Exploring a syndemic of poverty, cumulative violence, and HIV vulnerability among refugee youth: multi-method insights from a humanitarian setting in Uganda.

Synergistic associations between social inequities and HIV vulnerabilities - known as a syndemic - are understudied with youth in humanitarian settings. We explored refugee youths' HIV prevention needs in Bidi Bidi Refugee Settlement, Uganda. This multi-methods study involved 6 focus groups and 12 in-depth individual interviews (IDI) with refugee youth (n = 60) aged 16-24, and IDI with refugee elders (n = 8) and healthcare providers (n = 8). We then conducted cross-sectional surveys with refugee youth (16-24 years) (n = 115) to assess: poverty, recent sexual and gender-based violence (SGBV), and condom engagement motivation (CEM) (wanting to learn about condoms for HIV prevention). Multivariable logistic regression was used to estimate adjusted odds ratios for associations between poverty and SGBV with CEM. Qualitative narratives revealed poverty and trauma elevated substance use, and these converged to exacerbate SGBV. SGBV and transactional sex increased HIV vulnerabilities. Among survey participants, poverty and recent SGBV were associated with reduced odds of CEM. The interaction between poverty and recent SGBV was significant: the predicted probability of CEM among youth who experienced both poverty and SGBV was almost half than among youth who experienced poverty alone, SGBV alone, or neither. Findings signal the confluence of poverty, violence, and substance use elevate refugee youth HIV vulnerabilities.

Cisplatin toxicity in the developing brain displays an absolute requirement for caspase-3.

Cisplatin is a member of a widely utilized class of chemotherapeutic agent that initiates DNA damage response, cell cycle arrest, and p53-dependent apoptotic cell death in concert with DNA­platinum adduct formation. While normal programmed cell death (PCD) can occur in the developing neuroepithelium in the absence of caspase-3 within certain genetic backgrounds, we observed an absolute dependency upon this executioner caspase with respect to cisplatin-induced PCD in the developing central nervous system (CNS). We therefore examined the nature of this genotoxic injury in the CNS in vivo, in which cisplatin treatment causes widespread cellular injury consistent with hallmarks of apoptosis which are averted upon caspase-3 inhibition. Examination of cisplatin-mediated injury as a function of time revealed the presence of an alternative, delayed form of necroptosis-like cell death which manifests in Casp3-/- neuroepithelia for several days following the normal pattern of apoptosis. Together, these findings suggest a coordinated regulation of these disparate PCD pathways in response to genotoxic stress in vivo and highlight the unique and critical role which caspase-3 plays among executioner caspases in coordinating apoptotic versus necroptotic responsiveness of the developing CNS to genotoxic injury.

Relational Factors and HIV Testing Practices: Qualitative Insights from Urban Refugee Youth in Kampala, Uganda.

Despite the global phenomenon of refugee urbanization, little is known of relational contexts that shape HIV testing among urban refugee youth. We explored perspectives, experiences, and preferences for social support in HIV testing among refugee youth aged 16-24 in Kampala, Uganda. We conducted five focus groups with refugee youth (n = 44) and five in-depth key informant interviews. Participant narratives signaled relational contexts shaping HIV testing included informal sources (intimate partners and family members) and formal sources (peer educators and professionals). There was heterogeneity in perspectives based on relationship dynamics. While some felt empowered to test with partners, others feared negative relationship consequences. Participant narratives reflected kinship ties that could facilitate testing with family, while others feared coercion and judgment. Peer support was widely accepted. Professional support was key for HIV testing as well as conflict-related trauma. Findings emphasize bonding and bridging social capital as salient components of enabling HIV testing environments.

Ngutulu Kagwero (agents of change): study design of a participatory comic pilot study on sexual violence prevention and post-rape clinical care with refugee youth in a humanitarian setting in Uganda.

With over 1.4 million refugees, Uganda is Sub-Saharan Africa's largest refugee-hosting nation. Bidi Bidi, Uganda's largest refugee settlement, hosts over 230,000 residents. There is a dearth of evidence-based sexual violence prevention and post-rape clinical care interventions in low- and middle-income humanitarian contexts tailored for refugee youth. Graphic medicine refers to juxtaposing images and narratives, often through using comics, to convey health promotion messaging. Comics can offer youth-friendly, low-cost, scalable approaches for sexual violence prevention and care. Yet there is limited empirical evaluation of comic interventions for sexual violence prevention and post-rape clinical care. This paper details the study design used to develop and pilot test a participatory comic intervention focused on sexual violence prevention through increasing bystander practices, reducing sexual violence stigma, and increasing post exposure prophylaxis (PEP) knowledge with youth aged 16-24 and healthcare providers in Bidi Bidi. Participants took part in a single-session peer-facilitated workshop that explored social, sexual, and psychological dimensions of sexual violence, bystander interventions, and post-rape clinical care. In the workshop, participants completed a participatory comic book based on narratives from qualitative data conducted with refugee youth sexual violence survivors. This pilot study employed a one-group pre-test/post-test design to assess feasibility outcomes and preliminary evidence of the intervention's efficacy. Challenges included community lockdowns due to COVID-19 which resulted in study implementation delays, political instability, and attrition of participants during follow-up surveys. Lessons learned included the important role of youth facilitation in youth-centred interventions and the promise of participatory comics for youth and healthcare provider engagement for developing solutions and reducing stigma regarding SGBV. The Ngutulu Kagwero (Agents of change) project produced a contextually and age-tailored comic intervention that can be implemented in future fully powered randomized controlled trials to determine effectiveness in advancing sexual violence prevention and care with youth in humanitarian contexts.

Exploring resource scarcity and contextual influences on wellbeing among young refugees in Bidi Bidi refugee settlement, Uganda: findings from a qualitative study.

BACKGROUND: Contextual factors including poverty and inequitable gender norms harm refugee adolescent and youths' wellbeing. Our study focused on Bidi Bidi refugee settlement that hosts more than 230,000 of Uganda's 1.4 million refugees. We explored contextual factors associated with wellbeing among refugee adolescents and youth aged 16-24 in Bidi Bidi refugee settlement. METHODS: We conducted 6 focus groups (n = 3: women, n = 3: men) and 10 individual interviews with young refugees aged 16-24 living in Bidi Bidi. We used physical distancing practices in a private outdoor space. Focus groups and individual interviews explored socio-environmental factors associated with refugee youth wellbeing. Focus groups were digitally recorded, transcribed verbatim, and coded by two investigators using thematic analysis. Analysis was informed by a social contextual theoretical approach that considers the interplay between material (resource access), symbolic (cultural norms and values), and relational (social relationships) contextual factors that can enable or constrain health promotion. RESULTS: Participants included 58 youth (29 men; 29 women), mean age was 20.9 (range 16-24). Most participants (82.8%, n = 48) were from South Sudan and the remaining from the Democratic Republic of Congo (17.2% [n = 10]). Participant narratives revealed the complex interrelationships between material, symbolic and relational contexts that shaped wellbeing. Resource constraints of poverty, food insecurity, and unemployment (material contexts) produced stress and increased sexual and gender-based violence (SGBV) targeting adolescent girls and women. These economic insecurities exacerbated inequitable gender norms (symbolic contexts) to increase early marriage and transactional sex (relational context) among adolescent girls and young women. Gendered tasks such as collecting water and firewood also increased SGBV exposure among girls and young women, and this was exacerbated by deforestation. Participants reported negative community impacts (relational context) of COVID-19 that were associated with fear and panic, alongside increased social isolation due to business, school and church closures. CONCLUSIONS: Resource scarcity produced pervasive stressors among refugee adolescents and youth. Findings signal the importance of gender transformative approaches to SGBV prevention that integrate attention to resource scarcity. These may be particularly relevant in the COVID-19 pandemic. Findings signal the importance of developing health enabling social contexts with and for refugee adolescents and youth.

Conceptualizing LGBT Stigma and Associated HIV Vulnerabilities Among LGBT Persons in Lesotho.

Social marginalization harms lesbian, gay, bisexual, and transgender (LGBT) persons' wellbeing in Lesotho. Socio-cultural mechanisms linking LGBT stigma, depression, substance use, and HIV among LGBT persons in Lesotho are understudied. We explore associations between LGBT stigma, mental health stressors, and HIV vulnerabilities among LGBT persons in Lesotho. We conducted in-depth, semi-structured interviews with 46 LGBT persons and six key informants (e.g. healthcare providers). Participants described depression, substance use, and HIV as mutually reinforcing and situated in larger social contexts of stigma. Alcohol use was a stigma coping strategy and a way to build LGBT connections. At the same time, alcohol use elevated HIV vulnerabilities by lowering condom use uptake. Pervasive stigma reinforced barriers to healthcare engagement. Community-led support and services were leveraged to navigate stigma, reduce HIV vulnerabilities, and ultimately improve health. Findings emphasize the key role contexts play in shaping sexual and mental health among LGBT persons in Lesotho.

Endothelin-1-mediated cerebral ischemia in mice: early cellular events and the role of caspase-3.

Over the past 30 years a number of animal models of cerebral ischemic injury have been developed. Middle cerebral artery occlusion (MCAO) in particular reproduces both ischemic and reperfusion elements and is widely utilized as a model of ischemic stroke in rodents. However substantial variability exists in this model even in clonal inbred mice due to stochastic elements of the cerebral vasculature. Models such as MCAO thus exhibit significant irreducible variabilities with respect to their zone of injury as well as inducing a sizable volume of injury to the cerebrum with damage to sub-cortical structures, conditions not typically seen for the majority of human clinical strokes. An alternative model utilizes endothelin-1 application focally to cerebral vasculature, resulting in an ischemic reperfusion injury which more closely mimics that seen in human clinical stroke. In order to further define this model we demonstrate that intra-cortical administration of ET-1 results in a highly reproducible pattern of tissue injury which is limited to the cerebral cortex, characterizing the early cellular and molecular events which occur during the first 24 h post-injury. In addition we demonstrate that caspase-3 is both necessary and sufficient to regulate a majority of cortical cell death observed during this period. The enhanced survival effects seen upon genetic deletion of caspase-3 appear to arise as a result of direct modification of cell autonomous PCD signaling as opposed to secondary effectors such as granulocyte infiltration or microglia activation. Taken together these findings detail the early mechanistic features regulating endothelin-1-mediated ischemic injury.