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.

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.

"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.

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.

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.

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.

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.

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.

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.