Community Assessment on Colorectal Cancer Screening Knowledge, Attitudes, Behavior, and Health Literacy in American Samoa: Methods and Results

urpose/Background: “Weaving” Indigenous and Western knowledges are understood to advance health equity for the Indigenous community whose own knowledge and values are often subsumed. Partnerships that support Indigenous leadership and bring Indigenous knowledge to greater parity with Western knowledge are imperative. Indigenous people living in Small Island Developing States like the U.S. territories experience health disparities. The WHO has declared non- communicable diseases as a global health epidemic, including cancer disparities. In American Samoa (AS) less than 7% of age-eligible adults participated in colorectal cancer (CRC) screening, while the Healthy People 2020 target is 70% screened. CRC may be prevented through screening and early detection. The relationship between CRC screening with knowledge, attitudes, beliefs (KAB), and health literacy has never been locally assessed in AS. AS based community researchers partnered with regional academic researchers in local research training, instrument development, data collection, and data analysis. Community relevant approaches guided assessment of CRC screening rates, CRC screening KAB, and health literacy. Objective: This abstract describes the community engaged approaches and results through the National Institute of Minority Health Disparities funded INdigenous Samoan Partnership to Initiate Research Excellence (INSPIRE), introduced at the 2015 CTR-IN annual meeting. Materials & Methods: INSPIRE principal Investigators are based in AS, operated through the American Samoa Community Coalition, a community-based organization, partnering with academic co-investigators in Hawaii and California. To assess CRC KAB and health literacy, two validated assessment instruments were adapted: The KAB survey, from self-developed and population-based instruments, and Short Test for Functional Health Literacy in Adults (S-TOFHLA). Community partners translated then back translated both surveys with three focus groups. Twenty cognitive interviews were conducted to test translation cogency. Seven AS INSPIRE research trainees participating in year-long workshops were trained on Respondent Driven Sampling (RDS). Initial participants (seeds) were recruited by social characteristics. Upon survey completion participants received coupons to each recruit three eligible participants. 713 community respondents participated in three months. An INSPIRE researcher (epidemiologist) analyzed data, with technical assistance from an academic biostatistician in Hawaii when needed fostering research capacity training. Bivariate and multivariate statistics analyzed CRC knowledge, attitudes, health literacy as correlates and predictors of self-reported screening. Results: About 65 percent of respondents finished high school; 68.9% had no insurance. Only 2 respondents completed CRC screening, but 63.3% and 82.3% of English vs Samoan survey respondents respectively would get colonoscopy. Among the 11 knowledge questions, 5 items were “don’t know” while 2 items were incorrect responses on English and Samoan surveys respectively. Almost twice as many Samoan compared to English survey respondents (81% vs. 44%) scored “inadequate” in the S-TOFHLA. Correlates and predictors of CRC screening behavior and differences in results between the respondents who took English vs Samoan surveys will be reported. Discussion/Conclusion: Almost all participants have not received CRC screening, lower than other reported AS nationwide figures. This first ever study, led by and for American Samoans obtained robust results on knowledge, attitudes, and health literacy of CRC screening to allow continued research and interventions to increase very low CRC screening rates

Understanding disparities in clinical trials for Native Hawaiian men

Understanding low rates of participation by minority populations in clinical trials is critical for reducing and eliminating disparities. We examined beliefs and attitudes of Native Hawaiian men related to illness and cancer to better understand their rates of participation in clinical trials. We conducted face-to-face interviews with Native Hawaiian key informants throughout the State of Hawai‘i using quota sampling methods to obtain a range of perspectives about attitudes towards health care seeking to provide insight into low clinical trials participation. Interviews were audio-taped, transcribed, and independently coded by researchers. Thematic analysis guided the extraction of relevant data from the discussions. Key informants (N=16) suggested the following beliefs and attitudes regarding clinical trials participation: 1) mistrust in the healthcare system, 2) external locus of control, 3) gender norms, and 4) the customary pono (righteousness, to make right) practice towards family/community to model and maintain good health, including participation in cancer clinical trials. Native Hawaiian men in this study expressed hesitation in the benefits of formalized health care. Many men described experiences of racism, inequity, and injustice associated their interactions with health care providers. These encounters were factors that influenced their healthcare practices and beliefs towards maintaining health and longevity

Knowledge and Attitudes of Guam Residents Towards Cancer Clinical Trial Participation

Purpose/Background: Currently there are no cancer clinical trials conducted in Guam, but interest is growing. Limited information exists on the knowledge and attitudes of Guam’s population towards cancer clinical research, yet cancer is the second highest cause of death in Guam and among the CHamoru people, Guam’s indigenous population. CHamoru people suffer the highest rates of cancer mortality compared to other ethnic groups in Guam. The purpose of this study was to determine differences in knowledge and attitudes towards cancer clinical trials participation, and attitudes towards traditional medicine. Materials & Methods: A telephone survey instrument was designed, pilot-tested, IRB-approved, and implemented using a third-party marketing company. Questions were adapted from existing surveys and new questions were developed to address unique, Guam-specific interests. Recruited subjects were Guam residents adults 18 years of age and older with telephone service. Guam residents were called from October 6 to 10, 2018 to assess levels of knowledge and attitudes towards cancer clinical trials and the attitudes towards using traditional medicine to treat cancer. Descriptive statistics were computed for demographic variables by response category. Univariate logistic regression was conducted to investigate the bivariate association between a survey question and demographic variables. Odds ratios (ORs) and associated 95% confidence intervals (CIs) were calculated. Multivariable logistic regression model was developed for each question, adjusting for important covariates. Hosmer-Lemeshow tests and c-statistics were used to evaluate goodness of fit. Results: The survey respondents’ (n=152) demographic data closely reflected the US Census ethnicity data for Guam: CHamoru (47.0%), Filipino (26.5%), Caucasian (11.3%) and Other (15.2%). Fifty-three percent understood the term “clinical trial”; 73.7% would be willing to participate if they had cancer, and 59.9% believed they would receive good quality treatment from a clinical trial offered in Guam. Approximately 56.0% thought they would have to pay out-of-pocket expenses; and 67.0% disagreed or were not sure that clinical trial sponsors pay for the study drug while other costs are billed to the insurance company. Physician ethnicity was not important to 100% of Caucasians, but was important to at least 30.0% of non-Caucasians; family support was very important to 94.7% of respondents, while religious community support was important to 55.4%. Approximately 65.1% did not believe that people participating in clinical trials were treated like ‘guinea pigs’. Having college education (OR = 3.26; 95% CI: 1.53 – 6.98) and knowing English language well (OR=5.86; 95% CI: 1.21 – 28.38) were significantly associated with higher aggregated knowledge about clinical trials. Although the majority (67.2%) would seek traditional healing practices if diagnosed with cancer, most (84.9%) did not think a suruhano (CHamoru traditional healer) could treat cancer, and 94.7% did not believe cancer was caused by taotaomo’na (ancient spirits). Discussion/Conclusion: Knowledge and attitudes towards cancer clinical trials and the use of traditional medicine to treat cancer were significantly associated with key demographic variables including ethnicity, income, employment status, place of birth and insurance type. Knowledge about cancer clinical trials was as expected: more participants who are Caucasian, have a higher level of education, were born in U.S., are employed, have a higher income, private insurance, self-report that they speak English well, and do not follow religion, were more aware of what a clinical trial is than the other respondents. Though knowledge about cancer clinical trials is limited, attitudes towards participation in cancer clinical trials offered in Guam were largely positive

Viscous-Inviscid Interactions in a Boundary-Layer Flow Induced by a Vortex Array

In this paper we investigate the asymptotic validity of boundary layer theory. For a flow induced by a periodic row of point-vortices, we compare Prandtl's solution to Navier-Stokes solutions at different $Re$ numbers. We show how Prandtl's solution develops a finite time separation singularity. On the other hand Navier-Stokes solution is characterized by the presence of two kinds of viscous-inviscid interactions between the boundary layer and the outer flow. These interactions can be detected by the analysis of the enstrophy and of the pressure gradient on the wall. Moreover we apply the complex singularity tracking method to Prandtl and Navier-Stokes solutions and analyze the previous interactions from a different perspective

Utility of Self-Rated Adherence for Monitoring Dietary and Physical Activity Compliance and Assessment of Participant Feedback of the Healthy Diet and Lifestyle Study pilot.

We examined the utility of self-rated adherence to dietary and physical activity (PA) prescriptions as a method to monitor intervention compliance and facilitate goal setting during the Healthy Diet and Lifestyle Study (HDLS). In addition, we assessed participants’ feedback of HDLS. HDLS is a randomized pilot intervention that compared the effect of intermittent energy restriction combined with a Mediterranean diet (IER + MED) to a Dietary Approaches to Stop Hypertension (DASH) diet, with matching PA regimens, for reducing visceral adipose tissue area (VAT)

Menthol Cigarette Smoking and Obesity in Young Adult Daily Smokers in Hawaii

This study investigates 1) the relationship between menthol cigarette smoking and obesity and 2) the association of body mass index with the nicotine metabolite ratio among menthol and non-menthol daily smokers aged 18–35 (n = 175). A brief survey on smoking and measures of height and weight, carbon monoxide, and saliva samples were collected from participants from May to December 2013 in Honolulu, Hawaii. Multiple regression was used to estimate differences in body mass index among menthol and non-menthol smokers and the association of menthol smoking with obesity. We calculated the log of the nicotine metabolite ratio to examine differences in the nicotine metabolite ratio among normal, overweight, and obese smokers. Sixty-eight percent of smokers used menthol cigarettes. Results showed that 62% of normal, 54% of overweight, and 91% of obese smokers used menthol cigarettes (p = .000). The mean body mass index was significantly higher among menthol compared with non-menthol smokers (29.4 versus 24.5, p = .000). After controlling for gender, marital status, educational attainment, employment status, and race/ethnicity, menthol smokers were more than 3 times as likely as non-menthol smokers to be obese (p = .04). The nicotine metabolite ratio was significantly lower for overweight menthol smokers compared with non-menthol smokers (.16 versus .26, p = .02) in the unadjusted model, but was not significant after adjusting for the covariates. Consistent with prior studies, our data show that menthol smokers are more likely to be obese compared with non-menthol smokers. Future studies are needed to determine how flavored tobacco products influence obesity among smokers

Association of cardiometabolic microRNAs with COVID-19 severity and mortality

AIMS: Coronavirus disease 2019 (COVID-19) can lead to multiorgan damage. MicroRNAs (miRNAs) in blood reflect cell activation and tissue injury. We aimed to determine the association of circulating miRNAs with COVID-19 severity and 28 day intensive care unit (ICU) mortality. METHODS AND RESULTS: We performed RNA-Seq in plasma of healthy controls (n = 11), non-severe (n = 18), and severe (n = 18) COVID-19 patients and selected 14 miRNAs according to cell- and tissue origin for measurement by reverse transcription quantitative polymerase chain reaction (RT–qPCR) in a separate cohort of mild (n = 6), moderate (n = 39), and severe (n = 16) patients. Candidates were then measured by RT–qPCR in longitudinal samples of ICU COVID-19 patients (n = 240 samples from n = 65 patients). A total of 60 miRNAs, including platelet-, endothelial-, hepatocyte-, and cardiomyocyte-derived miRNAs, were differentially expressed depending on severity, with increased miR-133a and reduced miR-122 also being associated with 28 day mortality. We leveraged mass spectrometry-based proteomics data for corresponding protein trajectories. Myocyte-derived (myomiR) miR-133a was inversely associated with neutrophil counts and positively with proteins related to neutrophil degranulation, such as myeloperoxidase. In contrast, levels of hepatocyte-derived miR-122 correlated to liver parameters and to liver-derived positive (inverse association) and negative acute phase proteins (positive association). Finally, we compared miRNAs to established markers of COVID-19 severity and outcome, i.e. SARS-CoV-2 RNAemia, age, BMI, D-dimer, and troponin. Whilst RNAemia, age and troponin were better predictors of mortality, miR-133a and miR-122 showed superior classification performance for severity. In binary and triplet combinations, miRNAs improved classification performance of established markers for severity and mortality. CONCLUSION: Circulating miRNAs of different tissue origin, including several known cardiometabolic biomarkers, rise with COVID-19 severity. MyomiR miR-133a and liver-derived miR-122 also relate to 28 day mortality. MiR-133a reflects inflammation-induced myocyte damage, whilst miR-122 reflects the hepatic acute phase response

An African-Specific Variant of TP53 Reveals PADI4 as a Regulator of p53-Mediated Tumor Suppression

TP53 is the most frequently mutated gene in cancer, yet key target genes for p53-mediated tumor suppression remain unidentified. Here, we characterize a rare, African-specific germline variant of TP53 in the DNA-binding domain Tyr107His (Y107H). Nuclear magnetic resonance and crystal structures reveal that Y107H is structurally similar to wild-type p53. Consistent with this, we find that Y107H can suppress tumor colony formation and is impaired for the transactivation of only a small subset of p53 target genes; this includes the epigenetic modifier PADI4, which deiminates arginine to the nonnatural amino acid citrulline. Surprisingly, we show that Y107H mice develop spontaneous cancers and metastases and that Y107H shows impaired tumor suppression in two other models. We show that PADI4 is itself tumor suppressive and that it requires an intact immune system for tumor suppression. We identify a p53–PADI4 gene signature that is predictive of survival and the efficacy of immune-checkpoint inhibitors. Significance: We analyze the African-centric Y107H hypomorphic variant and show that it confers increased cancer risk; we use Y107H in order to identify PADI4 as a key tumor-suppressive p53 target gene that contributes to an immune modulation signature and that is predictive of cancer survival and the success of immunotherapy