The role of substance use treatment in reducing stigma after release from incarceration: A qualitative analysis

Abstract Background People with substance use disorders (SUD) who have been involved in the legal system often experience stigma upon reentry into the community after incarceration. Although substance use treatment can sometimes be a source of stigma, it may also reduce stigma by facilitating connections with providers, reducing distress, or helping people feel more integrated in their community. However, research has rarely examined the potential for treatment to reduce stigma. Methods This study examined stigma experiences and the degree to which substance use treatment reduced stigma among 24 people with SUDs who were receiving care in an outpatient treatment facility after release from incarceration. Qualitative interviews were conducted and analyzed using a content analysis approach. Results Participants reported negative self-judgements as well as perceiving negative judgments from the community upon reentry. With regard to stigma reduction, themes emerged around substance use treatment repairing strained family relationships and reducing participants’ self-stigma. Aspects of treatment that reportedly reduced stigma included the treatment facility having a nonjudgmental atmosphere, patients trusting the staff, and working with peer navigators who had lived experience of SUD and incarceration. Conclusions Results from this study suggest that substance use treatment has the potential to decrease the negative impacts of stigma upon release from incarceration, which continues to be a major barrier. Though more research on stigma reduction is needed, we suggest some preliminary considerations for treatment programs and providers

Complement component C5a mediates hemorrhage-induced intestinal damage

Background: Complement has been implicated in the pathogenesis of intestinal damage and inflammation in multiple animal models. Although the exact mechanism is unknown, inhibition of complement prevents hemodynamic alterations in hemorrhage. Materials/Methods: C57Bl/6, complement 5 deficient (C5-/-) and sufficient (C5+/+) mice were subjected to 25% blood loss. In some cases, C57Bl/6 mice were treated with C5a receptor antagonist (C5aRa) post-hemorrhage. Intestinal injury, leukotriene B4, and myeloperoxidase production were assessed for each treatment group of mice. Results: Mice subjected to significant blood loss without major trauma develop intestinal inflammation and tissue damage within two hours. We report here that complement 5 (C5) deficient mice are protected from intestinal tissue damage when subjected to hemorrhage (Injury score = 0.36 compared to wildtype hemorrhaged animal injury score = 2.89; p<0.05). We present evidence that C5a represents the effector molecule because C57Bl/6 mice treated with a C5a receptor antagonist displayed limited intestinal injury (Injury score = 0.88), leukotriene B4 (13.16 pg/mg tissue) and myeloperoxidase (115.6 pg/mg tissue) production compared to hemorrhaged C57Bl/6 mice (p<0.05). Conclusion: Complement activation is important in the development of hemorrhage-induced tissue injury and C5a generation is critical for tissue inflammation and damage. Thus, therapeutics targeting C5a may be useful therapeutics for hemorrhage-associated injury

A SNP in the flt-1 promoter integrates the VEGF system into the p53 transcriptional network

The VEGF system is essential for angiogenesis. VEGF overexpression frequently correlates with increased microvascularity and metastasis and decreased spontaneous apoptosis. Although a precise mechanism has not been established, studies suggest that VEGF expression is negatively regulated by p53, a master regulator and tumor suppressor. There are no reports of additional components of the VEGF signal transduction pathway being part of the p53 transcriptional network. A target of VEGF, the VEGF receptor 1/flt-1, can regulate growth and migration of endothelial cells and modulate angiogenesis. VEGF appears to be up-regulated in various cancers in which flt-1 may have a role in tumor progression and metastasis. We identified a C-to-T SNP upstream of the transcriptional start site in ≈6% of the people examined. The SNP is located within a putative p53 response element. Only the promoter with the T SNP (FLT1-T) was responsive to p53 when examined with reporter assays or by endogenous gene expression analysis in cell lines with different SNP status. In response to doxorubicin-induced DNA damage, there was clear allele discrimination based on p53 binding at the FLT1-T but not FLT1-C promoters as well as p53-dependent induction of flt-1 mRNA, which required the presence of FLT1-T. Our results establish that p53 can differentially stimulate transcription at a polymorphic variant of the flt-1 promoter and directly places the VEGF system in the p53 stress-response network via flt-1 in a significant fraction of the human population. We suggest that the p53-VEGF-flt-1 interaction is relevant to risks in angiogenesis-associated diseases, including cancer