Abstract
Background
The experiences and perceived support needs of harm reduction workers in the USA have been understudied. While previous research has explored staff burnout and role-related ...stress, there is a research gap around potential supports for staff wellbeing and individual longevity in their roles. This is especially critical given the growing overdose crisis and the need for sustainable harm reduction programming. Thus, we sought to describe the experiences of harm reduction staff and identify the perceived support that could empower harm reduction staff to successfully navigate their roles.
Methods
Purposive sampling methods were used to recruit harm reduction staff working in Connecticut. Seventeen semi-structured, one-on-one interviews were conducted between December 2022 and March 2023. Participants were asked about their experiences with role-related stressors and supports. Informed by the Social-Ecological Model, transcripts were coded using both inductive and deductive codes, and themes were developed using thematic analysis approaches.
Results
Study participants described their experiences working in harm reduction and the numerous ways they already are or could be receiving support in their roles. These experiences were organized into eight themes according to the levels of the Social-Ecological Model. At the individual level, participants explained that support could help them navigate the variability of the physical environment, boundary setting, and self-care. Relationships between clients and co-workers were both identified as means of support at the interpersonal level, helping participants navigate difficult situations and feelings of stress. At the organizational level, study participants explained how they look to their organization to provide sufficient support by way of training, staffing, compensation, and benefits. Additionally, participants stressed the importance of having supervisors who valued their work and provided emotional support. Lastly, at the community level, participants discussed how support was needed to help them navigate complex systems while working with a stigmatized population in an often-stigmatized field.
Conclusions
To best support harm reduction staff in their day-to-day roles, our findings underscore the need for support on multiple levels. Future research could explore how the provision of support to harm reduction staff impacts not only staff perceptions of support but also the success of clients accessing harm reduction services.
Extracellular vesicles (EVs) are nanoscale particles secreted by almost all cell types to facilitate intercellular communication. Stem cell-derived EVs theoretically have the same biological ...functions as stem cells, but offer the advantages of small size, low immunogenicity, and removal of issues such as low cell survival and unpredictable long-term behaviour associated with direct cell transplantation. They have been an area of intense interest in regenerative medicine, due to the potential to harness their anti-inflammatory and pro-regenerative effects to induce healing in a wide variety of tissues. However, the potential of using stem cell-derived EVs for treating joint injury and osteoarthritis has not yet been extensively explored. The pathogenesis of osteoarthritis, with or without prior joint injury, is not well understood, and there is a longstanding unmet clinical need to develop new treatments that provide a therapeutic effect in preventing or stopping joint degeneration, rather than merely relieving the symptoms of the disease. This review summarises the current evidence relating to stem cell-derived EVs in joint injury and osteoarthritis, providing a concise discussion of their characteristics, advantages, therapeutic effects, limitations and outlook in this exciting new area.
Cryptococcus neoformans (Cn) and Cryptococcus gattii (Cg) cause neurological disease and cross the BBB as free cells or in mononuclear phagocytes via the Trojan horse mechanism, although evidence for ...the latter is indirect. There is emerging evidence that Cn and the North American outbreak Cg strain (R265) more commonly cause neurological and lung disease, respectively. We have employed a widely validated in vitro model of the BBB, which utilizes the hCMEC/D3 cell line derived from human brain endothelial cells (HBEC) and the human macrophage-like cell line, THP-1, to investigate whether transport of dual fluorescence-labelled Cn and Cg across the BBB occurs within macrophages. We showed that phagocytosis of Cn by non-interferon (IFN)-γ stimulated THP-1 cells was higher than that of Cg. Although Cn and Cg-loaded THP-1 bound similarly to TNF-activated HBECs under shear stress, more Cn-loaded macrophages were transported across an intact HBEC monolayer, consistent with the predilection of Cn for CNS infection. Furthermore, Cn exhibited a higher rate of expulsion from transmigrated THP-1 compared with Cg. Our results therefore provide further evidence for transmigration of both Cn and Cg via the Trojan horse mechanism and a potential explanation for the predilection of Cn to cause CNS infection.
Opioid overdoses are a leading cause of preventable death in the United States. There is limited research linking decedents’ receipt of controlled substances and presence of controlled substances on ...post-mortem toxicology (PMT).
We linked data on opioid-detected deaths in Connecticut between May 3, 2016, and December 31, 2017 from the Office of the Chief Medical Examiner, Department of Consumer Protection, and Department of Mental Health and Addiction Services. Exposure was defined as receipt of an opioid or benzodiazepine prescription within 90 days prior to death. Our primary outcome was concordance between medication received and metabolites in PMT.
Our analysis included 1412 opioid-detected overdose deaths. 47 % received an opioid or benzodiazepine 90 days prior to death; 36 % received an opioid and 27 % received a benzodiazepine. Concordance between receipt of an opioid or benzodiazepine and its presence in PMT was observed in 30 % of opioid-detected deaths. Concordance with an opioid was present in 17 % of opioid-detected deaths and concordance with a benzodiazepine was present in 21 % of opioid-detected deaths. Receipt of an opioid or benzodiazepine and concordance with PMT were less common in fentanyl or heroin-detected deaths and more common in pharmaceutical opioid-detected deaths.
Our results suggest medically supplied opioids and benzodiazepines potentially contributed to a substantial number, though minority, of opioid-detected deaths during the study period. Efforts to reduce opioid and benzodiazepine prescribing may reduce risk of opioid-detected deaths in this group, but other approaches will be needed to address most opioid-detected deaths that involved non-pharmaceutical opioids.
•1 in 3 people who experienced an opioid-detected fatal overdose received an opioid prescription in the 90 days prior.•In 17 % of opioid-detected fatal overdoses, an opioid was present on post-mortem toxicology concordant with an opioid received via prescription.•In 1 of opioid-detected fatal overdoses, an opioid was present on post-mortem toxicology concordant with an opioid received via prescription.•1 in 4 people who experienced an opioid-detected fatal overdose received a benzodiazepine prescription in the 90 days prior.•Efforts to reduce opioid and benzodiazepine prescribing may reduce risk of opioid-involved deaths in this group.
Endothelial cells (EC) form the inner lining of blood vessels and are positioned between circulating lymphocytes and tissues. Hypotheses have formed that EC may act as antigen presenting cells based ...on the intimate interactions with T cells, which are seen in diseases like multiple sclerosis, cerebral malaria (CM) and viral neuropathologies. Here, we investigated how human brain microvascular EC (HBEC) interact with and support the proliferation of T cells. We found HBEC to express MHC II, CD40 and ICOSL, key molecules for antigen presentation and co-stimulation and to take up fluorescently labeled antigens via macropinocytosis. In co-cultures, we showed that HBEC support and promote the proliferation of CD4(+) and CD8(+) T cells, which both are key in CM pathogenesis, particularly following T cell receptor activation and co-stimulation. Our findings provide novel evidence that HBEC can trigger T cell activation, thereby providing a novel mechanism for neuroimmunological complications of infectious diseases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We assessed if leptin, a cytokine hormone known to enhance energy expenditure by promoting lipid and carbohydrate catabolism in response to physiologic stress, might directly regulate cellular ...glycolysis. A transcriptomic analysis of prolactin cells in the tilapia (
) pituitary rostral pars distalis (RPD) revealed that recombinant leptin (rtLep) differentially regulates 1,995 genes,
. Machine learning algorithms and clustering analyses show leptin influences numerous cellular gene networks including metabolism; protein processing, transport, and metabolism; cell cycle and the hypoxia response. Leptin stimulates transcript abundance of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (
) in a covariate manner to the hypoxic stress gene network. Orthogonal tests confirm that rtLepA dose-dependently increases
gene expression in the RPD along with transcript abundance of 6-phosphofructo-1-kinase (
), the rate limiting glycolytic enzyme. Functional testing demonstrated that leptin stimulates PFK activity and glycolytic output, while Stattic (a STAT3 blocker) was sufficient to suppress these responses, indicating leptin stimulates glycolysis through a STAT3-dependent mechanism. Leptin also stimulated
gene expression and lactate production in primary hepatocyte incubations in a similar manner to those shown for the pituitary RPD. This work characterizes a critical metabolic action of leptin to directly stimulate glycolysis across tissue types in a teleost model system, and suggest that leptin may promote energy expenditure, in part, by stimulating glycolysis. These data in a teleost fish, suggest that one of leptin's ancient, highly-conserved functions among vertebrates may be stimulation of glycolysis to facilitate the energetic needs associated with various stressors.
Low engagement in contact tracing for COVID-19 dramatically reduces its impact, but little is known about how experiences, environments and characteristics of cases and contacts influence engagement.
...We recruited a convenience sample of COVID-19 cases and contacts from the New Haven Health Department's contact tracing program for interviews about their contact tracing experiences. We analyzed transcripts thematically, organized themes using the Capability, Opportunity, Motivation, Behavior (COM-B) model, and identified candidate interventions using the linked Behavior Change Wheel Framework.
We interviewed 21 cases and 12 contacts. Many felt physically or psychologically incapable of contact tracing participation due to symptoms or uncertainty about protocols. Environmental factors and social contacts also influenced engagement. Finally, physical symptoms, emotions and low trust in and expectations of public health authorities influenced motivation to participate.
To improve contact tracing uptake, programs should respond to clients' physical and emotional needs; increase clarity of public communications; address structural and social factors that shape behaviors and opportunities; and establish and maintain trust. We identify multiple potential interventions that may help achieve these goals.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aquaporins (Aqps) are expressed within key osmoregulatory tissues where they mediate the movement of water and selected solutes across cell membranes. We leveraged the functional plasticity of ...Mozambique tilapia (Oreochromis mossambicus) gill epithelium to examine how Aqp3, an aquaglyceroporin, is regulated in response to osmoregulatory demands. Particular attention was paid to the actions of critical osmoregulatory hormones, namely, prolactin (Prl), growth hormone and cortisol. Branchial aqp3 mRNA levels were modulated following changes in environmental salinity, with enhanced aqp3 mRNA expression upon transfer from seawater to freshwater (FW). Accordingly, extensive Aqp3 immunoreactivity was localized to cell membranes of branchial epithelium in FW-acclimated animals. Upon transferring hypophysectomized tilapia to FW, we identified that a pituitary factor(s) is required for Aqp3 expression in FW. Replacement with ovine Prl (oPrl) was sufficient to stimulate Aqp3 expression in hypophysectomized animals held in FW, an effect blocked by coinjection with cortisol. Both oPrl and native tilapia Prls (tPrl177 and tPrl188) stimulated aqp3 in incubated gill filaments in a concentration-related manner. Consistent with in vivo responses, coincubation with cortisol blocked oPrl-stimulated aqp3 expression in vitro. Our data indicate that Prl and cortisol act directly upon branchial epithelium to regulate Aqp3 in tilapia. Thus, within the context of the diverse actions of Prl on hydromineral balance in vertebrates, we define a new role for Prl as a regulator of Aqp expression.
The pathogenesis of fatal cerebral malaria (CM) is not well understood, in part because data from patients in whom a clinical diagnosis was established prior to death are rare. In a murine CM model, ...platelets accumulate in brain microvasculature, and antiplatelet therapy can improve outcome. We determined whether platelets are also found in cerebral vessels in human CM, and we performed immunohistopathology for platelet-specific glycoprotein, GPIIb-IIIa, on tissue from multiple brain sites in Malawian children whose fatal illness was severe malarial anemia, CM, or nonmalarial encephalopathy. Platelets were observed in 3 locations within microvessels: between malaria pigment and leukocytes, associated with malaria pigment, or alone. The mean surface area of platelet staining and the proportion of vessels showing platelet accumulation were significantly higher in patients with CM than in those without it. Platelet accumulation occurs in the microvasculature of patients with CM and may play a role in the pathogenesis of the disease
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