Barriers and facilitators to health during prison reentry to Miami, FL.

BACKGROUND: People face numerous barriers to reentry and community integration following incarceration, and these obstacles manifest themselves as barriers to economic stability, housing security, healthcare, community acceptance, and educational attainment, ultimately leading to poor health. This study aims to understand healthcare needs of reentrants post release within the unique political and service context of Miami Dade County, FL, and seeks to uncover the structural facilitators and barriers to sustaining health during reentry. METHODS: We report on a subset of data from a larger reentry asset mapping project. We conducted a qualitative thematic analysis based on 12 semi-structured interviews with community stakeholders, including reentrants who were released in the past year (n = 5) and with community providers who have provided support services to returning citizens for at least one year (n = 7). Narratives were coded through an iterative process using NVivo software and were analyzed using the general inductive approach. RESULTS: Three themes emerged from the analysis: (1) social and structural barriers and facilitators to health during reentry, (2) challenges with medical care following release, and (3) long-term impacts of receiving poor healthcare in prison. Reentrants describe the carceral environment as non-conducive to health and cite an urgent need for systemic change within correctional institutions to promote their well-being. Respondents identified substance use disorder (SUD) treatment, trauma informed therapy, and chronic disease management as the primary healthcare needs of reentrants, and cite social support, stable housing, education, and employment as the key social and structural needs upon release. CONCLUSION: This study identifies prevalent resource gaps in Miami Dade County during reentry. Respondents advocate for more inclusive governmental housing programs, Medicaid expansion, and more holistic reentry programs to support reentrants. Understanding the barriers and facilitators to health during reentry can inform future interventions to better support reentrants in their transition post-incarceration.

Oxidized mC modulates synthetic lethality to PARP inhibitors for the treatment of leukemia.

TET2 haploinsufficiency is a driving event in myeloid cancers and is associated with a worse prognosis in patients with acute myeloid leukemia (AML). Enhancing residual TET2 activity using vitamin C increases oxidized 5-methylcytosine (mC) formation and promotes active DNA demethylation via base excision repair (BER), which slows leukemia progression. We utilize genetic and compound library screening approaches to identify rational combination treatment strategies to improve use of vitamin C as an adjuvant therapy for AML. In addition to increasing the efficacy of several US Food and Drug Administration (FDA)-approved drugs, vitamin C treatment with poly-ADP-ribosyl polymerase inhibitors (PARPis) elicits a strong synergistic effect to block AML self-renewal in murine and human AML models. Vitamin-C-mediated TET activation combined with PARPis causes enrichment of chromatin-bound PARP1 at oxidized mCs and γH2AX accumulation during mid-S phase, leading to cell cycle stalling and differentiation. Given that most AML subtypes maintain residual TET2 expression, vitamin C could elicit broad efficacy as a PARPi therapeutic adjuvant.

Epigenetic Regulation of Genomic Stability by Vitamin C.

DNA methylation plays an important role in the maintenance of genomic stability. Ten-eleven translocation proteins (TETs) are a family of iron (Fe2+) and α-KG -dependent dioxygenases that regulate DNA methylation levels by oxidizing 5-methylcystosine (5mC) to generate 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). These oxidized methylcytosines promote passive demethylation upon DNA replication, or active DNA demethylation, by triggering base excision repair and replacement of 5fC and 5caC with an unmethylated cytosine. Several studies over the last decade have shown that loss of TET function leads to DNA hypermethylation and increased genomic instability. Vitamin C, a cofactor of TET enzymes, increases 5hmC formation and promotes DNA demethylation, suggesting that this essential vitamin, in addition to its antioxidant properties, can also directly influence genomic stability. This review will highlight the functional role of DNA methylation, TET activity and vitamin C, in the crosstalk between DNA methylation and DNA repair.