Optimizing the Delivery of mRNA to Mesenchymal Stem Cells for Tissue Engineering Applications.

Messenger RNA (mRNA) represents a promising therapeutic tool in the field of tissue engineering for the fast and transient production of growth factors to support new tissue regeneration. However, one of the main challenges to optimizing its use is achieving efficient uptake and delivery to mesenchymal stem cells (MSCs), which have been long reported as difficult-to-transfect. The aim of this study was to systematically screen a range of nonviral vectors to identify optimal transfection conditions for mRNA delivery to MSCs. Furthermore, for the first time, we wanted to directly compare the protein expression profile from three different types of mRNA, namely, unmodified mRNA (uRNA), base-modified mRNA (modRNA), and self-amplifying mRNA (saRNA) in MSCs. A range of polymer- and lipid-based vectors were used to encapsulate mRNA and directly compared in terms of physicochemical properties as well as transfection efficiency and cytotoxicity in MSCs. We found that both lipid- and polymer-based materials were able to successfully condense and encapsulate mRNA into nanosized particles (<200 nm). The overall charge and encapsulation efficiency of the nanoparticles was dependent on the vector type as well as the vector:mRNA ratio. When screened in vitro, lipid-based vectors proved to be superior in terms of mRNA delivery to MSCs cultured in a 2D monolayer and from a 3D collagen-based scaffold with minimal effects on cell viability, thus opening the potential for scaffold-based mRNA delivery. Modified mRNA consistently showed the highest levels of protein expression in MSCs, demonstrating 1.2-fold and 5.6-fold increases versus uRNA and saRNA, respectively. In summary, we have fully optimized the nonviral delivery of mRNA to MSCs, determined the importance of careful selection of the mRNA type used, and highlighted the strong potential of mRNA for tissue engineering applications.

A Mixed Methods Analysis of Southern HIV Service Organizations' Implementation of Harm Reduction to Address the HIV and Opioid Syndemic.

Southern HIV Service Organizations (SHSOs) are promising sites for the adoption and implementation of harm reduction as a means for addressing the HIV and opioid syndemic. However, little research to date has examined exactly how harm reduction is operationalized within and among SHSOs. Using program evaluation data (i.e., organizational assessment data and semi-structured qualitative group interview data with SHSO staff), this study aimed to characterize organizational implementation of harm reduction among SHSOs that sought harm reduction capacity-building assistance (i.e., training, coaching, funding) from the SUSTAIN Center. Authors utilized a convergent mixed methods design in which quantitative and qualitative approaches were employed in parallel to gain simultaneous insights into how harm reduction was operationalized in SHSOs and how the local context influenced implementation. Means and proportions of each organizational assessment domain were compared. Thematic analysis of group interview transcripts examined SHSO staff perceptions of harm reduction implementation in their respective communities. Quantitative results revealed that SHSOs most commonly operationalize harm reduction in the Outreach, Advocacy, and Principles domains but struggle to do so in terms of Services and Organizational Infrastructure. Qualitative results revealed that various factors in SHSOs' local context, such as the community's lack of knowledge and understanding of harm reduction, limited harm reduction services, and a challenging socio-political context, influence SHSOs implementation of harm reduction. Taken together, analyses reveal that (1) SHSOs expend significant effort conducting outreach activities because Southern communities are generally unaware of harm reduction, (2) SHSOs continually advocate for harm reduction in the midst of a challenging socio-political context, and (3) SHSOs offer fewer harm reduction services and integrate harm reduction into their organizational infrastructure to a lesser extent due to external, contextual factors. The combination of organizational-level data and SHSO staff insights provided by this mixed methods study have implications for policy advocacy, funding initiatives, and capacity-building efforts.

"We do it ourselves": strengths and opportunities for improving the practice of harm reduction.

BACKGROUND: Unprecedented increases in substance-related overdose fatalities have been observed in Texas and the U.S. since the onset of the COVID-19 pandemic and have made clear there is considerable need to reduce harms associated with drug use. At the federal level, initiatives have called for widespread dissemination and implementation of evidence-based harm reduction practices to reduce overdose deaths. Implementation of harm reduction strategies is challenging in Texas. There is a paucity of literature on understanding current harm reduction practices in Texas. As such, this qualitative study aims to understand harm reduction practices among people who use drugs (PWUD), harm reductionists, and emergency responders across four counties in Texas. This work would inform future efforts to scale and spread harm reduction in Texas. METHODS: Semi-structured qualitative interviews were conducted with N = 69 key stakeholders (25 harm reductionists; 24 PWUD; 20 emergency responders). Interviews were transcribed verbatim, coded for emergent themes, and analyzed using Applied Thematic Analysis with Nvivo 12. A community advisory board defined the research questions, reviewed the emergent themes, and assisted with interpretation of the data. RESULTS: Emergent themes highlighted barriers to harm reduction at micro and macro levels, from the individual experience of PWUD and harm reductionists to systemic issues in healthcare and the emergency medical response system. Specifically, (1) Texas has existing strengths in overdose prevention and response efforts on which to build, (2) PWUD are fearful of interacting with healthcare and 911 systems, (3) harm reductionists are in increasing need of support for reaching all PWUD communities, and (4) state-level policies may hinder widespread implementation and adoption of evidence-based harm reduction practices. CONCLUSIONS: Perspectives from harm reduction stakeholders highlighted existing strengths, avenues for improvement, and specific barriers that currently exist to harm reduction practices in Texas.

Pathways Through Early Psychosis Care for U.S. Youths From Ethnically and Racially Minoritized Groups: A Systematic Review.

OBJECTIVE: The authors of this systematic review examined service utilization and outcomes among youths from ethnoracially minoritized groups after the youths initiated treatment for a psychotic disorder-that is, the youths' "pathway through care." Also examined were potential moderating variables in pathways through care for these youths at the clinic, family, and cultural levels. The goal was to describe methodologies, summarize relevant findings, highlight knowledge gaps, and propose future research on pathways through care for young persons from ethnoracially minoritized groups who experience early psychosis. METHODS: The PubMed, PsycInfo, and Web of Science literature databases were systematically searched for studies published between January 1, 2010, and June 1, 2021. Included articles were from the United States and focused on young people after they initiated treatment for early psychosis. Eighteen studies met inclusion criteria. RESULTS: Sixteen of the 18 studies were published in the past 5 years, and 11 had an explicit focus on race and ethnicity as defined by the studies' authors. Studies varied in terminology, outcomes measures, methodologies, and depth of analysis. Being an individual from an ethnoracially minoritized group appeared to affect care utilization and outcomes. Insufficient research was found about potential moderating variables at the clinic, family, and cultural levels. CONCLUSIONS: Studies of pathways through care for persons from minoritized groups warrant further funding and attention.

The landscape of trauma informed care in community-based HIV service organizations in the United States south.

Among people living with HIV, trauma is associated with increased viral loads and obstructed access to HIV care. Trauma-Informed Care (TIC), a SAMHSA Evidence Based Practice, responds to the impact of trauma for service users by focusing on all aspects of service delivery systems and structures. TIC could be potentially lifesaving in regions where HIV rates continue to rise, like the U.S. South. Thus, the purpose of this study is to (1) understand the extent to which HIV service organizations in the U.S. South provide mental health and substance use services and referrals; (2) the extent to which they employ trauma informed care and (3) the barriers of employing trauma informed care. Analyzing quantitative data of 207 organizations, we found that less than a third of organizations provided a trauma informed intervention. Only 44% of organizations had participated in TIC training but 84% expressed interest in TIC training. Organizations who completed TIC training were 10 times more likely than those who did not to report that they implemented at least one trauma informed care strategies. Barriers to TIC implementation included lack of training, capacity, and resources. Building the capacity of organizations to implement TIC will be a key to ending the HIV epidemic.

The POWER of LEARNing and LEADing Together: Shared Learning Communities.

Southern community-based organizations often lack adequate resources to implement high-quality, culturally appropriate HIV programs and services. Shared learning communities (SLCs) combine in-depth training, tailored coaching, and peer-to-peer learning to strengthen HIV programs and services. This paper describes five SLCs, participant characteristics, and their capacity-building components.

A Gender Affirmative Model of Training and Service Provision Among HIV Service Organizations in the U.S. South.

Research on gender affirmative models (GAM) of training and service provision is emerging. This study aims 1) to summarize 2018-2019 survey data on GAM training and service provision at Southern HIV Service Organizations (HSOs) in the U.S. South and 2) identify barriers in the region. METHODS: Data were collected from Southern HSOs (n=207). Relations between GAM training and service provision were examined through frequency distributions and logistic regressions. RESULTS: Few (46.6%) received training. Most (73%) used clients' asserted names and pronouns. Only 62% engaged with transgender, nonbinary, and gender nonconforming (TGNC) communities and 55% provided a gender autonomous (i.e., based on self-determination) facility. Gender affirmative model-trained HSOs had at least twice the odds of implementing GAM elements compared with non-trained HSOs. Barriers included funding (61%), expertise/knowledge (59%), capacity/staff-ing (52%), and political climate (23%). DISCUSSION: This study identifies gaps and highlights the urgent need for funding, training, and meaningful TGNC community partnerships.

Southern Care: A Rapid Response to Supporting Southern CBOs at the onset of COVID-19.

Southern community-based and HIV/AIDS service organizations (CBOs) were particularly vulnerable to the onset of COVID-19 due to already fragile infrastructures and underfunded budgets. At the height of the pandemic, the Gilead COMPASS Coordinating Centers launched the Southern CARE Grant, awarding 41 grants to provide supplemental operational support funds.

Operationalizing Equity-centered Implementation Through Person-centered Care Capacity-building with HIV Service Organizations: The SUSTAIN Approach.

Capacity-building in trauma-informed care and harm reduction approaches with Southern HIV service organizations must be implemented in ways that foster trust and spur organizational change. Using an equity-centered implementation science framework, this study examines implementation strategies of the SUSTAIN COMPASS Coordinating Center's person-centered care (PCC) capacity-building interventions. METHODS: Fifty-eight (58) in-depth qualitative interviews with staff (N=116) who received PCC capacity-building were analyzed using modified grounded theory. RESULTS: Analysis identified four factors of equity-centered implementation that facilitated PCC capacity-building implementation. 1) Innovation factors: SUSTAIN models PCC approaches when implementing PCC capacity-building. 2) Inner factors: SUSTAIN employs PCC approaches. 3) Outer factors: SUSTAIN highlights socio-political factors that may influence PCC implementation. 4) Bridging factors: SUSTAIN facilitates partnerships to promote PCC learning and sustainability. CONCLUSION: SUSTAIN PCC capacity-building advances health equity through operationalizing personcentered care in capacity-building implementation.

Mental Health Service Experiences Among Transition-Age Youth: Interpersonal Continuums that Influence Engagement in Care.

Purpose. Transition-age youth (TAY) who have experienced or are experiencing complex trauma, system involvement and homelessness are at increased risk for serious mental health needs and related challenges. However, these vulnerable and historically marginalized TAY typically have low rates of mental health service engagement. This study examines how and why TAY experiencing system involvement, homelessness, and serious mental health and substance use symptoms engage in mental health services, and what facilitates and/or hinders their engagement in services. Methods. Twenty-one TAY completed a virtual interview about their previous and current mental health service experiences, and why they did or did not engage with mental health services. A modified grounded theory qualitative analysis approach was used to understand how participants' personal sense of meaning interacted with programmatic factors to construct participant experiences with mental health services. Results. Most participants (81%, n = 17) received mental health services, namely psychiatry (76%, n = 16) and counseling/therapy (48%, n = 10), and peer support (10%, n = 2). Participants described their mental health service experiences along three interpersonal and relational continuums between themselves and their providers: feeling (mis)understood, being treated with (dis)respect, and experiencing (dis)trust. Discussion. Study findings reveal that for these particularly vulnerable and marginalized TAY, relational and interpersonal factors significantly influenced their engagement in mental health services. Study findings call for providers to re-imagine their working alliance with highly vulnerable TAY through culturally-attuned practices that promote understanding, respect, and trust. Findings also call for TAY-serving programs and policies to re-imagine peer support as a mental health service option for this highly vulnerable population.

Harm reduction implementation among HIV service organizations (HSOs) in the U.S. south: a policy context analysis and results from a survey of HSOs.

BACKGROUND: HIV service organizations are integral to serving communities disproportionately impacted by the HIV and opioid epidemics in the U.S. South. Addressing these intersecting epidemics requires implementation of evidence-based approaches, such as harm reduction. However, little is known about the extent to which Southern HIV service organizations implement harm reduction. This manuscript examines: 1) the implementation context of harm reduction in the South, 2) Southern HIV service organization implementation of harm reduction, and 3) the impact of different contexts within the South on HIV service organization implementation of harm reduction. METHODS: To examine implementation context, authors analyzed nation-wide harm reduction policy and drug-related mortality data. To examine HIV service organization implementation of harm reduction, authors performed frequency distributions on survey data (n = 207 organizations). Authors then constructed logistic regressions, using state mortality data and policy context as predictors, to determine what contextual factors predicted HIV service organization implementation of harm reduction. RESULTS: Drug-related mortality data revealed an increased need for harm reduction, and harm reduction policy data revealed an increased political openness to harm reduction. Frequency distributions revealed that approximately half of the HIV service organizations surveyed reported that their organizations reflect a harm reduction orientation, and only 26% reported providing harm reduction services. Despite low utilization rates, HIV service organizations indicated a strong interest in harm reduction. Logistic regressions revealed that while increased mortality rates do not predict HIV service organization implementation of harm reduction, a harm reduction-friendly policy context does. DISCUSSION: This study highlights how regions within a high-income country can face unique barriers to healthcare and therefore require a unique understanding of implementation context. Study findings indicate a rapidly changing implementation context where increased need meets increased political opportunity to implement harm reduction, however there is a lag in HIV service organization adoption of harm reduction. Financial resources, capacity building, and continued policy advocacy are required for increased HIV service organization adoption of harm reduction.

Virtual Technology's Critical Role in Sustaining Coordinated Specialty Care in Texas During the COVID-19 Pandemic.

OBJECTIVE: This report examined challenges and adaptations to sustaining multidisciplinary team-based coordinated specialty care (CSC) for early-onset psychosis during the COVID-19 pandemic in Texas. METHODS: In June 2020, team leaders from 23 Texas CSC sites participated in semistructured phone interviews about CSC implementation barriers and adaptations. Transcripts were analyzed with thematic analysis. RESULTS: CSC implementation barriers included difficulty delivering critical CSC components (i.e., community education and vocational exploration) and client recruitment limitations. Virtual technology integration (i.e., texting and videoconferencing) largely sustained CSC outreach, service delivery, and client engagement. However, sites faced virtual competency and accessibility issues, exhaustion from virtual technology use, lack of structural support, and unanticipated disengagement. CONCLUSIONS: The surveyed sites rapidly integrated virtual technology into CSC delivery. This integration promoted CSC engagement during the pandemic, especially in rural areas, and increased insight into what resources and policies are needed to sustain virtual technology use among community mental health providers.

HIV and Mental Health Services in the US South: A Meso Analysis.

The US South is disproportionately impacted by HIV. Social, cultural, economic, and political characteristics of the South shape access to mental health services leaving adverse impacts on health and wellness outcomes among People Living with HIV. The aim of this paper was to: (a) identify meso factors (at individual, organizational and community-level manifestations) which impact mental health services among People living with HIV in the South of those factors and (b) pose community-articulated recommendation and strategies. Through qualitative interviews with People Living with HIV and service providers, this study found that the meso factors of restricted funding and compounding stigma shaped mental health services in the South. Given the disproportionate rate of HIV, lack of mental health care, and landscape of socio-political factors unique to the region, attention to intervenable meso factors and community-based strategies are needed to enhance mental health services and respond to the HIV epidemic in the US South.