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Abstract
No full textWe sought to evaluate a novel PPARδ inhibitor and explore whether this compound could synergize with known chemotherapeutic compounds to kill cancer cells in culture. Methods: A novel PPARδ inhibitor compound, Compound 9, was obtained from the College of Pharmacy at Ferris State University for investigation. A cell line with literature-supported PPAR expression, HCT116 (colorectal cancer), was evaluated by Western blot technique to confirm presence and level of expression of PPAR within each line. HeLa cell lines were used as a negative control. Efficacy of Compound 9 to achieve apoptosis in vitro was evaluated using dose response curves with increasing concentrations of inhibitor. Doxorubicin served as the standard chemotherapeutic agent for comparison. Final evaluation included exposure of Compound 9 to a variety of known PPAR subtype agonists and antagonists to determine if further synergy of apoptosis or reversal of PPAR-mediated suppression of downstream targets occurred. Results: Western blot technique confirmed the presence of high level expression of PPARδ in HCT116 cells and undetectable levels of expression in the HeLa cell lines. Dose response curves using concentrations from 0.3 to 50μM of Compound 9 demonstrated apoptotic cell death at concentrations as low as 40-50 μM. Doxorubicin and Compound 9 did not demonstrate appreciable synergy of apoptotic death when combined at concentrations between 0.3-50μM. When combined with a commercially known PPARδ agonist or antagonist, Compound 9 apoptotic death was also not synergized or blocked. Additionally, alpha, beta and gamma agonists and antagonists did not shown potentiation or blocking of cell death, suggesting that Compound 9 functions through a different mechanism at the PPAR receptor. Conclusions: Compound 9 demonstrates initial efficacy at apoptotic cell death of HCT116 cancer cells. However, further investigation into its interaction at the PPARδ receptor and the exact mechanism by which it causes cell death is warranted
Testing Novel Phenolic Fluorophores as Palladium Sensors at Different Concentrations
Get PDFPalladium is often used in the synthesis of Active Pharmaceutical Ingredients (APIs), although it is toxic to ingest. As it is difficult to remove, it is imperative to develop optimal palladium sensors that can be utilized in quality control of pharmaceutical synthesis in order to ensure that all residual palladium catalyst is removed from APIs. The goal of this project is to study a novel series of phenolic fluorophores in order see which, if any, are capable of functioning as palladium sensors. Through a Tsuji-Trost substitution reaction, palladium functions as a catalyst that facilitates the removal of the allyl group from these phenolic compounds and produces a fluorescent molecule that can be quantified. The fluorescence signals of these product compounds were measured over using a Carey Eclipse Fluorimeter in the organic chemistry laboratory at Wabash College. Each phenolic compound was introduced to seven different solutions of varying concentrations of palladium and immediately placed in the Fluorimeter for analysis. The initial rates of the deallylation reaction were measured over 15 minutes, which tells us at what concentrations of palladium the phenolic compound can be distinguished from the blank and be considered an effective palladium sensor. The lower limits of detection amongst these four compounds allowed us to determine the effects that additional functional groups had on the palladium sensing capabilities of these fluorophores. The unsubstituted compound fluoresced more and at an increased initial rate than either the bromo- or methoxy-substituted compounds at every concentration of palladium. However, the unsubstituted compound also fluoresced more over time in the absence of palladium, which is not ideal for a palladium sensor, while the substituted compounds only fluoresced in the presence of palladium. Future work should be directed towards introducing weakly electron-withdrawing groups to the unsubstituted compound in order to optimize its palladium sensing capabilities
Scientific Process Flowchart Assessment (SPFA): A Method for Evaluating Changes in Understanding and Visualization of the Scientific Process in a Multidisciplinary Student Population
Get PDFThe scientific process is nonlinear, unpredictable, and ongoing. Assessing the nature of science is difficult with methods that rely on Likert-scale or multiple-choice questions. This study evaluated conceptions about the scientific process using student-created visual representations that we term flowcharts. The methodology, Scientific Process Flowchart Assessment (SPFA), consisted of a prompt and rubric that was designed to assess students\u27 understanding of the scientific process. Forty flowcharts representing a multidisciplinary group without intervention and 26 flowcharts representing pre- and postinstruction were evaluated over five dimensions: connections, experimental design, reasons for doing science, nature of science, and interconnectivity. Pre to post flowcharts showed a statistically significant improvement in the number of items and ratings for the dimensions. Comparison of the terms used and connections between terms on student flowcharts revealed an enhanced and more nuanced understanding of the scientific process, especially in the areas of application to society and communication within the scientific community. We propose that SPFA can be used in a variety of circumstances, including in the determination of what curricula or interventions would be useful in a course or program, in the assessment of curriculum, or in the evaluation of students performing research projects
Characterizing The Patient Population With 30-Day Readmissions From COPD and Heart Failure
Get PDFUnder the Hospital Readmission Reduction Program (HRRP), hospitals with high readmission rates are penalized by reductions in Medicare reimbursements. In particular, Parkview Noble hospital has experienced high readmission rates for chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), and acute myocardial infarction (AMI). Parkview Noble’s combined 30-day readmission rates for these conditions is 18.19% compared to the national average of 15.86%. Objective: In order to effectively reduce the readmission rate for COPD and CHF patients at Parkview Noble, this study examined the socioeconomic and clinical factors that can be used to target this patient population for healthcare driven interventions. Design/Methods: Data was collected in the form of a retrospective chart review and phone interview of 260 patients. The data obtained was then analyzed using student t-test, chi-square test, and multi-variable regression to determine statistically promising variables. A linear regression using statistically promising variables was performed to obtained preliminary predictive algorithms for COPD and CHF readmission. The sensitivity and specificity of these equations was then plotted using various cut-off values to determine their practical effectiveness. Results: The statistical analysis determined four factors with strong predictive value including: past ED visits in the last 6 months (p=1.4E-6), past ED admissions in the last year (p=0.03), heart failure with coronary artery disease (p=0.05), and stage of COPD (p=0.06). The sensitivity and specificity plots suggest that it is possible to target 20% of readmission patients while still maintaining over 85% specificity. Conclusions: From this preliminary data it is seen that several variables have value in determining a patient’s likelihood of readmission. Using this data as a benchmark, this study will be expanded to include up to 1,028 more patients before a final predictive algorithm is computed and tested
Mouse Model of Marfan Syndrome Accelerates Aneurysmal Formation through Well-Characterized TGF-β Signaling Pathways
Get PDFMarfan syndrome (MFS) represents a genetic disorder with ranging clinical presentation, most notably ascending aortic aneurysms. There has been extensive research to elucidate the mechanistic biochemistry of this disease. In this regard, the abundance of TGF-β from a mutation in fibrillin-1 is the suggested etiology. Many important signaling pathways downstream of TGF-β have been well-characterized. Our laboratory has previously demonstrated a unique murine model of MFS resulting in the accelerated formation of ascending aortic aneurysms. This study aims to characterize the relevance of this model to known signaling mechanisms in MFS
3D Visualization of Two Surgical Approaches for Correcting a Congenital Heart Defect
Get PDFBackground: Transposition of the Great Vessels (TGV) is a congenital heart defect (CHD) in which the great vessels are reversed – the aorta arises off of the right ventricle and the pulmonary trunks arises off the left ventricle. The Mustard Procedure and the Arterial Switch Operation (ASO) are two primary examples of surgical correction approaches that have been used for patients with TGV without other congenital anomalies. This project aims to present 3D visual reconstructions of these two approaches, to compare the final anatomy of the heart post-surgery, and to better understand why the ASO has been the preferred method over the Mustard procedure since 1975. Methods: Computerized tomography (CT) scans of two de-identified individuals were utilized to create 3D visual reconstructions. The first scan was a post-Mustard procedure correction and the second was a post-ASO correction, facilitated with the LeCompte Maneuver. The 3D computer reconstructions, animations, and 3D models were completed using a variety of computer programs, including image analysis software Amira, video editing software Camtasia, and object assembly software Adobe 3D toolkit. A thorough journal review was also conducted for the two surgical procedures in question. Conclusion/Significance of Project: The project demonstrated real life anatomy after two different and complicated surgical repairs and allowed for a comparison between the two. Journal review revealed that the Mustard Procedure often results in long-term complications including right ventricle failure and atrial arrhythmias. The use of 3D imaging allows for easier visualization of perhaps why these complications may occur, as the Mustard procedure results in the right ventricle abnormally becoming the main pump of the body and baffles being constructed through the atria. The benefits of 3D visualization of post-surgical congenital heart anomalies to health care professionals are vast. These techniques can aid students in learning CHDs, physicians in post-surgical treatment, and for patients in understanding their own disease
Establishing Relevant ADC-based Texture Analysis Metrics for Quantifying Early Treatment-Induced Changes in Head and Neck Squamous Cell Carcinomas
Get PDFPurpose: The purpose of this study is to identify which texture analysis metrics calculated from apparent diffusion coefficient (ADC) maps from patients with head and neck squamous cell carcinomas (HNSCC) provide quantifiable measures of tumor physiology changes. We discerned which imaging metrics were relevant using baseline agreement and variations during early treatment. Methods: For selective patients with stages II-IV HNSCC, ADC maps were generated from two baselines, taken 1 week apart, and one early treatment scan, obtained during the 2nd week of curative-intent chemoradiation therapy. Regions of interest (ROI), consisting of primary and nodal disease were drawn onto resampled ADC maps. Four 3D texture matrices describing local and regional relationships between voxel intensities in the ROIs were generated. From these, 38 texture metrics and 7 histogram features were calculated for each patient, including the mean and median ADC. Agreement between the two baseline measures was estimated with the intra-class correlation coefficient (ICC). For each metric with an ICC≥0.80, the Wilcoxon signed-rank test was used to test if the difference between the mean of the baselines and the early treatment was non-zero. Results: Texture analysis was implemented on nine patients that had both baselines and early treatment images. Due to baseline agreement, only 9 of the 45 metrics had an ICC ≥0.80, including ADC mean and median. Six of these 9 metrics had a p-value \u3c 0.05. Only 1 of the 9 metrics remained of interest, after applying the Holm correction to the alpha levels: the run length non-uniformity metric (p = 0.004) in the Gray Level Run Length Matrix. Conclusion: The feasibility of texture analysis is dependent on the baseline agreement of each metric, which disqualifies many texture characteristics. However, metrics with high ICC have potential to provide additional quantitative information for the assessment of early treatment changes for HNSCC
Sr. Rose Marie McCann
Get PDFIn her oral history, Sr. Rose Marie McCann describes what it means to have left the world upon entering religious life in 1951. She details various circumstances of her eventual entrance to the convent at Oldenburg, namely her family\u27s encouragement and previous history with the Sisters. Additionally, she describes the process of postulancy and obedience assigned to newly entered Sisters. In doing so, Sr. Rose Marie also relates the changes that religious life imposed upon Sisters in terms of their dress as well as their interaction and expected conduct toward each other. This is highlighted by her initial jealousy but eventual friendship with fellow postulant Janet.https://mushare.marian.edu/wrp/1012/thumbnail.jp
3D Methods for Medical Education and Clinical Practice
Get PDFNew imaging technologies and 3D rendering software, in addition to being useful diagnostic tools, allow us to augment patient education and further medical student and physician knowledge. 3D imaging modalities such as CT and MRI expedite the learning process for medical students, allow physicians to better visualize the anatomy and potential pathologies present, and aid in educating patients to help them better understand their conditions. We present here 3D interpretations from a sample of CT imaging studies of the cerebral vasculature, optic neural pathways, and paranasal sinuses. These data were obtained from the NIH Cancer Database, among other sources. The raw imaging data was imported into a third-party image analysis software called Amira, which was used to primarily facilitate 3D renderings. From there, the project images were further manipulated and enhanced utilizing other third-party programs, including Autodesk, Mesh Mixer, Adobe 3D Toolkit, and Softwarecasa Camtasia Studio, so that they could be exported as 3D prints, interactive 3D PDFs, and 3D animations. Analysis of data, 3D rendering, and construction of the final products all took place in the Marian University College of Osteopathic Medicine 3D Research Lab. Our intent for the first step in using these projects for medical education includes making these 3D models available to first-year gross anatomy curricula, with the goal of helping students better visualize structures that may otherwise be problematic to view in a cadaver. Our ultimate goal is to have 3D visualization technology incorporated into various facets of medical practice and education: for instance, this technology may help physicians incorporate 3D visualizations of various pathologies (e.g. exact locations of berry aneurysms) into their everyday practice and patient interactions