M.S. - Clinical and Translational Research

Permanent URI for this collectionhttps://hdl.handle.net/10125/76267

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The Exocyst Is Required For CD36 Fatty Acid Translocase Trafficking And Free Fatty Acid Uptake In Skeletal And Cardiac Muscle Cells
(University of Hawaii at Manoa, 2023) Nakamura, Nicole Kazuyo; Polgar, Noemi; Clinical & Translational Research
The prevalence of obesity is increasing at an alarming rate with nearly 93.3 million adults affected in the US alone (Han and Boyko 2018). Obesity-associated insulin resistance is a major risk for type-2 diabetes and as obesity is on the rise, it is important to determine the potential mechanisms behind these diseases in order to determine effective interventions. In obesity-associated lipid overload, chronic membrane-localization of the fatty acid translocase CD36, but not other FFA transporters, enhances FFA uptake. This excess FFA within the ectopic tissues, such as skeletal muscle, will lead to an imbalance in lipid homeostasis leading to the accumulation of bioactive lipid metabolites (Borén et al. 2013). Ectopic lipid accumulation in skeletal muscle promotes insulin resistance by inhibiting insulin-induced GLUT4 glucose transporter trafficking and glucose uptake. Thus, increased circulating FFA levels and impaired lipid oxidation are often associated with insulin resistant states including type-2 diabetes. Downregulation of lipid uptake may provide therapeutic targets preventing insulin resistance. (Dresner et al. 1999) The uptake of skeletal muscle free fatty acids (FFAs) correlates with the presence of CD36 FFA translocase on the plasma membrane, and the downregulation of lipid uptake through CD36 may play a vital role in preventing insulin resistance. While we gathered detailed knowledge in the past decades on GLUT4 trafficking, the mechanisms regulating CD36 membrane delivery and subsequent FFA uptake in skeletal muscle are not fully understood. Our study is the first to demonstrate that the exocyst trafficking complex is necessary for insulin- and contraction-induced CD36 membrane trafficking and FFA uptake in muscle cells and further studies will elucidate if the exocyst is a viable target in combating obesity-related intramyocellular lipid accumulation and contributing to skeletal and cardiac muscle insulin-resistance and type-2 diabetes.
Alzheimer's Disease Behavioral and Psychological Symptoms of Dementia: Analysis of Symptoms and Interventions in a Multi-Ethnic Cohort
(University of Hawaii at Manoa, 2022) Takasato, Lauren Kumiko; Lim, Eunjung; Clinical & Translational Research
INTRODUCTION Alzheimer’s Disease (AD) is a complex and difficult diagnosis for caregivers, clinicians, and patients. Behavioral and psychological symptoms of dementia (BPSD) are a set of symptoms that can range in severity from change in sleep patterns to violent outbursts. There are also different intervention options for BPSD including complementary, environmental, psychosocial, and pharmacologic interventions. Our multi-ethnic cohort provides a look into an understudied population on demographics, BPSD manifestations, interventions used, and efficacy of those treatments. METHODS We conducted a retrospective chart review to quantify and analyze our research questions. Data and variables collected were monitored and approved by physicians practicing at Hawaii Pacific Neuroscience Clinics. Using R for analysis we evaluated the associations between interventions and BPSD and demographic variables using chi-square tests or Fisher’s exact test. Multiple logistic regression models were used to assess the associations between interventions with BPSD, adjusting for the demographic variables. For descriptive statistics we used frequencies and percentages while modeling data using the ggplot2 package and table1 functions. Patients were grouped into four race/ethnicity categories, Asian (n=160), Caucasian (n=122), Pacific Islander (n=53), and Mixed Ethnic (n=33) based on a self reported demographics questionnaire. RESULTS Bivariate analyses between ethnicity and BPSD symptoms were not statistically significant. Differences between our two groups of early onset AD and late onset AD showed statistical significance for rates of sleep problems, anxiety, stress, and apathy (p-values=0.003, 0.002, 0.006, and <0.001, respectively) with early onset seeing higher rates in all four symptoms. We see overall that psychosocial interventions are used most frequently (87.2%, n=321) amongst all patients and complementary interventions (20.7%, n=76) are used the least. The odds of having a change in appetite among Asians is 2.57 times higher than Caucasians (95% CI=1.31-5.26). Regarding the demographic variable, years since diagnosis were positively associated with apathy (OR=1.14, 95% CI=1.01-1.30), jitteriness (OR=1.34, 95% CI=1.02-1.73), and sleep problems (OR=1.16, 95% CI=1.03-1.30). The odds of having depression for women are 2.09 times higher than men (95% CI=1.13-4.06). Regarding the demographic variable, number of hospitalization was negatively associated with use of nonpharmacologic interventions (OR=0.79, 95% CI=0.64-0.99) and years since diagnosis were positively associated with use of pharmacologic interventions (OR=1.25, 95% CI=1.08-1.47). CONCLUSION Our four race/ethnicity groups did not show any statistical significance in difference between prevalence rates of BPSD or use of interventions. We did however see differences in BPSD prevalence between our two groups of early onset AD and late onset AD which is to be expected of the diagnosis. We also saw some significant associations between demographic variables and BPSD manifestations. This data as a whole adds to current knowledge and work to develop better more effective intervention and treatment options including information on an understudied population in AD research. It also adds key information on BPSD prevalence and manifestations using a multi-ethnic cohort applicable to Hawaii and other Pacific Island communities.
The Impact of COVID-19 on Health, Day-to-day Life, and Health-related Behaviors: the Multiethnic Cohort Study
(University of Hawaii at Manoa, 2022) Mak, Victoria; Le Marchand, Loïc; Clinical & Translational Research
The highly contagious SARS-CoV-2 virus and the disease that it causes - Coronavirus Disease 2019 (COVID-19) - has impacted the health and day-to-day life of individuals, especially the elderly and people with certain preexisting medical conditions, including cancer. The purpose of this cross-sectional study was to better understand how COVID-19 impacted health, day-to-day life, access to care, and health-related behaviors, including breast and colorectal cancer screening, by studying the participants in the University of Hawaii Cancer Center Multiethnic Cohort (MEC) study. The MEC was established in 1993 – 1996 and has been following over 215,000 residents of Hawai’i and Los Angeles for the development of cancer and other chronic diseases. It includes men and women of five ethnic groups: Japanese Americans, Native Hawaiians, African Americans, Latinos, and Whites. MEC participants were sent an invitation to participate in an online survey on the impact of COVID-19 on their daily life activities, including adherence to cancer screening. Approximately 7,000 MEC members responded. Responses were compared between males and females and by race/ethnicity to describe the differences between the groups. African American men (compared to White men), women (compared to men), and men and women with more education, were more likely to make changes to their lifestyle or daily activities during the COVID-19 pandemic. So were men with heart disease, hypertension, or lung disease, COPD, or asthma, and women with hypertension or lung disease, COPD, or asthma, compared to their healthy counterparts. Native Hawaiian men and women, and men and women of Other race/ethnicity, compared to Whites, and older men and women were less likely to make changes to their lifestyle or daily activities. Men with more education, women compared to men, men with heart disease, and women with hypertension, kidney disease, and diagnosed with cancer in the past 5 years, compared to their healthy counterparts, were more likely to postpone regular health care visits during the COVID-19 pandemic. Latino and Native Hawaiian men, Native Hawaiian women, and older women were less likely to postpone regular health care visits. Men with more education, men with heart disease and those diagnosed with cancer in the past 5 years, and women with hypertension, lung disease, COPD, or asthma, kidney disease, and those diagnosed with cancer in the past 5 years were more likely to postpone surgical procedures during the COVID-19 pandemic. Japanese American men and women and Native Hawaiian women were less likely to postpone any surgical procedure(s). Lastly, women with more education, women compared to men, men diagnosed with cancer in the past 5 years, and women with lung disease, COPD, or asthma, and those diagnosed with cancer in the past 5 years were more likely to postpone any cancer screening test/procedure due to the COVID-19 pandemic. Japanese American men and women and older women were less likely to postpone any cancer screening test/procedure. This study revealed specific associations of factors like race/ethnicity, age, education level, and comorbidities with the healthcare decisions of MEC participants during the COVID-19 pandemic in Hawaiʻi and Los Angeles. Increased monitoring of patients in high-risk groups for cancer and other diseases is of the utmost importance as the chance of undiagnosed cases or poor prognosis due to delayed screening and treatment increases.
Investigating the Interactions Between the Gut Microbiome and Inflammation During Pregnancy in a Multiethnic Cohort
(University of Hawaii at Manoa, 2021) Rubas, Noelle C.; Maunakea, Alika K.; Clinical & Translational Research
Preterm birth rates are decreasing across the United States; however, the state of Hawai‘i continues to experience higher risks of adverse pregnancy outcomes. Research is limited within this diverse population and therefore exemplifies a lack of understanding in pathologies related to Indigenous communities. This study aims to investigate dietary influences on the labile maternal microbiome which may contribute to ethnic health disparities. Dietary factors are a significant modulator of microbiota composition and can induce microbial shifts causing changes in metabolite production and cytokine regulation. This interaction subsequently alters systemic immune responses that contribute to many metabolic pathologies which may be implicated in adverse pregnancy outcomes. Forty-one pregnant women were recruited from the four most prominent ethnic groups in Hawai‘i, i.e., Native Hawaiian, Filipino, Japanese, and non-Hispanic White. Rectal microbial swabs were collected during each trimester (12 weeks, 20 weeks, and 34-36 weeks), followed by DNA extraction for 16s RNA sequencing to assess changes in microbiome composition and butyrate production capacity. Blood specimen were collected at two time points (12 weeks and within 24 hours of labor) for inflammatory cytokine profiling using Luminex technology. During the first trimester, inflammatory markers correlated with one another while microbiome characteristics, such as F:B ratio and alpha diversity, were weakly correlated with cytokines. Progression into the third trimester altered correlations of immune response, in that inflammatory markers were no longer strongly associated and there was a shift to slight positive correlations among inflammation states and microbiome characteristics. While there were no ethnic differences observed in cytokine profiles or microbiome characteristics and composition in the first trimester, progression to the third trimester reported differences in physiological responses to pregnancy in an ethnicity dependent manner. Unlike the other ethnic groups, Japanese women did not experience a reduction in F:B ratios over time. Similarly, cytokines IL-6, IL-8 and chemokine MCP-1 and VEGF-A experienced ethnic-specific differences in the third trimester. In the early stages of pregnancy, there was an observed relationship between the gut microbiome and immune responses indicating ethnicity did not impact baseline characteristics. However, the loss of cytokine relationships over the course of pregnancy is likely due to the observed ethnic differences in third trimester immune responses, suggesting ethnicity may be a variable in pregnancy trajectories. Therefore, characterization of ethnic differences in the physiological responses to pregnancy offers novel insight that may help explain the increased prevalence of adverse pregnancy outcomes in Hawai‘i.
Ethnic and Socioeconomic Disparities in the Staging, Treatment, and Overall Survival of Colorectal Cancer Patients in Hawai‘i
(University of Hawaii at Manoa, 2021) Acidera, Heather Dawn; Acoba, Jared; Clinical & Translational Research
There has been a decline in colorectal cancer (CRC) mortality rates, which reflects the declining incidence rates and medical advances in early detection and treatment. Despite this progress, CRC incidence and mortality varies considerably by ethnicity and socioeconomic status (SES). Evidence also shows that these medical advances are significantly under-utilized in vulnerable populations including minority and less affluent groups. In Hawai‘i, incidence rates are highest in Japanese Americans, and the majority of late stage CRC are diagnosed in Native Hawaiian/Pacific Islanders (NHPIs), who also have the highest mortality from this disease.The purpose of this study was to investigate ethnic and socioeconomic disparities in the staging, treatment, and overall survival of CRC patients in Hawaiʻi. This study was a retrospective analysis of CRC patients who have been diagnosed and/or treated at The Queen’s Medical Center (QMC) in Honolulu, Hawaiʻi. Data was collected and analyzed from 1,939 CRC patients from all islands of Hawaiʻi who were seen at QMC from January 1, 2007 to December 31, 2018. Both ethnicity (p=0.0499) and insurance (p=0.0005) were significantly associated with AJCC staging. NHPIs and individuals who were under-insured were more likely to be diagnosed with an AJCC stage 4. SES was found to have a significant effect on overall survival (p<0.0001), date of initial diagnosis to date of first treatment (p<0.0001), date of initial diagnosis to date of surgery (p<0.0001), and date of surgery to date of first chemotherapy (p<0.0001), whereas ethnicity had no significant effect. Ethnic disparities are slowly diminishing, whereas socioeconomic disparities persist. The results of this study may be applicable to other underserved populations--particularly other minority ethnic groups and those of low SES. Increasing health discussions and promoting CRC screening within these high-risk groups, lowering financial barriers, and increasing access to healthcare for the under-insured could potentially increase screening participation, which can ultimately address and reduce any ethnic or socioeconomic disparities in all CRC patients.

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