Search

Indigenous women encounter increased stressful life experiences such as socioeconomic insecurities as well as inequities in health services and outcomes. These stress inequities, which stem from the historical and ongoing effects of settler colonialism, also worsen health outcomes for those women living with HIV. As a part of a broader research project on the impacts of stress-reducing interventions for indigenous women, this study examines the experiences of the women who facilitated the intervention. This research was conducted to evaluate the impacts of a biweekly stress-reducing intervention conducted in Thunder Bay, Ontario. The facilitators of the intervention participated in a focus group in 2019 where they detailed the reach, effectiveness, adoption, and implementation of the intervention. The results suggest that effective stress-reducing interventions should strive to be accessible and inclusive and that doing so can increase program engagement with the service organization hosting the intervention. Further, the results highlight the strengths and challenges of the intervention, including how it helped foster leadership skills and increased indigenous cultural learning among facilitators. These findings demonstrate the strength of community-led interventions and subsequent opportunities for facilitators to grow as leaders. Further, the study highlights how this style of intervention can also encourage participants to engage in other health and wellbeing programs offered by the community partner hosting the intervention. These findings suggest that interventions aimed at reducing stress among indigenous women facing socioeconomic insecurities, including those living with HIV, are both feasible and beneficial for participants, facilitators, and the nonprofit service organizations delivering them.

Supplemental material, sj-docx-1-anp-10.1177_00048674221089837 for Systematic review of Indigenous involvement and content in mental health interventions and their effectiveness for Indigenous populations by Rachel Seungyun Lee, Hilary K Brown, Sarah Salih and Anita C Benoit in Australian & New Zealand Journal of Psychiatry

Supplemental material, sj-doc-1-aln-10.1177_11771801221117164 for Systematic review of interventions addressing suicide among Indigenous adults and reporting Indigenous-specific content and involvement in the interventions by Catherine Moses, Hilary K Brown, Priya Prabhakar, Nadine Eltayeb and Anita C Benoit in AlterNative: An International Journal of Indigenous Peoples

We aimed to identify the association between stress and antiretroviral therapy (ART) adherence among women in HIV care in Toronto, Ontario participating in the Ontario HIV Treatment Network Cohort Study (OCS) between 2007 and 2012. We conducted cross-sectional analyses with women on ART completing the AIDS Clinical Trial Group (ACTG) Adherence Questionnaire. Data closest to, or at the last completed interview, were collected from medical charts, through record linkage with Public Health Ontario Laboratories, and from a standardized self-reported questionnaire comprised of socio-demographic and psycho-socio-behavioral measures (Center for Epidemiologic Studies Depression Scale (CES-D), Alcohol Use Disorders Identification Test (AUDIT)), and stress measures (National Population Health Survey). Logistic regression was used to quantify associations with optimal adherence (≥95% adherence defined as missing ≤ one dose of ART in the past 4 weeks). Among 307 women, 65.5% had optimal adherence. Women with suboptimal compared to optimal adherence had higher median total stress scores (6.0 [interquartile range (IQR): 3.0–8.1] vs. 4.1 [IQR: 2.0–7.1], p = 0.001), CES-D scores (16 [IQR: 6–28] vs. 12 [IQR: 3–22], p = 0.008) and reports of hazardous and harmful alcohol use (31.1% vs. 17.9%, p = 0.008). In our multivariable model, we found an increased likelihood of optimal adherence with the absence of hazardous and harmful alcohol use (Adjusted Odds Ratio (AOR)=2.20, 95% confidence interval (CI): 1.12–4.32) and a decreased likelihood of optimal adherence with more self-reported stress (AOR = 0.56, 95% CI: 0.33–0.94). Interventions supporting optimal ART adherence should address stress and include strategies to reduce or eliminate hazardous and harmful alcohol use for women living with HIV.

Cytotoxic CD8 T lymphocytes kill virus-infected cells and are critical for viral clearance from the body. Cytokines, particularly those sharing the common gamma receptor chain (gamma c), play a key role in this cytotoxic function as well as in the growth, differentiation and homeostasis of CD8 T lymphocytes. In order to exert these biological effects, cytokine-dependent signal transduction via the Janus kinase (Jak) / Signal Transducers and Activators of Transcription (STAT) pathway, the phosphoinositide 3-kinase (PI3-K) and mitogen-activated protein kinase (MAPK) pathways is required. In HIV infection however, the CD8 T lymphocytes become defective and are characterized by impaired cytotoxicity, altered differentiation patterns, and increased susceptibility to apoptosis. I hypothesized that impaired cytokine responsiveness resulting from defects in cytokine-dependent signal transduction contributes to the CD8 T cell impairment observed in HIV+ patients. I investigated the activation of the Jak/STAT signaling pathway to cytokines in CD8 T cells from HIV+ patients. Interestingly, these cells were responsive to IL-2, IL-4, IL-10, IL-15, and IL-21 at the level of their respective STAT activation. However, impairment of the IL-7 / IL-7Ralpha signaling axis was identified and characterized by a defect in STAT5 signaling. The impaired STAT5 activation correlated with a low IL-7Ralpha surface expression. The expanded population of IL- 7Ralphalow-expressing CD8 T cells, found particularly in viremic HIV+ patients, expressed higher levels of the transcriptional repressor Growth Factor Independent-1 (GFI1) compared to their IL-7Ralphahigh counterparts. This prompted further investigations into the role of GFI1 in IL-7Ralpha regulation in primary human CD8 T cells as a model. Though silencing of GFI1 did not modulate basal IL-7Ralpha expression, exogenous overexpression negatively regulated IL-7Ra surface levels. The gc cytokines, IL-2, IL-4, IL-7, and IL-15, but not IL-21, were found to efficiently suppress IL-7Ralpha expression however, only IL-4 simultaneously upregulated GFI1 expression. RNA interference studies targeting GFI1 in IL-4 stimulated CD8 T cells established a specific role for GFI1 in sustaining the suppression of IL-7Ralpha expression. Furthermore, transient downregulation of GFI1 in CD8 T cells subjected to IL- 4-dependent proliferation reduced their proliferative capacity. Other functions identified for GFI1 were in the suppression of CXCR4 and Bax expression in CD8 T cells. Studies aimed at identifying the signal transduction pathways responsible for regulating GFI1 and IL-7Ralpha expression revealed that IL-4-mediated downregulation of IL-7Ralpha expression required activation of the Jak/STAT and the PI3K pathways. On the other hand, IL-4-induced upregulation of GFI1 expression was mediated via the PI3K pathway. The JNK and P38 MAPK pathways appeared to be important as regulators of basal IL-7Ralpha expression levels, but had no statistically significant effects on GFI1 expression. To conclude, these studies have clarified the important biological effects of GFI1 in mature human CD8 T lymphocytes. Furthermore, exposure to IL-4 may generate CD8 T cell populations with an exhausted phenotype similar to those found in chronically-infected HIV+ patients, characterized by reduced cytotoxic activity and increased IL-4 production. Thus, the IL-4 study model may prove valuable for investigating the activity of human CD8 T cells in such chronic diseases and those characterized by a type 2 cytokine profile.