Patient-centricity in digital measure development: co-evolution of best practice and regulatory guidance.

Digital health technologies (DHTs) have the potential to modernize drug development and clinical trial operations by remotely, passively, and continuously collecting ecologically valid evidence that is meaningful to patients' lived experiences. Such evidence holds potential for all drug development stakeholders, including regulatory agencies, as it will help create a stronger evidentiary link between approval of new therapeutics and the ultimate aim of improving patient lives. However, only a very small number of novel digital measures have matured from exploratory usage into regulatory qualification or efficacy endpoints. This shows that despite the clear potential, actually gaining regulatory agreement that a new measure is both fit-for-purpose and delivers value remains a serious challenge. One of the key stumbling blocks for developers has been the requirement to demonstrate that a digital measure is meaningful to patients. This viewpoint aims to examine the co-evolution of regulatory guidance in the United States (U.S.) and best practice for integration of DHTs into the development of clinical outcome assessments. Contextualizing guidance on meaningfulness within the larger shift towards a patient-centric drug development approach, this paper reviews the U.S. Food and Drug Administration (FDA) guidance and existing literature surrounding the development of meaningful digital measures and patient engagement, including the recent examples of rejections by the FDA that further emphasize patient-centricity in digital measures. Finally, this paper highlights remaining hurdles and provides insights into the established frameworks for development and adoption of digital measures in clinical research.

Developing the Feast for the Future Program through a Community Visioning Process.

BACKGROUND: Three tribal communities in the Southwestern United States have a long-standing partnership with the Johns Hopkins Center for Indigenous Health (JHCIH). OBJECTIVES: In response to community concerns about obesity, three tribal communities and Johns Hopkins Center for Indigenous Health partnered to develop culturally relevant plans for a new program. METHODS: Using a "community visioning" process, a community advisory board (CAB) from each community identified opportunities, challenges, goals, and visions for their communities. The CABs consulted with experts in pediatrics, nutrition, food distribution, agricultural restoration, and community and school gardening. RESULTS: The CABs developed seven components for Feast for the Future: 1) Edible School Gardens; 2) Traditional Food-ways Education Program; 3) Community Gardens, Orchards, and Greenhouses; 4) Farmers Markets; 5) Farmers Workshops; 6) Family Gardens; and 7) a Mobile Grocery Store. CONCLUSIONS: A community-based participatory action research (CBPAR) process was critical to developing a culturally appropriate program that built on community strengths.

Carbohydrate ingestion attenuates the reduction in complex cognitive function and cerebral blood flow during prolonged passive heat stress in humans.

PURPOSE: To determine whether carbohydrate ingestion would reduce cognitive dysfunction in humans following long duration passive heat stress (PHS) versus consuming electrolytes alone. METHODS: Fifteen young (27 ± 4 y) healthy adults were exposed to 120 min of PHS through the use of a liquid perfused suit (50 °C) on two randomized visits. Subjects consumed fluids supplemented with electrolytes (E) or electrolytes + carbohydrates (E + C). Pre- and post-heat stress, body mass (BM) and plasma osmolality (pOsm) were measured. Heart rate (HR), blood pressure (BP), Physiological Strain Index (PSI), core temperature (Tc), plasma glucose, respiration rate (RR), end-tidal CO2 (PetCO2) and internal carotid artery (ICA) blood flow were recorded at baseline and every 15 min of heat stress. Cognitive function was assessed via the Automated Neuropsychological Assessment Metric at baseline and at 30- and 120 min during heat stress. RESULTS: There were no significant differences between fluid conditions for BM, pOsm, PSI, Tc, RR or PetCO2. Plasma glucose was ∼75% greater in the E + C condition compared to the E condition after 90 min of PHS (P < 0.05). Cognitive function (120 min) was impaired following PHS only in E condition (P < 0.05) and performance on complex cognitive tasks were better by ∼22-340% in the E + C vs. E (P < 0.05). Compared to the E condition, HR and BP were lower and ICA blood flow, vascular conductance, and glucose delivery was ∼90% greater in the E + C after 90 min of PHS (P < 0.05). CONCLUSIONS: These data are the first to demonstrate that carbohydrate ingestion may have a protective effect on cognitive function during long duration PHS. Furthermore, this protection was associated with preserved ICA blood flow and glucose delivery to the brain.

Gut microbiology of UK care home residents: a cross-sectional analysis from a randomised controlled trial.

OBJECTIVE: To describe the prevalence of potentially clinically relevant gut pathogens and associations with the carriage of resistant organisms in UK care home residents. METHODS: Stool samples were collected pre-randomisation from care home residents participating in a randomised placebo-controlled trial. Cultivable clinically relevant bacteria were analysed. Antimicrobial susceptibility testing was performed by agar dilution (amoxicillin, co-amoxiclav, gentamicin, trimethoprim, nitrofurantoin, and ciprofloxacin). We also aimed to detect resistance to third-generation cephalosporins, carbapenems, and vancomycin. RESULTS: Stool samples were available for 159/310 residents participating in the trial (51%) from 23 care homes between 2016 and 2018. In total, 402 bacterial isolates were cultured from 158 stool samples and 29 different species were cultured. The five most common species were Escherichia coli (155/158, 98%), Pseudomonas aeruginosa (40/158, 25%), Enterococcus faecalis (35/158, 22%), Enterococcus faecium (30/158, 19%), and Proteus mirabilis (25/158, 16%). Enterobacterales isolates were cultured from 157 samples (99%), and resistance to at least one of the tested antimicrobials was found in 119 of these (76%). There were high levels of variation in outcomes by care home. DISCUSSION: We demonstrated that care home residents harbour significant levels of antimicrobial-resistant organisms in their stool. This work emphasises the importance of both enhanced infection control practices and antimicrobial stewardship programmes to support the appropriate use of antimicrobials in this setting.

Using environmental health dialogue in a Diné-centered approach for individualized results reporting in an environmental exposure study following the Gold King Mine Spill.

BACKGROUND: On August 5, 2015, the Gold King Mine Spill (GKMS) resulted in 3 million gallons of acid mine drainage spilling into the San Juan River impacting the Diné Bikeyah (traditional homelands of the Navajo people). The Gold King Mine Spill Diné Exposure Project was formed to understand the impacts of the GKMS on the Diné (Navajo). Reporting individualized household results in an exposure study is becoming more common; however, materials are often developed with limited community input with knowledge flowing in one direction - from researcher to participant. In this study we examined the development, dissemination, and evaluation of individualized results materials. METHODS: In August 2016, Navajo Nation Community Health Representatives (Navajo CHRs) sampled household water, dust, and soil, and resident blood and urine for lead and arsenic, respectively. From May-July 2017, iterative dialogue with a wide range of community partners and a community focus groups guided the development of a culturally-based dissemination process. In August 2017, Navajo CHRs reported individualized results and they surveyed the participants on the report-back process at that time. RESULTS: All of the 63 Diné adults (100%) who participated in the exposure study received their results by a CHR in person and 42 (67%) completed an evaluation. Most of those participants (83%) were satisfied with the result packets. Respondents ranked the individual and overall household results as the most important information they received (69% and 57%, respectively), while information on metals exposures and their health effects were the least helpful. CONCLUSIONS: Our project illustrates how a model of environmental health dialogue, defined by iterative, multidirectional communication among Indigenous community members, trusted Indigenous leaders, Indigenous researchers, non-Indigenous researchers, can improve reporting individualized study results. Findings can inform future research to encourage multi-directional environmental health dialogue to craft more culturally responsive and effective dissemination and communication materials.

Effectiveness of COVID-19 mRNA Vaccines in Preventing COVID-19-Associated Outpatient Visits and Hospitalizations Among American Indian and Alaska Native Persons, January-November 2021: A Test-Negative Case-Control Analysis Using Surveillance Data.

Background: Despite the disproportionate morbidity and mortality experienced by American Indian and Alaska Native (AI/AN) persons during the coronavirus disease 2019 (COVID-19) pandemic, few studies have reported vaccine effectiveness (VE) estimates among these communities. Methods: We conducted a test-negative case-control analysis among AI/AN persons aged ≥12 years presenting for care from January 1, 2021, through November 30, 2021, to evaluate the effectiveness of mRNA COVID-19 vaccines against COVID-19-associated outpatient visits and hospitalizations. Cases and controls were patients with ≥1 symptom consistent with COVID-19-like illness; cases were defined as those test-positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and controls were defined as those test-negative for SARS-CoV-2. We used unconditional multivariable logistic regression to estimate VE, defined as 1 minus the adjusted odds ratio for vaccination among cases vs controls. Results: The analysis included 207 cases and 267 test-negative controls. Forty-four percent of cases and 78% of controls received 2 doses of either BNT162b2 or mRNA-1273 vaccine. VE point estimates for 2 doses of mRNA vaccine were higher for hospitalized participants (94.6%; 95% CI, 88.0-97.6) than outpatient participants (86.5%; 95% CI, 63.0-95.0), but confidence intervals overlapped. Conclusions: Among AI/AN persons, mRNA COVID-19 vaccines were highly effective in preventing COVID-associated outpatient visits and hospitalizations. Maintaining high vaccine coverage, including booster doses, will reduce the burden of disease in this population.

Conceptualizing Indigenous strengths-based health and wellness research using group concept mapping.

BACKGROUND: In recent years public health research has shifted to more strengths or asset-based approaches to health research but there is little understanding of what this concept means to Indigenous researchers. Therefore our purpose was to define an Indigenous strengths-based approach to health and well-being research. METHODS: Using Group Concept Mapping, Indigenous health researchers (N = 27) participated in three-phases. Phase 1: Participants provided 218 unique responses to the focus prompt "Indigenous Strengths-Based Health and Wellness Research…" Redundancies and irrelevant statements were removed using content analysis, resulting in a final set of 94 statements. Phase 2: Participants sorted statements into groupings and named these groupings. Participants rated each statement based on importance using a 4-point scale. Hierarchical cluster analysis was used to create clusters based on how statements were grouped by participants. Phase 3: Two virtual meetings were held to share and invite researchers to collaboratively interpret results. RESULTS: A six-cluster map representing the meaning of Indigenous strengths-based health and wellness research was created. Results of mean rating analysis showed all six clusters were rated on average as moderately important. CONCLUSIONS: The definition of Indigenous strengths-based health research, created through collaboration with leading AI/AN health researchers, centers Indigenous knowledges and cultures while shifting the research narrative from one of illness to one of flourishing and relationality. This framework offers actionable steps to researchers, public health practitioners, funders, and institutions to promote relational, strengths-based research that has the potential to promote Indigenous health and wellness at individual, family, community, and population levels.

Quality over quantity: A transactional model of social withdrawal and friendship development in late adolescence.

The aim of this study was to test a longitudinal, transactional model that describes how social withdrawal and friendship development are interrelated in late adolescence, and to investigate if post-secondary transitions are catalysts of change for highly withdrawn adolescents' friendships. Unilateral friendship data of 1,019 adolescents (61.3% female, 91% Dutch-origin) from the Tracking Adolescents' Individual Lives Survey (TRAILS) cohort were collected five times from ages 17 to 18 years. Social withdrawal was assessed at 16 and 19 years. The transactional model was tested within a Structural Equation Modeling framework, with intercepts and slopes of friendship quantity, quality, and stability as mediators and residential transitions, education transitions, and sex as moderators. The results confirmed the presence of a transactional relation between withdrawal and friendship quality. Whereas higher age 16 withdrawal predicted having fewer, lower-quality, and less-stable friendships, only having lower-quality friendships, in turn, predicted higher age 19 withdrawal, especially in girls. Residential transitions were catalysts of change for highly withdrawn youth's number of friends: higher withdrawal predicted a moderate increase in number of friends for adolescents who relocated, and no change for those who made an educational transition or did not transition. Taken together, these results indicate that the quality of friendships-over and above number of friends and the stability of those friendships-is particularly important for entrenching or diminishing withdrawal in late adolescence, and that relocating provides an opportunity for withdrawn late adolescents to expand their friendship networks.

Feasibility and Acceptability of Virtual Implementation of a Sexual Reproductive Health Teen Pregnancy Prevention Program for Native Youth.

American Indian/Alaska Native (Native) youth face high rates of substance use, teen pregnancy and sexually transmitted infections. In response to the COVID-19 pandemic, Respecting the Circle of Life (RCL), a sexual reproductive health and teen pregnancy prevention program for Native youth and their trusted adult, was adapted and delivered in a virtual format with Native youth in a rural, reservation-based Native community. This manuscript describes the adaptation process, feasibility, and acceptability of virtual program implementation. The manuscript describes the process of rapidly shifting the RCL program into a virtual format. In addition, a mixed-methods process evaluation of implementation forms, program feedback forms, in-depth interviews with participants, and staff debriefing sessions was completed. Results show virtual implementation of RCL is both feasible and acceptable for Native youth and their trusted adults. A key benefit of virtual implementation is the flexibility in scheduling and ability to have smaller groups of youth, which offers greater privacy for youth participants compared to in-person implementation with larger groups. However, internet connectivity did present a challenge for virtual implementation. Ultimately, sexual and reproductive health programs seeking to reach Native youth and families should consider virtual implementation methods, both during and outside of pandemic situations.

Between Two Worlds: Impacts of COVID-19 on the AI/AN Health Research Workforce.

The COVID-19 pandemic has had devastating global and national impacts including major loss of life, economic downturns, and ongoing impairments to mental and physical health. Conducting health research has remained a priority and has helped mitigate some of the COVID-19 devastation; however, challenges to research have arisen due to COVID-19 prevention strategies and changing community priorities for research. The purpose of this article is to focus on a critical piece of the health research process with American Indian and Alaska Native (AI/AN) communities and the AI/AN health research workforce. Throughout this editorial, we provide challenges faced while conducting research with AI/AN communities during the COVID-19 pandemic including changes to research processes and ongoing research studies, taking on multiple roles in academic spaces, and mourning for continuous community loss while continuing to conduct research that may benefit AI/AN communities. Using a strengths-based lens, we also provide examples of flexibility, adaptation, and resilience in the face of the ongoing COVID-19 pandemic.

In silico identification of two peptides with antibacterial activity against multidrug-resistant Staphylococcus aureus.

Here we report two antimicrobial peptides (AMPs), HG2 and HG4 identified from a rumen microbiome metagenomic dataset, with activity against multidrug-resistant (MDR) bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA) strains, a major hospital and community-acquired pathogen. We employed the classifier model design to analyse, visualise, and interpret AMP activities. This approach allowed in silico discrimination of promising lead AMP candidates for experimental evaluation. The lead AMPs, HG2 and HG4, are fast-acting and show anti-biofilm and anti-inflammatory activities in vitro and demonstrated little toxicity to human primary cell lines. The peptides were effective in vivo within a Galleria mellonella model of MRSA USA300 infection. In terms of mechanism of action, HG2 and HG4 appear to interact with the cytoplasmic membrane of target cells and may inhibit other cellular processes, whilst preferentially binding to bacterial lipids over human cell lipids. Therefore, these AMPs may offer additional therapeutic templates for MDR bacterial infections.

Rho-kinase inhibition improves haemodynamic responses and circulating ATP during hypoxia and moderate intensity handgrip exercise in healthy older adults.

Skeletal muscle haemodynamics and circulating adenosine triphosphate (ATP) responses during hypoxia and exercise are blunted in older (OA) vs. young (YA) adults, which may be associated with impaired red blood cell (RBC) ATP release. Rho-kinase inhibition improves deoxygenation-induced ATP release from OA isolated RBCs. We tested the hypothesis that Rho-kinase inhibition (via fasudil) in vivo would improve local haemodynamic and ATP responses during hypoxia and exercise in OA. Healthy YA (25 ± 3 years; n = 12) and OA (65 ± 5 years; n = 13) participated in a randomized, double-blind, placebo-controlled, crossover study on two days (≥5 days between visits). A forearm deep venous catheter was used to administer saline/fasudil and sample venous plasma ATP ([ATP]V ). Forearm vascular conductance (FVC) and [ATP]V were measured at rest, during isocapnic hypoxia (80% SpO2${S_{{\rm{p}}{{\rm{O}}_{\rm{2}}}}}$ ), and during graded rhythmic handgrip exercise that was similar between groups (5, 15 and 25% maximum voluntary contraction (MVC)). Isolated RBC ATP release was measured during normoxia/hypoxia. With saline, ΔFVC was lower (P < 0.05) in OA vs. YA during hypoxia (∼60%) and during 15 and 25% MVC (∼25-30%), and these impairments were abolished with fasudil. Similarly, [ATP]V and ATP effluent responses from normoxia to hypoxia and rest to 25% MVC were lower in OA vs. YA and improved with fasudil (P < 0.05). Isolated RBC ATP release during hypoxia was impaired in OA vs. YA (∼75%; P < 0.05), which tended to improve with fasudil in OA (P = 0.082). These data suggest Rho-kinase inhibition improves haemodynamic responses to hypoxia and moderate intensity exercise in OA, which may be due in part to improved circulating ATP. KEY POINTS: Skeletal muscle blood flow responses to hypoxia and exercise are impaired with age. Blunted increases in circulating ATP, a vasodilator, in older adults may contribute to age-related impairments in haemodynamics. Red blood cells (RBCs) are a primary source of circulating ATP, and treating isolated RBCs with a Rho-kinase inhibitor improves age-related impairments in deoxygenation-induced RBC ATP release. In this study, treating healthy older adults systemically with the Rho-kinase inhibitor fasudil improved blood flow and circulating ATP responses during hypoxia and moderate intensity handgrip exercise compared to young adults, and also tended to improve isolated RBC ATP release. Improved blood flow regulation with fasudil was also associated with increased skeletal muscle oxygen delivery during hypoxia and exercise in older adults. This is the first study to demonstrate that Rho-kinase inhibition can significantly improve age-related impairments in haemodynamic and circulating ATP responses to physiological stimuli, which may have therapeutic implications.

Phenylalanyl tRNA synthetase (PheRS) substrate mimics: design, synthesis, molecular dynamics and antimicrobial evaluation.

Antimicrobial resistance is a very challenging medical issue and identifying novel antimicrobial targets is one of the means to overcome this challenge. Phenylalanyl tRNA synthetase (PheRS) is a promising antimicrobial target owing to its unique structure and the possibility of selectivity in the design of inhibitors. Sixteen novel benzimidazole based compounds (5a-b), (6a-e), (7a-d), (9a-e) and three N,N-dimethyl-7-deazapurine based compounds (16a-c) were designed to mimic the natural substrate of PheRS, phenylalanyl adenylate (Phe-AMP), that was examined through flexible alignment. The compounds were successfully synthesised chemically in two schemes using 4 to 6-steps synthetic pathways, and evaluated against a panel of five microorganisms with the best activity observed against Enterococcus faecalis. To further investigate the designed compounds, a homology model of E. faecalis PheRS was generated, and PheRS-ligand complexes obtained through computational docking. The PheRS-ligand complexes were subjected to molecular dynamics simulations and computational binding affinity studies. As a conclusion, and using data from the computational studies compound 9e, containing the (2-naphthyl)-l-alanine and benzimidazole moieties, was identified as optimal with respect to occupancy of the active site and binding interactions within the phenylalanine and adenosine binding pockets.

Diné (Navajo) Female Perspectives on Mother-Daughter Cultural Assets Around the Transition to Womanhood: A Qualitative Study.

INTRODUCTION: American Indian (AI) people have protective factors embedded in cultural teachings that buffer against high-risk behaviors. This study applies a qualitative, grounded theory approach to identify cultural assets for a Diné (Navajo) mother-daughter intervention aimed at preventing substance abuse and teen pregnancy. METHOD: Focus groups and in-depth interviews were conducted with 28 AI females' ages 8 years and older from the Navajo Nation. RESULTS: Key themes were (a) preserving the Diné way of life, (b) cultural assets related to being a healthy Diné woman, (c) matrilineal networks as a source of strength/pride, (d) historical trauma as a source of resilience, (e) male influences as protective health factors, (f) Western education as a measure of success, and (g) integrating different belief systems. DISCUSSION: Study findings may be applied as foundational elements for culturally grounded AI substance abuse and teen pregnancy prevention strategies, as well as culturally safe nursing practice.

Continuity of Psychopathology Throughout Adolescence and Young Adulthood.

OBJECTIVE: This study tested two opposing hypotheses on the continuity of psychopathology throughout adolescence and young adulthood; differentiation versus dynamic mutualism. Differentiation predicts that co-occurrence decreases, while dynamic mutualism predicts that co-occurrence increases due to causal interactions amongst mental health problems. METHOD: Using data from the Dutch TRacking Adolescents' Individual Lives Survey (n = 2228, 51% female), we studied the development of self-reported internalizing, externalizing, and attention problems at ages 11 to 26 across six waves. Random-intercept cross-lagged panel modeling was employed to distinguish within-person development from stable between-person processes. RESULTS: Large stable between-person associations indicated that adolescents with internalizing problems tended to have both externalizing and attention problems as well. On a within-person level, mental health problems showed partial stability and strong cross-sectional co-occurrence. Within-wave associations of internalizing with externalizing or attention problems decreased between age 11 and 16 years, after which they increased again. Little heterotypic continuity was found: age 11 externalizing predicted age 13 attention, which in turn predicted age 16 externalizing problems, and internalizing predicted externalizing problems across ages 22 to 26. Findings were similar for males and females. CONCLUSIONS: Our findings suggest co-occurrence decreases during early and middle adolescence, supporting differentiation. While co-occurrence increased again into young adulthood, this could not be labeled as dynamic mutualism because little evidence for heterotypic continuity was found in this phase of life. The strong stable links between internalizing, externalizing, and attention problems stress the importance of targeting these mental health problems and their shared risk factors together.

Self-control, Mental Health Problems, and Family Functioning in Adolescence and Young Adulthood: Between-person Differences and Within-person Effects.

Adolescents' self-control develops in the context of mental health and family functioning, but it is unclear how the interplay of self-control, mental health, and family functioning unfolds across time within individuals. Separating within-person from between-person effects, random-intercept cross-lagged panel models were applied to adolescents (from ages 11 to 26) from a Dutch cohort (n = 2228, 51% female). Adolescents with low self-control were likely to have mental health problems and poorly functioning families. Although within-person changes in the study variables were not meaningfully associated in a reciprocal manner, changes in self-control and mental health were concurrently associated. This suggests that besides stable connections between self-control, mental health, and family functioning in adolescence and young adulthood, changes in self-control and mental health are developmentally linked as well.

Design, computational studies, synthesis and in vitro antimicrobial evaluation of benzimidazole based thio-oxadiazole and thio-thiadiazole analogues.

BACKGROUND: Two series of benzimidazole based thio-oxadiazole and thio-thiadiazole analogues were designed and synthesised as novel antimicrobial drugs through inhibition of phenylalanyl-tRNA synthetase (PheRS), which is a promising antimicrobial target. Compounds were designed to mimic the structural features of phenylalanyl adenylate (Phe-AMP) the PheRS natural substrate. METHODS: A 3D conformational alignment for the designed compounds and the PheRS natural substrate revealed a high level of conformational similarity, and a molecular docking study indicated the ability of the designed compounds to occupy both Phe-AMP binding pockets. A molecular dynamics (MD) simulation comparative study was performed to understand the binding interactions with PheRS from different bacterial microorganisms. The synthetic pathway of the designed compounds proceeded in five steps starting from benzimidazole. The fourteen synthesised compounds 5a-d, 6a-c, 8a-d and 9a-c were purified, fully characterised and obtained in high yield. RESULTS: In vitro antimicrobial evaluation against five bacterial strains showed a moderate activity of compound 8b with MIC value of 32 µg/mL against S. aureus, while all the synthesised compounds showed weak activity against both E. faecalis and P. aeruginosa (MIC 128 µg/mL). CONCLUSION: Compound 8b provides a lead compound for further structural development to obtain high affinity PheRS inhibitors.

Development of a Culturally Anchored Qualitative Approach to Conduct and Analyze Focus Group Narratives Collected in Diné (Navajo) Communities to Understand the Impacts of the Gold King Mine Spill of 2015.

The Gold King Mine Spill (Spill) occurred in August 2015 upstream from Silverton, Colorado and released three million gallons of contaminated water into the Animas River, a tributary to the San Juan River that flows across the Navajo Nation. Using principles of community-engaged research, the Gold King Mine Spill Diné Exposure Project co-developed a culturally anchored approach to conduct focus groups and analyze narratives collected in three Diné (Navajo) communities along the San Juan River within 9 months of the Spill. Focus group questions were designed to document the socio-cultural impacts of the Spill. This paper: (1) outlines the partnerships and approvals; (2) describes focus group design, training, data collection and analysis; and (3) reflects on the use of a culturally anchored approach in Indigenous, specifically Diné-centered research. Diné social and cultural etiquette and concepts of relationality were used to adapt standard (non-Indigenous) qualitative methods. Findings describe community perceptions of short-term impacts of the disaster, as well as past and present injustices, communication related to the Spill, and concerns of persistent threats to Diné lifeways. The culturally anchored approach was critical in fostering trust with Diné participants and aligned with the candor of the discussions.