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Background North American communities are severely impacted by the overdose crisis, particularly in British Columbia (BC), which has the highest toxic drug overdose death rate in Canada. Most fatal overdoses in BC occurred among individuals using alone and in private residences. This study aimed to assess prevalence and reasons for using drugs alone among people accessing harm reduction services in BC. Methods We recruited harm reduction supply distribution site clients from 22 communities across BC. Descriptive statistics and multivariable logistic regression were used to describe factors associated with using alone. Thematic analysis of free-text responses providing reasons for using alone were grouped with survey data and additional themes identified. Results Overall, 75.8% (n = 314) of the study sample (N = 414) reported using drugs alone within the last week. Those that reported using alone did not differ from those that did not by gender, age, urbanicity, or preferred drug use method. Among those that used alone, 73.2% (n = 230) used opioids, 76.8% (n = 241) used crystal meth, 41.4% (n = 130) used crack/cocaine, and 44.6% (n = 140) used alcohol in the past week. Polysubstance use involving stimulants, opioids, and/or benzodiazepines was reported by 68.5% (n = 215) of those that used alone. Additionally, 22.9% (n = 72) of those that used alone had experienced an opioid and/or stimulant overdose in the past 6 months. In a multivariable logistic regression model, having no regular housing and past week crack/cocaine use were associated with using alone (adjusted odds ratio (AOR): 2.27; 95% CI 1.20–4.27 and AOR: 2.10; 95% CI 1.15–3.82, respectively). The most common reason reported for using alone was convenience and comfort of using alone (44.3%). Additional reasons included: stigma/hiding drug use (14.0%); having no one around (11.7%); safety (9.6%); and not wanting to share drugs with others (8.6%). Conclusions Using drugs alone, particularly for convenience and comfort, is ubiquitous among people accessing harm reduction services. Overdose prevention measures that go beyond individual behaviour changes, including providing a safer supply of drugs and eliminating stigma, are paramount to mitigate harms. These interventions are especially necessary as emergence of coronavirus disease may further exacerbate unpredictability of illicit drug content and overdose risk.

Introduction Increased use of crystal methamphetamine (“crystal meth”) has been observed across North America and international jurisdictions, including a notable increase in the presence of methamphetamines in illicit drug toxicity deaths in British Columbia (BC), Canada. We used data from a cross-sectional survey and urine toxicology screening to report the prevalence, correlates, and validity of self-reported crystal meth use among clients of harm reduction sites in BC. Materials and methods Survey data were collected from 1,107 participants across 25 communities in BC, through the 2018 and 2019 Harm Reduction Client Survey. We described reported substance use and used a multivariate logistic regression model to characterize crystal meth use. Urine samples provided by a subset of participants were used to derive validity of self-reported three-day crystal meth use compared to urine toxicology screening. Results Excluding tobacco, crystal meth was the most frequently reported substance used in the past three days in 2018 and 2019 (59.7% and 71.7%, respectively). Smoking was the dominant route of administration for crystal meth, crack, heroin, and fentanyl. Multivariate analysis determined significantly higher odds of crystal meth use among those who used opioids (Adjusted Odds Ratio [AOR] = 3.13), cannabis (AOR = 2.10), and alcohol (1.41), and among those who were not regularly housed (AOR = 2.08) and unemployed (AOR = 1.75). Age ≥50 was inversely associated with crystal meth use (AOR = 0.63). Sensitivity of self-reported crystal meth use was 86%, specificity was 86%, positive predictive value was 96%, and negative predictive value was 65%. Conclusions Crystal meth was the most commonly used substance among clients of harm reduction sites in BC in 2018 and 2019, and was frequently used concurrently with opioids. Comparison to urine samples demonstrated high validity of self-reported crystal meth use. Understanding evolving patterns of substance use will be imperative in tailoring harm reduction and substance use services for individuals that use crystal meth.

Abstract. There are limited data about the epidemiology of fascioliasis in Cuzco, Peru. We studied children 3-12 years old from six communities in the highlands of Cuzco to evaluate the epidemiology of fascioliasis; 227 children were included, one-half were female, the mean age was 7.5 (±2.6) years, and 46.2±% had one or more parasites, including Fasciola (9.7%), Ascaris (12.8%), Hymenolepis (9.3%), Trichuris (1.3%), hookworm (1.8%), Strongyloides (0.9%), and Giardia (27.8%). Fasciola was associated with the number of siblings in the household, drinking untreated water, and giardiasis. Eosinophilia was encountered in 21% of children and more common in those drinking untreated water at home and those infected with a parasite, but the differences were not significant. Eating water plants was not associated with Fasciola or eosinophilia. Fascioliasis and eosinophilia were common in the highlands of Cuzco. Fascioliasis was associated with socioeconomic factors and drinking water. BACKGROUND

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Aim Oridonin, isolated from Rabdosia rubescens, has been proven to possess various anti-neoplastic and anti-inflammatory properties. Previously, we reported the anti-fibrogenic effects of oridonin for liver in vitro. In the present study, we investigated the effects of a newly designed analogue CYD0692 in vitro. Methods Cell viability was measured by Alamar Blue assay. Cell apoptosis was assessed by Cell Death ELISA and Yo-Pro-1 staining. Western Blots were performed for cellular proteins. Flow Cytometry was used to measure cell cycle regulation. Results CYD0692 significantly inhibited LX-2 cells proliferation in a dose- and time-dependent manner with an IC50 value of ~0.7 μM for 48 hours, ~10 –fold greater potency than oridonin. Similar results were observed in HSC-T6 cells. In contrast, on the human hepatocyte cell line C3A, only 12% of the cell growth was inhibited with 5 μM of CYD0692 treatment for 48h, while 30% inhibited at 10 μM. After CYD0692 treatment on LX-2 cells, apoptosis and S-phase cell cycle arrest were induced; cleaved-PARP, p21, and p53 were activated while cyclin-B1 levels declined. In addition, α-smooth muscle actin, type I Collagen, and fibronectin (FN) were markedly down regulated. Transforming growth factor β1 (TGF β1) has been identified as a dominant stimulator for ECM production in HSC. Our results indicated that pre-treatment with CYD0692 blocked TGF β1-induced FN expression, thereby decreasing the downstream factors of TGF β1 signaling, such as Phospho-Smad2/3 and phospho-ERK. Conclusion In comparison with oridonin, its novel derivative CYD0692 has demonstrated to be a more potent and potentially safer anti-fibrogenic agent for the treatment of hepatic fibrosis.

Activated hepatic stellate cells (HSC) are responsible for excess extracellular matrix (ECM) protein deposition in liver fibrosis. Previously, our group reported that the natural compound oridonin induces apoptosis, inhibits cell proliferation, and down-regulates ECM proteins in activated HSC. In this study, the anti-fibrogenic effects of oridonin derivative CYD0682 on the activated human LX-2 and rat HSC-T6 stellate cell lines were investigated. Methods Cell proliferation was measured by Alamar Blue assay. Apoptosis was detected by Cell Death ELISA and staining of Yo-Pro-1 and propidium iodide. Cell cycle was determined by flow cytometry. Immunoblot and Immunofluorescence staining were performed for cellular protein expression. Results CYD0682 treatment significantly inhibited LX-2 cells proliferation in a dose- and time-dependent manner with an IC50 value of 0.49 μM for 48 hours, ~10–fold greater potency than oridonin. Similar results were observed in HSC-T6 cells. In contrast, 2.5 μM of CYD0682 treatment had no significant effects on proliferation of the human hepatocyte cell line C3A. CYD0682 treatment induced LX-2 cell apoptosis and S-phase cell cycle arrest, and was associated with activation of p53, p21, and cleaved-caspase-3. The myofibroblast marker protein α-smooth muscle actin and major ECM proteins type I collagen and fibronectin were markedly suppressed in a time- and dose-dependent fashion by CYD0682. Furthermore, pre-treatment with CYD0682 blocked TGFβ-induced type I collagen and fibronectin production. Conclusion In comparison with oridonin, its novel derivative CYD0682 may act as a more potent anti-hepatic fibrosis agent.

Background British Columbia (BC) is in the midst of an opioid overdose crisis. Since 2017, smoking illicit drugs has been the leading mode of drug administration causing overdose death. Yet, little is known about people who smoke opioids, and factors underlying choice of mode of administration. The study objectives are to identify the prevalence and correlates associated with smoking opioids. Methods The Harm Reduction Client Survey is a monitoring tool used by the BC Centre for Disease Control since 2012. This survey is disseminated to harm reduction sites across BC to understand drug use trends and drug-related harms. We examined data from the survey administered October–December 2019 and performed descriptive, univariate, and multivariate analyses to better understand factors associated with smoking opioids. Results A total of 369 people who used opioids in the past 3 days were included, of whom 251 (68.0%) reported smoking opioids. A total of 109 (29.5%) respondents experienced an overdose in the past 6 months; of these 79 (72.5%) smoked opioids. Factors significantly associated with smoking opioids were: living in a small community (AOR =2.41, CI =1.27–4.58), being a woman (AOR = 1.84, CI = 1.03–3.30), age under 30 (AOR = 5.41, CI = 2.19–13.40) or 30–39 (AOR = 2.77, CI = 1.33–5.78) compared to age ≥ 50, using drugs alone (AOR = 2.98, CI = 1.30–6.83), and owning a take-home naloxone kit (AOR = 2.01, CI = 1.08–3.72). Reported use of methamphetamines within the past 3 days was strongly associated with smoking opioids (AOR = 6.48, CI = 3.51–11.96). Conclusions Our findings highlight important correlates associated with smoking opioids, particularly the recent use of methamphetamines. These findings identify actions to better respond to the overdose crisis, such as targeted harm reduction approaches, educating on safer smoking, advocating for consumption sites where people can smoke drugs, and providing a regulated supply of opioids that can be smoked.