"We don't separate out these things. Everything is related": Partnerships with Indigenous Communities to Design, Implement, and Evaluate Multilevel Interventions to Reduce Health Disparities.

Multilevel interventions (MLIs) are appropriate to reduce health disparities among Indigenous peoples because of their ability to address these communities' diverse histories, dynamics, cultures, politics, and environments. Intervention science has highlighted the importance of context-sensitive MLIs in Indigenous communities that can prioritize Indigenous and local knowledge systems and emphasize the collective versus the individual. This paradigm shift away from individual-level focus interventions to community-level focus interventions underscores the need for community engagement and diverse partnerships in MLI design, implementation, and evaluation. In this paper, we discuss three case studies addressing how Indigenous partners collaborated with researchers in each stage of the design, implementation, and evaluation of MLIs to reduce health disparities impacting their communities. We highlight the following: (1) collaborations with multiple, diverse tribal partners to carry out MLIs which require iterative, consistent conversations over time; (2) inclusion of qualitative and Indigenous research methods in MLIs as a way to honor Indigenous and local knowledge systems as well as a way to understand a health disparity phenomenon in a community; and (3) relationship building, maintenance, and mutual respect among MLI partners to reconcile past research abuses, prevent extractive research practices, decolonize research processes, and generate co-created knowledge between Indigenous and academic communities.

American Indian Alaska Native (AIAN) adolescents and obesity: the influence of social determinants of health, mental health, and substance use.

OBJECTIVE: To explore the prevalence of obesity among American Indian and Alaska Native (AIAN) adolescents aged 12-19 years in association with social determinants of health (SDOH), and mental health and substance use disorders. METHODS: Guided by the World Health Organization's Social Determinants of Health Framework, we examined data from the Indian Health Service (IHS) Improving Health Care Delivery Data Project from Fiscal Year 2013, supplemented by county-level data from the U.S. Census and USDA. Our sample included 26,226 AIAN adolescents ages 12-19 years. We described obesity prevalence in relationship to SDOH and adolescents' mental health and substance use disorder status. We then fit a multivariable logit generalized linear mixed model to estimate the relationships after adjusting for other individual and county level characteristics. RESULTS: We observed a prevalence of 32.5% for obesity, 13.8% for mental health disorders, and 5.5% for substance use disorders. Females had lower odds of obesity than males (OR = 0.76, p < 0.001), which decreased with age. Having Medicaid coverage (OR = 1.09, p < 0.01), residing in a county with lower education attainment (OR = 1.17, p < 0.05), and residing in a county with higher rates of poverty (OR = 1.51, p < 0.001) were each associated with higher odds of obesity. Residing in a county with high access to a grocery store (OR = 0.73, p < 0.001) and residing in a county with a higher proportion of AIANs (OR = 0.83, p < 0.01) were each associated with lower odds of obesity. Those with mental health disorders had higher odds of obesity (OR = 1.26, p < 0.001); substance use disorders were associated with decreased odds of obesity (OR = 0.73, p < 0.001). CONCLUSIONS: Our findings inform future obesity prevention and treatment programs among AIAN youth; in particular, the need to consider mental health, substance use, and SDOH.

Social determinants of obesity in American Indian and Alaska Native peoples aged ≥ 50 years.

OBJECTIVE: American Indian and Alaska Native peoples (AI/ANs) have a disproportionately high rate of obesity, but little is known about the social determinants of obesity among older AI/ANs. Thus, our study assessed social determinants of obesity in AI/ANs aged ≥ 50 years. DESIGN: We conducted a cross-sectional analysis using multivariate generalized linear mixed models to identify social determinants associated with the risk of being classified as obese (BMI ≥ 30.0 kg/m2). Analyses were conducted for the total study population and stratified by median county poverty level. SETTING: Indian Health Service (IHS) data for AI/ANs who used IHS services in FY2013. PARTICIPANTS: 27,696 AI/ANs aged ≥ 50 years without diabetes. RESULTS: Mean BMI was 29.8 ± 6.6 with 43% classified as obese. Women were more likely to be obese than men, and younger ages were associated with higher obesity risk. While having Medicaid coverage was associated with lower odds of obesity, private health insurance was associated with higher odds. Living in areas with lower rates of educational attainment and longer drive times to primary care services were associated with higher odds of obesity. Those who lived in a county where a larger percentage of people had low access to a grocery store were significantly less likely to be obese. CONCLUSIONS: Our findings contribute to the understanding of social determinants of obesity among older AI/ANs and highlight the need to investigate AI/AN obesity, including longitudinal studies with a life course perspective to further examine social determinants of obesity in older AI/ANs.

Associations Between Rurality, pre-pregnancy Health Status, and Macrosomia in American Indian/Alaska Native Populations.

OBJECTIVES: To examine the relationships between pre-pregnancy diabetes mellitus (DM), gestational diabetes mellitus (GDM), pre-pregnancy body mass index (BMI) and county-level social determinants of health, with infant macrosomia within a sample of American Indian/Alaska Native (AI/AN) women receiving Indian Health Service (IHS) care. METHODS: The sample included women-infant dyads representing 1,136 singleton births from fiscal year 2011 (10/1/2019-9/30/2011). Data stemmed from the IHS Improving Health Care Delivery Data Project. Multivariate generalized linear mixed models were fitted to assess the association of macrosomia with pre-pregnancy health status and social determinants of health. RESULTS: Nearly half of the women in the sample were under age 25 years (48.6%), and most had Medicaid health insurance coverage (76.7%). Of those with a pre-pregnancy BMI measure, 66.2% were overweight or obese. Although few women had pre-pregnancy DM (4.0%), GDM was present in 12.8% of women. Most women had a normal term delivery (85.4%). Overweight, obesity, pre-pregnancy DM, and county-level rurality were all significantly associated with higher odds of infant macrosomia.

Formative Research and Cultural Tailoring of a Substance Abuse Prevention Program for American Indian Youth: Findings From the Intertribal Talking Circle Intervention.

Background. Substance use among American Indians (AIs) is a critical health issue and accounts for many health problems such as chronic liver disease, cirrhosis, behavioral health conditions, homicide, suicide, and motor vehicle accidents. In 2013, the highest rates of substance use and dependence were seen among AIs when compared to all other population groups, although these rates vary across different tribes. Among AI adolescents, high rates of substance use have been associated with environmental and historical factors, including poverty, historical trauma, bicultural stress, and changing tribal/familial roles. Our project, the Intertribal Talking Circle intervention, involved adapting, tailoring, implementing, and evaluating an existing intervention for AI youth of three tribal communities in the United States. Formative Results. Community partnership committees (CPCs) identified alcohol, marijuana, and prescription medications as high priority substances. CPC concerns focused on the increasing substance use in their communities and the corresponding negative impacts on families, stating a lack of coping skills, positive role models, and hope for the future as concerns for youth. Cultural Tailoring Process Results. Each site formed a CPC that culturally tailored the intervention for their tribal community. This included translating Keetoowah-Cherokee language, cultural practices, and symbolism into the local tribal customs for relevance. The CPCs were essential for incorporating local context and perceived concerns around AI adolescent substance use. These results may be helpful to other tribal communities developing/implementing substance use prevention interventions for AI youth. It is critical that Indigenous cultures and local context be factored into such programs.

"Being on the Walk Put It Somewhere in My Body": The Meaning of Place in Health for Indigenous Women.

Relationship to place is integral to Indigenous health. A qualitative, secondary phenomenological analysis of in-depth interviews with four non-Choctaw Indigenous women participating in an outdoor, experiential tribally-specific Choctaw health leadership study uncovered culturally grounded narratives using thematic analysis as an analytic approach. Results revealed that physically being in historical trauma sites of other Indigenous groups involved a multi-faceted process that facilitated embodied stress by connecting participants with their own historical and contemporary traumas. Participants also experienced embodied resilience through connectedness to place and collective resistance. Implications point to the role of place in developing collective resistance and resilience through culturally and methodologically innovative approaches.

Growing from Our Roots: Strategies for Developing Culturally Grounded Health Promotion Interventions in American Indian, Alaska Native, and Native Hawaiian Communities.

Given the paucity of empirically based health promotion interventions designed by and for American Indian, Alaska Native, and Native Hawaiian (i.e., Native) communities, researchers and partnering communities have had to rely on the adaptation of evidence-based interventions (EBIs) designed for non-Native populations, a decidedly sub-optimal approach. Native communities have called for development of Indigenous health promotion programs in which their cultural worldviews and protocols are prioritized in the design, development, testing, and implementation. There is limited information regarding how Native communities and scholars have successfully collaborated to design and implement culturally based prevention efforts "from the ground up." Drawing on five diverse community-based Native health intervention studies, we describe strategies for designing and implementing culturally grounded models of health promotion developed in partnership with Native communities. Additionally, we highlight indigenist worldviews and protocols that undergird Native health interventions with an emphasis on the incorporation of (1) original instructions, (2) relational restoration, (3) narrative-[em]bodied transformation, and (4) indigenist community-based participatory research (ICBPR) processes. Finally, we demonstrate how culturally grounded interventions can improve population health when they prioritize local Indigenous knowledge and health-positive messages for individual to multi-level community interventions.

Identifying Perspectives About Health to Orient Obesity Intervention Among Urban, Transitionally Housed Indigenous Children.

Drawing from a socioecological framework of health, this community-based participatory research study examined key cultural health perspectives of transitionally housed, food insecure Indigenous children (aged 8-12 years) by utilizing talking circles and a 4-day photovoice (PV) curriculum. In total, 18 Indigenous children portrayed their health perceptions by taking photographs of their living environment and categorizing photos as healthy, unhealthy, or mixed. And, 10 of the 18 children completed pre- and post-evaluations, where data elucidated that urban Indigenous children experiencing food and housing insecurity demonstrate unique holistic and socioecological perceptions about health. Healthy themes included nutrition, gardening, interpersonal relationships, food sovereignty, water quality, and natural and built environments. Unhealthy themes included cumulative stress, food insecurity, access and cost, screen time, smoking, and violence. We found that implementing these robust insights into urban Indigenous obesity prevention interventions could significantly drive success. This approach may benefit children with similar socioecological strengths and vulnerabilities.

IRAK-1 bypasses priming and directly links TLRs to rapid NLRP3 inflammasome activation.

Pathogenic infections and tissue injuries trigger the assembly of inflammasomes, cytosolic protein complexes that activate caspase-1, leading to cleavage of pro-IL-1ß and pro-IL-18 and to pyroptosis, a proinflammatory cell death program. Although microbial recognition by Toll-like receptors (TLRs) is known to induce the synthesis of the major caspase-1 substrate pro-IL-1ß, the role of TLRs has been considered limited to up-regulation of the inflammasome components. During infection with a virulent microbe, TLRs and nucleotide-binding oligomerization domain-like receptors (NLRs) are likely activated simultaneously. To examine the requirements and outcomes of combined activation, we stimulated TLRs and a specific NLR, nucleotide binding and oligomerization, leucine-rich repeat, pyrin domain-containing 3 (NLRP3), simultaneously and discovered that such activation triggers rapid caspase-1 cleavage, leading to secretion of presynthesized inflammatory molecules and pyroptosis. This acute caspase-1 activation is independent of new protein synthesis and depends on the TLR-signaling molecule IL-1 receptor-associated kinase (IRAK-1) and its kinase activity. Importantly, Listeria monocytogenes induces NLRP3-dependent rapid caspase-1 activation and pyroptosis, both of which are compromised in IRAK-1-deficient macrophages. Our results reveal that simultaneous sensing of microbial ligands and virulence factors by TLRs and NLRP3, respectively, leads to a rapid TLR- and IRAK-1-dependent assembly of the NLRP3 inflammasome complex, and that such activation is important for release of alarmins, pyroptosis, and early IFN-γ production by memory CD8 T cells, all of which could be critical for early host defense.

Mentoring the Mentors of Underrepresented Racial/Ethnic Minorities Who are Conducting HIV Research: Beyond Cultural Competency.

The majority of literature on mentoring focuses on mentee training needs, with significantly less guidance for the mentors. Moreover, many mentoring the mentor models assume generic (i.e. White) mentees with little attention to the concerns of underrepresented racial/ethnic minorities (UREM). This has led to calls for increased attention to diversity in research training programs, especially in the field of HIV where racial/ethnic disparities are striking. Diversity training tends to address the mentees' cultural competency in conducting research with diverse populations, and often neglects the training needs of mentors in working with diverse mentees. In this article, we critique the framing of diversity as the problem (rather than the lack of mentor consciousness and skills), highlight the need to extend mentor training beyond aspirations of cultural competency toward cultural humility and cultural safety, and consider challenges to effective mentoring of UREM, both for White and UREM mentors.

Identification of geographic clustering and regions spared by cutaneous T-cell lymphoma in Texas using 2 distinct cancer registries.

BACKGROUND: Cutaneous T-cell lymphomas (CTCLs) (mycosis fungoides and its leukemic variant, Sezary syndrome) are rare malignancies. Reports of the occurrence of mycosis fungoides in married couples and families raise the possibility of an environmental trigger for this cancer. Although it has been suggested that CTCL arises from inappropriate T-cell stimulation, to the authors' knowledge no preventable trigger has been identified to date. METHODS: Using region, zip code, age, sex, and ethnicity, the authors analyzed the demographic data of 1047 patients from Texas who were seen in a CTCL clinic at The University of Texas MD Anderson Cancer Center during 2000 through 2012 (the MDACC database) and 1990 patients who were recorded in the population-based Texas Cancer Registry between 1996 and 2010. Subsequently, data from both databases were cross-analyzed and compared. RESULTS: The current study findings, based on the MDACC database, documented geographic clustering of patients in 3 communities within the Houston metropolitan area, in which CTCL incidence rates were 5 to 20 times higher than the expected population rate. Analysis of the Texas Cancer Registry database defined the CTCL population rate for the state to be 5.8 cases per million individuals per year (95% confidence interval, 5.5-6.0 per million individuals per year), thus confirming the observations from the MDACC database and further highlighting additional areas of geographic clustering and regions spared from CTCL in Texas. CONCLUSIONS: The current study documented geographic clustering of CTCL cases in Texas and argued for the existence of yet unknown external causes/triggers for this rare malignancy.

Use of culturally focused theoretical frameworks for adapting diabetes prevention programs: a qualitative review.

INTRODUCTION: Diabetes disproportionately affects underserved racial/ethnic groups in the United States. Diabetes prevention interventions positively influence health; however, further evaluation is necessary to determine what role culture plays in effective programming. We report on the status of research that examines cultural adaptations of diabetes prevention programs. METHODS: We conducted database searches in March and April 2014. We included studies that were conducted in the United States and that focused on diabetes prevention among African Americans, American Indians/Alaska Natives, Asian Americans/Pacific Islanders, and Latinos. RESULTS: A total of 58 studies were identified for review; 29 were excluded from evaluation. Few adaptations referenced or followed recommendations for cultural adaptation nor did they justify the content modifications by providing a rationale or evidence. Cultural elements unique to racial/ethnic populations were not assessed. CONCLUSION: Future cultural adaptations should use recommended processes to ensure that culture's role in diabetes prevention-related behavioral changes contributes to research.

United States colorectal cancer screening practices among American Indians/Alaska Natives, blacks, and non-Hispanic whites in the new millennium (2001 to 2010).

BACKGROUND: The objectives of this study were to describe, examine, and compare prevalence estimates of colorectal cancer (CRC) screening practices and to determine whether disparities exist for American Indians/Alaska Natives (AIANs) and blacks compared with whites. METHODS: Behavioral Risk Factor Surveillance System (2001-2010) data from respondents aged ≥ 50 years (n = 356,073) were used. The primary outcome was self-reported CRC screening according to US Preventive Services Task Force guidelines for endoscopy (colonoscopy or sigmoidoscopy), fecal occult blood test (FOBT), or mixed screening (endoscopy or FOBT). RESULTS: From 2001 to 2010, endoscopy screening increased in the AIAN population by 44.8% (P < .001) compared with black respondents (51.7%) and white respondents (26.5%). AIANs were less likely to report endoscopy screening (45%) compared with both blacks (56%) and whites (55%). For mixed CRC screenings, AIAN rates increased by 34.5%, compared with 29.7% for blacks and 15% for whites. In 2010, AIANs (51%) had the lowest prevalence of mixed CRC screening compared with blacks (61%) and whites (60%; P < .001). Factors that enabled health care attenuated the lowered likelihood of CRC screenings, but disparities remained for AIAN CRC screening. In contrast, once enabling factors were controlled, the odds ratios of CRC screening among blacks were higher compared with whites. CONCLUSIONS: Between 2001 and 2010, AIANs had the lowest CRC screening rates in the United States compared with blacks and whites, presenting a CRC disparity, as rigorously defined. The current findings indicate that, although considerable progress has been made to increase CRC screening for blacks and whites, progress for AIANs continues to lag behind in the first decade of 21st century.

Palliative radiotherapy and the introduction of a Rapid Access Palliative Clinic in a national radiation oncology network.

BACKGROUND: Palliative radiotherapy (PRT) is commonly used to treat symptoms of advanced cancer. PRT has been associated with elevated 30-day mortality (30DM). A Rapid Access Palliative Clinic (RAPC) can streamline the treatment process for patients receiving treatment. AIMS: We reviewed the PRT practices in a radiation oncology network in Ireland, and the implementation of a RAPC. Patient outcomes were assessed to inform future treatment decisions. METHODS: A retrospective review of all patients who received PRT over 6 months in 2018 in St. Luke's Radiation Oncology Network (SLRON) was undertaken. We assessed 30DM rates, demographics and referral to specialist palliative care (SPC) services. Subsequently, a retrospective analysis was conducted of a RAPC which ran for 6 months from 2019 to 2020. We assessed treatment data and mortality. RESULTS: Over 6 months, 645 patients commenced PRT in the SLRON. The 30DM for this cohort was 15.8% (n = 102), with most patients having lung primaries. Of the 30DM cohort, only 55% (n = 56) were referred to SPC services and only 26.4% (n = 27) had performance status recorded. Over 6 months, 40 patients attended 28 RAPCs. Of these, 88% (n = 35) received PRT. Single fraction therapy was utilised in 60% and 48% of patients underwent CT simulation and treatment on the same day. Ultimately, 75% of patients received SPC referral. CONCLUSIONS: Referral rates to SPC services and documentation of performance status were low in our 30DM retrospective review cohort. The RAPC facilitated quick treatment turnaround, fewer hospital visits and referral to SPC services.

Storytelling of Indigenous patient and family advocates engaged in patient-oriented research initiatives in the field of inflammatory bowel disease.

Background and aim: The history of colonization and its ongoing impact poses significant health disparities among Indigenous communities. We aimed to centre the voices and stories of Indigenous patients and family advocates (IPFAs-Indigenous patients living with inflammatory bowel disease [IBD] and family members of Indigenous individuals with IBD) engaged in patient-oriented research projects and who are part of the IBD among Indigenous Peoples Research Team (IBD-IPRT). Methods: IPFAs and Indigenous and non-Indigenous researchers of the IBD-IPRT followed a storytelling research methodology to let IPFAs share their stories as research team members. Four IPFAs documented their experiences as IBD patients, advocates, and research partners. The stories were analyzed for themes. The identified themes were collaboratively verified with the IPFAs. Results: The full stories shared by the IPFAs were transcribed and presented in this paper. Following a background analysis of themes in the 4 narratives, we were also able to identify 4 key themes that could be relevant to improving patient-oriented research initiatives: (1) health promotion, (2) leadership and voice, (3) community engagement, and (4) disease awareness and access to care. Trust building, strong relationships, and effective partnerships are core components for conducting patient-oriented research with Indigenous community members. Conclusions: Indigenous patient engagement in health research is crucial to ensure that lived experiences, knowledge, and cultural values are adequately adopted to improve research outcomes. Centering IPFAs in IBD research can promote cultural awareness and actionable recommendations to improve health outcomes for individuals with IBD and their families and caregivers.

Mitochondria-localized caveolin in adaptation to cellular stress and injury.

We show here that the apposition of plasma membrane caveolae and mitochondria (first noted in electron micrographs >50 yr ago) and caveolae-mitochondria interaction regulates adaptation to cellular stress by modulating the structure and function of mitochondria. In C57Bl/6 mice engineered to overexpress caveolin specifically in cardiac myocytes (Cav-3 OE), localization of caveolin to mitochondria increases membrane rigidity (4.2%; P<0.05), tolerance to calcium, and respiratory function (72% increase in state 3 and 23% increase in complex IV activity; P<0.05), while reducing stress-induced generation of reactive oxygen species (by 20% in cellular superoxide and 41 and 28% in mitochondrial superoxide under states 4 and 3, respectively; P<0.05) in Cav-3 OE vs. TGneg. By contrast, mitochondrial function is abnormal in caveolin-knockout mice and Caenorhabditis elegans with null mutations in caveolin (60% increase free radical in Cav-2 C. elegans mutants; P<0.05). In human colon cancer cells, mitochondria with increased caveolin have a 30% decrease in apoptotic stress (P<0.05), but cells with disrupted mitochondria-caveolin interaction have a 30% increase in stress response (P<0.05). Targeted gene transfer of caveolin to mitochondria in C57Bl/6 mice increases cardiac mitochondria tolerance to calcium, enhances respiratory function (increases of 90% state 4, 220% state 3, 88% complex IV activity; P<0.05), and decreases (by 33%) cardiac damage (P<0.05). Physical association and apparently the transfer of caveolin between caveolae and mitochondria is thus a conserved cellular response that confers protection from cellular damage in a variety of tissues and settings.

What do parents have to do with my cognitive reserve? Life course perspectives on twelve-year cognitive decline.

BACKGROUND/AIMS: To examine the cognitive reserve hypothesis by comparing the contribution of early childhood and life course factors related to cognitive functioning in a nationally representative sample of older Americans. METHODS: We examined a prospective, national probability cohort study (Health and Retirement Study; 1998-2010) of older adults (n=8,833) in the contiguous 48 United States. The main cognitive functioning outcome was a 35-point composite of memory (recall), mental status, and working memory tests. The main predictors were childhood socioeconomic position (SEP) and health, and individual-level adult achievement and health. RESULTS: Individual-level achievement indicators (i.e., education, income, and wealth) were positively and significantly associated with baseline cognitive function, while adult health was negatively associated with cognitive function. Controlling for individual-level adult achievement and other model covariates, childhood health presented a relatively small negative, but statistically significant association with initial cognitive function. Neither individual achievement nor childhood SEP was statistically linked to decline over time. CONCLUSIONS: Cognitive reserve purportedly acquired through learning and mental stimulation across the life course was associated with higher initial global cognitive functioning over the 12-year period in this nationally representative study of older Americans. We found little supporting evidence that childhood economic conditions were negatively associated with cognitive function and change, particularly when individual-level achievement is considered.

Native American undergraduate students' persistence intentions: a psychosociocultural perspective.

Attending to persistence intentions among Native American students enrolled in institutions of higher education is critical, given low retention rates. The purpose of the study was twofold: (a) we developed and examined the psychometric properties of a new measure, the Native American Collective Pursuits of Education (NACOPE), and (b) we explored persistence attitudes among 156 Native American students using Gloria and Rodriguez's (2000) psychosociocultural framework. Pilot data and exploratory analysis supported the psychometric properties of the NACOPE and its use to understand educational experiences for Native American students. Results also supported the prediction of culturally relevant noncognitive variables to persistence intentions. Limitations, directions for future research, and implications for higher education are discussed.

Family Structure and Adolescent Alcohol Use Problems: Extending Popular Explanations to American Indians.

Competing explanations of the relationship between family structure and alcohol use problems are examined using a sample of American Indian adolescents from the National Longitudinal Study of Adolescent Health. Living in a single-parent family is found to be a marker for the unequal distribution of stress exposure and parental alcohol use, but the effects of other family structures like non-parent families and the presence of under 21-year-old extended family or non-family members emerge or remain as risk or protective factors for alcohol use problems after a consideration of SES, family processes, peer socialization, and social stress. In particular, a non-parent family structure that has not been considered in prior research emerged as a protective family structure for American Indian adolescent alcohol use problems.

All systems are interrelated: Multilevel interventions with indigenous communities.

Colonial historical trauma and ongoing structural racism have impacted Indigenous peoples for generations and explain the ongoing health disparities. However, Indigenous peoples have been engaging in multilevel, clinical trial interventions with Indigenous and allied research scientists resulting in promising success. In this paper, National Institutes of Health funded scientists in the field of Indigenous health have sought to describe the utility and need for multilevel interventions across Indigenous communities (Jernigan et al., 2020). We posit limitations to the existing socioecological, multilevel frameworks and propose a dynamic, interrelated heuristic framework, which focuses on the inter-relationships of the collective within the environment and de-centers the individual. We conclude with identified calls for action within multilevel clinical trial research.