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Abstract Background The increasing incidence of fatal opioid overdose is a public health crisis in Canada. Given growing consensus that this crisis is related to the presence of highly potent opioid adulterants (e.g., fentanyl) in the unregulated drug supply, drug checking services (DCS) have emerged as part of a comprehensive approach to overdose prevention. In Canada’s largest city, Toronto, a network of DCS launched in 2019 to prevent overdose and overdose-related risk behaviors. This network employs mass spectrometry technologies, with intake sites co-located with supervised consumption services (SCS) at three frontline harm reduction agencies. The protocol and rationale for assessing the impact of this multi-site DCS network in Toronto is described herein. The aims of this study are to (1) evaluate the impact of DCS access on changes in and factors influencing overdose and related risk behaviors, (2) investigate the perceived capacity of DCS to prevent overdose, and (3) identify composition (qualitative and quantitative) trends in Toronto’s unregulated drug supply. Methods We will use a parallel-mixed-methods design with complementary data sources (including data from chemical analysis of drug samples, quantitative intake and post-test surveys, SCS, coroners, paramedic services, and qualitative interviews), followed by a meta-inference process wherein results from analyses are synthesized. Results Whereas most DCS globally target “recreational drug users,” in Toronto, this networked DCS will primarily target marginalized people who use drugs accessing frontline services, many of whom use drugs regularly and by injection. This evolution in the application of DCS poses important questions that have not yet been explored, including optimal service delivery models and technologies, as well as unique barriers for this population. Increasing information on the unregulated drug supply may modify the risk environment for this population of people who use drugs. Conclusions This study addresses evidence gaps on the emerging continuum of overdose prevention responses and will generate critical evidence on a novel approach to reducing the ongoing high incidence of drug-related morbidity and mortality in Canada and elsewhere.

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen chronically infecting the lungs of patients with chronic obstructive pulmonary disease (COPD), pneumonia, cystic fibrosis (CF), and bronchiectasis. Cif (PA2934), a bacterial toxin secreted in outer membrane vesicles (OMV) by P. aeruginosa, reduces CFTR-mediated chloride secretion by human airway epithelial cells, a key driving force for mucociliary clearance. The aim of this study was to investigate the mechanism whereby Cif reduces CFTR-mediated chloride secretion. Cif redirected endocytosed CFTR from recycling endosomes to lysosomes by stabilizing an inhibitory effect of G3BP1 on the deubiquitinating enzyme (DUB), USP10, thereby reducing USP10-mediated deubiquitination of CFTR and increasing the degradation of CFTR in lysosomes. This is the first example of a bacterial toxin that regulates the activity of a host DUB. These data suggest that the ability of P. aeruginosa to chronically infect the lungs of patients with COPD, pneumonia, CF, and bronchiectasis is due in part to the secretion of OMV containing Cif, which inhibits CFTR-mediated chloride secretion and thereby reduces the mucociliary clearance of pathogens.

Journal of Applied Ecology (2004) 41, 114–123 [ABSTRACT FROM AUTHOR]

Chloride (Cl) secretion by the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) located in the apical membrane of respiratory epithelial cells plays a critical role in maintenance of the airway surface liquid and mucociliary clearance of pathogens. Previously, we and others have shown that the serum and glucocorticoid-inducible kinase-1 (SGK1) increases wild type CFTR (wt-CFTR) mediated Cl transport in Xenopus oocytes by increasing the amount of wt-CFTR protein in the plasma membrane. However, the effect of SGK1 on the membrane abundance of wt-CFTR in airway epithelial cells has not been examined, and the mechanism whereby SGK1 increases membrane wt-CFTR has also not been examined. Thus, the goal of this study was to elucidate the mechanism whereby SGK1 regulates the membrane abundance of wt-CFTR in human airway epithelial cells.We report that elevated levels of SGK1, induced by dexamethasone, increase plasma membrane abundance of wt-CFTR. Reduction of SGK1 expression by siRNA (siSGK1) and inhibition of SGK1 activity by the SGK inhibitor GSK 650394 abrogated the ability of dexamethasone to increase plasma membrane wt-CFTR. Overexpression of a constitutively active SGK1 (SGK1-S422D) increased plasma membrane abundance of wt-CFTR. To understand the mechanism whereby SGK1 increased plasma membrane wt-CFTR, we examined the effects of siSGK1 and SGK1-S442D on the endocytic retrieval of wt-CFTR. While siSGK1 increased wt-CFTR endocytosis, SGK1-S442D inhibited CFTR endocytosis. Neither siSGK1 nor SGK1-S442D altered the recycling of endocytosed wt-CFTR back to the plasma membrane. By contrast, SGK1 increased the endocytosis of the epidermal growth factor receptor (EGFR).This study demonstrates for the first time that SGK1 selectively increases wt-CFTR in the plasma membrane of human airway epithelia cells by inhibiting its endocytic retrieval from the membrane.

The present study used a revised online version of the College Student Bereavement Survey (the CSBS-R) to study the effects of student grief on college academics and social life. Of the 969 respondents, 408 (42%) reported grieving a relatively recent death of a person of significance in their lives. Hierarchical multiple regressions using gender, multiple deaths, closeness to the deceased, and/or social media use as independent variables revealed closeness to the deceased explaining a significant proportion of the variance of academic and social/peer experiences. Findings underscore the need for student bereavement policies, and how social media and closeness to the deceased affect the college experience.

The Americas encompass the entirety of the continents of North America and South America, representing 49 countries. Together, they make up most of Earth's western hemisphere. The population is over 1 billion (2006 figure), with over 65 % living in one of the three most populated countries (the United States, Brazil, and Mexico). The Americas have low-, middle-, and high-income countries. Data from this region have not been readily and consistently available. There are several English-speaking Caribbean nations and countries in South America that have not had updated information. This chapter will focus on suicide prevention within North America (United States and Canada), some countries in the Caribbean region, and some countries in South America. Guyana, Suriname, and Trinidad and Tobago have severe issues with pesticide suicide, with average rates of 44.2 (global rank 1); 27.8 (global rank 5) and 13.0 (global rank 41) per 100,000 respectively. Jamaica, however, had one of the lowest rates: 1.2 per 100,000 (global rank 166). General, regional, and country-specific prevention proposals are suggested, highlighting intersectoral, private collaboration, attention to at-risk persons, substance abuse and mental health interventions, training, and reducing access to lethal means.

Supervised consumption services (SCS) have been integrated into community health centres in Toronto. We draw on qualitative interviews and ethnographic observations to examine the implementation contexts of these SCS. Participants' perspectives on the integration of SCS within CHCs were mixed. Some participants identified the benefits of integrated SCS such as convenience and access to other health and social services. However, others identified negative consequences of integration, including building design, lack of privacy and anonymity, and limited hours of operation. These perspectives highlight the ways in which contextual factors affect the experiences of clients in accessing SCS, and suggest that various factors need to be considered in order to improve service uptake., Competing Interests: Declaration of competing interest None., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The operation of supervised consumption services (SCS), programs that offer supervised locations for the consumption of drugs such as heroin, other opioids, cocaine, other stimulants, and other drugs, is contingent on cooperative relationships with police. In this manuscript, we focus on an under studied topic: how active duty police officers understand their role with respect to SCS, and their recommendations for improving relationships with these programs. Methods: During 2018, we audio-recorded and transcribed focus group discussions conducted in four police divisions with 26 police constables and 3 officers of other ranks in Toronto, Canada. Officers were asked about their roles relative to SCS, perceived training needs, and how to build cooperative relationships with SCS. We followed an iterative thematic approach to analyze the data. Results: Participants in three divisions were unclear about their roles, duties, and policy governing policing of SCS. Participants in the fourth division had received instructions from the division commander to observe a "distance and discretion policy". However, these participants believed that developing familiarity with the new SCS, instead of keeping a distance, would be a more effective approach to building working relationships with staff, clients, and the local community. There was nearly unanimous skepticism about the willingness of SCS workers to work cooperatively with the police. These perceptions were commonly linked to previous negative experiences with harm reduction workers and, in some cases, staff at the new SCS. Several participants also linked problems in communication to fundamental differences between the philosophies or worldviews of SCS staff versus those of police. Conclusions: Building collaborative SIS-police relationships can be assisted by demystifying the operation of SCS for police, articulating policies, and working toward mutual respect.

Background: Supervised consumption services (SCS) are being implemented across Canada in response to a variety of drug-related harms. We explored the implementation context of newly established SCS in Toronto and the role of policing in shaping program access by people who inject drugs (PWID)., Methods: We conducted one-to-one qualitative semi-structured interviews with 24 PWID. Participants were purposively recruited. Ethnographic observations were conducted at each of the study sites as well as in their respective neighbourhoods. Relevant policy documents were also reviewed., Results: Policing was overwhelmingly discussed by participants from both SCS sites. However, participant responses varied depending on the site in question. Subthemes from participant responses on policing at site #1 described neighbourhood police presence and fears of police harassment and drug arrests before, during, or after accessing SCS. Conversely, subthemes from participant responses on policing at site #2 described immunity and protection from police while using the SCS, as well as a lack of police presence or fears of police harassment and arrests. These differences in implementation contexts were largely shaped by differences in local neighbourhoods and drug scenes. Police policies highlighted federal laws protecting PWID within SCS, but also the exercise of discretion when applying the rule of law outside of these settings., Conclusions: Participants' perspectives on, and experiences with, policing as they relate to accessing SCS were shaped by the implementation contexts of each SCS site and how neighbourhoods, drug scenes, and differences in policing practices affected service use. Our findings also demonstrate the disconnect between the goals of policing and those of SCS. Until larger structural barriers are addressed (e.g. criminalization), future SCS programming should consider the impact of policing on the SCS implementation context to improve client experience with, and access to, SCS.

Background: Crystal methamphetamine smoking is associated with many negative health consequences, including the potential for transmission of hepatitis. We examined whether or not a kit for crystal methamphetamine smoking might have some potential to reduce the negative health effects of crystal methamphetamine smoking., Methods: Five focus groups were conducted with crystal methamphetamine smokers recruited by community health agencies and youth shelters in Toronto, Canada. Target groups included homeless/street-involved youth, sex workers, men who have sex with men, and youth in the party scene. Participants (n = 32) were asked questions about motivations for crystal methamphetamine use, the process of smoking, health problems experienced, sharing behaviour, risky sexual practices, and the ideal contents of a harm reduction kit., Results: Pipe sharing was widespread among participants and was deemed integral to the social experience of smoking crystal methamphetamine. Heated pipes were unlikely to cause direct injuries, but participants mentioned having dry, cracked lips, which may be a vector for disease transmission. Many reported having sex with multiple partners and being less likely to use condoms while on the drug. Demand for harm reduction kits was mixed., Conclusions: Changing pipe sharing behaviours may be difficult because many participants considered sharing to be integral to the social experience of smoking crystal methamphetamine. Within the context of a broader health promotion and prevention program, pilot testing of safer smoking kits to initiate discussion and education on the risks associated with sharing pipes and unprotected sex for some communities (e.g., homeless/street-involved youth) is worth pursuing.

This study examined the prevalence of Axis I disorders and associated risk factors in a sample of sexual minority men and women in Jamaica, a country that is widely known for its high societal rejection of homosexuality. Poor relationships with family, negative or abusive experiences related to one's sexual orientation, and greater openness about one's sexual orientation were independent risk factors for Axis I disorders. Prevention of mental disorders in sexual minorities in Jamaica should focus on rebuilding family support and promoting social acceptance of sexual minorities.

This study investigated factors leading to premature discharge from the residential substance abuse treatment programme at the University Hospital of the West Indies (UHWI). Two hundred and twenty-four patients, mean age 36 +/- 9.75 and age range of 16-66 years were studied The patients, 87.5% men, were admitted to the programme over the period July 1999 to June 2002. Sources of data, including a routine patient-monitoring form and patients' medical records, were reviewed. Data analysis, performed using the Statistical Package for Social Sciences (SPSS), included frequencies, cross-tabulations and analyses of variance (ANOYA). Crack cocaine was the drug of impact for 60% of patients, alcohol for 17% and marijuana for 8%. Treatment ended prematurely for 22.8% of persons whose reasons for leaving included signing out against medical advice or self-discharge (27.4%), absconding (19.6%), fighting (9.8%), drug use (5.9%) and other rule breaking, including sexual acting out (15.7%). Premature discharge was uninfluenced by gender, age, marital status, schooling, employment status or geographical location. There were significantly more premature discharges in persons admitted primarily for crack dependence versus those admitted primarily for alcoholism (p < 0.05). There were also significantly more premature discharges in persons with 0-10 years of using their most problematic substance when compared with 21-30 years of use (p < 0.05) but not when compared with 11-20 years or over 30 years of use (p > 0.05). The influence of duration of substance use requires further elucidation.

A case of Alcohol-Induced Persisting Dementia (AIPD) in a 62-year-old man is presented. His progress on treatment with the acetylcholinesterase inhibitor, rivastigmine, is followed. The significant improvement observed suggests that AIPD may be a new indication for this class of drug.