Service restrictions from emergency shelters among people experiencing homelessness: Uncovering pathways into unsheltered homelessness and institutional circuitry.

Service restrictions refer to temporary or permanent bans of individuals from a program or an organization's services, and are widely used in emergency shelter systems. Limited research exists on how service restrictions unfold and their impacts on people experiencing homelessness. This qualitative study used in-depth interviews with timeline mapping to examine the antecedents and consequences of service restrictions from emergency shelters among people experiencing homelessness in two cities in Ontario, Canada. A total of 49 people experiencing homelessness who had been restricted from an emergency shelter program in the past year were recruited and included in the study analysis. A pragmatic and integrative approach was used for data analysis that involved the development of meta-matrices to identify prominent and divergent perspectives and experiences with regard to service restriction antecedents and consequences. Study findings underscored that service restrictions were often the result of violence and aggression, primarily between service users. There were regional differences in other service restriction reasons, including substance use and possession. Service restrictions affected the shelter status of almost all participants, with many subsequently experiencing unsheltered homelessness, and cycling through institutional health, social, and criminal justice services (i.e., institutional circuitry). Other health and social consequences included substance use relapses and hospitalizations; cold-related injuries due to post-restriction unsheltered homelessness; suicidality; food insecurity; diminished contact with support network and connections; and intense feelings of anger, fear, and hopelessness. Overall, the study findings advance our understanding of the role of homeless services in pathways into unsheltered homelessness and institutional circuitry, which raise critical questions about how to mitigate the harms associated with service restrictions, while concurrently facilitating safety and upholding the rights of people experiencing homelessness and emergency shelter staff.

"I feel like I'm in a revolving door, and COVID has made it spin a lot faster": The impact of the COVID-19 pandemic on youth experiencing homelessness in Toronto, Canada.

PURPOSE: Research has shown that youth experiencing homelessness (YEH) face barriers to social inclusion and are at risk for poor mental health. With the COVID-19 pandemic threatening the health, wellbeing, and economic circumstances of people around the world, this study aims to assess the impacts of the pandemic on YEH in Toronto, Ontario, as well as to identify recommendations for future waves of COVID-19. METHODS: Semi-structured interviews were conducted with YEH (ages 16-24, n = 45) and staff who work in one of four downtown emergency shelters for youth (n = 31) in Toronto, Ontario. RESULTS: YEH experienced both structural changes and psychosocial impacts resulting from the pandemic. Structural changes included a reduction in services, barriers to employment and housing, and changes to routines. Psychosocial outcomes included isolation, worsened mental health, and increased substance use. Impacts were magnified and distinct for subpopulations of youth, including for youth that identified as Black, 2SLGBTQ+, or those new to Canada. CONCLUSIONS: The COVID-19 pandemic increased distress among YEH while also limiting access to services. There is therefore a need to balance health and safety with continued access to in-person services, and to shift the response to youth homelessness to focus on prevention, housing, and equitable supports for subpopulations of youth.

A Tale of Two Bioconjugations: pH Controlled Divergent Reactivity of Protein α-oxo-Aldehydes in Competing α-oxo-Mannich and Catalyst-Free Aldol Ligations.

Site-selective chemical methods for protein bioconjugation have revolutionized the fields of cell and chemical biology through the development of novel protein/enzyme probes bearing fluorescent, spectroscopic, or even toxic cargos. Herein, we report two new methods for the bioconjugation of α-oxo aldehyde handles within proteins using small molecule aniline and/or phenol probes. The "α-oxo-Mannich" and "catalyst-free aldol" ligations both compete for the electrophilic α-oxo aldehyde, which displays pH divergent reactivity proceeding through the "Mannich" pathway at acidic pH to afford bifunctionalized bioconjugates, and the "catalyst-free aldol" pathway at neutral pH to afford monofunctionalized bioconjugates. We explore the substrate scope and utility of both of these bioconjugations in the construction of neoglycoproteins, in the process formulating a mechanistic rationale for how both pathways intersect with each other at different reaction pH's.

Promoting Wellness and Recovery of Young Women Experiencing Gender-Based Violence and Homelessness: The Role of Trauma-Informed Health Promotion Interventions.

Little is known regarding the types of interventions most effective in supporting wellness and recovery of victims of gender-based violence, particularly those simultaneously experiencing homelessness. This qualitative study explored the experiences of 18 young women experiencing gender-based violence and homelessness who participated in a community-based, trauma-informed group intervention in Toronto, Canada. Participants completed audio-recorded and transcribed semi-structured interviews, analyzed using thematic content analysis. Participants described valuing the safe, women-only space, shared lived experiences, and tailored psychoeducation and resulting improvements in confidence, coping, health, relationships, and future directedness. Findings suggest community-based, trauma-informed group interventions can facilitate wellness and recovery in this population.

Supporting Female Survivors of Gender-Based Violence Experiencing Homelessness: Outcomes of a Health Promotion Psychoeducation Group Intervention.

Homelessness is an important risk factor for gender-based violence (GBV), particularly among youth, and disproportionally affects women and girls. Survivors of GBV experience enduring and severe physical, psychological, and sexual health problems. Although key elements in service delivery for survivors of GBV have been identified, little is known about outcomes of community-based programs aiming to assist homeless and unstably housed youth experiencing GBV. This longitudinal study aimed to quantitatively evaluate changes in mental health and well-being outcomes in female identified youth experiencing GBV and homelessness, 12 months after enrolment in a community-based, trauma-informed, brief group psychoeducation intervention. Standardized survey measures were administered at baseline, 6 and 12 months for 70 participants, recruited between February 2017 and April 2019, assessing quality of life, psychological distress, traumatic symptoms, substance use, resilience, victimization, and sense of mastery. Linear mixed models were used to examine longitudinal changes in quality of life as well as secondary outcomes among study participants. After 12 months, quality of life increased significantly among participants (p = 0.009), and the 12-month victimization score was significantly decreased relative to baseline (p = 0.05). Changes in other outcomes were not statistically significant. Findings suggest that community-based brief group psychoeducation interventions may be a promising approach to improving outcomes for this disadvantaged population.

Implementing a trauma-informed intervention for homeless female survivors of gender-based violence: Lessons learned in a large Canadian urban centre.

Gender-based violence is associated with an elevated risk of physical and psychological harm for girls and women. This study examines service user and provider experiences of a trauma-informed, peer-facilitated group psychosocial intervention (Peer Education and Connection through Empowerment [PEACE]) targeting female-identified youth experiencing homelessness and gender-based violence. Participants were recruited among service users and providers of the intervention, delivered in Toronto, Canada. We conducted 19 semi-structured interviews between May and October 2017, engaging 12 service users and 7 additional stakeholders (including social service providers, peers and program administrators). We elicited participant perspectives on the acceptability of the intervention and key enablers of successful implementation and engagement of the target population. Qualitative transcripts were analysed using thematic analysis. Service users, including survivors of sexual exploitation, forced marriage and honour crimes, described satisfaction with and acceptability of the intervention. A number of factors were perceived by service users and providers as contributing to the intervention's successful implementation, including a focus on service user needs, program quality, flexibility and accessibility and strong inter-and intra-agency networks. Introducing peers as mentors led to challenges that could be mitigated through peer mentor education and training to maintain healthy boundaries and enhance peer mentor retention. The need for clear guidelines on the management of trauma disclosures in community settings and a systems-wide approach to service provider and administrator training in the effective integration of peer support services also emerged as important areas for future development. A group-based, trauma-informed and peer-supported psychosocial intervention was acceptable to service users and providers and successfully engaged female-identified survivors of gender-based violence who were also experiencing homelessness. Findings add to the scant knowledge base on interventions to support this population and identify important areas for future research.

Phospholipase D2 in prostate cancer: protein expression changes with Gleason score.

BACKGROUND: Phospholipases D1 and D2 (PLD1/2) are implicated in tumorigenesis through their generation of the signalling lipid phosphatidic acid and its downstream effects. Inhibition of PLD1 blocks prostate cell growth and colony formation. Here a role for PLD2 in prostate cancer (PCa), the major cancer of men in the western world, is examined. METHODS: PLD2 expression was analysed by immunohistochemistry and western blotting. The effects of PLD2 inhibition on PCa cell viability and cell motility were measured using MTS, colony forming and wound-healing assays. RESULTS: PLD2 protein is expressed about equally in luminal and basal prostate epithelial cells. In cells from different Gleason-scored PCa tissue PLD2 protein expression is generally higher than in non-tumorigenic cells and increases in PCa tissue scored Gleason 6-8. PLD2 protein is detected in the cytosol and nucleus and had a punctate appearance. In BPH tissue stromal cells as well as basal and luminal cells express PLD2. PLD2 protein co-expresses with chromogranin A in castrate-resistant PCa tissue. PLD2 inhibition reduces PCa cell viability, colony forming ability and directional cell movement. CONCLUSIONS: PLD2 expression correlates with increasing Gleason score to GS8. PLD2 inhibition has the potential to reduce PCa progression.

Assessing the Advantages, Limitations and Potential of Human Primary Prostate Epithelial Cells as a Pre-clinical Model for Prostate Cancer Research.

Choosing an appropriate cell model(s) is the first decision to be made before starting a new project or programme of study. Here, we address the rationale that can be behind this decision and we summarize the current cell models that are used to study prostate cancer. Researchers face the challenge of choosing a model that recapitulates the complexity and heterogeneity of prostate cancer. The use of primary prostate epithelial cells cultured from patient tissue is discussed, and the necessity for close clinical-academic collaboration in order to do this is highlighted. Finally, a novel quantitative phase imaging technique is described, along with the potential for cell characterization to not only include gene expression and protein markers but also morphological features, cell behaviour and kinetic activity.

Phospholipase D inhibitors reduce human prostate cancer cell proliferation and colony formation.

BACKGROUND: Phospholipases D1 and D2 (PLD1/2) hydrolyse cell membrane glycerophospholipids to generate phosphatidic acid, a signalling lipid, which regulates cell growth and cancer progression through effects on mTOR and PKB/Akt. PLD expression and/or activity is raised in breast, colorectal, gastric, kidney and thyroid carcinomas but its role in prostate cancer (PCa), the major cancer of men in the western world, is unclear. METHODS: PLD1 protein expression in cultured PNT2C2, PNT1A, P4E6, LNCaP, PC3, PC3M, VCaP, 22RV1 cell lines and patient-derived PCa cells was analysed by western blotting. PLD1 protein localisation in normal, benign prostatic hyperplasia (BPH), and castrate-resistant prostate cancer (CRPC) tissue sections and in a PCa tissue microarray (TMA) was examined by immunohistochemistry. PLD activity in PCa tissue was assayed using an Amplex Red method. The effect of PLD inhibitors on PCa cell viability was measured using MTS and colony forming assays. RESULTS: PLD1 protein expression was low in the luminal prostate cell lines (LNCaP, VCaP, 22RV1) compared with basal lines (PC3 and PC3M). PLD1 protein expression was elevated in BPH biopsy tissue relative to normal and PCa samples. In normal and BPH tissue, PLD1 was predominantly detected in basal cells as well in some stromal cells, rather than in luminal cells. In PCa tissue, luminal cells expressed PLD1. In a PCa TMA, the mean peroxidase intensity per DAB-stained Gleason 6 and 7 tissue section was significantly higher than in sections graded Gleason 9. In CRPC tissue, PLD1 was expressed prominently in the stromal compartment, in luminal cells in occasional glands and in an expanding population of cells that co-expressed chromogranin A and neurone-specific enolase. Levels of PLD activity in normal and PCa tissue samples were similar. A specific PLD1 inhibitor markedly reduced the survival of both prostate cell lines and patient-derived PCa cells compared with two dual PLD1/PLD2 inhibitors. Short-term exposure of PCa cells to the same specific PLD1 inhibitor significantly reduced colony formation. CONCLUSIONS: A new specific inhibitor of PLD1, which is well tolerated in mice, reduces PCa cell survival and thus has potential as a novel therapeutic agent to reduce prostate cancer progression. Increased PLD1 expression may contribute to the hyperplasia characteristic of BPH and in the progression of castrate-resistant PCa, where an expanding population of neuroendocrine-like cells express PLD1.

Incorporating a public health approach in drug law: lessons from local expansion of treatment capacity and access under California's Proposition 36.

A major state drug abuse initiative, California's Proposition 36 of 2000, mandated that adults convicted of drug possession be offered treatment in lieu of incarceration. While the law expanded public treatment for arrestees, the counties were given discretion in structuring their systems of care and procedures to manage clients. Using data from a study of key informants in eight counties, this article examines local planning to increase drug treatment capacity and manage clients' access to treatment. In both these planning domains, it describes the counties' strategies and concerns, reasons for their differences in approaches, and whether and how this state initiative, which explicitly incorporated treatment objectives into penal drug law, will shift the debate over drug abuse policy toward greater consideration of public health goals.

Early implementation of Proposition 36: criminal justice and treatment system issues in eight counties.

This article examines key differences emerging in implementation of California's Proposition 36 voter initiative across eight diverse large, medium, and small counties. The data were collected in 2001 in a key informant survey of county policymakers. Unlike most major California criminal justice initiatives of recent years, Proposition 36 represents a potential lessening of adjudicatory and penal controls rather than an increase in their severity, in this case in response to charges of drug use, possession, or transportation. Furthermore, Proposition 36 was written broadly enough to allow considerable discretion in implementation across the counties, including the specification of funding to support mandated provisions of the Act and division of oversight responsibilities among criminal justice and treatment stakeholders. Hence actual content and scope of criminal justice system procedural changes, and impact of the proposition on criminal justice and treatment systems and on arrestees, are likely to vary by county. The article identifies key approaches and decisions made in the sampled counties that are predicted to affect the proposition's impact in the areas of treatment versus criminal justice resources, prosecutorial implementation, defendant and defense responses, assessing criminal histories and treatment needs, treatment versus criminal justice supervisory responsibility, and procedural variations and client behavior.