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.

Microbial stimulation fully differentiates monocytes to DC-SIGN/CD209(+) dendritic cells for immune T cell areas.

Dendritic cells (DCs), critical antigen-presenting cells for immune control, normally derive from bone marrow precursors distinct from monocytes. It is not yet established if the large reservoir of monocytes can develop into cells with critical features of DCs in vivo. We now show that fully differentiated monocyte-derived DCs (Mo-DCs) develop in mice and DC-SIGN/CD209a marks the cells. Mo-DCs are recruited from blood monocytes into lymph nodes by lipopolysaccharide and live or dead gram-negative bacteria. Mobilization requires TLR4 and its CD14 coreceptor and Trif. When tested for antigen-presenting function, Mo-DCs are as active as classical DCs, including cross-presentation of proteins and live gram-negative bacteria on MHC I in vivo. Fully differentiated Mo-DCs acquire DC morphology and localize to T cell areas via L-selectin and CCR7. Thus the blood monocyte reservoir becomes the dominant presenting cell in response to select microbes, yielding DC-SIGN(+) cells with critical functions of DCs.

Physical pain among urban Native American emerging adults: Socio-cultural risk and protective factors.

OBJECTIVE: American Indian/Alaska Native (AI/AN) people have high rates of physical pain. Pain is understudied in urban-dwelling, AI/AN emerging adults, a group with unique socio-cultural risk and protective factors. We explore associations between socioeconomic disadvantage, additional socio-cultural factors, and pain among urban AI/AN emerging adults. METHODS: AI/AN participants aged 18-25 (N = 417) were recruited via social media. Regression models tested associations between socioeconomic disadvantage (income and ability to afford healthcare) and pain as well as additional socio-cultural factors (discrimination, historical loss, cultural pride and belonging, visiting tribal lands) and pain. Multi-group regression models tested whether associations between socio-cultural factors and pain differed between participants who were socioeconomically disadvantaged and those who were less disadvantaged. RESULTS: In the full sample, lower income (b = 1.00 - 1.48, p < .05), inability to afford healthcare (b = 1.00, p = .011), discrimination (b = 0.12, p = .001), and historical loss (b = 0.24, p = .006) were positively associated with pain, whereas visiting tribal lands was negatively associated with pain (b = -0.86 - -0.42, p < .05). In the multi-group model, visiting tribal lands 31+ days was negatively associated with pain only among the less socioeconomically disadvantaged group (b = -1.48, p < .001). CONCLUSIONS: Socioeconomic disadvantage may, in part, drive pain disparities among AI/AN emerging adults and act as a barrier to benefitting from visiting tribal lands. Results support a biopsychosocial approach to targeting pain in this population, including addressing socioeconomic challenges and developing culturally informed, strengths-based interventions.

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.

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.

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.

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.

Discrimination experiences and problematic alcohol and cannabis use in young adulthood.

BACKGROUND AND OBJECTIVES: Limited research has examined how discrimination in young adulthood relates to substance use. We examined how multiple and specific types (e.g., race-based) of experiences of unfair treatment are related to problematic alcohol and cannabis use. METHODS: We analyzed cross-sectional data from a diverse cohort of young adults (mean age 24.7) predominantly residing in southern California (n = 2303) to examine associations of multiple (count) and specific experiences (race-, sexual orientation-, gender-based) of perceived everyday discrimination with self-reported alcohol and cannabis use outcomes (consequences, use disorders, and solitary use). We also tested interactions between the three specific discrimination experiences and sociodemographic characteristics (e.g., race-based discrimination × race/ethnicity). RESULTS: In this diverse sample (e.g., 47% Latinx/o and 22% Asian; 22% sexual/gender diverse; 56% female) of young adults, about 46% reported up to four different discrimination experiences and 27% reported race-, 26% gender-, and 5% sexual orientation-based discrimination. Race- and gender-based discrimination and experiencing more types of discrimination were associated with worse cannabis use outcomes. Race-based discrimination was associated with fewer alcohol consequences and lower Alcohol Use Disorders Identification Test (AUDIT) scores. Associations with sexual orientation-based discrimination and the interactions were not significant. DISCUSSION AND CONCLUSIONS: Findings build on limited research on associations of discrimination with cannabis use in young adults. More work is needed to understand the mechanisms by which discrimination influences drinking behaviors. SCIENTIFIC SIGNIFICANCE: This study advances the field by examining the unique contributions of specific and multiple types of discrimination experiences in young adulthood, a critical developmental period in which substance use peaks.

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.

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.

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.

Retinal pathological features and proteome signatures of Alzheimer's disease.

Alzheimer's disease (AD) pathologies were discovered in the accessible neurosensory retina. However, their exact nature and topographical distribution, particularly in the early stages of functional impairment, and how they relate to disease progression in the brain remain largely unknown. To better understand the pathological features of AD in the retina, we conducted an extensive histopathological and biochemical investigation of postmortem retina and brain tissues from 86 human donors. Quantitative examination of superior and inferior temporal retinas from mild cognitive impairment (MCI) and AD patients compared to those with normal cognition (NC) revealed significant increases in amyloid ß-protein (Aß42) forms and novel intraneuronal Aß oligomers (AßOi), which were closely associated with exacerbated retinal macrogliosis, microgliosis, and tissue atrophy. These pathologies were unevenly distributed across retinal layers and geometrical areas, with the inner layers and peripheral subregions exhibiting most pronounced accumulations in the MCI and AD versus NC retinas. While microgliosis was increased in the retina of these patients, the proportion of microglial cells engaging in Aß uptake was reduced. Female AD patients exhibited higher levels of retinal microgliosis than males. Notably, retinal Aß42, S100 calcium-binding protein B+ macrogliosis, and atrophy correlated with severity of brain Aß pathology, tauopathy, and atrophy, and most retinal pathologies reflected Braak staging. All retinal biomarkers correlated with the cognitive scores, with retinal Aß42, far-peripheral AßOi and microgliosis displaying the strongest correlations. Proteomic analysis of AD retinas revealed activation of specific inflammatory and neurodegenerative processes and inhibition of oxidative phosphorylation/mitochondrial, and photoreceptor-related pathways. This study identifies and maps retinopathy in MCI and AD patients, demonstrating the quantitative relationship with brain pathology and cognition, and may lead to reliable retinal biomarkers for noninvasive retinal screening and monitoring of AD.

Electronic health record (EHR)-based PROMIS measures among neurology clinic decedents and survivors: a retrospective cohort analysis.

BACKGROUND: In addition to their standard use to assess real-time symptom burden, patient-reported outcomes (PROs), such as the Patient-Reported Outcomes Measurement Information System (PROMIS), measures offer a potential opportunity to understand when patients are experiencing meaningful clinical decline. If PROs can be used to assess decline, such information can be used for informing medical decision making and determining patient-centered treatment pathways. We sought to use clinically implemented PROMIS measures to retrospectively characterize the final PROMIS report among all patients who completed at least one PROMIS assessment from December 2017-March 2020 in one large health system, stratified by decedents vs. survivors. We conducted a retrospective cohort analysis of decedents (N = 1,499) who received care from outpatient neurology clinical practice within a single, large health system as part of usual care. We also compared decedents to survivors (360 + days before death; N = 49,602) on PROMIS domains and PROMIS-Preference (PROPr) score, along with demographics and clinical characteristics. We used electronic health record (EHR) data with built-in PROMIS measures. Linear regressions assessed differences in PROMIS domains and aggregate PROPr score by days before death of the final PROMIS completion for each patient. RESULTS: Among decedents in our sample, in multivariable regression, only fatigue (range 54.48-59.38, p < 0.0029) and physical function (range 33.22-38.38, p < 0.0001) demonstrated clinically meaningful differences across time before death. The overall PROPr score also demonstrated statistically significant difference comparing survivors (0.19) to PROPr scores obtained 0-29 days before death (0.29, p < 0.0001). CONCLUSIONS: Although clinic completion of PROMIS measures was near universal, very few patients had more than one instance of PROMIS measures reported, limiting longitudinal analyses. Therefore, patient-reported outcomes in clinical practice may not yet be robust enough for incorporation in prediction models and assessment of trajectories of decline, as evidenced in these specialty clinics in one health system. PROMIS measures can be used to effectively identify symptoms and needs in real time, and robust incorporation into EHRs can improve patient-level outcomes, but further work is needed for them to offer meaningful inputs for defining patient trajectories near the end of life. Assessing symptom burden provides an opportunity to understand clinical decline, particularly as people approach the end of life. We sought to understand whether symptoms reported by patients can be used to assess decline in health. Such information can inform decision-making about care and treatments. Of eight symptoms that we assessed, patient reports of fatigue and physical function were associated with clinical decline, as was an overall score of symptom burden. Because few symptoms were associated with decline, patient-reported outcomes in clinical practice may not yet be robust enough for incorporation in prediction models and assessment of trajectories of decline.

Crosswalking the National Institutes of Health Impact Stratification Score to the PEG.

OBJECTIVE: To crosswalk the National Institutes of Health (NIH) Pain Consortium's Research Task Force proposed Impact Stratification Score (ISS) to the PEG (Pain Intensity, Interference With Enjoyment of Life, Interference With General Activity) Scale. DESIGN: Cross-sectional data collected in 2021. Ordinary least squares regression analyses of ISS and PEG. SETTING: Amazon Mechanical Turk workers. PARTICIPANTS: 1931 adults with back pain with an average age of 41 (range, 19-77); 48% were female, 16% Hispanic, 7% non-Hispanic Black, 5% non-Hispanic Asian, and 71% non-Hispanic White (N=1931). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The Patient-Reported Outcomes Measurement Information System (PROMIS)-29+2 v2.1 survey that includes the ISS, and the 3-item PEG. RESULTS: The ISS and PEG had a correlation coefficient of 0.74. The ISS accounted for 55% of the adjusted variance in the PEG and the standardized average deviation between observed and predicted scores (normalized mean absolute error) was 0.53. Likewise, the PEG explained 55% of the variance in the ISS with a normalized mean absolute error of 0.52. CONCLUSIONS: This study provides a crosswalk between the ISS and PEG that can be used to predict one from the other. The regression equations can facilitate comparisons in studies that use different measures.

Classifying patients with non-specific chronic low back pain using the impact stratification score in an online convenience sample.

BACKGROUND: In 2014, the National Institute of Health Pain Consortium's research task force (RTF) on research standards for chronic low back pain (CLBP) proposed the Impact Stratification Score (ISS) as a patient-reported outcome measure that could stratify patients by the impact CLBP has on their lives. This work compares three newly developed ISS-based classifications to the RTF's original to provide an optimal recommendation. METHODS: The online sample included 1226 individuals from Amazon's Mechanical Turk who indicated having non-specific CLBP, average age of 40, 49% female, and 67% White. Participants completed the PROMIS-29 v2.1 profile survey that contains the 9 ISS items as well the Roland-Morris Disability Questionnaire (RMDQ) and Graded Chronic Pain Scale (GCPS). Other items included high-impact chronic pain; not working due to health problems; overall health; and number of healthcare visits for back pain in the past 6 months. Three new classifications were created using quartiles (Classification 2), latent profile analysis (Classification 3), and one modeled after the GCPS (Classification 4). Classifications were subsequently compared to the RTF-proposed classification (Classification 1) on several concurrent and prognostic criteria. RESULTS: Classification 1 had three CLBP severity groups, four in Classification 2, three in Classification 3, and four in Classification 4. All novel classifications improved upon the original. Classification 2 performed best at minimizing the classification of those with negative outcomes into the lowest severity groups at baseline (e.g., 11% with RMDQ ≥ 7) and 6 months (e.g., 8.2% had fair/poor health). Classification 4 performed best at maximizing classification of those with negative outcomes into the most severe group concurrently (e.g., 100% had GCPS grade ≥ 2) and at 6 months (e.g., 100% with RMDQ ≥ 7). CONCLUSIONS: We developed three ISS-based classification schemes and tested them against several outcomes. All three improved upon the original scheme. While appearing more optimal than other classifications in the lowest severity groups, Classification 2 presents some considerations and limitations. Given that Classification 4 was an improvement at the lowest end of severity and was the best at the highest end, it is our tentative recommendation that this approach be adopted to classify individuals with non-specific CLBP.

Effects of Excluding Those Who Report Having "Syndomitis" or "Chekalism" on Data Quality: Longitudinal Health Survey of a Sample From Amazon's Mechanical Turk.

BACKGROUND: Researchers have implemented multiple approaches to increase data quality from existing web-based panels such as Amazon's Mechanical Turk (MTurk). OBJECTIVE: This study extends prior work by examining improvements in data quality and effects on mean estimates of health status by excluding respondents who endorse 1 or both of 2 fake health conditions ("Syndomitis" and "Chekalism"). METHODS: Survey data were collected in 2021 at baseline and 3 months later from MTurk study participants, aged 18 years or older, with an internet protocol address in the United States, and who had completed a minimum of 500 previous MTurk "human intelligence tasks." We included questions about demographic characteristics, health conditions (including the 2 fake conditions), and the Patient Reported Outcomes Measurement Information System (PROMIS)-29+2 (version 2.1) preference-based score survey. The 3-month follow-up survey was only administered to those who reported having back pain and did not endorse a fake condition at baseline. RESULTS: In total, 15% (996/6832) of the sample endorsed at least 1 of the 2 fake conditions at baseline. Those who endorsed a fake condition at baseline were more likely to identify as male, non-White, younger, report more health conditions, and take longer to complete the survey than those who did not endorse a fake condition. They also had substantially lower internal consistency reliability on the PROMIS-29+2 scales than those who did not endorse a fake condition: physical function (0.69 vs 0.89), pain interference (0.80 vs 0.94), fatigue (0.80 vs 0.92), depression (0.78 vs 0.92), anxiety (0.78 vs 0.90), sleep disturbance (-0.27 vs 0.84), ability to participate in social roles and activities (0.77 vs 0.92), and cognitive function (0.65 vs 0.77). The lack of reliability of the sleep disturbance scale for those endorsing a fake condition was because it includes both positively and negatively worded items. Those who reported a fake condition reported significantly worse self-reported health scores (except for sleep disturbance) than those who did not endorse a fake condition. Excluding those who endorsed a fake condition improved the overall mean PROMIS-29+2 (version 2.1) T-scores by 1-2 points and the PROMIS preference-based score by 0.04. Although they did not endorse a fake condition at baseline, 6% (n=59) of them endorsed at least 1 of them on the 3-month survey and they had lower PROMIS-29+2 score internal consistency reliability and worse mean scores on the 3-month survey than those who did not report having a fake condition. Based on these results, we estimate that 25% (1708/6832) of the MTurk respondents provided careless or dishonest responses. CONCLUSIONS: This study provides evidence that asking about fake health conditions can help to screen out respondents who may be dishonest or careless. We recommend this approach be used routinely in samples of members of MTurk.

Methodological Strategies for Prospective Harmonization of Studies: Application to 10 Distinct Outcomes Studies of Preventive Interventions Targeting Opioid Misuse.

The Helping to End Addiction Long-Term (HEAL) Prevention Cooperative (HPC) is rapidly developing 10 distinct evidence-based interventions for implementation in a variety of settings to prevent opioid misuse and opioid use disorder. One HPC objective is to compare intervention impacts on opioid misuse initiation, escalation, severity, and disorder and identify whether any HPC interventions are more effective than others for types of individuals. It provides a rare opportunity to prospectively harmonize measures across distinct outcomes studies. This paper describes the needs, opportunities, strategies, and processes that were used to harmonize HPC data. They are illustrated with a strategy to measure opioid use that spans the spectrum of opioid use experiences (termed involvement) and is composed of common "anchor items" ranging from initiation to symptoms of opioid use disorder. The limitations and opportunities anticipated from this approach to data harmonization are reviewed. Lastly, implications for future research cooperatives and the broader HEAL data ecosystem are discussed.

Differential item functioning of the Acculturation, Habits, and Interests Multicultural Scale for Adolescents (AHIMSA) by race/ethnicity.

Background: Acculturation is a complex multidimensional construct that plays in important role in various outcomes across many domains (e.g., psychological, behavioral, social, and developmental). While there are many acculturation measures for specific racial/ethnic groups, few multigroup measures exists. Even fewer have been psychometrically evaluated for differential item functioning (DIF; e.g., measurement invariance). This is a critical step in determining whether item properties are equivalent across groups and thus, whether scores obtained from different groups are in fact comparable. Methods: The Acculturation, Habits, and Interests, Multicultural Scale for Adolescents (AHIMSA) was completed by first and second generation participants identifying as White, Hispanic, or Asian (n = 1,399). The scale can be used to compute scores on four acculturation orientation subscales: Assimilated, Separated, Integrated, and Marginalized. Racial/ethnic DIF was evaluated for the Assimilation, Integration, and Separation subscales. Results: Analyses revealed racial/ethnic DIF was present for two items on the Separation scale based on McFadden's pseudo R2. No DIF was identified for the Assimilation and Integration scales. Supplemental analyses revealed no evidence of longitudinal DIF or by generation status and some DIF by sex for Assimilation and Integration. Based on evaluation of test characteristic curves and DIF plots, it was determined that DIF was trivial and could likely be ignored. Conclusions: Psychometric properties were generally equivalent across the three racial/ethnic groups for each of the subscales evaluated. This indicates that scores obtained from each subscale could be compared across racial/ethnic groups. By establishing cross-group usability of the scale, racial/ethnic differences in acculturation orientation can be examined, and, more importantly, used in the context of research on related mental, physical, and behavioral health outcomes.

Cross-Lagged Associations of Insecure Attachment Style, Alcohol Use, and Sexual Behavior During Emerging Adulthood.

Insecure romantic attachment style has been associated with greater substance use and higher risk sexual behavior, but the temporal nature of these associations is not well-understood. This study examined whether having a more insecure attachment style was associated with greater engagement in higher-risk sexual behavior over time and, if so, whether this was mediated by more frequent alcohol use. We used three annual waves of survey data from a diverse California cohort (N = 2371) who were assessed from ages 19 to 21-22 years. Separate cross-lagged models examined temporal associations of insecure romantic attachment style (anxious and avoidant), past month alcohol use frequency, and sexual behavior (number of sex partners, condomless sex with casual and steady partners). Attachment anxiety was not directly associated with sexual behavior. Rather, a consistent pattern across waves showed that greater attachment anxiety was associated with more frequent alcohol use at the next wave, which, in turn, was associated with having more sex partners and condomless sex with casual and steady partners one year later. In contrast, greater attachment avoidance was directly associated with having fewer sex partners, and its associations with condomless sex differed across partner type and assessment waves. Attachment avoidance was unrelated to alcohol use frequency. Results indicated that both anxious and avoidant attachment styles were associated with higher-risk sexual behavior, but in different ways and through different mechanisms. Future research may want to examine whether the effectiveness of sexual risk reduction programs for young people is enhanced by discussing attachment style and tailoring the curriculum accordingly.

Loneliness and multiple health domains: associations among emerging adults.

Emerging adults (18-25 years), particularly racially/ethnically diverse and sexual and gender minority populations, may experience loneliness following major life transitions. How loneliness relates to health and health disparities during this developmental period is not well understood. We examine associations of loneliness with physical (self-rated health), behavioral (alcohol/marijuana consequences; nicotine dependence), and health behavior outcomes (weekday and weekend sleep; trouble sleeping), and investigate moderating effects by sex, race/ethnicity, and sexual/gender minority (SGM) status. Adjusted models using cross-sectional data from 2,534 emerging adults, predominantly in California, examined associations between loneliness and each outcome and tested interactions of loneliness with sex, race/ethnicity, and SGM status. Higher loneliness was significantly associated with worse self-rated health, higher marijuana consequences, less weekday sleep, and greater odds of feeling bothered by trouble sleeping. None of the interactions were significant. Findings suggest that interventions to reduce loneliness may help promote healthy development among emerging adults across subgroups.