Health Sciences – Page 30 – UROP Spring Symposium 2021

Health Sciences

Genetic Impact on Low Diversity Microbiomes in Patients with Inflammatory Bowel Disease

Inflammatory Bowel Disease (IBD), a term that is used to generalize Ulcerative Colitis (UC) and Crohn’s Disease, is a disorder that involves chronic inflammation in the digestive tracts. UC is restricted to the colon, while Crohn’s disease can involve all segments of the GI tract. The pathogenesis of IBD is still unclear but several proposed mechanisms are being investigated which lead to a loss of homeostatic host-microbe interaction in the GI tract. Our study focuses on one of those mechanisms whereby a mutation in a gene that encodes an NADPH oxidase called Duox2 might lead to a loss of host-microbe homeostasis in the gut. In addition, we aim to better understand the possible environmental and hereditary factors that may contribute to IBD. Our study aimed to recruit 100 sibling pairs to take a survey that asked questions about diet, sleep, exercise, and their living environment. One of the siblings had IBD while the other was a control subject. Each sibling pair had a first degree relative with IBD, indicating a possible genetic component (e.g., Duox2 mutation). There was a parallel study conducted in Taiwan to also compare differences in ethnicity. Through our survey, we predicted that results will show trends among families who have IBD. The second phase of the study, identified patients who may be more likely to have a mutation in the Duox2 gene by screening for congenital hypothyroidism known to share a common genetic risk gene in Duox2. By collecting a blood and stool sample from families, we predict that we will be able to better understand the determinants of genetics, environment, and gut microbiota in the pathogenesis of IBD.

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Precision Medicine for Patients with Glomerular Disease

Frequently relapsing/steroid dependent nephrotic syndrome (FR/SDNS) is a chronic health condition in children that is treated with long term immunosuppression therapies with variable response and significant treatment-associated toxicities. Precise, safe and effective therapies are needed. Objective: in order to address drug development needs, we undertook a project to prioritize FR/SDNS clinical trial outcomes and generate standard of care outcome estimates for use in clinical trial design. Methods: A clinician-investigator stakeholder group was polled to elicit input on FR/SDNS trial endpoint priorities. A literature review was conducted using PubMed and enriched with assessment of trial listings from Clinicaltrials.gov. Search terms included: Idiopathic Nephrotic Syndrome and Minimal Change Disease. Publications were required to be clinical trials in humans for inclusion. Data collection included population type, year of publication, age of participants, trial treatment groups, participants in each arm and the prioritized outcome relapse rate. A summary of the results by treatment arm was generated using forest plot of relapse rate point estimates and 95% confidence intervals by trial treatment arm. Results: Relapse rate was one of two prioritized FR/SDNS clinical trial endpoints. From published clinical trials, relapse rate point estimates varied by clinical trial treatment groups but were generally between 0.02 and 0.2 relapses per patient month. Conclusions: The identified relapse rates and distribution can be used in the design of FR/SDNS clinical trials for power and sample size estimations.

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The effect of statins on the progression of Nonalcoholic fatty liver disease: A systematic review and meta-analysis

Nonalcoholic fatty liver disease (NAFLD) is characterized by the accumulation of fat in the liver due to causes unrelated to excessive alcohol consumption. Around 25% of the global population is affected by NAFLD, with some countries having even higher rates.[1] However, most people with this condition are just suggested to change their lifestyle.[2] Often associated with these underlying causes are cardiovascular disease (CVD) and high cholesterol levels, which the class of drugs known as statins are often prescribed to help treat. Statins have been shown to lead to some liver injury and therefore they have not been a popular medication physicians consider for NAFLD.[3] Thus, the aim of this study will be to explore the impact of statins on treating the progression of NAFLD. While some studies have been performed on the effects of statins on liver disease associated with varying causes,[4] it is not well-known what effect these medications have on the progression of NAFLD. Some have suggested that there is a beneficial effect in reducing the time it takes the disease to progress[5,6] and generally improving liver blood tests,[7] but there are not many systematic reviews synthesizing all recent data. Our goal is to conduct an updated systematic review and meta-analysis of the current literature investigating the effects of statins on NAFLD to determine the consensus on whether these medications do have a beneficial effect in disease progression. To investigate this relationship, we used Cochrane Library, PubMed, and EMBASE to gather all the references, utilizing the Boolean search method to collect the past research studies using all keywords relating to NAFLD and statins. The relevant, qualified studies were then compiled into EndNote X9, and Microsoft Excel and R statistical software were used to conduct a formal meta-analysis (i.e., inclusion of forest plot, funnel plot, etc.). The data is expected to show that statins do help improve the condition of NAFLD patients due to decreasing the build-up of fat and improving NAFLD test scores. The implications of this study will allow for physicians to more easily reject or approve of the use of statins in NAFLD treatment.

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The effect of statins on the progression of Nonalcoholic fatty liver disease: A systematic review and meta-analysis

Nonalcoholic fatty liver disease (NAFLD) is characterized by the accumulation of fat in the liver due to causes unrelated to excessive alcohol consumption. Around 25% of the global population is affected by NAFLD, with some countries having even higher rates. However, most people with this condition are just suggested to change their lifestyle. Often associated with these underlying causes are Cardiovascular disease (CVD) and high cholesterol levels, which the class of drugs known as statins are often prescribed to help treat. Statins have been shown to lead to some liver injury in extreme cirrhotic cases and therefore they have not been a popular medication physicians consider for NAFLD. Thus, the aim of this study will be to explore the impact of statins on treating the progression of NAFLD.

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The Contribution of PM2.5 to Depressive Disorders and Alzheimer’s Disease and Related Dementias (ADRD)

Background: Poor air quality can have negative consequences for multiple organ systems throughout the body with some of the most severe effects linked to PM2.5 (particulate matter with an aerodynamic diameter = 2.5 µm). Systemic inflammation and oxidative stress are key biological mechanisms by which PM2.5 exposure is believed to influence health, and also interact with the central nervous system and brain. However, the impact of PM2.5 on common neuropsychiatric and neurological conditions of depression and Alzheimer’s Disease and Related Dementias (ADRD) is not well established. Objectives: The goal of this project was to review existing literature in order to determine the potential for PM2.5 to contribute to depressive disorders and ADRD. Exposure of Interest: PM2.5

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