In flux: Associations of substance use with instability in housing, employment, and income among young adults experiencing homelessness.

Young adults experiencing homelessness (YAEH) are faced with instabilities in many areas of their lives, including their living situation, employment, and income. Little is known about how the experience of instability in these different domains might be associated with substance use. Leveraging data collected on 276 YAEH in Los Angeles County, regression analyses examine associations between three distinct types of instability (housing, employment, income) and participants' self-reported alcohol use, alcohol consequences, non-cannabis drug use, and substance use symptoms. Results indicated that recent instability in income, employment, and secure housing for those with access to it (but not housing in general or non-secure housing) were significantly associated with greater alcohol/drug use or substance use symptoms. Depression was also found to moderate the association between employment instability and alcohol use. Our findings suggest that efforts to reduce instability in income, employment, and secure housing may have positive benefits for substance using YAEH, especially those with depressive symptoms.

Voices of Identity: Exploring Identity Development and Transformation among Urban American Indian/Alaska Native Emerging Adults.

Emerging adulthood shapes personal, professional, and overall well-being through identity exploration. This study addresses a gap in the minority identity literature by investigating how urban AI/AN emerging adults think about their identity and discussing challenges and protective factors associated with exploring their identity holistically. This mixed-methods study created a sampling framework based on discrimination experiences, cultural identity, social network support, mental health, and problematic substance use. We recruited 20 urban AI/AN emerging adults for interviews. We sought to gain deeper insights into their experiences and discussions surrounding identity formation and exploration. We provide descriptives for demographic characteristics and conducted a thematic analysis of the qualitative data from the interviews. Four themes emerged: a) being an urban AI/AN emerging adult means recognizing that one's identity is multifaceted; b) a multifaceted identity comes with tension of living in multiple worlds; c) the trajectory of one's identity grows over time to a deeper desire to connect with Native American culture; and d) understanding one's Native American background affects one's professional trajectory. Findings underscore the importance of developing programs to support well-being and identity development through cultural connection for urban AI/AN emerging adults.

Associations between service use and behavioral health trajectories among young adults experiencing homelessness.

Purpose: To examine associations of service use (housing, mental health, substance use, education, and employment) with depression and substance use disorder (SUD) trajectories among young adults experiencing homelessness. Method: Secondary data come from 276 young adults who participated in an intervention to reduce substance use and sexual risk behaviors. Participants were recruited from three drop-in centers in Los Angeles County from 2018 to 2020, and completed surveys at baseline, 3-, 6-, 12-, and 24-months post-baseline. Latent growth curve models examined trajectories of depression and SUD; service use in the past three months was used to predict growth trajectories. Results: More frequent use of mental health services (but not other services) at baseline was associated with greater depression symptoms at baseline, linear declines in depression, and a quadratic increase in depression. Service use at baseline was not associated with likelihood of SUD at baseline or changes in SUD over time. Conclusions: Young adults in most need of behavioral services are likely to receive services for mental health, but not SUD. Use of mental health services may reduce depression symptoms over time, but continuing care may be needed to prevent symptom returns. More work is needed to connect young adults with SUD treatment and improve effectiveness of these services.

The PROMIS-16 reproduces the PROMIS-29 physical and mental health summary scores accurately in a probability-based internet panel.

PURPOSE: The Patient-Reported Outcomes Measurement Information System® (PROMIS)-16 assesses the same multi-item domains but does not include the pain intensity item in the PROMIS-29. We evaluate how well physical and mental health summary scores estimated from the PROMIS-16 reproduce those estimated using the PROMIS-29. METHODS: An evaluation of data collected from 4130 respondents from the KnowledgePanel. Analyses include confirmatory factor analysis to assess physical and mental health latent variables based on PROMIS-16 scores, reliability estimates for the PROMIS measures, mean differences and correlations of scores estimated by the PROMIS-16 with those estimated by the PROMIS-29, and associations between differences in corresponding PROMIS-16 and PROMIS-29 scores by sociodemographic characteristics. RESULTS: A two-factor (physical and mental health) model adequately fits the PROMIS-16 scores. Reliability estimates for the PROMIS-16 measures were slightly lower than for the PROMIS-29 measures. There were minimal differences between PROMIS physical and mental health summary scores estimated using the PROMIS-16 or the PROMIS-29. PROMIS-16 and PROMIS-29 score differences by sociodemographic characteristics were small. Using the PROMIS pain intensity item when scoring the PROMIS-16 produced similar estimates of physical and mental health summary scores. CONCLUSION: The PROMIS-16 provides similar estimates of the PROMIS-29 physical and mental health summary scores. The high reliability of these scores indicates they are accurate enough for use with individual patients.

Health system implementation of the PROMIS Cognitive Function Screener in the Medicare Annual Wellness Visit: framing as abilities versus concerns.

BACKGROUND: Cognitive assessment is a required component of the Medicare Annual Wellness Visit (AWV). In this prospective study, we evaluated acceptability and usefulness of a patient-reported outcome measure (the PROMIS® Cognitive Function Screener, or PRO-CS) to screen for cognitive impairment during the AWV. We compared two versions of the PRO-CS: Abilities and Concerns. METHODS: We developed PRO-CS Abilities and PRO-CS Concerns using items from the PROMIS Cognitive Function item banks. We partnered with a large health system in Pennsylvania to implement an electronic health record (EHR)-integrated version of the 4-item PRO-CS into their AWV workflow. PRO-CS Abilities was implemented in June 2022 and then replaced with PRO-CS Concerns in October 2022. We used EHR data to evaluate scores on Abilities versus Concerns and their association with patient characteristics. We gathered feedback from providers on experiences with the PRO-CS and conducted cognitive interviews with patients to evaluate their preferences for Abilities versus Concerns. RESULTS: Between June 2022 and January 2023, 3,088 patients completed PRO-CS Abilities and 2,614 patients completed PRO-CS Concerns. Mean T-scores for Abilities (54.8) were slightly higher (indicating better cognition) than for Concerns (52.6). 10% of scores on Abilities and 13% of scores on Concerns indicated concern for cognitive impairment (T-score < 45). Both Abilities and Concerns were associated with clinical characteristics as hypothesized, with lower scores for patients with cognitive impairment diagnoses and those requiring assistance with instrumental activities of daily living. Abilities and Concerns had similar negative correlations with depression (r= -0.31 versus r= -0.33) and anxiety (r= -0.28 for both), while Abilities had a slightly stronger positive correlation with self-rated health (r = 0.34 versus r = 0.28). In interviews, providers commented that the PRO-CS could be useful to facilitate conversations about cognition, though several providers noted potential limitations of patient self-report. Feedback from patients indicated a preference for PRO-CS Concerns. CONCLUSIONS: Our findings suggest potential utility of the PRO-CS for cognitive screening in the Medicare AWV. PRO-CS Abilities and Concerns had similar associations with patient clinical characteristics, but the Concerns version was more acceptable to patients.

The diversity of well-being indicators: a latent profile analysis.

Introduction: Research on the dimensional structure of subjective well-being (SWB) suggests a five-dimensional solution, consisting of the three established dimensions of life satisfaction, positive affect, and negative affect, and two additional empirically supported dimensions: domain satisfaction and happiness. While these dimensions can be aggregated into a superordinate SWB construct, little research has explored how these dimensions differ in their variation across subpopulations of individuals. Methods: The present study addresses this gap via secondary analysis of a sample of 1,487 partnered individuals, using the five dimensions of SWB as indicators for latent profile analysis. Results: Analyses returned five profiles, which we labeled Satisfied, Ambivalent, Indifferent, Dissatisfied, and Very Dissatisfied. In the Ambivalent and Indifferent profiles, the dimensions of negative affect and happiness exhibit discrepant behavior, resulting in shape differences. The five profiles are organized with reference to the external criterion of couple satisfaction. At the theoretical level, the results of the present study have the potential to inform current debates about the structure of well-being. Discussion: These findings suggest that, while SWB can usually be measured as a unidimensional construct, there is still merit to using multidimensional approaches and alternative forms of measurement-such as LPA-that capture complexities normally absent from unidimensional treatments. At the practical level, the results of the current study have the potential to inform well-being interventions (both clinical and otherwise), suggesting that those dealing with well-being in real life situations should pause before concluding that the absence of negativity implies the presence of positivity, or vice versa.

Understanding effects of the group process on drinking outcomes for emerging adults experiencing homelessness.

BACKGROUND: There is little research on group process for motivational interviewing-based group interventions with young people. We examine how change talk, group climate and cohesion, and facilitator empathy among emerging adults experiencing homelessness affect their drinking outcomes. METHODS: Data come from a clinical trial at three drop-in centers serving emerging adults experiencing homelessness in Los Angeles County and focus on those who received the intervention (n = 132). Participants completed baseline, 3-, 6-, and 12-month follow-up surveys. They were predominantly male and non-white. Group sessions were digitally recorded and coded for percentage change talk (PCT), group climate and cohesion, and facilitator empathy. RESULTS: Because baseline alcohol use was significantly higher at site 1 than sites 2 and 3, we examined associations separately by site. At 6 months, higher PCT was associated with fewer drinks per drinking day for sites 2 and 3, whereas higher PCT was associated with more drinks per drinking day for site 1. There were no effects of PCT at 12 months. Higher group cohesion scores were associated with fewer drinking days at 6 months; higher facilitator empathy was associated with fewer maximum drinks in a day at both 6 and 12 months. Group climate was not associated with drinking outcomes. CONCLUSIONS: These findings highlight the importance of measuring multiple factors in the group process to understand outcomes. What is "uttered" during group and what is observed provide different methods to evaluate the group process and allow us to better bridge the gap between research and practice.

Trajectories of alcohol and cannabis use among emerging adults with a history of unstable housing: Associations with functioning over a two-year period.

INTRODUCTION: Research has documented high rates of alcohol and cannabis use among emerging adults experiencing homelessness. However, little is known about trajectories of use over time or how trajectories are associated with functioning (e.g., risk behaviors, mental and physical health, social functioning, economic well-being). METHODS: Data come from a cohort of 18-25 year olds experiencing homelessness who were surveyed 5 times over 24 months. Parallel process growth mixture models were used to model heterogeneity in alcohol and cannabis use across the 5 timepoints, which allowed for the extraction of classes based on both alcohol and cannabis use trajectories. Classes were compared on demographics and functioning at baseline and 24-months. RESULTS: Two trajectory classes of alcohol and cannabis use emerged: moderate decreasing cannabis and low stable alcohol use (75% of the sample) and heavy cannabis and alcohol use (25% of the sample). The heavy cannabis and alcohol use class reported a significantly higher likelihood for any non-cannabis drug use at baseline and 24-months, as well as greater depression and physical ailments at 24-months. In addition, at 24-months this class had a marginally higher likelihood of a positive screen for at least moderate anxiety and being recently unhoused. CONCLUSIONS: The effects of heavy continued cannabis and alcohol co-use on multiple domains of functioning (e.g., risk behavior, mental and physical health) highlight the importance of a coordinated systems approach that addresses the often complex and interrelated challenges facing emerging adults with a history of homelessness.

Development of an ultra-short measure of eight domains of health-related quality of life for research and clinical care: the patient-reported outcomes measurement information system® PROMIS®-16 profile.

PURPOSE: We describe development of a short health-related quality of life measure, the patient-reported outcomes measurement information system® (PROMIS®)-16 Profile, which generates domain-specific scores for physical function, ability to participate in social roles and activities, anxiety, depression, sleep disturbance, pain interference, cognitive function, and fatigue. METHODS: An empirical evaluation of 50 candidate PROMIS items and item pairs was conducted using data from a sample of 5775 respondents from Amazon's Mechanical Turk (MTurk). Results and item response theory information curves for a subset of item pairs were presented and discussed in a stakeholder meeting to narrow the candidate item sets. A survey of the stakeholders and 124 MTurk adults was conducted to solicit preferences among remaining candidate items and finalize the measure. RESULTS: Empirical evaluation showed minimal differences in basic descriptive statistics (e.g., means, correlations) and associations with the PROMIS-29 + 2 Profile, thus item pairs were further considered primarily based on item properties and content. Stakeholders discussed and identified subsets of candidate item pairs for six domains, and final item pairs were agreed upon for two domains. Final items were selected based on stakeholder and MTurk-respondent preferences. The PROMIS-16 profile generates eight domain scores with strong psychometric properties. CONCLUSION: The PROMIS-16 Profile provides an attractive brief measure of eight distinct domains of health-related quality of life, representing an ideal screening tool for clinical care, which can help clinicians quickly identify distinct areas of concern that may require further assessment and follow-up. Further research is needed to confirm and extend these findings.

Because We Love You (BeWeL): A protocol for a randomized controlled trial of two brief interventions focused on social and cultural connectedness to reduce risk for suicide and substance misuse in young Alaska Native people.

Background: Suicide among young people in Alaska Native (AN) communities was nearly unheard of through the establishment of statehood in 1959, but in the 1970s, AN suicide rates began to double every five years, with most of the increase due to suicide among 15 to 25-year-olds. From 1960-1995, the suicide rate increased by approximately 500% during this period of rapid, imposed social transition. For example, families were forced to live in settlements and children were sent to boarding schools. These disruptions increased conditions associated with suicide risk (e.g., substance use disorders, cultural disconnection), and challenged the community-level social safety net of youth protective factors that might have moderated effects of these traumas. The present study addresses the significant gap in culturally appropriate evidence-based programming to address suicide prevention among AN young people as part of aftercare. Our key research questions and methodology have been informed by AN stakeholders, and the intervention approach is Indigenous-led. Methods: Our interventions are targeted toward Alaska Native young people ages 14-24 who present with suicide attempt, ideation, or associated risk behaviors, including alcohol-related injury in the Yukon-Kuskokwim region or the Interior. In a randomized controlled trial, 14-24-year-old AN individuals will receive either BeWeL (n = 185), which comprises a 45-minute virtual cultural talk addressing family and ancestral strengths and increasing protective factors, or BeWeL plus motivational interviewing with social networks, which includes an additional 15 minutes focused on discussion of the individual's social networks (n = 185). We will evaluate intervention effects on primary outcomes of suicide-intent risk, depression, anxiety, frequency of alcohol use, and alcohol consequences. Some of our secondary outcomes include individual and community protective factors, social networks, and awareness of connectedness. Discussion: This project has the potential to expand the range and effectiveness of suicide prevention services for AN young people and will help meet the need in Alaska to link clinical behavioral health services to AN community-based networks, and to engage local cultural resources in aftercare for individuals at risk for suicide. Findings have potential to provide practical information to advance the field of suicide prevention and enhance protective factors and resiliency among this population. Trial registration: ClinicalTrials.gov Identifier: NCT05360888.

Mapping of the PROMIS global health measure to the PROPr in the United States.

BACKGROUND: The Patient-Reported Outcomes Measurement and Information System (PROMIS®) global health items (global-10) yield physical and mental health scale scores and the PROMIS-Preference (PROPr) scoring system estimated from PROMIS domain scores (e.g., PROMIS-29 + 2) produces a single score anchored by 0 (dead or as bad as being dead) to 1 (full health). A link between the PROMIS global-10 and the PROPr is needed. METHODS: The PROMIS-29 + 2 and the PROMIS global-10 were administered to 4102 adults in the Ipsos KnowledgePanel in 2022. The median age was 52 (range 18-94), 50% were female, 70% were non-Hispanic White, and 64% were married or living with a partner. The highest level of education completed for 26% of the sample was a high school degree or general education diploma and 44% worked full-time. We estimated correlations of the PROPr with the PROMIS global health items and the global physical and mental health scales. We examined the adjusted R2 and estimated correlations between predicted and observed PROPr scores. RESULTS: Product-moment correlations between the PROMIS global health items and the PROPr ranged from 0.50 to 0.63. The PROMIS global physical health and mental health scale scores correlated 0.74 and 0.60, respectively, with the PROPr. The adjusted R2 in the regression of the PROPr on the PROMIS global health items was 64%. The equated PROPr preference scores correlated (product-moment) 0.80 (n = 4043; p < 0.0001) with the observed PROPr preference scores, and the intra-class correlation (two-way random effects model) was 0.80. The normalized mean absolute error (NMAE) was 0.45 (SD = 0.43). The adjusted R2 in the OLS regression of the PROPr on the PROMIS global health scales was 59%. The equated PROPr preference scores correlated (product-moment) was 0.77 (n = 4046; p < 0.0001) with the observed PROPr preference scores, and the intra-class correlation was 0.77. The NMAE was 0.49 (SD = 0.45). CONCLUSIONS: Regression equations provide a reasonably accurate estimate of the PROPr preference-based score from the PROMIS global health items or scales for group-level comparisons. These estimates facilitate cost-effectiveness research and meta-analyses. The estimated PROPr scores are not accurate enough for individual-level applications. Future evaluations of the prediction equations are needed.

Predictors of Housing Trajectories Among Young Adults Experiencing Homelessness in Los Angeles.

Experiencing homelessness during young adulthood is associated with negative health outcomes and understanding housing trajectories of young adults experiencing homelessness may aid in the development of evidence-based public health programs designed to serve this at-risk age group. In the present study, the authors examined baseline predictors of 24-month trajectories of housing stability and unsheltered housing among a sample of 271 young adults aged 18 to 25 recruited from drop-in centers in Los Angeles. In multivariate models, the authors found that identifying as multi-racial/other and better friendship quality at baseline were associated with less steep increases in the likelihood of stable housing over time. Being employed at baseline was associated with a less steep decrease in the probability of being unsheltered over time, while illicit drug use days associated with a steeper decrease in the probability of being unsheltered over time. Continued research is needed to establish important factors determining young adults' long-term housing trajectories in the effort to promote greater access and engagement with housing services.

How Well Do Seven Self-Report Measures Represent Underlying Back Pain Impact?

BACKGROUND: The extent to which different measures of back pain impact represent an underlying common factor has implications for decisions about which one to use in studies of pain management and estimating one score from others. AIMS: To determine if different self-report back pain impact measures represent an underlying pain latent variable and estimate associations with it. METHOD: Seven pain impact measures completed by Amazon Mechanical Turk adults are used to estimate internal consistency reliability and associations: Oswestry Disability Index (ODI), Roland-Morris Disability Questionnaire (RMDQ), short form of the Örebro Musculoskeletal Pain Questionnaire (OMPQ), Subgroups for Targeted Treatment (STarT) Back Tool, the Graded Chronic Pain Scale (GCPS) disability score, PEG (Pain intensity, interference with Enjoyment of life, interference with General activity), and Impact Stratification Score (ISS). RESULTS: The sample of 1,874 adults with back pain had an average age of 41 and 52% were female. Sixteen percent were Hispanic, 7% non-Hispanic Black, 5% non-Hispanic Asian, and 71% non-Hispanic White. Internal consistency reliability estimates ranged from 0.710 (OMPQ) to 0.923 (GCPS). Correlations among the measures ranged from 0.609 (RMDQ with OMPQ) to 0.812 (PEG with GCPS). Standardized factor loadings on the pain latent variable ranged from 0.782 (RMDQ) to 0.870 (ISS). CONCLUSIONS: Scores of each measure can be estimated from the others for use in research.

Sociodemographic and Behavioral Risk Correlates of PrEP Interest and Use Among Young Adults Experiencing Homelessness in Los Angeles.

Young adults experiencing homelessness (YAEH) are at elevated risk for HIV compared to their stably housed peers. Preexposure prophylaxis (PrEP) is highly effective at preventing HIV infection, yet YAEH have been largely overlooked in PrEP efforts to date despite YAEH reporting high overall interest in PrEP. We assessed individual, social, and structural variables associated with PrEP interest and use among a sample of 195 YAEH (ages 18-25) recruited from drop-in centers across Los Angeles County who met criteria for HIV risk. In the current sample, though most had heard of PrEP (81.0%), the majority were not interested in taking PrEP (68.2%) and only a minority had used/were using PrEP (11.8%). YAEH who identified as sexual and/or gender minority, reported knowing someone who had used PrEP, or recently accessed sexual health services were more likely to have used and/or reported interest in using PrEP. Those who reported more episodes of heavy drinking were less likely to report having used PrEP. Suggestions are provided for better integrating PrEP-related services into existing behavioral and health service programs for YAEH, as well as leveraging peers and fostering positive social norms to reduce PrEP-related stigma and increase interest and use of PrEP among YAEH.

Mechanical Regulation of Retinal Vascular Inflammation and Degeneration in Diabetes.

Vascular inflammation is known to cause degeneration of retinal capillaries in early diabetic retinopathy (DR), a major microvascular complication of diabetes. Past studies investigating these diabetes-induced retinal vascular abnormalities have focused primarily on the role of molecular or biochemical cues. Here we show that retinal vascular inflammation and degeneration in diabetes are also mechanically regulated by the increase in retinal vascular stiffness caused by overexpression of the collagen-cross-linking enzyme lysyl oxidase (LOX). Treatment of diabetic mice with LOX inhibitor ß-aminopropionitrile (BAPN) prevented the increase in retinal capillary stiffness, vascular intracellular adhesion molecule-1 overexpression, and leukostasis. Consistent with these anti-inflammatory effects, BAPN treatment of diabetic mice blocked the upregulation of proapoptotic caspase-3 in retinal vessels, which concomitantly reduced retinal capillary degeneration, pericyte ghost formation, and the diabetes-induced loss of contrast sensitivity in these mice. Finally, our in vitro studies indicate that retinal capillary stiffening is sufficient to increase the adhesiveness and neutrophil elastase-induced death of retinal endothelial cells. By uncovering a link between LOX-dependent capillary stiffening and the development of retinal vascular and functional defects in diabetes, these findings offer a new insight into DR pathogenesis that has important translational potential.

Sober Curiosity and Participation in Temporary Alcohol Abstinence Challenges in a Cohort of U.S. Emerging Adults.

OBJECTIVE: Thus far, behavioral health research in the United States has not explored the prevalence or correlates of sober curiosity (SC; exploratory or experimental abstinence or moderation) or temporary alcohol abstinence challenges (TAACs; e.g., "Dry January"), despite significant attention in media and popular discourse. We explored these activities in a sample of U.S. emerging adults (e.g., ages 18-29), a population with higher-risk drinking behavior yet some of the lowest rates of treatment engagement for alcohol use problems. METHOD: Survey data were collected in 2021-2022 among participants (n = 1,659; M age = 24.7 years). We assessed SC awareness/engagement and past-year TAAC participation, and differences across demographics and behavioral characteristics. RESULTS: Overall, 9% of emerging adults were familiar with SC and 7% had participated in a TAAC in the past year. Half of TAAC participants reported drinking less after the TAAC, and 15% remained abstinent after the TAAC ended. SC familiarity and TAAC were both associated with past-month heavy drinking, cannabis use, higher Alcohol Use Disorders Identification Test (AUDIT) scores, more past-year alcohol and cannabis consequences, past-year substance use treatment, and greater readiness to quit alcohol. CONCLUSIONS: Both SC and TAACs may have potential to engage young people with a desire to moderate or eliminate their alcohol consumption. This may occur directly through use of these strategies or by helping them connect to additional services. Future research can help the field understand the uptake of SC and TAACs, gauge efficacy, and identify avenues to link young people to resources and interventions.

Comparison of patient-reported outcomes measurement information system (PROMIS®)-29 and PROMIS global physical and mental health scores.

PURPOSE: The Patient-Reported Outcomes Measurement and Information System (PROMIS®): includes the PROMIS-29 physical and mental health summary and the PROMIS global physical and mental health scores. It is unknown how these scores coincide with one another. This study examines whether the scores yield similar or different information. METHODS: The PROMIS-29 and the PROMIS global health items were administered to 5804 adults from Amazon's Mechanical Turk (MTurk) in 2021-2022 and to 4060 adults in the Ipsos KnowledgePanel (KP) in 2022. RESULTS: The median age of those in MTurk (KP) was 36 (54) and 53% (50%) were male. Mean T-scores on the PROMIS-29 and PROMIS global physical health scales were similar, but PROMIS global mental health was 3-4 points lower than the PROMIS-29 mental health summary score. Product-moment correlations ranged from 0.69 to 0.81 between the PROMIS-29 physical health and PROMIS global physical health scales and 0.56-0.69 between the mental health scales. Multi-trait multimethod analyses indicated that only a small proportion of the correlations between the two methods of measuring mental health were significantly more highly correlated with one another than correlations between physical and mental health. CONCLUSIONS: PROMIS-29 and PROMIS global mental health scales provide different information and, therefore, study conclusions may vary depending on which measure is used. Interpretation of results needs to consider that the PROMIS-29 mental health scale is a weighted combination of specific domains while the PROMIS global mental health scale is based on general mental health perceptions. Further comparisons of methods of assessing mental health are needed.

Social Networks, Cultural Pride, and Historical Loss Among Non-Reservation American Indian / Alaska Native Emerging Adults.

Health disparities among American Indian/Alaska Native (AI/AN) populations in the United States are the result of historical traumas, such as colonization, forced relocation, and federal policies focused on cultural assimilation. Culturally-tailored health interventions aim to address intergenerational trauma by emphasizing cultural strengths and building positive social connections. In this article, we explore the social network characteristics of participants of the first culturally-tailored health intervention for AI/AN emerging adults (18-25) living outside of tribal lands. Participants (N = 150; 86% female) were recruited across the United States via social media and completed online egocentric network interviews prior to the start of intervention workshops. Participants' networks were diverse in composition and structure. They were primarily composed of family and friends, were people they had regular contact with, were similar age, and provided participants with support. We tested for significant associations between network characteristics, individual characteristics (age, gender, travel to reservations, speaking tribal languages, etc.) and two dependent measures: 1) cultural pride and belongingness and 2) thoughts of historical loss. Multiple regression results show that higher proportions of network members who discussed AI/AN identity with participants and having more network members who engage in traditional practices was associated with stronger cultural pride and belongingness. Higher proportions of network members having discussion of AI/AN identity with participants was also associated with more frequent thoughts of historical loss. Controlling for network factors, no individual characteristics were associated with either dependent variable. We discuss implications for the development of culturally-tailored health interventions.

Hyperactive Rac stimulates cannibalism of living target cells and enhances CAR-M-mediated cancer cell killing.

The 21kD GTPase Rac is an evolutionarily ancient regulator of cell shape and behavior. Rac2 is predominantly expressed in hematopoietic cells where it is essential for survival and motility. The hyperactivating mutation Rac2E62K also causes human immunodeficiency, although the mechanism remains unexplained. Here, we report that in Drosophila, hyperactivating Rac stimulates ovarian cells to cannibalize neighboring cells, destroying the tissue. We then show that hyperactive Rac2E62K stimulates human HL60-derived macrophage-like cells to engulf and kill living T cell leukemia cells. Primary mouse Rac2+/E62K bone-marrow-derived macrophages also cannibalize primary Rac2+/E62K T cells due to a combination of macrophage hyperactivity and T cell hypersensitivity to engulfment. Additionally, Rac2+/E62K macrophages non-autonomously stimulate wild-type macrophages to engulf T cells. Rac2E62K also enhances engulfment of target cancer cells by chimeric antigen receptor-expressing macrophages (CAR-M) in a CAR-dependent manner. We propose that Rac-mediated cell cannibalism may contribute to Rac2+/E62K human immunodeficiency and enhance CAR-M cancer immunotherapy.

Convergent Total Synthesis of (-)-Cyclopamine.

A concise and enantioselective total synthesis of the Veratrum alkaloid cyclopamine is disclosed. This highly convergent synthesis with a 16-step longest linear sequence (LLS) was enabled by a de novo synthesis of the trans-6,5-heterobicycle via a strain-inducing halocyclization process, a key Tsuji-Trost cyclization to construct the fully substituted, spirocyclic THF motif with exquisite diastereocontrol, and a late-stage ring-closing metathesis (RCM) reaction to forge the central tetrasubstituted olefin.