an initial distance, the leg manipulated, and final distance from pin measured. Ultimately, excursion was deemed final distance minus initial distance from the pin.
Results:The brace decreases Visual Analogue Scale (VAS) scores, increases Patient Reported Outcomes, and decreases Sciatica Bothersome Indexes. There was a significant difference in VAS pre- versus post-brace values at initial and 7-day post-visit but not at 21- or 42-day postvisit. Sciatic nerve excursion was greatest at the ankle.
Conclusion and Potential Impact:Brace use decreases pain levels, increases functionality, and decreases bothersome level of symptoms. The distal nerve moves more upon manipulation and therefore is more prone to tensioning than the proximal nerve. Dissection data illustrates how the brace positions the limb in a way that promotes “detensioning” of the nerve, alleviating sciatica. More cadaver data is needed
Utility of Cardiac POCUS in the Evaluation of Pediatric Chest Pain in the Emergency Department
Get PDFBackground/Objective:Chest pain in children is rarely caused by a life-threatening pathology. Despite the rarity of potentially life-threatening disease, most children presenting to EDs are evaluated with chest radiographs and laboratory tests without yielding helpful information that significantly changes immediate management. While the utilization of cardiac Point-of-Care Ultrasound (POCUS) by adult emergency physicians has become standard of practice, the data in pediatric emergency departments (PED) is not as robust. This study aims to describe practice patterns in the evaluation of pediatric chest pain presenting in a PED and determine clinical outcomes.
Methods:We reviewed charts of previously healthy children aged <18 years old who presented to Riley Children’s Hospital from January 2019 to July 2020 with a chief complaint of chest pain. Patients with known medical history, prior evaluations by a pediatric cardiologist, transfers from other hospital with existing workup were excluded. Patient demographics, laboratory tests and imaging ordered while in the ED, electrocardiography (EKG), consults with subspecialties, disposition and follow up plans were analyzed. We categorized clinical significance of PED interventions as minor, moderate, or major.
Results:Out of three hundred and nineteen patients included in the study, 79.6% (254) received chest radiographs, 93.4% (298) underwent EKG, and 4.1% (13) received cardiac POCUS. The findings of these orders prompted minor interventions in 92.8% (296) of patients, moderateintervention in 4.7% (15) of patients, and major intervention in 2.5% (8) of patients.
Conclusion and Implications:These results show a lack of use for POCUS in pediatric patients presenting with chest pain while chest radiography is preferred in the ED. Additionally, POCUS did not result in any moderate or major significant clinical outcomes
Using Botulinum Toxin for the Treatment of Gastroparesis (GP) for the selection of Patients with Higher Clinical Success, Improved Quality of Life (QOL), and Improved Social Functioning Post Gastric Peroral Endoscopic Myotomy (GPOEM)
Get PDFBackground/Objective:While G-POEM remains an effective and exciting treatment for GP patients, predictors of clinical success remain poorly characterized. Botox injection of the pylorus prior to committing to GPOEM can help differentiate those who might have a favorable clinical response to this procedure in patients with GP.
Methods:To evaluate the utility of Botox injection prior to G-POEM, 124 patients with clinically diagnosed GP who underwent a GPOEM were assessed in this retrospective cohort study. All G-POEM procedures were conducted at a single center and were completed between February 2018 and May 2023. Patients who had received intrapyloric Botox injection (n=79) had QoL and clinical success rates compared to patients who received other treatment options (n=45). Results were assessed at 1-, 3-, 6-, 12-, 24-, 36-, 48-months post G-POEM.
Results:When assessing symptom severity, the difference between the change in GCSI values for Botox patients and patients receiving other prior therapy was statistically significant at 6 months post-GPOEM; +1.27 for Botox patients vs +0.55 for other treatments (p-value of 0.03). At this 6-month checkpoint, 64% of the Botox group achieved clinical success compared to 37.5% for the other treatment group. When comparing QoL, intrapyloric Botox injection has statistically significant improvements in SF-36 total score at 1, 3-, 6-, 12-, and 36-months post G-POEM, while patients receiving other treatments had no statistically significant improvements in their SF-36 total scores.
Conclusion:We hypothesize that clinical improvement on pre GPOEM Botox selects patients with a higher component of pyloric spasm who end up responding more favorably to G-POEM.
Scientific/Clinical/Policy Impact and Implications:Intrapyloric Botox injection is technically feasible in almost all patients with GP and does not require special expertise, training, or equipment; therefore, this should be strongly considered prior to referring a patient for G-POEM
Length of Stay Index – A Retrospective Chart Review on In-patient Dermatology Consults
Get PDFBackground and Objective: In monitoring inpatient care quality and efficiency, one metric of interest is Length of Stay (LOS) by diagnosis-related group (DRG) system and how this compares to peer institutions. Vizient Inc. provides a source of such benchmarking - collecting and analyzing individual case-level data from community and academic medical center hospitals nationwide. Using this data, Vizient calculates an expected LOS by DRGs and adjusts for severity of illness and other factors for inter-hospital comparison. Because LOS reduction is an important mechanism for improving outcomes and efficiency of care, The Department of Dermatology would like to understand which dermatologic consults are exceeding the Vizient expected LOS (LOS index > 1).
Project Methods: Consecutive charts of 663 patients with dermatology-related diagnoses in the inpatient setting at IU University and Methodist Hospitals between January 2021 and January 2023 were reviewed. Parameters identified included: category of dermatologic disorder, LOS index, time to consult, and quarter of encounter. Data was organized and analyzed using paired t-tests, linear regression, and descriptive statistics in JMP software.
Results: The mean LOS index for Dermatology inpatient consults was 1.89 (n=469). Patients whose dermatologic diagnosis fell under chronic wound, mechanical, infectious, drug adverse event, autoimmune, neoplasm, inflammatory, vascular, and blistering had a significant increase in observed length of stay compared to expected length of stay (p < 0.05). Time to dermatology consult was not found to correlate to shortening or prolonging LOS index.
Potential Impact: The data from this review will help direct the Department of Dermatology to the dermatologic consults with the highest need for potential interventions.  
Decoding the Link Between XPC and Lung Cancer Susceptibility: A Study of Cigarette Smoke-Induced DNA Damage in the Setting of XPC Deficiency
Get PDFBackground/Objective:
Despite the known mutagenicity of cigarette smoke, only 10-15% of smokers will develop lung cancer in their lifetimes. What determines a smoker’s susceptibility to lung cancer is poorly understood. We identify the nucleotide excision repair (NER) protein Xeroderma pigmentosum Complementation Group C (XPC) as a tumor suppressor that may contribute to lungtumorigenesis when mutated and combined with cigarette smoke. Micronuclei, which are chromosome fragments and/or lagging chromosomes separated from the main nucleus, occur in many cancers, and indicate genomic instability. We hypothesize that cigarette smoke and XPC knockdown will cause genomic instability that will activate the DNA Damage Response (DDR) and increase the frequency of micronuclei and nuclear aberrancies.
Methods:
A human bronchial epithelial cell line (Beas-2B), and two lung adenocarcinoma cell lines (H1299 and A549) with stable XPC lentiviral knock-down (shXPC) or control shRNA (shCtrl) were treated with cigarette smoke extract (CSE) or air control (AC). DNA Damage Response (DDR) proteins were analyzed via immunoblot (Western). Micronuclei and nuclear aberrancies were quantified through cytokinesis-block micronucleus assay (CBMT) using immunofluorescence microscopy (DAPI).
Results:
Both CSE and XPC knockdown independently amplify expression of phospho-ATM (pATM), a DDR protein, in H1299 cells. Nuclear aberrancies increased significantly (p<0.05) with CSE in all three cell lines. Micronucleus frequency increased significantly with CSE in H1299 and Beas-2B cells (p<0.05) and with XPC knockdown in Beas-2B cells compared to shCtrl (p<0.001).
Scientific Impact and Implications:
We identified a previously uncharacterized role of XPC deficiency in augmenting cigarette smoke induced chromosomal breaks manifesting as micronuclei, particularly in non-cancerous Beas-2B cells. These findings offer insight into tumorigenesis in cigarette smoking and shed light on mechanisms of continued DNA damage in cancer cells. Future research should clarify the mechanisms of micronucleus formation in human translational specimens and pinpoint additional functions of XPC beyond NER, including in replication repair
Review of Trauma-Informed Music Therapy: Theory and Practice, edited by Laura E. Beer and Jacqueline C. Birnbaum
No full textBook review for Trauma-Informed Music Therapy: Theory and Practice as solicited by Virginia Driscol
Delayed Prescribing of Non-Vitamin K Antagonist Oral Anticoagulants (NOACs) in Patients with Low Socioeconomic Status
Get PDFBackground/Objective: Atrial fibrillation (AF) and venous thromboembolism (VTE) are conditions with significant morbidity and mortality when left untreated. American Heart Association guidelines changed in 2019 to make non-vitamin K antagonist oral anticoagulants (NOACs) the preferred method for preventing stroke and systemic embolism in patients with AF or history of VTE. NOACs were first introduced to the United States in 2010 and now include dabigatran, apixaban, rivaroxaban, and edoxaban. There is a dearth of research concerning the speed with which new treatments are prescribed to those in different socioeconomic status (SES) groups. We hypothesized that patients with lower SES were prescribed NOACs later than higher SES counterparts following the introduction of NOACs in 2010.
Methods: The IU Cardiovascular Research Consortium/Sidus Dataset was mined for AF and VTE patients prescribed a NOAC between 2010 and 2022. The SES groups were determined using 2020 U.S. Census income data that correlated to patients’ zip codes. The yearly number ofpatients in each SES group were compared to assess for proportional uptake of NOAC prescribing. The primary outcome was the proportion of low SES to high SES prescribing over each year between 2010 and 2022.
Results: Low SES patients (n=101,945) were prescribed NOACs at an average of 0.65 times the rate of high SES patients (n= 89,130) from 2010 to 2012, the first three years of NOAC market availability. Prescribing rates equilibrated in 2013 and low SES prescribing has outpaced high SES prescribing since 2021.
Conclusion/Impact: Low SES patients experienced a three year delay in receiving NOAC prescriptions at the same rate as their high SES counterparts. Systemic changes, like more frequent prescribing guideline updates and improved evidence-based education amongst providers in low-income areas, could prevent a similar delay when introducing similarly transformative treatments in the future
Evaluation of Insertion Speed and Hand Kinematics During Cochlear Implantation in a Fixed Cadaveric Temporal Bone Model
Get PDFBackground:Cochlear implant is the treatment of choice for replacement of sensory deprivation from severe to profound sensorineural hearing loss. Slower insertion of the electrode into the cochlea leads to less intracochlear trauma. Accurate measures of hand motion and insertion speed during live cochlear implant electrode insertions on human subjects are limited.
Methods:Data from a single surgeon was collected during insertion of a cochlear electrode into a cadaveric temporal bone using inertial measurement units (IMUs), devices that measure linear acceleration in 3 dimensions (x,y,z). The sensors were affixed as follows: dorsal second digit, dorsal hand, and dorsal wrist with three trials at each position. The extremity inserting the electrode into the inner ear was labeled “inserting limb,” while the other extremity was labeled “non-inserting limb.” Root mean square (RMS) calculations were utilized to record the net acceleration, from which average speed per trial was calculated using the midpoint method.
Results:Mean speeds for first digit, hand, and wrist for the inserting limb were 0.23 ± 0.11, 0.15 ± 0.06, 0.16 ± 0.04 mm/s respectively. Mean speeds for first digit, hand, and wrist for the non-inserting limb were 0.26 ± 0.10, 0.13 ± 0.03, 0.16 ± 0.09 mm/s, respectively. The difference in speed between “inserting” and “non-inserting” limbs for all three IMU positions, as well as the relative speeds between all three positions, were statistically significant (p<0.001).
Conclusion and Potential Impact:Available literature suggests the mean insertion speed during live cochlear implant surgery is 96.5 mm/min (1.60 mm/s), which is significantly faster than the mean speeds collected during this fixed cadaveric temporal bone study regarding all three positions (p<0.001). Though preliminary, this data of insertions speeds highlights the need for further investigation during live cochlear implant surgery on human subjects using IMUs
Interferon Beta Modulation of Brain Endothelial Cell Activation in Ischemic Stroke
Get PDFBackground and Hypothesis:Every year, more than 690,000 people in the United States suffer an ischemic stroke. Many survivors are left with long-term disability. While the initial insult to the brain is caused by hypoxia resulting from cerebral artery occlusion, a secondary insult is caused by peripheral immune cell infiltration across the blood brain barrier (BBB) and subsequent cytotoxic insult. Previous studies have demonstrated that interferon beta (IFNβ) limits peripheral immune cell infiltration across the BBB and reduces brain infarction volume. We hypothesize that during ischemic stroke IFNβ suppresses brain endothelial cells (bECs) activation to reduce their expression of adhesion molecules as one of the mechanisms by which it decreases peripheral immune cell infiltration across the BBB.
Experimental Design:In this project, bEnd.3 cells, a cell line of bECs, were activated by TNF-α, a pro-inflammatory cytokine. Tissue plasminogen activator (tPA), an FDA-approved thrombolytic for ischemic stroke, was included in the study. bEnd.3 cells were treated with IFNβ at 1.5 hours prior TNF-α or TNF-α + tPA stimulation to evaluate its modulation of adhesion cell expression. The adhesion molecule expression was determined by flow cytometry. Results were further confirmed by in vivo studies in which stroke animals were subjected to tPA treatment in the presence or absence of IFNβ.
Results:Our results showed that TNF-α induced ICAM-1, VCAM-1, E-selectin, and P-selectin expression. Importantly, we found IFNβ suppressed the expression of aforementioned adhesion molecules in bEnd.3 cells treated with TNF-α or TNF-α+tPA. Our in vivo results demonstrated that IFNβ treatment reduced ICAM-1 and E-selectin, but not VCAM-1 or P-selectin expression in the ischemic brain.
Conclusion and Potential Impact:Our study demonstrates that IFNβ modulates bEC expression of adhesion molecules in vitro and in vivo of ischemic stroke, suggesting IFNβ, an FDA-approved drug for Multiple Sclerosis, shows potential to improve ischemic stroke outcomes