Using drugs alone in single room occupancy housing: Understanding environmental drivers of overdose risk.

BACKGROUND: Across North America most overdose deaths occur in housing, largely due to individuals using drugs alone. In cities, fatalities are disproportionately concentrated in low-income housing, including single room occupancy (SRO) housing. While research has highlighted how SROs operate as risk environments for various poor outcomes, there has been little attention to specific drug use practices (i.e., using alone) associated with overdose vulnerability in these spaces. This study explores how environmental contexts of SROs shape overdose risks, with specific attention to practices of using drugs alone. METHODS: In-depth semi-structured interviews were conducted with 30 people who use drugs (PWUD) living in Vancouver SROs. Interviews covered topics such as social-structural environments of housing, drug use practices, and housing-based harm reduction. Thematic analysis drew on the intersectional risk environment framework. RESULTS: Narratives positioned SROs as extensions of public space, with similar expectations of risks and behaviours as in public spaces. For some participants, using alone in their room was characterized as a practice in claiming privacy within the context of a public existence. Participants highlighted how certain features of SRO's social-structural environments were routinely leveraged against them (e.g., security cameras, staff surveillance), suggesting using alone as a tactic to minimize risks of hyper-surveillance and punitive policies. Further, participants discussed using alone as "safer," describing how this practice mitigated place-based risks of social-structural harms (e.g., violence, criminalization) in ways that eclipsed overdose risk. CONCLUSION: Using drugs alone may be understood as a spatial negotiation of vulnerability to diverse harms produced by environmental contexts of SROs. Interventions accounting for broader contextual factors (e.g., improvements housing quality/quantity, providing a safer supply of drugs) that render using alone as instrumental to survival, and that reduce the implicit threat of punishment from intensive surveillance and control practices are critical to reduce vulnerability to overdose and other harms.

Perceptions of prospective pharmaceutical stimulant substitution treatments among people who use illicit stimulants in Vancouver, Canada.

BACKGROUND: Stimulant-involved overdose deaths are increasing, driven by polysubstance use and adulteration of the illicit drug supply. While emerging evidence for prescription stimulant substitution is promising, there are no approved treatment options for stimulant use disorder that address the realities of an unpredictable drug supply. This study explores treatment experiences of people who use illicit stimulants (PWUS) to identify gaps and perceptions of prospective pharmaceutical stimulant substitution treatments (SST). METHODS: In-depth qualitative interviews were conducted with 86 PWUS in Vancouver, Canada. Thematic analysis focused on experiences of available treatment options for stimulant use and perceptions of prospective SST. RESULTS: Participants identified how primarily behavioral treatment approaches do not meet the unique needs of PWUS, in contrast with the range of medical treatments available for opioid use disorder. Participants anticipated health and social benefits if they were able to access SST, including avoiding the toxic illicit stimulant supply, reduced engagement in criminalized activities, and greater economic security. Perceptions of prospective SST were informed by knowledge of existing opioid treatments. This led some participants to be unsupportive of SST, citing concerns around agency and highly regulated operational contexts that do not align with the lived realities of stimulant use. CONCLUSION: Findings demonstrate the need for SST pilot programs in real-world settings and underscore the health and social advantages SST may offer; although drawing on existing opioid treatment models to implement SST pilots may limit success. Thus, any novel treatments for stimulant use must centre the lived realities of PWUS.

Using alone at home: What's missing in housing-based responses to the overdose crisis?

BACKGROUND: Against the backdrop of North America's overdose crisis, most overdose deaths are occurring in housing environments, largely due to individuals using drugs alone. Overdose deaths in cities remain concentrated in marginal housing environments (e.g., single-room occupancy housing, shelters), which are often the only forms of housing available to urban poor and drug-using communities. This commentary aims to highlight current housing-based overdose prevention interventions and to situate them within the broader environmental contexts of marginal housing. In doing so, we call attention to the need to better understand marginal housing as sites of overdose vulnerability and public health intervention to optimize responses to the overdose crisis. HARM REDUCTION AND OVERDOSE PREVENTION IN HOUSING: In response to high overdose rates in marginal housing environments several interventions (e.g., housing-based supervised consumption rooms, peer-witnessed injection) have recently been implemented in select jurisdictions. However, even with the growing recognition of marginal housing as a key intervention site, housing-based interventions have yet to be scaled up in a meaningful way. Further, there have been persistent challenges to tailoring these approaches to address dynamics within housing environments. Thus, while it is critical to expand coverage of housing-based interventions across marginal housing environments, these interventions must also attend to the contextual drivers of risks in these settings to best foster enabling environments for harm reduction and maximize impacts. CONCLUSION: Emerging housing-focused interventions are designed to address key drivers of overdose risk (e.g., using alone, toxic drug supply). Yet, broader contextual factors (e.g., drug criminalization, housing quality, gender) are equally critical factors that shape how structurally vulnerable people who use drugs navigate and engage with harm reduction interventions. A more comprehensive understanding of these contextual factors within housing environments is needed to inform policy and programmatic interventions that are responsive to the needs of people who use drugs in these settings.

Housing-based syringe services programs to improve access to safer injecting equipment for people who inject drugs in Vancouver, Canada: a spatially oriented qualitative study.

BACKGROUND: Housing environments shape injection drug-related risks and harms and thus represent a critical implementation setting for syringe services programs (SSPs). As critical harm reduction measures, SSPs provide safe injecting equipment to people who inject drugs (PWID). Vancouver, Canada, has well-established syringe distribution programs through which PWID have low-threshold access to unlimited syringes and related injecting equipment, including through non-profit operated supportive housing and single-room occupancy hotels. This study examines the role of housing-based SSPs in distributing injecting equipment to PWID in Vancouver. METHODS: Between January and March 2020, semi-structured, in-depth interviews were conducted in Vancouver with 26 PWID. Interviews were audio-recorded, transcribed, and coded. Salient themes were identified using inductive and deductive approaches. RESULTS: Many participants accessed SSPs in housing facilities and expressed preference for these programs over those offered at other locations and through other health and social services. Three major themes emerged to explain this preference. First, most participants injected in the buildings where they resided, and housing-based SSPs made injecting equipment available when and where it was most needed. Second, many participants preferred to avoid carrying syringes outside of the places where they inject due to fears that syringe possession may lead to criminal charges or confiscation of syringes and/or illicit drugs by police. Third, for some participants, anti-drug user stigma and concerns over unwillingly disclosing their drug use hindered access to SSPs outside of housing settings. Programs operated within housing facilities often offered greater client anonymity along with more supportive and less stigmatizing environments, particularly in the presence of peer staff. CONCLUSION: The current study advances understanding of access to injecting equipment in a setting with city-wide syringe distribution programs. Our findings underscore the benefits of housing-based SSPs and encourage the expansion of such services to maximize access to harm reduction supports for PWID.

"It's no foundation, there's no stabilization, you're just scattered": A qualitative study of the institutional circuit of recently-evicted people who use drugs.

People who use drugs (PWUD) commonly experience housing instability due to intersecting structural vulnerabilities (e.g., drug prohibition, discriminatory housing policies), and prejudicial or illegal evictions are common. In Vancouver, Canada, evictions have proliferated in the Downtown Eastside, a historically low-income neighbourhood with high rates of drug use and housing instability, resulting in many PWUD being evicted into homelessness. This study characterizes housing trajectories of recently-evicted PWUD through the lens of the institutional circuit of homelessness, and explores how wider contexts of structural vulnerability shape experiences within this. Qualitative interviews were conducted with PWUD recently evicted in the Downtown Eastside (<60 days). Peer research assistants recruited 58 PWUD through outreach activities. All PWUD participated in baseline interviews on the causes and contexts of evictions. Follow-up interviews were completed with 41 participants 3-6 months later, focusing on longer-term impacts of eviction, including housing trajectories. Most participants were evicted into homelessness, remaining so at follow-up. Participants described patterns of residential instability consisting of frequent cycling between shelters, streets, and kin-based networks. While participants normalized this cycling as characteristic of their marginalized social positions, narratives revealed how the demands of the institutional circuit deepened vulnerabilities and prolonged experiences of homelessness. Experiences were framed by participants' (in)ability to navigate survival needs (e.g., shelter, drug use), with tensions and trade-offs between needs increasing participants' and their peers' risks of harms. Constructions of agency further shaped experiences; accounts highlighted tensions between the control inherent to indoor spaces and participants' need for autonomy. Findings demonstrate how the demands of the institutional circuit foregrounded structural vulnerabilities to perpetuate cycles of instability. Interventions that address survival needs and preserve agency will be necessary to mitigate risks within the institutional circuit, in tandem with upstream interventions that target housing vulnerability and broader social-structural conditions (e.g., poverty, affordability) that entrap recently-evicted PWUD in the institutional circuit.

Ascl1 phospho-site mutations enhance neuronal conversion of adult cortical astrocytes in vivo.

Direct neuronal reprogramming, the process whereby a terminally differentiated cell is converted into an induced neuron without traversing a pluripotent state, has tremendous therapeutic potential for a host of neurodegenerative diseases. While there is strong evidence for astrocyte-to-neuron conversion in vitro, in vivo studies in the adult brain are less supportive or controversial. Here, we set out to enhance the efficacy of neuronal conversion of adult astrocytes in vivo by optimizing the neurogenic capacity of a driver transcription factor encoded by the proneural gene Ascl1. Specifically, we mutated six serine phospho-acceptor sites in Ascl1 to alanines (Ascl1 SA 6) to prevent phosphorylation by proline-directed serine/threonine kinases. Native Ascl1 or Ascl1 SA 6 were expressed in adult, murine cortical astrocytes under the control of a glial fibrillary acidic protein (GFAP) promoter using adeno-associated viruses (AAVs). When targeted to the cerebral cortex in vivo, mCherry+ cells transduced with AAV8-GFAP-Ascl1 SA 6-mCherry or AAV8-GFAP-Ascl1-mCherry expressed neuronal markers within 14 days post-transduction, with Ascl1 SA 6 promoting the formation of more mature dendritic arbors compared to Ascl1. However, mCherry expression disappeared by 2-months post-transduction of the AAV8-GFAP-mCherry control-vector. To circumvent reporter issues, AAV-GFAP-iCre (control) and AAV-GFAP-Ascl1 (or Ascl1 SA 6)-iCre constructs were generated and injected into the cerebral cortex of Rosa reporter mice. In all comparisons of AAV capsids (AAV5 and AAV8), GFAP promoters (long and short), and reporter mice (Rosa-zsGreen and Rosa-tdtomato), Ascl1 SA 6 transduced cells more frequently expressed early- (Dcx) and late- (NeuN) neuronal markers. Furthermore, Ascl1 SA 6 repressed the expression of astrocytic markers Sox9 and GFAP more efficiently than Ascl1. Finally, we co-transduced an AAV expressing ChR2-(H134R)-YFP, an optogenetic actuator. After channelrhodopsin photostimulation, we found that Ascl1 SA 6 co-transduced astrocytes exhibited a significantly faster decay of evoked potentials to baseline, a neuronal feature, when compared to iCre control cells. Taken together, our findings support an enhanced neuronal conversion efficiency of Ascl1 SA 6 vs. Ascl1, and position Ascl1 SA 6 as a critical transcription factor for future studies aimed at converting adult brain astrocytes to mature neurons to treat disease.

The practice and embodiment of "goofballs": A qualitative study exploring the co-injection of methamphetamines and opioids.

BACKGROUND: Polysubstance use is common among people who use drugs, including the co-use of stimulants and opioids. Research suggests the practice of simultaneous co-injection of methamphetamines and opioids, often referred to as "goofballs", is increasing. As a relatively unique drug use practice, little qualitative research currently exists on goofball injecting. This study explores the practice and embodied experiences of goofball injecting. METHODS: This article draws on in-depth interviews conducted across two qualitative studies undertaken in Vancouver, Canada's Downtown Eastside neighbourhood examining changing dynamics in relation to stimulant use and experiences with an overdose prevention site-based safer supply intervention, respectively. Interviews containing discussions of goofball use (n=29) were extracted from each study and merged into a single qualitative dataset. Data were analysed thematically and focused on the practices and embodied experiences of goofball injection. RESULTS: Our analysis uncovered how goofball injection represented a complex drug use practice driven by the desire to achieve particular embodied experiences not attainable by using either drug individually. We identified three distinct practices of goofball use: 1) to alter or enhance the effects of opioids; 2) to alter or enhance the effects of methamphetamines; and 3) to balance out the effects of both drugs. CONCLUSION: Our study fills an important gap in the polysubstance use literature specifically exploring the co-injection of methamphetamines and opioids. Our findings highlight the need to implement and expand interventions and services attentive to polysubstance use and the role of pleasure in drug taking practices, including expanding non-medicalized opioid and stimulant safer supply initiatives across North America.

Beyond Genetics: The Role of Metabolism in Photoreceptor Survival, Development and Repair.

Vision commences in the retina with rod and cone photoreceptors that detect and convert light to electrical signals. The irreversible loss of photoreceptors due to neurodegenerative disease leads to visual impairment and blindness. Interventions now in development include transplanting photoreceptors, committed photoreceptor precursors, or retinal pigment epithelial (RPE) cells, with the latter protecting photoreceptors from dying. However, introducing exogenous human cells in a clinical setting faces both regulatory and supply chain hurdles. Recent work has shown that abnormalities in central cell metabolism pathways are an underlying feature of most neurodegenerative disorders, including those in the retina. Reversal of key metabolic alterations to drive retinal repair thus represents a novel strategy to treat vision loss based on cell regeneration. Here, we review the connection between photoreceptor degeneration and alterations in cell metabolism, along with new insights into how metabolic reprogramming drives both retinal development and repair following damage. The potential impact of metabolic reprogramming on retinal regeneration is also discussed, specifically in the context of how metabolic switches drive both retinal development and the activation of retinal glial cells known as Müller glia. Müller glia display latent regenerative properties in teleost fish, however, their capacity to regenerate new photoreceptors has been lost in mammals. Thus, re-activating the regenerative properties of Müller glia in mammals represents an exciting new area that integrates research into developmental cues, central metabolism, disease mechanisms, and glial cell biology. In addition, we discuss this work in relation to the latest insights gleaned from other tissues (brain, muscle) and regenerative species (zebrafish).

Implementation of Safe Supply Alternatives During Intersecting COVID-19 and Overdose Health Emergencies in British Columbia, Canada, 2021.

Objectives. To explore the implementation and effectiveness of the British Columbia, Canada, risk mitigation guidelines among people who use drugs, focusing on how experiences with the illicit drug supply shaped motivations to seek prescription alternatives and the subsequent impacts on overdose vulnerability. Methods. From February to July 2021, we conducted qualitative interviews with 40 people who use drugs in British Columbia, Canada, and who accessed prescription opioids or stimulants under the risk mitigation guidelines. Results. COVID-19 disrupted British Columbia's illicit drug market. Concerns about overdose because of drug supply changes, and deepening socioeconomic marginalization, motivated participants to access no-cost prescription alternatives. Reliable access to prescription alternatives addressed overdose vulnerability by reducing engagement with the illicit drug market while allowing greater agency over drug use. Because prescriptions were primarily intended to manage withdrawal, participants supplemented with illicit drugs to experience enjoyment and manage pain. Conclusions. Providing prescription alternatives to illicit drugs is a critical harm reduction approach that reduces exposure to an increasingly toxic drug supply, yet further optimizations are needed. (Am J Public Health. 2022;112(S2):S151-S158. https://doi.org/10.2105/AJPH.2021.306692).

Characterizing stimulant overdose: A qualitative study on perceptions and experiences of "overamping".

BACKGROUND: The dominant focus of North America's current overdose crisis has been opioids, resulting in considerable research and harm reduction efforts to address opioid-related overdose risks. Less attention has been paid to people who use stimulants (PWUS) despite recent increases in stimulant use and stimulant-involved overdoses (i.e., "overamping"). Stimulant users' definitions, risk factors and experiences of, and responses to, overamping are poorly understood, thereby putting PWUS at heightened risk of adverse health outcomes. This study explores how PWUS understand, experience, and respond to overamping. METHODS: In-depth qualitative interviews were conducted with 61 PWUS in Vancouver, Canada's Downtown Eastside neighbourhood. Thematic analysis of interviews focused on contextualizing stimulant overdoses, including how PWUS understand, define, experience, and respond to overamping. RESULTS: Participants associated overamping experiences with commonly identified signs and symptoms, such as rapid onset, elevated heart rate, incontinence, and audiovisua hallucinations, but also reported more serious indicators of overamping, such as unconsciousness, cardiac arrests and seizures. Our findings demonstrate that, among PWUS, there was no unified understanding of overamping such as with opioid overdose and individual experiences had substantial variation in severity and presentation. This impacted the ability to adequately respond to stimulant overdoses, which were primarily self-managed through methods including stabilizing breathing, polysubstance use, and cold showers. CONCLUSION: Given the growing role of stimulants in North America's overdose crisis, there is an urgent need to improve the identification of stimulant overdoses in real world settings. Our findings identify a gap in current understandings of stimulant overdose, and demonstrate the need for public health and harm reduction interventions to better address overamp risk among PWUS, including harm reduction campaigns to disseminate information regarding identifying signs of, and proper responses to, overamping.

Direct Neuronal Reprogramming: Bridging the Gap Between Basic Science and Clinical Application.

Direct neuronal reprogramming is an innovative new technology that involves the conversion of somatic cells to induced neurons (iNs) without passing through a pluripotent state. The capacity to make new neurons in the brain, which previously was not achievable, has created great excitement in the field as it has opened the door for the potential treatment of incurable neurodegenerative diseases and brain injuries such as stroke. These neurological disorders are associated with frank neuronal loss, and as new neurons are not made in most of the adult brain, treatment options are limited. Developmental biologists have paved the way for the field of direct neuronal reprogramming by identifying both intrinsic cues, primarily transcription factors (TFs) and miRNAs, and extrinsic cues, including growth factors and other signaling molecules, that induce neurogenesis and specify neuronal subtype identities in the embryonic brain. The striking observation that postmitotic, terminally differentiated somatic cells can be converted to iNs by mis-expression of TFs or miRNAs involved in neural lineage development, and/or by exposure to growth factors or small molecule cocktails that recapitulate the signaling environment of the developing brain, has opened the door to the rapid expansion of new neuronal reprogramming methodologies. Furthermore, the more recent applications of neuronal lineage conversion strategies that target resident glial cells in situ has expanded the clinical potential of direct neuronal reprogramming techniques. Herein, we present an overview of the history, accomplishments, and therapeutic potential of direct neuronal reprogramming as revealed over the last two decades.

Navigating post-eviction drug use amidst a changing drug supply: A spatially-oriented qualitative study of overlapping housing and overdose crises in Vancouver, Canada.

BACKGROUND: North American cities are experiencing intersecting housing and overdose crises as illicit drug markets become marked by the proliferation of fentanyl and methamphetamine. Despite recent research documenting associations between evictions and drug-related risks and harms, including overdose, the mechanisms through which these occur remain poorly understood. This study to examines how evictions shape the drug use practices of people who use drugs in Vancouver's Downtown Eastside - a neighbourhood with an established drug scene - as the illicit drug supply changed. METHODS: Qualitative interviews and geo-spatial data collection were conducted with 56 recently evicted PWUD. Data were analyzed by interfacing qualitative and geo-spatial data, and interpreted focusing on how structural vulnerability shaped spatial practices and drug-related risks post-eviction. RESULTS: Findings demonstrate how post-eviction spatial practices and routines produced risk and harm as participants navigated the uncertainties of housing vulnerability and drug supply changes. Post-eviction disruptions complicated participants' ability to engage with trusted drug sellers. Changes to spatial patterns and access to private spaces rendered public drug use inevitable, though this was mitigated to some degree by harm reduction supports. Abrupt changes to drug use patterns occurred due to post-eviction disruptions and included instrumental uses of methamphetamine to increase alertness and navigate survival amidst severe hardship. CONCLUSIONS: Findings demonstrate how post-eviction changes to routines and spatial patterns are framed by structural vulnerability and can exacerbate drug-related harms, particularly in the context of a changing drug supply. There is an urgent need for structural interventions and harm reduction responses to mitigate harms associated with evictions.

A qualitative investigation of HIV treatment dispensing models and impacts on adherence among people living with HIV who use drugs.

Antiretroviral therapy (ART) dispensing is strongly associated with treatment adherence. Among illicit drug-using populations, whom experience greater structural barriers to adherence, directly administered antiretroviral therapy (DAAT) is often regarded as a stronger predictor of optimal adherence over self-administered medications. In Vancouver, Canada, people living with HIV (PLHIV) who use drugs and live in low-income housing are a critical population for treatment support. This group is typically able to access two key DAAT models, daily delivery and daily pickup, in addition to ART self-administration. This ethno-epidemiological qualitative study explores how key dispensing models impact ART adherence among PLHIV who use drugs living in low-income housing, and how this is framed by structural vulnerability. Semi-structured interviews lasting 30-45 minutes were conducted between February and May 2018 with 31 PLHIV who use drugs recruited from an ongoing prospective cohort of PLHIV who use drugs. Interviews were audio-recorded, transcribed verbatim, and analyzed using QSR International's NVivo 12 software. Interviews focused on housing, drug use, and HIV management. Models that constrained agency were found to have negative impacts on adherence and quality of life. Treatment interruptions were framed by structural vulnerabilities (e.g., housing vulnerability) that impacted ability to maintain adherence under certain dispensing models, and led participants to consider other models. Participants using DAAT models which accounted for their structural vulnerabilities (e.g., mobility issues, housing instability), credited these models for their treatment adherence, but also acknowledged factors that constrained agency, and the negative impacts this could have on both adherence, and quality of life. Being able to integrate ART into an established routine is key to supporting ART adherence. ART models that account for the structural vulnerability of PLHIV who use drugs and live in low-income housing are necessary and housing-based supports could be critical, but the impacts of such models on agency must be considered to ensure optimal adherence.

Women's multiple uses of an overdose prevention technology to mitigate risks and harms within a supportive housing environment: a qualitative study.

BACKGROUND: North America is amidst an opioid overdose epidemic. In many settings, particularly Canada, the majority of overdose deaths occur indoors and impact structurally vulnerable people who use drugs alone, making targeted housing-based interventions a priority. Mobile applications have been developed that allow individuals to solicit help to prevent overdose death. We examine the experiences of women residents utilizing an overdose response button technology within a supportive housing environment. METHODS: In October 2019, we conducted semi-structured qualitative interviews with 14 residents of a women-only supportive housing building in an urban setting where the overdose response button technology was installed. Data was analyzed thematically and framed by theories of structural vulnerability. RESULTS: While participants described the utility and disadvantages of the technology for overdose response, most participants, unexpectedly described alternate adoptions of the technology. Participants used the technology for other emergency situations (e.g., gender-based violence), rather than its intended purpose of overdose response. CONCLUSIONS: Our findings highlight the limitations of current technologies while also demonstrating the clear need for housing-based emergency response interventions that address not just overdose risk but also gender-based violence. These need to be implemented alongside larger strategies to address structural vulnerabilities and provide greater agency to marginalized women who use drugs.

Acceptability of a hypothetical preventative HIV vaccine among people who use drugs in Vancouver, Canada.

BACKGROUND: As research on HIV vaccines continues to advance, studies exploring the feasibility of this intervention are necessary to inform uptake and dissemination strategies with key populations, including people who use drugs (PWUD). METHODS: We conducted 25 in-depth qualitative interviews examining HIV vaccine acceptability among PWUD in Vancouver, Canada. Participants were recruited from an ongoing prospective cohort of HIV-negative PWUD. Data were coded using NVivo, and analyzed thematically. RESULTS: Acceptability was framed by practical considerations such as cost and side effects, and was influenced by broader trust of government bodies and health care professionals. While an HIV vaccine was perceived as an important prevention tool, willingness to be vaccinated was low. Results suggest that future vaccine implementation must consider how to minimize the burden an HIV vaccine may place on PWUD. Centering the role of health care providers in information dissemination and delivery may assist with uptake. CONCLUSIONS: Our findings suggest improvements in care and improved patient-provider relationships would increase the acceptability of a potential HIV vaccine among this population.

The Emerging Role of Extracellular Vesicles in the Glioma Microenvironment: Biogenesis and Clinical Relevance.

Gliomas are a diverse group of brain tumors comprised of malignant cells ('tumor' cells) and non-malignant 'normal' cells, including neural (neurons, glia), inflammatory (microglia, macrophage) and vascular cells. Tumor heterogeneity arises in part because, within the glioma mass, both 'tumor' and 'normal' cells secrete factors that form a unique microenvironment to influence tumor progression. Extracellular vesicles (EVs) are critical mediators of intercellular communication between immediate cellular neighbors and distantly located cells in healthy tissues/organs and in tumors, including gliomas. EVs mediate cell-cell signaling as carriers of nucleic acid, lipid and protein cargo, and their content is unique to cell types and physiological states. EVs secreted by non-malignant neural cells have important physiological roles in the healthy brain, which can be altered or co-opted to promote tumor progression and metastasis, acting in combination with glioma-secreted EVs. The cell-type specificity of EV content means that 'vesiculome' data can potentially be used to trace the cell of origin. EVs may also serve as biomarkers to be exploited for disease diagnosis and to assess therapeutic progress. In this review, we discuss how EVs mediate intercellular communication in glioma, and their potential role as biomarkers and readouts of a therapeutic response.

Home and health among people living with HIV who use drugs: A qualitative study.

INTRODUCTION: Housing is a critical determinant of HIV-related outcomes among people living with HIV (PLHIV) who use drugs, including on HIV treatment adherence. Research shows that sense of home may have important implications for mitigating harms associated with low-income housing environments among PLHIV who use drugs, but how this shapes treatment is poorly understood. METHODS: Semi-structured interviews were conducted with 31 PLHIV who use drugs recruited from an ongoing prospective cohort in Vancouver, Canada. Recruitment was targeted towards individuals living in single room occupancy housing who had previously reported low treatment adherence. Interviews were co-led with a peer research assistant, and focused on housing conditions, drug use patterns, and HIV management. Interviews were transcribed, analyzed thematically, and interpreted by drawing on concepts of home and place-making. RESULTS: The ability to exert control over housing environments contributed to participants' perceptions of home by fostering feelings of safety and allowing for creation of personalized space. Participants readily identified the importance of housing stability and quality in maintaining health (e.g. food storage, pest-free), including HIV care. However, informed by social-structural mechanisms that undermined agency, negative experiences of home adversely impacted treatment adherence. CONCLUSIONS: Findings indicate that sense of home may enable ability to manage HIV care, and is promoted through feelings of security within, and control over, housing environments. Supports in navigating competitive housing markets are needed to address the role that home plays in HIV treatment adherence.

Stimulant safe supply: a potential opportunity to respond to the overdose epidemic.

BACKGROUND: Occurring against the backdrop of an overdose crisis, stimulant use and stimulant-involved deaths in North America are increasing at an alarming rate. Many of these deaths are being attributed to fentanyl and related analogs, which have been increasingly found within street-level stimulant supplies. Within this, people experiencing socio-economic marginalization are at the greatest risk of overdose and other harms from adulterated stimulants. Current treatments for stimulant use disorder have limited effectiveness, and even less applicability to the lived realities of marginalized stimulant users. Emerging technologies, such as drug checking, are being implemented to support safer stimulant use, but the accessibility and utility of these technologies to stimulant users are framed by experiences of vulnerability that render them largely ineffective. STIMULANT SAFE SUPPLY: Solutions that provide a legal and safe supply of non-adulterated stimulants of known quality, and within a health care framework, are needed to directly address the risk of an increasingly adulterated stimulant supply. Similar innovative opioid-focused interventions are being piloted with medications that have a similar pharmacological effect as their illicit counterparts. While there are currently no approved pharmacotherapies for stimulant use, research has demonstrated a number of stimulant medications that are promising substitutes for cocaine and methamphetamine use. Much like with opioid-focused pharmacotherapies, having a consistent and safe supply of stimulants can lead to improved health outcomes and will drastically reduce overdose risk. However, for a stimulant safe supply intervention to be a success, it must provide the high and performance-enhancing effects that people seek from the illicit market, which requires doses and user agency that trials to date have not provided. CONCLUSION: Efforts are needed to investigate the feasibility of pharmacological stimulant-based interventions that address safe supply needs. The promise of similar opioid-focused approaches in addressing both overdose-related risks and experiences related to vulnerability underscores the need to advance safe supply approaches targeted towards people who use stimulants. Given the current overdose crisis and rising stimulant use across North America, the implementation and evaluation of such novel stimulant-focused interventions should be a public health priority.

Insights Into the Role and Potential of Schwann Cells for Peripheral Nerve Repair From Studies of Development and Injury.

Peripheral nerve injuries arising from trauma or disease can lead to sensory and motor deficits and neuropathic pain. Despite the purported ability of the peripheral nerve to self-repair, lifelong disability is common. New molecular and cellular insights have begun to reveal why the peripheral nerve has limited repair capacity. The peripheral nerve is primarily comprised of axons and Schwann cells, the supporting glial cells that produce myelin to facilitate the rapid conduction of electrical impulses. Schwann cells are required for successful nerve regeneration; they partially "de-differentiate" in response to injury, re-initiating the expression of developmental genes that support nerve repair. However, Schwann cell dysfunction, which occurs in chronic nerve injury, disease, and aging, limits their capacity to support endogenous repair, worsening patient outcomes. Cell replacement-based therapeutic approaches using exogenous Schwann cells could be curative, but not all Schwann cells have a "repair" phenotype, defined as the ability to promote axonal growth, maintain a proliferative phenotype, and remyelinate axons. Two cell replacement strategies are being championed for peripheral nerve repair: prospective isolation of "repair" Schwann cells for autologous cell transplants, which is hampered by supply challenges, and directed differentiation of pluripotent stem cells or lineage conversion of accessible somatic cells to induced Schwann cells, with the potential of "unlimited" supply. All approaches require a solid understanding of the molecular mechanisms guiding Schwann cell development and the repair phenotype, which we review herein. Together these studies provide essential context for current efforts to design glial cell-based therapies for peripheral nerve regeneration.

Housing in crisis: A qualitative study of the socio-legal contexts of residential evictions in Vancouver's Downtown Eastside.

BACKGROUND: People who use drugs (PWUD) commonly experience housing vulnerability due to the intersection of drug laws, housing policies, gentrification, and social marginalization. Housing vulnerability produces social suffering amongst PWUD and is linked to health and social harms. In Vancouver, Canada, the rapid gentrification of the Downtown Eastside - a low-income inner-city neighbourhood - and the lack of affordable housing has led to residential evictions emerging as a key community concern. This study sought to understand the policies and practices that produced evictions among PWUD, situating vulnerabilities to evictions within the context of wider structural vulnerability of PWUD. METHODS: Between June 2015 and March 2016, baseline and 3-6 month follow-up qualitative interviews were conducted with recently evicted (past 60 days) PWUD in the Downtown Eastside. Participants were recruited by Peer Research Assistants. Baseline interviews (n = 56) focused on causes and socio-legal contexts of evictions, with follow-up interviews (n = 41) focusing on longer-term impacts. Interviews were analyzed thematically and interpreted by drawing on the concept of structural vulnerability. RESULTS: Most participants were evicted unlawfully, unfairly, and into homelessness. Participants were rendered structurally vulnerable to unlawful evictions by the shortcomings of existing residential tenancy laws and current dispute mechanisms. Residents of non-profit buildings, for whom it was unclear if provincial residential protections apply, found their housing security further undermined through the denial of rights extended to privately-housed tenants. Attempts to assert tenant rights further increased participants' vulnerability to eviction through landlord retaliation and targeting. CONCLUSION: Findings demonstrate the inadequacy of existing housing policies and tenancy supports to account for the structural vulnerability of PWUD and their role in driving harms. Policy reforms are needed to address unlawful evictions and increase tenancy security, and must be accompanied by low-barrier interventions to more fully address this key driver of social suffering among PWUD.