"We don't even know where it's kept": exploring perspectives on naloxone administration by provincial correctional workers in Manitoba, Canada.

PURPOSE: Prisonersare at disproportionate risk of suffering substance-related harms. The administration of naloxone is essential to reversing opioid overdose and minimizing substance-related harms in prison and the community. The purpose of this study is to examine how naloxone administration is practiced and perceived in prison settings. DESIGN/METHODOLOGY/APPROACH: The authors conducted surveys with correctional workers in Manitoba, Canada (n = 257) to examine how they understand and feel about the need for and practice of administering naloxone in their everyday work with criminalized populations. FINDINGS: Respondents reported feeling a great need to administer naloxone, but most did not feel adequately trained to administer naloxone, creating the perception that criminalized populations remain at enhanced risk. ORIGINALITY/VALUE: Findings provide emerging evidence of the need for training and accompanying policies and procedures for correctional workers on how to access and administer naloxone.

Prospective evaluation of clinical and radiographic 10-year results of Fitmore short-stem total hip arthroplasty.

BACKGROUND: Short stems were introduced into total hip arthroplasty (THA) to preserve bone stock, to transmit more load to the proximal femur, and to enable minimal invasive approaches. This study is the first long-term study (with a follow-up of 10 years) of the survival as well as the clinical and radiographic outcomes of the Fitmore hip stem, a short curved uncemented stem. METHODS: In total, 123 Fitmore hip stems were prospectively evaluated. At the final 10-year follow-up, 80 Fitmore stems (78 patients: 30 female, 48 male) were eligible for evaluation. Clinical parameters were thigh pain, EQ-5D, Harris Hip Score (HHS) and Oxford Hip Score. Radiographic parameters were cortical hypertrophy (CH), bone condensation, cortical thinning, radiolucency, reactive lines, calcar rounding, calcar resorption, subsidence and varus/valgus position. RESULTS: After 10 years, there was a survival rate of 99% (1 revision because of aseptic stem loosening). HHS had improved from 59 to 94 and Oxford Hip Score from 22 to 43. CH rate after 1 year was 69% and after 10 years 74%. In the first year, radiolucency was found in 58% and in 17.5% after 10 years. Subsidence after 1 year was 1.6 ± 1.6 mm and 5.0 ± 3.1 mm after 10 years. CONCLUSIONS: The Fitmore hip stem showed a survival rate of 99% as well as good clinical and radiographic outcomes in the long-term follow-up of 10 years.

Social and structural barriers and facilitators to HIV healthcare and harm reduction services for people experiencing syndemics in Manitoba: study protocol.

INTRODUCTION: In Manitoba, Canada, there has been an increase in the number of people newly diagnosed with HIV and those not returning for regular HIV care. The COVID-19 pandemic resulted in increased sex and gender disparities in disease risk and mortalities, decreased harm reduction services and reduced access to healthcare. These health crises intersect with increased drug use and drug poisoning deaths, houselessness and other structural and social factors most acutely among historically underserved groups. We aim to explore the social and structural barriers and facilitators to HIV care and harm reduction services experienced by people living with HIV (PLHIV) in Manitoba. METHODS AND ANALYSIS: Our study draws on participatory action research design. Guiding the methodological design are the lived experiences of PLHIV. In-depth semi-structured face-to-face interviews and quantitative questionnaires will be conducted with two groups: (1) persons aged ≥18 years living or newly diagnosed with HIV and (2) service providers who work with PLHIV. Data collection will include sex, gender, sociodemographic information, income and housing, experiences with the criminal justice system, sexual practices, substance use practices and harm reduction access, experiences with violence and support, HIV care journey (since diagnosis until present), childhood trauma and a decision-making questionnaire. Data will be analysed intersectionally, employing grounded theory for thematic analysis, sex-based and gender-based analysis and social determinants of health and syndemic framework to understand the experiences of PLHIV in Manitoba. ETHICS AND DISSEMINATION: We received approval from the University of Manitoba Health Ethics Research Board (HS25572; H2022:218), First Nations Health and Social Secretariat of Manitoba, Nine Circles Community Health Centre, Shared Health Manitoba (SH2022:194) and 7th Street Health Access Centre. Findings will be disseminated using community-focused knowledge translation strategies identified by participants, peers, community members and organisations, and reported in conferences, peer-reviewed journals and a website (www.alltogether4ideas.org).

Parole Work in Canada: Tensions in Supervising People Convicted of Sex Crimes.

Internationally, parole work is loaded with tensions, particularly when supervising a people convicted of sex crimes (PCSCs) who, due to their criminal history, are stigmatized and occupy the lowest rungs of the status hierarchy in prison and society more broadly. Drawing on analyses of interview data from federal parole officers (n = 150) employed by Correctional Service Canada, we interpret their perceptions and feelings about overseeing re-entry preparations and processes for the PCSCs on their caseloads. We unpack the "tensions" imbued in parole officers' internal reflections and negotiation of complexities in their efforts toward supporting client's rehabilitation efforts, desistance from crime while negotiating external factors (e.g., the lack of available programming), and being responsible for supervising PCSCs. We highlight facets of occupational stress parole officers experience, finding PCSCs may be more compliant when under supervision but may also require more of a parole officer's resources, including time and energy. We put forth recommendations for greater empirical nuance concerning parole officer work and their occupational experiences and beliefs about PCSC, particularly as related to parole officer health.

"It's just not the same": Exploring PWUD' perceptions of and experiences with drug policy and SCS services change in a Canadian City.

BACKGROUND AND AIMS: Shifting political contexts can significantly alter drug policy approaches and available supports for People Who Use Drugs (PWUD). The purpose of this study was to explore how shifts in provincial drug policy approaches, specifically the replacement of a Safe Consumption Site (SCS) with a smaller mobile Overdose Prevention Site (OPS) in Lethbridge, Alberta Canada, impacted PWUD' access to and experiences with harm reduction services. METHODS: We conducted semi-structured interviews with 50 PWUD in the City of Lethbridge, Canada. Through traditional fieldwork, we recruited participants within, and just outside of, downtown Lethbridge. Using a standardized general prompt guide to begin interviews, participants were asked a variety of questions about their experiences with and perceptions of SCS access and changes to SCS provisions. Interviews were audio recorded, then transcribed, coded, and analyzed. RESULTS: Participants reported regular and frequent access and overall positive experiences with the SCS, despite also noting certain operational barriers (e.g., long wait times). By contrast, participants reported more limited use of the new OPS compared to the SCS because of three main reasons: (1) concerns about location; (2) smoking room elimination; and (3) lack of social space and activities. Overall, changes to SCS provision produced a range of negative consequences for PWUD in Lethbridge. These relate to perceived increases in drug-related harms (e.g., increased overdoses) as well as negative social impacts (e.g., lack of place to meet other people). CONCLUSION: Findings from this study provide preliminary indications of the importance of understanding how contextual and locally-specific elements (location, limits on permitted route administration, and social aspects) can work together to facilitate SCS uptake and even overcome traditional SCS barriers. Conversely, the absence of such elements can hinder SCS uptake. Results show that the value of SCS might differ across locations, pointing to the need for further locally-grounded examinations of harm reduction service uptake and experience.

"Prison didn't change me, I have changed": Narratives of change, self, and prison time.

Drawing on interview data with over 50 male former prisoners in Ontario, Canada, we examine male ex-prisoners' narratives of change within prison settings. Specifically, we focus on how ex-prisoners talk about change to self and their persona, as they reflect back on both their pre-prison selves and the ways they believe prison changed them. We find that these ex-prisoners described prison as a time where they developed a more general sense of positive change. Ex-prisoners described how prison living made them "calmer," "stronger," and more "patient" overall. These descriptions stand in tension with the overall hostility of prison environments where prisoners are forced to focus on survival and basic well-being as they navigate the risks and threats of prison living. Overall, in this article, we seek to contribute to emerging discussions on positivity within prison settings, acknowledging that studying the more positive impacts of prison is a delicate yet important endeavor necessary to help better understand the experiential complexities of punishment.

A qualitative comparison of how people who use drugs' perceptions and experiences of policing affect supervised consumption services access in two cities.

BACKGROUND: Police presence near Supervised Consumption Services (SCS) and other harm reduction services has been shown to hamper access to these critical facilities for People Who Use Drugs (PWUD). However, few studies document the empirical nuances of these contextually dependant police-PWUD relationships, and how PWUD' experiences and perceptions of policing near harm reduction services shape SCS access. If the goal is to increase SCS uptake, understanding the complexities of PWUD-police relations near SCS is imperative for guiding both formal policy and informal best-practices. METHODS: We report findings from a larger qualitative study on PWUD' experiences with SCS in two Canadian cities. Data were collected through 75 face-to-face interviews and observations with street-involved PWUD near local SCS in Edmonton and Calgary, Alberta. RESULTS: Participants' perceptions of and experiences with policing varied across jurisdictions. Participants in Calgary reported concentrated police presence in and near SCS, in addition to harassment, negative encounters, fears about getting arrested, and experiences of being displaced from the area. Participants in Edmonton, despite also reporting heavy police presence near SCS, reported feeling relatively safe from police intervention and harassment, within SCS and the surrounding area. CONCLUSION: Rather than the presence/absence and quantity of policing near SCS, our findings show that the quality of policing experienced in the community shapes PWUD' perceptions, experiences, and willingness to access SCS.

A Polymorphism of Bactericidal/Permeability-Increasing Protein Affects Its Neutralization Efficiency towards Lipopolysaccharide.

Gram-negative sepsis driven by lipopolysaccharide (LPS) has detrimental outcomes, especially in neonates. The neutrophil-derived bactericidal/permeability-increasing protein (BPI) potently neutralizes LPS. Interestingly, polymorphism of the BPI gene at position 645 (rs4358188) corresponds to a favorable survival rate of these patients in the presence of at least one allele 645 A as opposed to 645 G. When we exploited the existing X-ray crystal structure, the corresponding amino acid at position 216 was revealed as surface exposed and proximal to the lipid-binding pocket in the N-terminal domain of BPI. Our further analysis predicted a shift in surface electrostatics by a positively charged lysine (BPI216K) exchanging a negatively charged glutamic acid (BPI216E). To investigate differences in interaction with LPS, we expressed both BPI variants recombinantly. The amino acid exchange neither affected affinity towards LPS nor altered bactericidal activity. However, when stimulating human peripheral blood mononuclear cells, BPI216K exhibited a superior LPS-neutralizing capacity (IC50 12.0 ± 2.5 pM) as compared to BPI216E (IC50 152.9 ± 113.4 pM, p = 0.0081) in respect to IL-6 secretion. In conclusion, we provide a functional correlate to a favorable outcome of sepsis in the presence of BPI216K.

CCWORK protocol: a longitudinal study of Canadian Correctional Workers' Well-being, Organizations, Roles and Knowledge.

INTRODUCTION: Knowledge about the factors that contribute to the correctional officer's (CO) mental health and well-being, or best practices for improving the mental health and well-being of COs, have been hampered by the dearth of rigorous longitudinal studies. In the current protocol, we share the approach used in the Canadian Correctional Workers' Well-being, Organizations, Roles and Knowledge study (CCWORK), designed to investigate several determinants of health and well-being among COs working in Canada's federal prison system. METHODS AND ANALYSIS: CCWORK is a multiyear longitudinal cohort design (2018-2023, with a 5-year renewal) to study 500 COs working in 43 Canadian federal prisons. We use quantitative and qualitative data collection instruments (ie, surveys, interviews and clinical assessments) to assess participants' mental health, correctional work experiences, correctional training experiences, views and perceptions of prison and prisoners, and career aspirations. Our baseline instruments comprise two surveys, one interview and a clinical assessment, which we administer when participants are still recruits in training. Our follow-up instruments refer to a survey, an interview and a clinical assessment, which are conducted yearly when participants have become COs, that is, in annual 'waves'. ETHICS AND DISSEMINATION: CCWORK has received approval from the Research Ethics Board of the Memorial University of Newfoundland (File No. 20190481). Participation is voluntary, and we will keep all responses confidential. We will disseminate our research findings through presentations, meetings and publications (e.g., journal articles and reports). Among CCWORK's expected scientific contributions, we highlight a detailed view of the operational, organizational and environmental stressors impacting CO mental health and well-being, and recommendations to prison administrators for improving CO well-being.

Upregulation of CD20 Positive B-Cells and B-Cell Aggregates in the Tumor Infiltration Zone is Associated with Better Survival of Patients with Pancreatic Ductal Adenocarcinoma.

Patients with pancreatic ductal adenocarcinoma (PDAC) normally have a poor long-term prognosis. However, some rare cases of long-term survivors have been reported. The tumor microenvironment, consisting of cellular and stromal components, possibly plays an important role and might influence prognosis. In this context, the role of tumor-infiltrating B-cells and its impact on the survival in patients with PDAC remains controversial. We therefore aimed to assess the prognostic value of CD20-positive B-cells and CD20-positive B-cell aggregates as well as CD138, IgM, Pax5, and Ki67 on the survival of patients with PDAC using immunohistochemistry of FFPE pancreatectomy tissue sections from patients that underwent primary surgery for pT3- and R0-pancreatic adenocarcinoma between 1995 and 2016. Patients with PDAC were matched and grouped in 16 long-term-survivors (LTS, median overall survival (OS): 96 months [range: 61-177 months]) and 16 short-term-survivors (STS, median OS: 16 months [range: 7-32 months]). CD20-positive B-cells and B-cell aggregates in the tumor infiltration zone were significantly upregulated in the LTS-group compared to the STS-group (p = 0.0499 respectively p = 0.0432). Regarding the entire patient cohort (n = 32) CD20 positive B-cell aggregates in the tumor infiltration zone were an independent prognostic marker for overall survival in multivariate analysis (HR 9.2, CI 1.6-51.4, p = 0.012). These results underline the importance of tumor-associated B-cells for prognosis of patients with PDAC. The detailed role of B cells in the pathomechanism of PDAC should be further investigated for predicting outcome, identifying appropriate treatment regimens, and developing novel therapeutic options.

Impact of geography and surgical approach on recurrence in global pilonidal sinus disease.

Pilonidal sinus disease (PSD) is increasing globally. A recent meta-analysis and merged-data analysis showed that recurrence rates in PSD depend essentially on follow-up time and specific surgical procedures. However, the global distribution of surgical approaches and respective recurrence rates have never been studied in PSD. We aimed at studying the impact of geographic distribution of surgical approaches to treat PSD and subsequent geography-specific recurrence rates. We searched relevant databases as described previously. Recurrence rates were then associated with reported follow-up times and geographic origin. We simulated individual patients to enable analogy across data. Globally, recurrence rates range from 0.3% for Limberg/Dufourmentel approaches (95% CI 0.2-0.4) and flaps (95% CI 0.1-0.5) and up to 6.3% for incision (95% CI 3.2-9.3) at 12 months. Recurrence rates range from 0.3% for Karydakis/Bascom approaches (95% CI 0.0-0.8) up to 67.2% for incision (95% CI 7.5-100) in the USA, and 0.0% for primary asymmetric closure in Germany (95% CI 0.0-0.0). Our analysis shows that recurrence rates in PSD not only depend on therapeutic approaches and follow-up time but also on geography. Primary asymmetric closure and various flap techniques remain superior regardless of the geographical region. Some approaches have extraordinarily good outcomes in specific countries.

Supramolecular nanopatterns of H-shaped molecules.

Alkoxy-substituted phenylene-ethynylene-butadiynylenes (PEBs) are connected via 1H-benzimidazole units to form H-shaped molecular scaffolds that self-assemble on graphite at the solid/liquid interface. Spacer lengths and end groups determine supramolecular tiling patterns, as shown via scanning tunneling microscopy (STM).

Biological markers for axonal degeneration in CSF and blood of patients with the first event indicative for multiple sclerosis.

Axonal degeneration is now recognized as an important pathological feature of multiple sclerosis (MS). Acute axonal damage happens early in the disease course, and therefore early changes might occur in markers in body fluids, such as cerebrospinal fluid (CSF) and blood. In our study we investigated the relevance of serum and CSF markers for axonal damage in patients with clinically isolated syndrome indicative for MS. We measured the concentration of tau, phospho-tau, S100B, Amyloid beta and neuron specific enolase (NSE) in CSF and serum. Interestingly, the NSE concentration in CSF and serum was decreased in clinically isolated syndrome (CIS)-patients in comparison to the control group indicating reduced neuronal metabolic activity in the early stage of the disease. Concerning other biomarkers, we did not observe any changes in the concentrations between groups. Moreover, we did not detect any correlation between Expanded Disability Status Scale (EDSS) and the concentration of investigated proteins.

Multiple neuroprotective mechanisms of minocycline in autoimmune CNS inflammation.

Axonal destruction and neuronal loss occur early during multiple sclerosis, an autoimmune inflammatory CNS disease that frequently manifests with acute optic neuritis. Available therapies mainly target the inflammatory component of the disease but fail to prevent neurodegeneration. To investigate the effect of minocycline on the survival of retinal ganglion cells (RGCs), the neurons that form the axons of the optic nerve, we used a rat model of myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis. Optic neuritis in this model was diagnosed by recording visual evoked potentials and RGC function was monitored by measuring electroretinograms. Functional and histopathological data of RGCs and optic nerves revealed neuronal and axonal protection when minocycline treatment was started on the day of immunization. Furthermore, we demonstrate that minocycline-induced neuroprotection is related to a direct antagonism of multiple mechanisms leading to neuronal cell death such as the induction of anti-apoptotic intracellular signalling pathways and a decrease in glutamate excitotoxicity. From these observations, we conclude that minocycline exerts neuroprotective effects independent of its anti-inflammatory properties. This hypothesis was confirmed in a non-inflammatory disease model leading to degeneration of RGCs, the surgical transection of the optic nerve.

Effects of glatiramer acetate and interferon-beta on neurodegeneration in a model of multiple sclerosis: a comparative study.

Axonal destruction and neuronal loss occur early during multiple sclerosis (MS), an autoimmune inflammatory central nervous system disease that frequently manifests with acute optic neuritis. Glatiramer acetate (GA) and interferon-beta-1b (IFN-beta-1b) are two immunomodulatory agents that have been shown to decrease the frequency of MS relapses. However, the question of whether these substances can slow neurodegeneration in MS patients is the subject of controversy. In a rat model of experimental autoimmune encephalomyelitis, we investigated the effects of GA and IFN-beta-1b on the survival of retinal ganglion cells (RGCs), the neurons that form the axons of the optic nerve. For each substance, therapy was started 14 days before immunization, on the day of immunization, or on the day of clinical disease onset. After myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis became clinically manifest, optic neuritis was monitored by recording visual evoked potentials. The function of RGCs was measured by electroretinograms. Although early GA or IFN-beta-1b treatment showed benefit on disease activity, only treatment with GA exerted protective effects on RGCs, as revealed by measuring neurodegeneration and neuronal function. Furthermore, we demonstrate that this GA-induced neuroprotection does not exclusively depend on the reduction of inflammatory infiltrates within the optic nerve.

Effects of interferon-beta-1a on neuronal survival under autoimmune inflammatory conditions.

Interferon-beta-1a (IFN-beta-1a) is an approved treatment for multiple sclerosis (MS). It improves the disease course by reducing the relapse rate as well as the persistent neurological deficits. Recent MRI and post-mortem studies revealed that neuronal and axonal damage are most relevant for chronic disability in MS patients. We have characterized previously time course and mechanisms of neuronal apoptosis in a rat model of myelin oligodendrocyte glycoprotein (MOG)-induced optic neuritis. In this animal model, application of IFN-beta-1a three times per week slightly decreases the loss of retinal ganglion cells (RGCs), the neurons that form the axons within the optic nerve. In contrast to neurotrophic factors, this cytokine does not directly protect cultured RGCs from apoptosis. We conclude that IFN-beta-1a is a suitable candidate to be combined with a directly neuroprotective agent in order to further decrease axonal and neuronal degeneration in MS patients.

HIV-Tat-mediated Bcl-XL delivery protects retinal ganglion cells during experimental autoimmune optic neuritis.

In multiple sclerosis (MS), post-mortem studies of human brain tissue as well as data from animal models have shown that apoptosis of neurons occurs to a significant extent during this disease. As neurodegeneration in MS correlates with permanent neurological deficits in patients, understanding the mechanisms would be an important pre-condition for designing appropriate neuroprotective therapies. Myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis often affects the optic nerve and leads to consecutive apoptosis of retinal ganglion cells (RGCs), the neurons that form its axons. In this study, we fused Bcl-XL to the protein transduction domain of the HIV-transactivator of transcription. Thereby, this anti-apoptotic member of the Bcl-2 family was delivered into RGCs of rats with electrophysiologically diagnosed optic neuritis. Transduction of Bcl-XL in our study led to significant rescue of RGCs indicating the relevance of this pathway for neuronal survival under autoimmune inflammatory conditions.

An international comparative study of blood pressure in populations of European vs. African descent.

BACKGROUND: The consistent finding of higher prevalence of hypertension in US blacks compared to whites has led to speculation that African-origin populations are particularly susceptible to this condition. Large surveys now provide new information on this issue. METHODS: Using a standardized analysis strategy we examined prevalence estimates for 8 white and 3 black populations (N = 85,000 participants). RESULTS: The range in hypertension prevalence was from 27 to 55% for whites and 14 to 44% for blacks. CONCLUSIONS: These data demonstrate that not only is there a wide variation in hypertension prevalence among both racial groups, the rates among blacks are not unusually high when viewed internationally. These data suggest that the impact of environmental factors among both populations may have been under-appreciated.

Combined therapy with methylprednisolone and erythropoietin in a model of multiple sclerosis.

Neurodegenerative processes determine the clinical disease course of multiple sclerosis, an inflammatory autoimmune CNS disease that frequently manifests with acute optic neuritis. None of the established multiple sclerosis therapies has been shown to clearly reduce neurodegeneration. In a rat model of experimental autoimmune encephalomyelitis, we recently demonstrated increased neuronal apoptosis under methylprednisolone therapy, although CNS inflammation was effectively controlled. In the present study, we combined steroid treatment with application of erythropoietin to target inflammatory as well as neurodegenerative aspects. After immunization with myelin oligodendrocyte glycoprotein (MOG), animals were randomly assigned to six treatment groups receiving different combinations of erythropoietin and methylprednisolone, or respective monotherapies. After MOG-induced experimental autoimmune encephalomyelitis became clinically manifest, optic neuritis was monitored by recording visual evoked potentials. The function of retinal ganglion cells, the neurons that form the axons of the optic nerve, was measured by electroretinograms. Functional and histo pathological data of retinal ganglion cells and optic nerves revealed that neuron and axon protection was most effective when erythropoietin treatment that was started at immunization was combined with high-dose methylprednisolone therapy given from days 1 to 3 of MOG-induced experimental autoimmune encephalomyelitis. In contrast, isolated neuronal or axonal protection without clinical benefit was achieved under monotherapy with erythropoietin or methylprednisolone, respectively.

Ciliary neurotrophic factor protects retinal ganglion cells from secondary cell death during acute autoimmune optic neuritis in rats.

Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS which leads to demyelination, axonal destruction and neuronal loss in the early stages. Available therapies mainly target the inflammatory component of the disease but fail to prevent neurodegeneration. To investigate the effect of ciliary neurotrophic factor (CNTF) on the survival of retinal ganglion cells (RGCs), the neurons that form the axons of the optic nerve, we used a rat model of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis. Optic neuritis in this model was diagnosed by recording visual evoked potentials, and RGC function was monitored by measuring electroretinograms. This study demonstrates that CNTF has a neuroprotective effect on affected RGCs during acute optic neuritis. Furthermore, we demonstrate that CNTF exerts its neuroprotective effect through activation of the Janus kinase/signal transducer and activator of transcription pathway, mitogen activated protein kinases and a shift in the Bcl-2 family of proteins towards the anti-apoptotic side. In summary, our results demonstrate that CNTF can serve as an effective neuroprotective treatment in a rat model of MS that especially reflects the neurodegenerative aspects of this disease.