Health Sciences – Page 24 – UROP Spring Symposium 2021

Health Sciences

Active for Life with chronic obstructive pulmonary disease (COPD)

COPD is a chronic lung-based disease that blocks airflow making it harder to breathe. Studies have also shown that muscle strength in people with COPD is lower than that of age-matched individuals without COPD. The decrease in muscle strength can impede individuals from partaking in physical activity (PA) which has been associated with a slower decline in lung function and reduced hospitalization in people with COPD. Traditional interventions for COPD have focused on moderate to vigorous physical activity (MVPA) but the Active For Life: COPD intervention program designed by Dr. Larson is novel in its emphasis on light physical activity (LPA) and decreased sedentary time. Participants were recruited and sorted into control or experimental groups, followed by 10 weeks of training classes for both groups. The experimental group did functional circuit training and learned self-regulation strategies. The control group did chair exercises and guided imagery for relaxation and health education. Both groups came back at 2 months, 3 months, 6 months, and 12 months to have various measures of strength, endurance, and physical activity tested. A study was undertaken to see the impact of this intervention on isometric strength measures through knee flexors and extensors. Due to the study being ongoing and having a partially blind setup in order to minimize bias, blinded group interim analysis will be analyzed. If this intervention is successful, in increasing physical activity and muscle strength it could change general physical activity guidelines for people with COPD shifting away from MVPA and towards LPA.

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Active for Life with chronic obstructive pulmonary disease (COPD): Physical activity and anxiety

Individuals with Chronic Obstructive Pulmonary Disease (COPD), tend to live a sedentary life which can increase the risk of mortality and heighten symptoms of COPD. In attempting to prevent this sedentary lifestyle in COPD patients, many exercise programs focus on vigorous physical activity which is not sustainable in the long run. The Principal Investigator of this study, Janet Larson, developed an exercise program, called Active Life. The Active Life program emphasizes light physical activity for patients with COPD. The study conducted is a randomized controlled clinical trial where COPD participants are randomly placed into two groups, the Active for Life intervention and the control intervention. The study is conducted to determine if the Active Life intervention is an effective program in promoting physical activity in COPD patients. The participants in the Active Life intervention complete an exercise program including functional circuit training (FCT), health education, and self-regulation strategies. The participants in the control group complete an exercise program that includes chair exercises, relaxation promotion, and health education. The participants complete 10 weeks of lab-based exercise, then a one-year follow-up which measures activity levels and home-based exercises. Through the data collected from the Active Life study, I decided to look into the effect that physical activity has on anxiety levels in patients with moderate to severe COPD. In the study, data was collected on anxiety levels throughout the study as well as different measurements of physical fitness and activity. I examined the long-term (52-week post-intervention) impact of light physical activity on self-reported anxiety compared to the control group.

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Mitochondrial trafficking is altered in insulin receptor knockout dorsal root ganglion sensory neurons

Diabetes is a global epidemic that affects 463 million individuals. Approximately 50% of diabetic patients develop a serious complication called diabetic neuropathy (DN) that can also develop in patients with pre-diabetes and obesity. DN is characterized by tingling or burning, sharp pains, and eventual loss of sensation in the hands or feet that results from significant nerve damage. Despite the severity of DN, there are no disease-modifying treatments for DN associated with type 2 diabetes, prediabetes, or obesity. Recent studies indicate that dyslipidemia correlates with DN, suggesting that fatty acids may contribute to DN onset or progression. Dorsal root ganglion (DRG) neurons are a cluster of primary sensory neurons located just outside the spinal cord that extend axons into the nerves and transmit sensory information from the peripheral nervous system to the central nervous system. DRG neurons depend on mitochondrial trafficking and function to produce ATP in the axons, and it has been reported that insulin signaling regulates mitochondrial function. In this study, we sought to determine whether the presence of the insulin receptor regulates axonal mitochondrial trafficking in fatty acid-treated DRG neurons. DRG neurons from insulin receptor knockout mice (IRKO) were given six different treatments to explore the effect of saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) on axonal mitochondrial trafficking. A kymographing analysis was used to analyze mitochondrial transport in individual DRG axons and identify the percent of mitochondria that were stationary or motile. Interestingly, we found significantly fewer motile mitochondria in the IRKO DRG axons compared to wild type DRG axons. The SFA treatments impaired mitochondrial trafficking, while the addition of MUFAs prevented the reduction in mitochondrial trafficking in both wild type and IRKO DRG neurons. This study suggests that the loss of the insulin receptor reduces basal mitochondrial trafficking in DRG neurons but does not contribute to fatty acid-induced alterations in mitochondrial trafficking.

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Understanding the Role of FGFR4, Insulin R, and MerTK Pathways in Tumor Metastasis

In 2017, the Cold Harbor Spring Laboratory in New York discovered a relationship between tumor metastasis and NETs (neutrophil extracellular traps). They found when neutrophils were blocked by NETs, the 4T1 cell line, a cell line that usually metastasizes, did not metastasize. 4T1 and 4T07 cells from a mouse mammary tumor share a common genetic background. Through background research, we know that the two cell lines produce different amounts of CXCR-2 ligands in vitro, but similar amounts when cultured in the presence of DHMs (DNA histone mesostructures). The work we performed was designed to identify what mutations are present in the metastatic 4T1 cells that are not present in the non-metastatic 4T07 cells, and to understand which points of difference between these cell lines might account for the difference in CXCR-2 ligand production. While our results are still pending, we have begun probing the role of the FGFR4, Insulin R, and MerTK pathways based on literature and data we have generated using protein microarrays.

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Promoting Breast and Cervical Cancer Screening among Asian American Women in West MI

Breast and cervical cancer disparities are growing issues among Michigan’s Asian American communities due to various barriers. Early detection and screening play an essential role in decreasing cancer morbidity and mortality, nevertheless, Asian American women are less likely to receive pap smears and mammograms due to language, cultural, socioeconomic, and healthcare access barriers. This reveals the pressing need for services tailored for ethnic groups to increase breast and cervical cancer screening for Asian American (AA) women in Western Michigan regions. The purpose of this study was to explore and compare the differences in perceived barriers for breast and cervical cancer screening and study the roles bilingual community health workers play in facilitating three Asian American groups. Specifically, our study includes Chinese, Vietnamese, and Nepali patients in Western Michigan enrolling in the Michigan Breast and Cervical Cancer Control Navigation Program (BC3NP). Research Questions are 1. What are the major barriers related to receiving breast and cervical cancer screening among AA women? and 2. What are the roles that bilingual community health workers in Western Michigan have in facilitating women’s enrollment into the Michigan BC3NP. Tracking form that measures demographic including insurance status, age, as well as screening status and results, will be collected. The results and conclusion of the survey are yet to be determined. The results will yield evidence-based recommendations to effectively promote breast and cervical cancer screening among AA women in Western Michigan, ultimately increasing screening rates in this population.

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Gamification of Diversity Training in STEM: Testing the Efficacy of the Academe Dream Board Game

Now, more than ever, diversity, equity, and inclusion are at the forefront of the change happening in society. Our project explores and presents current structural discrimination, aggressions, and inequities people of a vast array of communities face every day. The project itself is important because it not only displays these degrading structures in broad daylight, but it also facilitates discussion between people to help open their eyes to privileges they hold, or at the very least to recognize that these things do in fact happen in real life. As of now, the project has been developed (or is currently in the process of polishing over minute details) and is almost ready to perform pilot testing. The project consists of a “board game” or rather virtual game (due to COVID-19) which has people choose character cards, action cards, and game upgrades – simulating a competitive game atmosphere. The characters themselves are intended to be very unrelated from the player so as to produce a new perspective to consider. Inevitably, the players that make it the furthest/complete the game first are the more privileged communities of people and the people that fall behind are the players that experience discrimination in various settings. Because this study is in the stage of development, we haven’t collected much usable data – this will take place soon this Winter 2021 semester and in the coming 2021-2022 academic year. The hope is that our findings will be one of the contributing factors to much-needed change within the STEM field (specifically with the IRB and research mentorship).

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Gamification of Diversity Training in STEM: Testing the Efficacy of the Academe Dream Board Game

Now, more than ever, diversity, equity, and inclusion are at the forefront of the change happening in society. Our project explores and presents current structural discrimination, aggressions, and inequities people of a vast array of communities face every day. The project itself is important because it not only displays these degrading structures in broad daylight, but it also facilitates discussion between people to help open their eyes to privileges they hold, or at the very least to recognize that these things do in fact happen in real life. As of now, the project has been developed (or is currently in the process of polishing over minute details) and is almost ready to perform pilot testing. The project consists of a “board game” or rather virtual game (due to COVID-19) which has people choose character cards, action cards, and game upgrades – simulating a competitive game atmosphere. The characters themselves are intended to be very unrelated from the player so as to produce a new perspective to consider. Inevitably, the players that make it the furthest/complete the game first are the more privileged communities of people and the people that fall behind are the players that experience discrimination in various settings. Because this study is in the stage of development, we haven’t collected much usable data – this will take place soon this Winter 2021 semester and in the coming 2021-2022 academic year. The hope is that our findings will be one of the contributing factors to much-needed change within the STEM field (specifically with the IRB and research mentorship).

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Associations of adverse childhood experiences with chronic systemic inflammation in adulthood

Background: Childhood trauma and adverse childhood events (ACEs) contribute to adult physical and mental health. However, little is known about the underlying mechanisms that explain this relationship, which could inform the development of targeted interventions. Recent research has suggested that chronic systemic inflammation and immune dysfunction may play a key mediating role between ACEs and health outcomes across the lifespan. Objectives: The goal of this project was to review existing literature in order to determine the potential for chronic systemic inflammation to explain associations of ACEs with adult health outcomes. Exposure of interest: adverse childhood experiences Outcome of interest: chronic systemic inflammation Methods: Pubmed and Scopus were searched with subject headings “ËœChildhood Trauma’, “ËœAdverse Childhood Experiences’, “ËœChild Abuse’ cross referenced with “ËœInflammation’, “ËœC-reactive protein’, “ËœCRP’, “ËœInterleukin’, and “ËœIL-6′. A wide range of studies like literature reviews, human studies, and qualitative studies were considered. Results: Among existing studies, markers of chronic systemic inflammation included C-reactive protein (CRP), interleukin (IL)-6, fibrinogen, and tumour necrosis factor (TNF)-a. Findings indicated that chronic systemic inflammation is a mechanism by which ACEs influence health outcomes in adulthood. As an example of this, Lacey and colleagues (2020) observed that specific ACEs like household dysfunction and parental loss were associated with higher levels of CRP and fibrinogen among adults aged 44-45 years. Conclusions: Chronic systemic inflammation likely plays a role in the relationship between ACEs and adult health outcomes. This project highlights the role of early-life exposures in health across the lifespan and the need for strategies that reduce the burden of ACEs. Whether systemic inflammation can be targeted to buffer against the effects of ACEs on health will require further study.

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Current practices in sleep and circadian medicine

One crucial hurdle to the effective treatment of circadian misalignment in shift workers is a lack of knowledge about differences in circadian rhythms of workers with and without Shift Work Disorder (SWD). The objective of this study was to examine how circadian rhythms differed in SWD in order to help shift workers avoid developing sleep disorders as well as provide a stronger base for the development of successful treatments for those already diagnosed. We recruited 83 fixed night shift workers and examined melatonin profiles, circadian misalignment (Dim Light Melatonin Onset), and sleepiness profiles (Karolinska Sleepiness Scale). Melatonin profiles were determined and DLMO was assessed by means of 24 hourly saliva samples collected in dim light conditions (<10 lux). During these hourly collections, sleepiness was also measured using subjective patient judgment. Participants diagnosed with SWD on average secreted 26.6 pg/ml less melatonin from DLMO to DLMOffset than those without SWD. Further analysis also found that the amplitude of all participants' melatonin values amplitudes were significantly correlated with the amplitude of their sleepiness but not with average sleepiness. The correlation between melatonin and sleepiness was also comparable between the two groups, with both groups showing a 2 hour lag between subjective sleepiness and increases in melatonin. This study provides support that sleepiness in SWD is associated with changes in melatonin. Furthermore, it contributes new evidence that night shift workers with SWD secrete less melatonin on average than their counterparts while still experiencing increased symptoms of excessive sleepiness and other health problems.

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Systemic discovery of rare, pathogenic, germline variants in pediatric neuroblastoma.

Pediatric cancers often appear pathologically similar to their adult counterparts, yet they have different genetic makeups. Germline variants are common in pediatric cancers with approximately 7-8% of malignancies carrying a germline mutation.While it is understood that germline variants are important pathogenic drivers of pediatric cancers, there have been few studies to systematically identify pathogenic variants in pediatric tumors. Identifying pathogenic germline variants will play a central role in advancing understandings of pediatric cancer. This project seeks to systematically identify statically significant rare, pathogenic germline variants from a cohort of pediatric nuroblastoma tumors. Both patient tumor and genetic information was sequenced using with a matched normal. Variants were then annotated to produce a list of calls that were then matched with relevant database information when applicable. Following annotation of variants, functions were developed in R in order to sort and filter which variants are germline, pathogenic by both known association and protein impact, and rare using a GNOMAD allele frequency of less than 0.005. A separate filter was applied for variant quality. The resulting high confidence calls were then queried against databases to identify their relevance in nuroblastoma. Finally, the rare, pathogenic, germline variants were visualized using various plots. The project has yet to finish, however we hypothesize a moderate number of rare pathogenic germline variants to be present in each tumor sample based upon preliminary data. Identification of these rare variants will aid in oncologist’s understanding of the genetics of neuroblastomas and inform the development of personalized medicine

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