Identifying the Heterogeneity in the Association between Workforce Diversity and Retention in Opioid Treatment among Black clients.

Background: This study investigates the impact of workforce diversity, specifically staff identified as Black/African American, on retention in opioid use disorder (OUD) treatment, aiming to enhance patient outcomes. Employing a novel machine learning technique known as 'causal forest,' we explore heterogeneous treatment effects on retention. Methods: We relied on four waves of the National Drug Abuse Treatment System Survey (NDATSS), a nationally representative longitudinal dataset of treatment programs. We analyzed OUD program data from the years 2000, 2005, 2014 and 2017 (n = 627). Employing the 'causal forest' method, we analyzed the heterogeneity in the relationship between workforce diversity and retention in OUD treatment. Interviews with program directors and clinical supervisors provided the data for this study. Results: The results reveal diversity-related variations in the association with retention across 61 out of 627 OUD treatment programs (less than 10%). These programs, associated with positive impacts of workforce diversity, were more likely private-for-profit, newer, had lower percentages of Black and Latino clients, lower staff-to-client ratios, higher proportions of staff with graduate degrees, and lower percentages of unemployed clients. Conclusions: While workforce diversity is crucial, our findings underscore that it alone is insufficient for improving retention in addiction health services research. Programs with characteristics typically linked to positive outcomes are better positioned to maximize the benefits of a diverse workforce in client retention. This research has implications for policy and program design, guiding decisions on resource allocation and workforce diversity to enhance retention rates among Black clients with OUDs.

In situ production and secretion of proteins endow therapeutic benefit against psoriasiform dermatitis and melanoma.

Genetic medicines have the potential to treat various diseases; however, certain ailments including inflammatory diseases and cancer would benefit from control over extracellular localization of therapeutic proteins. A critical gap therefore remains the need to develop and incorporate methodologies that allow for posttranslational control over expression dynamics, localization, and stability of nucleic acid-generated protein therapeutics. To address this, we explored how the body's endogenous machinery controls protein localization through signal peptides (SPs), including how these motifs could be incorporated modularly into therapeutics. SPs serve as a virtual zip code for mRNA transcripts that direct the cell where to send completed proteins within the cell and the body. Utilizing this signaling biology, we incorporated secretory SP sequences upstream of mRNA transcripts coding for reporter, natural, and therapeutic proteins to induce secretion of the proteins into systemic circulation. SP sequences generated secretion of various engineered proteins into the bloodstream following intravenous, intramuscular, and subcutaneous SP mRNA delivery by lipid, polymer, and ionizable phospholipid delivery carriers. SP-engineered etanercept/TNF-α inhibitor proteins demonstrated therapeutic efficacy in an imiquimod-induced psoriasis model by reducing hyperkeratosis and inflammation. An SP-engineered anti-PD-L1 construct mediated mRNA encoded proteins with longer serum half-lives that reduced tumor burden and extended survival in MC38 and B16F10 cancer models. The modular nature of SP platform should enable intracellular and extracellular localization control of various functional proteins for diverse therapeutic applications.

Spleen SORT LNP Generated in situ CAR T Cells Extend Survival in a Mouse Model of Lymphoreplete B Cell Lymphoma.

Chimeric Antigen Receptor (CAR) T cell immunotherapy is revolutionizing treatment for patients suffering from B-cell lymphoma (BL). However, the current method of CAR T cell production is complicated and expensive, requiring collection of patient blood to enrich the T cell population, ex vivo engineering/activation, and quality assessment before the patient can receive the treatment. Herein we leverage Spleen Selective ORgan Targeted (SORT) Lipid Nanoparticles (LNPs) to produce CAR T cells in situ and bypass the extensive and laborious process currently used. Optimized Spleen SORT LNPs containing 10 % 18 : 1 PA transfected CD3+, CD8+, and CD4+ T cells in wild-type mice. Spleen SORT LNPs delivered Cre recombinase mRNA and CAR encoding mRNA to T cells in reporter mice and in a lymphoreplete B cell lymphoma model (respectively) after intravenous injection without the need for active targeting ligands. Moreover, in situ CAR T cells increased the overall survival of mice with a less aggressive form of B cell lymphoma. In addition, in situ transfected CAR T cells reduced tumor metastasis to the liver by increasing tumor infiltrating lymphocytes. Overall, these results offer a promising alternative method for CAR T cell production with pre-clinical potential to treat hematological malignancies.

What can we learn from COVID-19 to improve opioid treatment? Expert providers respond.

BACKGROUND: The COVID-19 pandemic has had devasting effects on drug abuse treatment systems already stressed by the opioid crisis. Providers within opioid use disorder (OUD) outpatient treatment programs have had to adjust to rapid change and respond to new service delivery provisions such as telehealth and take-home medication. Using the COVID-19 pandemic and subsequent organizational challenges as a backdrop, this study explores providers' perspectives about strategies and policies that, if made permanent, can potentially improve access to and quality of OUD treatment. METHODS: This qualitative study was conducted in Los Angeles County, which has one of the largest substance use disorder (SUD) treatment systems in the United States serving a diverse population, including communities impacted by the opioid crisis. We collected qualitative interview data from 30 high-performing programs (one manager/supervisor per program) where we based high performance on empirical measures of access, retention, and program completion outcomes. The study team completed data collection and analysis using constructivist grounded theory (CGT) to describe the social processes in which the participating managers engaged when faced with the pandemic and subsequent organizational changes. We developed 14 major codes and six minor codes with definitions. The interrater reliability tests showed pooled Cohen's kappa statistic of 93 %. RESULTS: Our results document the impacts of COVID-19 on SUD treatment systems, their programmatic responses, and the strategic innovations they developed to improve service delivery and quality and which managers plan to sustain within their organizations. CONCLUSION: Providers identified three primary areas for strategic innovation designed to improve access and quality: (1) designing better medication utilization, (2) increasing telemedicine capacity, and (3) improving reimbursement policies. These strategies for system transformation enable us to use lessons from the COVID-19 pandemic to direct policy and programmatic reform, such as expanding eligibility for take-home medication and enhancing access to telehealth services.

Theranostic applications of multifunctional carbon nanomaterials.

Nanobiotechnology is one of the leading research areas in biomedical science, developing rapidly worldwide. Among various types of nanoparticles, carbon nanomaterials (CNMs) have attracted a great deal of attention from the scientific community, especially with respect to their prospective application in the field of disease diagnosis and therapy. The unique features of these nanomaterials, including favorable size, high surface area, and electrical, structural, optical, and chemical properties, have provided an excellent opportunity for their utilization in theranostic systems. Carbon nanotubes, carbon quantum dots, graphene, and fullerene are the most employed CNMs in biomedical fields. They have been considered safe and efficient for non-invasive diagnostic techniques such as fluorescence imaging, magnetic resonance imaging, and biosensors. Various functionalized CNMs exhibit a great capacity to improve cell targeting of anti-cancer drugs. Due to their thermal properties, they have been extensively used in cancer photothermal and photodynamic therapy assisted by laser irradiation and CNMs. CNMs also can cross the blood-brain barrier and have the potential to treat various brain disorders, for instance, neurodegenerative diseases, by removing amyloid fibrils. This review has summarized and emphasized on biomedical application of CNMs and their recent advances in diagnosis and therapy.

Exploring Gender and Ethnoracial Differences and Trends in Methamphetamine Treatment.

Introduction: Given the significant rise in methamphetamine use and related mortality in the United States, it is critical to explore differences in treatment trends with particular attention to women and ethnoracial groups in hard-hit areas like Los Angeles County. Methods: We analyzed a large sample across 4 waves: 2011 (105 programs, 10 895 clients), 2013 (104 programs, 17 865 clients), 2015 (96 programs, 16 584 clients), and 2017 (82 programs, 15 388 clients). We completed a comparative analysis to identify differences across subgroups and a trend analysis of treatment episodes by gender and ethnoracial group to differentiate users of methamphetamine and users of other drugs. Results: Treatment clients using methamphetamine increased over time for each gender and race. There were also significant differences across age groups. Women comprised a greater proportion of treatment episodes involving methamphetamine use (43.3%) compared to all other drugs combined (33.6%). Latinas represented 45.5% of methadone-related admissions. Compared with other drug users, methamphetamine users had a lower successful treatment completion rate and were served by programs with less financial and culturally responsive capacity. Conclusions: Findings highlight a sharp increase in treatment admissions for methamphetamine users of all gender and ethnocultural groups. Women, especially Latinas, saw the most significant increases, with a widening gender gap over time. All subgroups of methamphetamine users had a lower treatment completion rate compared with users of other drugs, and critical differences existed in the programs where they received services.

Testing a Deliberative Democracy Engagement Intervention to Increase Guideline-Concordance Among Oral Health Providers: Results from the DISGO Cluster-Randomized, Stepped-Wedge Trial.

Background: Dental caries affects billions worldwide and in the U.S. is among the most prevalent noncommunicable diseases in both children and adults. Early in the caries process, it can be arrested by dental sealants, which are non-invasive and thus tooth sparing, however, few dentists have adopted this approach. Deliberative engagement processes enable participants to engage with diverse perspectives on a policy issue and develop and share with policy makers informed opinions about the policy issue. We examined the effects of a deliberative engagement process on the ability of oral health providers to endorse implementation interventions and to apply dental sealants. Methods: Using a stepped wedge design, 16 dental clinics were cluster randomized, and 680 providers and staff were exposed to a deliberative engagement process that included an introductory session, workbook, facilitated small group deliberative forum, and post-forum survey. Forum participants were assigned to forums to ensure diverse role representation. Mechanisms of action examined included sharing voice and diversity of opinion. Three months after each clinic's forum, the clinic manager was interviewed about implementation interventions deployed. There were 98 clinic-months in the non-intervention period and 101 clinic-months in the intervention period. Results: Compared with providers and staff in small clinics, providers and staff in medium and large clinics more strongly agreed that their clinic should adopt two of the three proposed implementation interventions targeting the first barrier and one of the two proposed implementation interventions targeting the second barrier. Compared with the non-intervention period, in the intervention period providers did not place more sealants on occlusal non-cavitated carious lesions. Survey respondents reported sharing both promotive and prohibitive voice. From the beginning to the end of the forums, most forum participants did not change their opinions about the possible implementation interventions. At the end of the forums, there was no significant within-group variability in implementation interventions endorsed. Conclusions: Deliberative engagement intervention may help clinic leadership identify implementation interventions when there is a challenging problem, a network of semi-autonomous clinics, and autonomous providers within those clinics. It remains to be determined whether there is a range of perspectives within clinics. Trial Registration: This project is registered at ClinicalTrials.gov with ID NCT04682730. The trial was first registered on 12/18/2020. https://clinicaltrials.gov/ct2/show/NCT04682730.

Predicting and responding to change: Perceived environmental uncertainty among substance use disorder treatment programs.

INTRODUCTION: Substance use disorder (SUD) treatment programs offering addiction health services (AHS) must be prepared to adapt to change in their operating environment. These environmental uncertainties may have implications for service delivery, and ultimately patient outcomes. To adapt to a multitude of environmental uncertainties, treatment programs must be prepared to predict and respond to change. Yet, research on treatment programs preparedness for change is sparse. We examined reported difficulties in predicting and responding to changes in the AHS system, and factors associated with these outcomes. METHODS: Cross-sectional surveys of SUD treatment programs in the United States in 2014 and 2017. We used linear and ordered logistic regression to examine associations between key independent variables (e.g., program, staff, and client characteristics) and four outcomes, (1) reported difficulties in predicting change, (2) predicting effect of change on organization, (3) responding to change, and (4) predicting changes to make to respond to environmental uncertainties. Data were collected through telephone surveys. RESULTS: The proportion of SUD treatment programs reporting difficulty predicting and responding to changes in the AHS system decreased from 2014 to 2017. However, a considerable proportion still reported difficulty in 2017. We identified that different organizational characteristics are associated with their reported ability to predict or respond to environmental uncertainty. Findings show that predicting change is significantly associated with program characteristics only, while predicting effect of change on organizations is associated with program and staff characteristics. Deciding how to respond to change is associated with program, staff, and client characteristics, while predicting changes to make to respond is associated with staff characteristics only. CONCLUSIONS: Although treatment programs reported decreased difficulty predicting and responding to changes, our findings identify program characteristics and attributes that could better position programs with the foresight to more effectively predict and respond to uncertainties. Given resource constraints at multiple levels in treatment programs, this knowledge might help identify and optimize aspects of programs to intervene upon to enhance their adaptability to change. These efforts may positively influences processes or care delivery, and ultimately translate into improvements in patient outcomes.

Understanding the role of financial capacity in the delivery of opioid use disorder treatment.

Opioid treatment programs must have adequate financial capacity to sustain operations and deliver a high standard of care for individuals suffering from opioid use disorder. However, there is limited consistency in the health services literature about the concept and relationship of organizational financial capacity and key outcome measures (wait time and retention). In this study, we explored five common measures of financial capacity that can be applied to opioid treatment programs: (a) reserve ratio, (b) equity ratio, (c) markup, (d) revenue growth, and (e) earned revenue. We used these measures to compare financial capacity among 135 opioid treatment programs across four data collection points: 2011 (66 programs), 2013 (77 programs), 2015 (75 programs), and 2017 (69 programs). We examined the relationship between financial capacity and wait time and retention. Findings from the literature review show inconsistencies in the definition and application of concepts associated with financial capacity across business and social service delivery fields. The analysis shows significant differences in components of financial capacity across years. We observed an increase in average earned revenue and markup in 2017 compared to prior years. The interaction between minorities and markup was significantly associated with higher likelihood of waiting (IRR = 1.077, p < .05). Earned revenue (IRR = 0.225, p < .05) was related to shorter wait time in treatment. The interaction between minorities and equity ratio is also significantly associated with retention (IRR = 0.796, p < .05). Our study offers a baseline view of the role of financial capacity in opioid treatment and suggests a framework to determine its effect on client-centered outcomes.

Identifying gender differences in risk profiles and in opioid treatment outcomes in Los Angeles County.

Policies and programs that aim to minimize wait time to enter opioid use disorder (OUD) treatment and maximize retention respond to potential differences in female and male clients' risk profiles. We conducted multigroup latent class analysis using significant individual risk factors. Our sample included 13,453 opioid treatment episodes from 135 unique substance use disorder treatment programs in Los Angeles County, California, in four waves: 2011 (66 programs, 1035 clients), 2013 (77 programs, 3671 clients), 2015 (75 programs, 4625 clients), and 2017 (69 programs, 4106 clients). Groups at risk of waiting longer included clients who were female, had mental health issues, received medication for OUD, had criminal justice involvement, received mandated referrals, had children in child protective services, and had caretaker responsibilities. All clients with children in protective services were likely to wait longer than those not in protective services, but women waited longer. Findings highlight that: (a) women and men in OUD treatment have significant health and social problems; (b) female and male clients have distinct risk profiles; and (c) targeted services responding to risk profiles may improve treatment access and engagement. Findings have implications for health policy and program evaluation and planning in the delivery of treatment services considering gendered risk factors.

Assessing the Impact of COVID-19 on the Health of Native Hawaiian/Pacific Islander People in the United States, 2021.

OBJECTIVES: Minimal research has assessed COVID-19's unique impact on the Native Hawaiian/Pacific Islander (NH/PI) population-an Indigenous-colonized racial group with social and health disparities that increase their risk for COVID-19 morbidity and mortality. To address this gap, we explored the scope of COVID-19 outcomes, vaccination status, and health in diverse NH/PI communities. METHODS: NH/PI staff at partner organizations collected survey data from April through November 2021 from 319 community-dwelling NH/PI adults in 5 states with large NH/PI populations: Arkansas, California, Oregon, Utah, and Washington. Data were analyzed with descriptive statistics, Pearson χ2 tests, independent and paired t tests, and linear and logistic regression analyses. RESULTS: During the COVID-19 pandemic, 30% of survey participants had contracted COVID-19, 16% had a close family member who died of the disease, and 64% reported COVID-19 vaccine uptake. Thirty percent reported fair/poor health, 21% currently smoked cigarettes, and 58% reported obesity. Survey participants reported heightened COVID-19-related psychosocial distress (mean score = 4.9 on 10-point scale), which was more likely when health outcomes (general health, sleep, obesity) were poor or a family member had died of COVID-19. Logistic regression indicated that age, experiencing COVID-19 distress, and past-year use of influenza vaccines were associated with higher odds of COVID-19 vaccine uptake (1.06, 1.18, and 7.58 times, respectively). CONCLUSIONS: Our empirical findings highlight the acute and understudied negative impact of COVID-19 on NH/PI communities in the United States and suggest new avenues for improving NH/PI community health, vaccination, and recovery from COVID-19.

Workforce Diversity and disparities in wait time and retention among opioid treatment programs.

BACKGROUND: Workforce diversity is a key strategy to improve treatment engagement among members of racial and ethnic minority groups. In this study, we seek to determine whether workforce diversity plays a role in reducing racial and ethnic differences in wait time to treatment entry and retention in different types of opioid use disorder treatment programs. METHODS: We conducted comparative and predictive analysis in a subsample of outpatient opioid treatment programs (OTPs), who completed access and retention survey questions in four waves of the National Drug Abuse Treatment System Survey (162 OTPs in 2000, 173 OTPs in 2005, 282 OTPs in 2014, and 300 OTPs in 2017). We sought to assess the associations between workforce diversity on wait time and retention, accounting for the role of Medicaid expansion and the moderating role of program ownership type (i.e., public, non-profit, for-profit) among OTPs located across the United States. RESULTS: We found significant differences in wait time to treatment entry and retention in treatment across waves. Average number of waiting days decreased in 2014 and 2017; post Medicaid expansion per the Affordable Care Act, while retention rates varied across years. Key findings show that programs with high diversity, measured by higher percent of African American staff and a higher percent of African American clients, were associated with longer wait times to enter treatment, compared to low diversity programs. Programs with higher percent of Latino staff and a higher percent of Latino clients were associated with lower retention in treatment compared with low diversity programs. However, program ownership type (public, non-profit and for-profit) played a moderating role. Public programs with higher percent of African American staff were associated with lower wait time, while non-profit programs with higher percent of Latino staff were related to higher retention. CONCLUSIONS: Findings show decreases in wait time over the years with significant variation in retention during the same period. Concordance in high workforce and client diversity was associated with higher wait time and lower retention. But these relations inverted (low wait time and high retention) in public and non-profit programs with high staff diversity. Findings have implications for building resources and service capacity among OTPs that serve a higher proportion of minority clients.

Native Hawaiian/Pacific Islander alcohol, tobacco and other drug use, mental health and treatment need in the United States during COVID-19.

INTRODUCTION: Before COVID-19, Native Hawaiians/Pacific Islanders (NH/PI) endured a heavy burden of alcohol, tobacco and other drug (ATOD) use in prior US data. Responding to reports that many NH/PI communities experienced severe COVID-19 disparities that could exacerbate their ATOD burden, we partnered with NH/PI communities to assess the substance use patterns and treatment needs of diverse NH/PIs during COVID-19. METHODS: Collaborating with NH/PI community organisations across five states with large NH/PI populations, we conducted a large-scale investigation of NH/PI ATOD use, mental health and treatment need during COVID-19. Between April and November 2021, NH/PI-heritage research staff from our community partners collected data involving 306 NH/PI adults using several community-based recruitment methods (e-mail, telephone, in-person) and two survey approaches: online and paper-and-pencil. Multivariate regressions were conducted to examine potential predictors of NH/PI alcohol use disorder and need for behavioural health treatment. RESULTS: During COVID-19, 47% and 22% of NH/PI adults reported current alcohol and cigarette use, while 35% reported lifetime illicit substance use (e.g., cannabis, opioid). Depression and anxiety were high, and alcohol use disorder, major depression and generalised anxiety disorder prevalence were 27%, 27% and 19%, respectively. One-third of participants reported past-year treatment need with lifetime illicit substance use, COVID-19 distress and major depression respectively associating with 3.0, 1.2, and 5.3 times greater adjusted odds for needing treatment. CONCLUSIONS: NH/PI adults reported heavy ATOD use, depression, anxiety and treatment need during COVID-19. Targeted research and treatment services may be warranted to mitigate COVID-19's negative behavioural health impact on NH/PI communities.

Disparities in opioid treatment access and retention among women based on pregnancy status from 2006 to 2017.

Background: The purpose of this study is to assess differences in wait time and retention in opioid use disorder (OUD) treatment among a sample of pregnant and non-pregnant women from low-income urban communities in Los Angeles, California. Methods: Data were collected in 9 waves consisting of consecutive years from 2006 to 2011, and then including 2013, 2015, and 2017. The sample consisted of 12,558 women, with 285 being pregnant and 12,273 being non-pregnant. We compared pregnant women with non-pregnant women at admission on key characteristics and relied on two multilevel negative binomial regressions analyses to examine factors related to access (days on the waiting list) and retention (days in treatment). Results: We detected disparities existed in access and retention. Pregnant women spent less time waiting to initate treatment than non-pregnant women and, once in treatment, had longer treatment episodes. Among pregnant women, clients identifying as Latina or Other waited longer to enter treatment compared to clients identifying as non-Latina White or Black. Women entering residential waited longer than those entering methadone or counseling services. Pregnant women were more likely to be in treatment longer if they had mental health issues, greater parenting responsibilities (number of children less than 18), and greater SUD severity (number of prior treatment episodes). Conclusions: Findings suggest pregnant women's access and retention can be improved through Medicaid coverage and through the implementation of a standard of care that includes MOUD (methadone) along with ancillary health and social services.

Disparities in expected driving time to opioid treatment and treatment completion: findings from an exploratory study.

BACKGROUND: Commuting time to treatment has been shown to affect healthcare outcomes such as engagement and initiation. The purpose of this study is to extend this line of research to investigate the effects of driving time to opioid programs on treatment outcomes. METHODS: We analyzed discharge survey data from 22,587 outpatient opioid use disorder treatment episodes (mainly methadone) in Los Angeles County and estimated the associated driving time to each episode using Google Maps. We used multivariable logistic regressions to examine the association between estimated driving time and odds of treatment completion after adjusting for possible confounders. RESULTS: Findings show an average driving time of 11.32 min and an average distance of 11.18 km. We observed differences in estimated driving time across age, gender, and socioeconomic status. Young, male, less formally educated, and Medi-Cal-ineligible clients drove longer to treatment. A 10-min drive was associated with a 33% reduction in the completion of methadone treatment plans (p < .01). CONCLUSION: This systemwide analysis provides novel time estimates of driving-based experiences and a strong relationship with completion rates in methadone treatment. Specifically, the result showing reduced treatment completion rates for drive times longer than 10 min may inform policies regarding the ideal geographic placement of methadone-based treatment programs and service expansion initiatives.

Using machine learning to advance disparities research: Subgroup analyses of access to opioid treatment.

OBJECTIVE: To operationalize an intersectionality framework using a novel statistical approach and with these efforts, improve the estimation of disparities in access (i.e., wait time to treatment entry) to opioid use disorder (OUD) treatment beyond race. DATA SOURCE: Sample of 941,286 treatment episodes collected in 2015-2017 in the United States from the Treatment Episodes Data Survey (TEDS-A) and a subset from California (n = 188,637) and Maryland (n = 184,276), states with the largest sample of episodes. STUDY DESIGN: This retrospective subgroup analysis used a two-step approach called virtual twins. In Step 1, we trained a classification model that gives the probability of waiting (1 day or more). In Step 2, we identified subgroups with a higher probability of differences due to race. We tested three classification models for Step 1 and identified the model with the best estimation. DATA COLLECTION: Client data were collected by states during personal interviews at admission and discharge. PRINCIPAL FINDINGS: Random forest was the most accurate model for the first step of subgroup analysis. We found large variation across states in racial disparities. Stratified analysis of two states with the largest samples showed critical factors that augmented disparities beyond race. In California, factors such as service setting, referral source, and homelessness defined the subgroup most vulnerable to racial disparities. In Maryland, service setting, prior episodes, receipt of medication-assisted opioid treatment, and primary drug use frequency augmented disparities beyond race. The identified subgroups had significantly larger racial disparities. CONCLUSIONS: The methodology used in this study enabled a nuanced understanding of the complexities in disparities research. We found state and service factors that intersected with race and augmented disparities in wait time. Findings can help decision makers target modifiable factors that make subgroups vulnerable to waiting longer to enter treatment.

Alcohol Use Disorder Risk and Protective Factors and Associated Harms Among Pacific Islander Young Adults.

Pacific Islander (PI) young adults (age 18 to 30 years) experience elevated rates of hazardous drinking, AUDs, and alcohol-related harms. Yet, we know little about the risk and protective factors that drive, or can prevent, PI young adult hazardous drinking behaviors and AUDs due to a lack of targeted alcohol disparities research. This large qualitative study presents data from 8 focus groups with 69 PIs (51 young adults, 18 informal providers) to explore the major risk factors, protective factors, and negative consequences associated with PI young adult hazardous drinking and AUDs. Findings revealed (1) major risk factors including the presence of significant life stressors that trigger alcohol self-medication, peer/social pressure to drink, permissive drinking norms, and frequent access to alcohol and (2) negative consequences involving physical fights, health and relationship problems, harm to personal reputation, and community harms including driving-under-the-influence and sexual violence. Protective factors against hazardous drinking and AUDs included the cultural norm of protecting the family's reputation by avoiding AUDs, church/religious faith, family responsibilities, and culturally relevant prosocial activities (e.g., sports, dance, choir). Obtaining this in-depth data revealed that an effective culturally grounded AUD prevention intervention for PI young adults-which does not currently exist-should (1) target these identified major risk factors for AUDs, while (2) integrating culturally responsive strategies that incorporate their reported protective factors.

Optimization of phospholipid chemistry for improved lipid nanoparticle (LNP) delivery of messenger RNA (mRNA).

Lipid nanoparticles (LNPs) have been established as an essential platform for nucleic acid delivery. Efforts have led to the development of vaccines that protect against SARS-CoV-2 infection using LNPs to deliver messenger RNA (mRNA) coding for the viral spike protein. Out of the four essential components that comprise LNPs, phospholipids represent an underappreciated opportunity for fundamental and translational study. We investigated this avenue by systematically modulating the identity of the phospholipid in LNPs with the goal of identifying specific moieties that directly enhance or hinder delivery efficacy. Results indicate that phospholipid chemistry can enhance mRNA delivery by increasing membrane fusion and enhancing endosomal escape. Phospholipids containing phosphoethanolamine (PE) head groups likely increase endosomal escape due to their fusogenic properties. Additionally, it was found that zwitterionic phospholipids mainly aided liver delivery, whereas negatively charged phospholipids changed the tropism of the LNPs from liver to spleen. These results demonstrate that the choice of phospholipid plays a role intracellularly by enhancing endosomal escape, while also driving organ tropism in vivo. These findings were then applied to Selective Organ Targeting (SORT) LNPs to manipulate and control spleen-specific delivery. Overall, selection of the phospholipid in LNPs provides an important handle to design and optimize LNPs for improved mRNA delivery and more effective therapeutics.