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The Role of Heterozygous PAI-1 Deficiency in Pathological Aging in the Human Cardiovascular System
Get PDFBackground and Objective: Plasminogen activator inhibitor (PAI-1) is a member of the fibrinolytic system and a marker and a mediator of cellular senescence. Experimental evidence in humans suggests that higher levels of PAI-1 are associated with increased pathological aging in several major organ systems of the human body. To better understand the role of PAI-1 in humans, specifically in the cardiovascular system, we studied the effects of a loss-of-function mutation in SERPINE1, the gene encoding PAI-1, in an Old Order Amish community in Berne, Indiana. Overall, carriers of the null SERPINE1 variant had greater leukocyte telomere lengths, lower fasting insulin levels, and less prevalent diabetes mellitus. To further the conclusions previously published, our goal is to continue to analyze data collected alongside demographic data to determine if there is a link between PAI-1 deficiency and protection against aging-related changes in the human cardiovascular system. We hypothesized that the differences between the cardiovascular endpoints between carriers and non-carriers will be most significant in older groups.
Methods: Participants included 177 members of the community, 43 of which were carriers for the SERPINE1 mutation. To test our hypothesis, we divided participants into tertiles and compared the results of selected cardiovascular parameters of those with and without the mutation in each tertile.
Results: Our analysis revealed a statistically significant difference in brachial pulse pressures between carriers of the null mutation and normal individuals in the third tertile, corresponding to individuals ages 55 to 82. Those heterozygous for the mutation in this age group had a lower brachial pulse pressure, suggesting there are protective effects of PAI-1 haploinsufficiency against endothelial senescence as people age.
Potential Impact: By identifying the age group with the most pronounced effects of PAI-1 deficiency, we can further investigate the means by which these results manifest in humans and better understand where in the aging process they are most significant
A Case Study on the Relationship Between a Multimodal Approach to Opioid Treatment and Opioid Cessation in Low-Income BIPOC Communities
Get PDFBackground and Hypothesis:In the United States, the opioid crisis has been centered around white individuals in suburban and rural areas. However, communities of color who have a low socioeconomic status (SES) are facing an increasing amount of opioid overdose related deaths. Even with pharmacological opioid agonist therapy, this specific population still does not have the support to remain abstinent from opioids. We have conducted a case study with Mr.G, a 32 year old black male patient with opioid use disorder (OUD) who is from a low SES. Mr. G suffered from four overdoses over a six-month period (two of them occurring within 24 hours). He was treated for each overdose at three different large academic medical centers. The first three academic medical center offered him solely Buprenorphine-Naloxone, whereas the current medical center took a multimodal approach. We hypothesize that populations of color with opioid use disorder who are from a low socioeconomic class will benefit more from a multimodal approach to OUD treatment.
Methods:In this work, we conducted a literature review to construct a multitude of questions to assess Mr.G’s experience at his previous academic medical centers versus his current academic center and why his current treatment has resulted in successful opioid cessation.
Results:Thus far, we have not received a response from Mr. G. However, since a multimodal approach was taken towards his treatment, he has enrolled in college courses, has gained employment, and has maintained sobriety.
Conclusion and Potential Impact:Patients like Mr. G who come from communities of color and lower socioeconomic status may benefit from a multimodal approach when treating their OUD. This study will potentially lead to more research focusing on how to address the holistic needs for communities of color with opioid use disorder who come from a lower socioeconomic status
The Quandary of Cellular Fractionation — Optimizing Ambion™ Paris System to Advance HPV16 Cancer Research
Get PDFBackground and Hypothesis: Human Papillomavirus (HPV) is the causative agent in nearly all cervical cancer cases. It has been shown that the HPV type 16 E6 protein interacts directly with the host protein NFX1-123. Short-term studies have shown that NFX1-123 remains in the cytoplasm; however, it has not been investigated whether NFX1-123 actually translocates to the nucleus in the long term. We hypothesize that over time, NFX1-123 translocates to the nucleus of the cell in long term cultures with 16E6. This present study seeks to optimize the AmbionTM Paris system to allow for pure, proper separation of the cytoplasmic and nuclear cellular compartments.
Project Methods: Three biologically unique backgrounds of human foreskin keratinocytes (HFKs) were cultured in a monolayer tissue culture dish. Using the AmbionTM Paris system, proteins were isolated as whole cell extracts, or nuclear and cytoplasmic fractions. For one lysis method, only protease inhibitors were added to the lysis buffers of the AmbionTM Paris system. For another lysis method, 1% NP-40 and protease inhibitors were added to the lysis buffers of the Paris system. Protein lysate concentrations were quantified, then purity of subcellular lysates was determined by western blotting. Histone H3 and GAPDH were used to identify nuclear and cytoplasmic compartments, respectfully.
Results: Western blotting confirmed that adding 1% NP-40 to the lysis reagents of the AmbionTM Paris kit optimized subcellular fractionization.
Potential Impact: Being able to efficiently separate the cytoplasmic and nuclear compartments will allow for accurate identification of NFX1-123 localization during long-term HPV16 infection. If NFX1-123 is found to move into the nucleus under the influence of HPV 16E6, then this could indicate potential transcriptional regulatory functions of the NFX1-123 protein during HPV infection, which is unique from its function in non-infected cells
Celiac Disease in Medical Curriculum
Get PDFIntroduction: Celiac disease is a common autoimmune illness precipitated by the ingestion of gluten, a protein contained in grains (e.g., wheat, barley, and rye). Celiac disease can present with a wide variety of manifestations across nearly any body system, but most individuals with celiac disease present with subclinical symptoms. Despite relatively inexpensive testing and an effective treatment (i.e., a gluten free diet), most individuals with celiac disease remain undiagnosed, leading to significant disease burden. Research suggests that physicians have poor knowledge of celiac disease, likely contributing to the high rates of missed diagnoses. This study sought to assess the information encountered by students in pre-clinical medical education regarding celiac disease.
Methods: Information was drawn from recent literature to create a rubric to evaluate the presentation of celiac disease in curricular and educational resources for pre-clinical medical students. Categories evaluated included prevalence, morbidity/mortality, manifestations, comorbidities, and testing recommendations. This rubric was used to assess the curriculum from a large US medical school and First Aid for the USMLE Step 1, a popular commercial resource used by medical students.
Results: The medical school curriculum scored higher overall than First Aid (31/48 and 12/48, respectively). The curriculum also scored higher in all categories except morbidity/mortality. The curriculum showed deficits predominantly in morbidity/mortality and testing recommendations. First Aid showed deficits in all categories.
Discussion: Results showed that the medical school curriculum provided more complete information about several aspects of celiac disease. First Aid did not thoroughly address any of the categories evaluated with the rubric. While First Aid may be an effective consolidation of Step 1 material, it seems likely that it is focused on “teaching to the test” rather than providing thorough medical education for future physicians. The medical curriculum is a more complete resource for students to learn about celiac disease
Public Health Research in the News: An Exploratory Study of Topics, Coverage, and Open Access Status
Get PDFObjectives: This study aims to identify and analyze the news outlets that reference research published by the Richard M. Fairbanks School of Public Health at Indiana University-Purdue University Indianapolis (FSPH). We analyzed the overall patterns of news sources, including the content type and overall coverage, the correlation with open access (OA) status, and the topics that received more attention in online news stories. We aim to contribute to a better understanding of the characteristics of news outlets that disseminate public health information, and the types of public health research referenced most often in the news.
Methods: We conducted a retrospective cohort study. The study population consisted of FSPH authors, the exposure was publishing journal articles by FSPH authors, and the outcome was news media attention. We compared the amount of media attention with otherstudies. We also compared open access journals versus commercially produced journals. We searched the Scopus database using an affiliation search to locate and retrieve the journal articles. Then we queried the Altmetric Explorer tool (altmetrics provider) for all the citations resulting from the Scopus search. We conducted a bibliometric analysis of publications from authors affiliated with the school of public health over five years (2015–2019). The searches were conducted in December 2021. We used the identifiers and the titles to compile the online news mention data and identify the titles featured in news outlets. The journal articles with news mentions and the news outlets that reference them were analyzed. The data were combined, cleaned up, and analyzed using Excel, and the subject analysis was produced using the VOSviewer software.
Results: For the 2015–2019 time frame, 778 publications were published by the FSPH. A total of 144 (18.5%) were highlighted in 2,079 online news stories from 655 news outlets. We analyzed the overall dataset of news outlets according to the source, content type, subject area, and country of publication. We also determined the attention likelihood of open access articles compared to those with closed access. We performed a co-occurrence analysis of the MeSH terms the articles featured in news outlets.
Discussion: Mentions in online news outlets can identify patterns and trends of attention and interest in research beyond academia. This bibliometric analysis helps to clarify the media outlets that distribute information on public health as well as the categories of research that are frequently featured in the media. The findings of this report, will help the library expand its research impact services and support the decision-making of leaders of public health schools for future publication and research strategy development directions
Trends in Melanoma Patient Survival Based on Tumor Depth and Anatomic Location
Get PDFSkin cancer is the most common cancer. Melanoma composes less than 4% of total cases but is the cause of most skin cancer deaths. However, in the United States, melanoma has the fifth highest rate of incidence of all cancers with an average 93.5% 5-year survival rate. However, when melanoma spreads either to regional lymph nodes or to distant organs, the prognosis drops significantly, so there is a critical need to identify patients at risk for tumor spread. The objective of this research project is to determine the correlation between tumor depth and anatomic location with metastasis outcomes. We identified a cohort of 923 Stage 1 & 2 patients (those without lymph node metastases) from the Indiana University Simon Cancer Center Registry with an average follow up of 4 years (Std. dev = 3.2). We retrieved the clinicopathologic descriptions of their melanomas using a database from the IU Pathology department. Patients were stratified by tumor stage, location, and depth of invasion, and survival rates were analyzed Cox proportional hazard models and log-rank tests. Kaplan-Meier plots were generated with the survminer package. The results of the study indicate that there is no difference in metastasis for patients with similar levels of tumor invasion but different anatomic locations. Unexpectedly, multivariate cox regression showed that mitotic count was a stronger predictor of metastasis than tumor invasion. These results indicate that there is a need for bioinformatic tools to more accurately quantify semi-quantitative measures of tumor morphology. This would allow for rigorous research and higher precisions prognostic tools
A Review of SNAP Nutritional Incentive Programs
Get PDFThere are over 40 million Americans in the Supplemental Nutrition Assistance Program (SNAP), formerly known as the Food Stamps Program. Despite this program attempting to eliminate food insecurity for people 130% below the poverty line, it does little to prevent nutrition related health disparities between SNAP participants and people who are more financially stable. Nearly every state has nutrition incentive programs attempting to address these nutritional health disparities that SNAP does not address. To synthesize a literature review of several of these programs, a search was conducted in PubMed, PubAg, and Google Scholar databases using terms such as “SNAP” and “nutritional incentive program,” along with date restrictions for 2013 or later. This search resulted in a total of 54 articles, however only 35 were used following screening. Included articles were screened first by abstract and then article content to determine relevancy. The literature suggests that programs address nutritional health disparities by providing financial interventions for SNAP participants to make nutritionally conscious decisions about the food they purchase and consume. There were three categories of interventions that were suggested by the literature: incentives, discounts, and restrictions. Regardless of the intervention, each of these categories of intervention were praised by SNAP participants. Participants were able to purchase and consume more fruits and vegetables, focus on nutrition, and financially support local farmers markets and supermarkets. This review discusses these different interventions to allow for new or existing programs to be developed to best address nutritional health disparities using scholarly evidence
Medicaid Reimbursement for Community Health Workers: A Comparative State Policy Analysis with Implications for Indiana
Get PDFBackground: Community health workers (CHWs) promote health education, address social determinants of health, and bridge the gap between healthcare systems and underserved populations, but the lack of sustainable funding remains a challenge to greater CHW utilization. Medicaid reimbursement has been identified as a promising mechanism to fund CHWs, however, state policies vary widely. A comparative policy analysis can guide future reimbursement strategies.
Methods: We conducted a comparative policy analysis of Medicaid reimbursement for CHWs. State government websites and legal databases were searched utilizing keyword search terms related to CHWs and Medicaid reimbursement. We identified and analyzed relevant statutes, regulations, and administrative codes for reimbursement mechanism, rates, supervision, certification, and scope of practice.
Results: 26 states currently reimburse CHWs through Medicaid; 3 states started reimbursement in the last six months. 16 states authorize payment through State Plan Amendments (SPAs), 3 use Section 1115 demonstration waivers, 10 use Medicaid managed care organization contracts, and 4 use blended strategies. 13 states require certification and supervision for reimbursement, although the supervising licensed professional can vary. The scope of practice of CHW also varies between states. There is a large range for reimbursement rates; for example, billing code 98960 currently used by 14 states varies from 55.25 in Arizona for a 30 minute visit.
Policy Implications: This study can inform sustainable reimbursement models through Medicaid for CHWs in Indiana and other states. An SPA may be the most expedient way for Indiana to increase reimbursement for CHWs, but its narrowness and inflexibility could hinder CHWs\u27 positive impact. The variety of strategies currently in use demonstrates that there is no single path to sustainable financing. Protocols for a set of scoping reviews will result from this comparative analysis for more in-depth investigations of key peer-reviewed and grey literature
Group Prenatal Care Models, Experiences, and Outcomes: An Integrative R
Get PDFBackground:The United States (US) has the highest maternal and infant mortality rates among developed countries. Indiana has the third highest maternal mortality rate in the US. Group Prenatal Care (GPC) was piloted in the early 1990s to improve perinatal experiences and outcomes through enhanced social support and education. Further research is needed as GPC is increasingly implemented in diverse contexts. This study critically synthesized current evidence on GPC models, experiences, and perinatal outcomes in the US to inform a Community Based Participatory Research Partnership between Indiana University School of Medicine-Northwest and Community HealthNet.
Methods:This integrative review utilized PRISMA guidelines to conduct a systematic search in Embase, CINAHL, and PubMed. Two researchers screened articles for inclusion criteria and quality. Studies were included if they were empirical research or meta-analyses conducted in the US and published in English between January 2013 and June 2023. Data synthesis utilized a qualitative analytical approach that sorted findings thematically.
Results:We retained 98 articles, including 8 meta-analyses, 4 randomized trials, 3 cluster randomized trials, 3 quasi-experimental studies, 4 prospective cohort studies, 12 observational studies, 19 qualitative studies, and 46 retrospective cohort studies. There were several GPC models adapted to high-risk groups such as persons living with HIV, gestational diabetes, pre-existing or pregnancy-induced hypertension, and substance use disorders. GPC was associated with decreased preterm births among low-income and minority women, with more significant reductions when attending 5 or more GPC sessions. GPC improved psychosocial outcomes including satisfaction with care, empowerment, and social connectedness. It was also associated with increased breastfeeding rates in adolescents and African Americans, and increased contraception use among adolescents.
Conclusions:Engaging in GPC may have benefits for high-risk pregnancies, adolescents, low-income, and minority populations. More studies are needed to evaluate GPC’s impacts on perinatal experiences and outcomes among high-risk women
Analysis of Perioperative Events in Bilateral vs Unilateral Staged Percutaneous Nephrolithotomy
Get PDFIntroduction: Kidney stones are a common medical condition that impact approximately 10% of US population. Management of stone disease is based on size and location of stones. Percutaneous nephrolithotomy (PCNL) is typically indicated in patients with large renal stone burden (typically >2 cm) or complex anatomy. In the setting of complex stones, multiple, staged PCNLs are required. We hypothesize that there is no significant difference in the perioperative change in lab values in bilateral PCNLs compared to unilateral PCNLs.
Methods: The data was gathered by retrospectively reviewing the electronic medical record of 50 patients in the IU health system who underwent planned staged PCNLs between January and December 2018. We identified patients who underwent both bilateral and unilateral staged procedures. Data for BMI, sex, ethnicity, hemoglobin, estimated glomerular filtration rate (GFR) (typically formula CKD-EPI or MDRD), urine and stone cultures, stone composition, and bilaterality vs. unilaterality was collected. Two-tailed T-tests were performed to analyze data between bilateral and unilateral cases.
Results: We identified a total of 50 patients, 19 men vs. 31 women; 9 men and 10 women underwent bilateral PCNLs, while 11 men and 20 women had unilateral PCNLs. BMI ranged from 14.2 to 62.3, and age ranged from 15 to 81. Significant differences were found between the changes in hemoglobin levels in patients who underwent bilateral PCNLs when compared to unilateral PCNLs (p value 0.018). No significant differences were noted when comparing changes of estimated GFR, BMI, age or any other variables.
Conclusion: Patients who underwent bilateral staged PCNLs demonstrated a greater drop in perioperative hemoglobin compared to unilateral PCNLs without an increase in blood transfusion. This finding suggests that Bilateral PCNLs requiring multiple stages are safe in complex stone patients