Changes in the incidence of cannabis-related disorders after the Cannabis Act and the COVID-19 pandemic in Québec, Canada.

BACKGROUND: The Canadian Cannabis Act (CCA, implemented in October 2018) and the COVID-19 pandemic (April 2020) might have contributed to cannabis-related harms in Québec, known for its stringent cannabis legal framework. We explored changes in incidence rates of cannabis-related disorders (CRD) diagnoses associated with these events in Québec. METHODS: We utilized linked administrative health data to identify individuals aged 15 year+ newly diagnosed with CRD during hospitalizations, emergency, and outpatients clinics across Québec, from January 2010 and March 2022 (147 months). Interrupted time-series analyses (ITSA) assessed differences (as percentage changes) in sex- and age-standardized, and sex-stratified, monthly incidence rates (per 100,000 population) attributed to the CCA and the COVID-19 pandemic, compared to counterfactual scenarios where pre-events trends would continue unchanged. RESULTS: The overall monthly mean rates of incident diagnoses nearly doubled from the pre-CCA period (1.56 per 100,000 population) to the COVID-19 pandemic period (3.02 per 100,000 population). ITSA revealed no statistically significant level or slope changes between adjacent study periods, except for a decrease in the slope of incidence rates among males by 1.84 % (95 % CI -3.41 to -0.24) during the COVID-19 pandemic compared to the post-CCA period. During the post-CCA period, the trends of incidence rates in the general and male populations grew significantly by 1.22 % (95 % CI 0.08 to 2.35) and 1.44 % (0.04 to 2.84) per month, respectively. Similarly significant increases were observed for the general and female populations during the COVID-19 pandemic, with monthly rates rising by 1.43 % (95 % CI 0.75 to 2.12) and 1.75 % (95 % CI 0.13 to 3.37), respectively. These increases more than doubled pre-CCA rates. CONCLUSIONS: The incidence rates of CRD diagnoses across Québec appears to have increased following the implementation of the CCA and during the COVID-19 pandemic. Our findings echo public health concerns regarding potential cannabis-related harms and are consistent with previous Canadian studies.

Environmental and sociodemographic factors associated with zoonotic pathogen occurrence in Norway rats (Rattus norvegicus) from Windsor, Ontario.

AIMS: Rat-associated zoonotic pathogen transmission at the human-wildlife interface is a public health concern in urban environments where Norway rats (Rattus norvegicus) thrive on abundant anthropogenic resources and live in close contact with humans and other animal species. To identify potential factors influencing zoonotic pathogen occurrence in rats, we investigated associations between environmental and sociodemographic factors and Leptospira interrogans and Bartonella spp. infections in rats from Windsor, Ontario, Canada, while controlling for the potential confounding effects of animal characteristics (i.e., sexual maturity and body condition). METHODS AND RESULTS: Between November 2018 and June 2021, 252 rats were submitted by collaborating pest control professionals. Kidney and spleen samples were collected for L. interrogans and Bartonella spp. PCR and sequencing, respectively. Of the rats tested by PCR, 12.7% (32/252) were positive for L. interrogans and 16.3% (37/227) were positive for Bartonella species. Associations between infection status and environmental and sociodemographic variables of interest were assessed via mixed multivariable logistic regression models with a random intercept for social group and fixed effects to control for sexual maturity and body condition in each model. The odds of L. interrogans infection were significantly higher in rats from areas with high building density (odds ratio [OR]: 3.76; 95% CI: 1.31-10.79; p = 0.014), high human population density (OR: 3.31; 95% CI: 1.20-9.11; p = 0.021), high proportion of buildings built in 1960 or before (OR: 11.21; 95% CI: 2.06-60.89; p = 0.005), and a moderate number of reports of uncollected garbage compared to a low number of reports (OR: 4.88; 95% CI: 1.01-23.63; p = 0.049). A negative association was observed between median household income and Bartonella spp. infection in rats (OR: 0.26; 95% CI: 0.08-0.89; p = 0.031). CONCLUSIONS: Due to the complexity of the ecology of rat-associated zoonoses, consideration of environmental and sociodemographic factors is of critical importance to better understand the nuances of host-pathogen systems and inform how urban rat surveillance and intervention efforts should be distributed within cities.

Nanoparticle endocytosis is driven by monocyte phenotype rather than nanoparticle size under high shear flow conditions.

Monocytes are members of the mononuclear phagocyte system involved in pathogen clearance and nanoparticle pharmacokinetics. Monocytes play a critical role in the development and progression of cardiovascular disease and, recently, in SARS-CoV-2 pathogenesis. While studies have investigated the effect of nanoparticle modulation on monocyte uptake, their capacity for nanoparticle clearance is poorly studied. In this study, we investigated the impact of ACE2 deficiency, frequently observed in individuals with cardiovascular complications, on monocyte nanoparticle endocytosis. Moreover, we investigated nanoparticle uptake as a function of nanoparticle size, physiological shear stress, and monocyte phenotype. Our Design of Experiment (DOE) analysis found that the THP-1 ACE2 - cells showed a greater preference for 100nm particles under atherosclerotic conditions than THP-1 wild-type cells. Observing how nanoparticles can modulate monocytes in the context of disease can inform precision dosing.

Evaluating the utility of pest control sourced rats for zoonotic pathogen surveillance.

Norway rats (Rattus norvegicus) inhabit cities worldwide and live in close association with humans. Studies of urban rat zoonoses often rely on live-trapping, with fewer studies using rats sourced through lethal pest control interventions. Our objectives were to evaluate the utility of rats collected by pest control professionals for zoonotic pathogen surveillance and determine whether we could detect Leptospira interrogans and Streptobacillus moniliformis in pest control sourced rats. Rat carcasses were submitted from Windsor, Canada by pest control professionals between November 2018 and March 2020. Submissions were categorized by season and land use. Necropsies were performed to classify carcass quality, collect tissue samples, and record demographic data. The association between carcass quality and the ability to collect tissue samples for pathogen surveillance was assessed via an exact logistic regression model. Using PCR, a subset of kidney and spleen samples were tested for L. interrogans and S. moniliformis, respectively. Our sample of pest control sourced rats had similar sex and age distributions to those of live-trapping studies. Rats were primarily submitted from residential and industrial locations during fall, winter, and spring, which may reflect pest control service areas and peak business periods, rather than rat distribution. Of 124 submissions, 98 (79.0%) of rats showed only mild decomposition. The odds of collecting all tissue samples were reduced for fair compared to good-quality carcasses (OR: 0.029; 95% CI: 0-0.25; p = .0009) and for poor compared to fair-quality carcasses (OR: 0.048; 95% CI: 0.00085-0.53; p = .0065). Leptospira interrogans and S. moniliformis were detected in 9.1% (4/44) and 27.3% (15/55) of a subset of rats tested, respectively. Our results suggest that pest control sourced rats are suitable for surveillance for multiple zoonotic pathogens in urban environments. This method of rat collection may provide preliminary information to guide more detailed ecological studies.

Tick infestations of wildlife and companion animals in Ontario, Canada, with detection of human pathogens in Ixodes scapularis ticks.

The growing risk of transmission of tick-borne zoonotic pathogens to humans in Ontario, Canada, warrants investigations into regional tick distribution, tick burdens of local peridomestic animals, and prevalence of tick-borne pathogens. The objectives of this study were to investigate the geographic distribution and magnitude of tick infestations in opportunistically sampled mammalian wildlife and companion animals (i.e., dogs) in southern Ontario and to test these ticks for evidence of zoonotic tick-borne pathogens. Ticks collected from wildlife carcasses, live-trapped wildlife and companion animals (2015-2016), as well as wildlife diagnostic cases (2011-2013), were identified to species and life stage. Ixodes scapularis ticks were tested by real-time PCR for Anaplasma phagocytophilum, Babesia microti, Borrelia miyamotoi and Borrelia burgdorferi sensu stricto (s.s.). Amblyomma americanum ticks were tested for Ehrlichia chaffeensis. A total of 1687 ticks of six species were collected from 334 animals, including 224 raccoons (n = 1381 ticks) and 50 dogs (n = 67 ticks). The most common tick species collected from parasitized raccoons were Ixodes texanus (n = 666 ticks) and Dermacentor variabilis (n = 600 ticks), which were removed from 58.5% (median: 2 ticks; range: 1-36) and 49.1% (median: 2 ticks; range: 1-64) of raccoons, respectively. Of I. scapularis tested, 9.3% (4/43) were positive for Bo. burgdorferi s.s. and 2.3% (1/43) for A. phagocytophilum. These results reveal that numerous tick species parasitize common, peridomestic wildlife and that at least two zoonotic, tick-borne pathogens circulate in southern Ontario. Host-tick vector-pathogen dynamics should continue to be monitored in the face of global climate change, landscape alterations and expanding human populations.

Powassan Virus and Other Arthropod-Borne Viruses in Wildlife and Ticks in Ontario, Canada.

Powassan virus (POWV) is a tick-borne zoonosis maintained in natural enzootic cycles between ixodid ticks and wild mammals. Reported human cases have increased in recent years; these infections can be fatal or lead to long-term neurologic sequelae. However, both the geographic distribution and the role of common, potential mammalian hosts in POWV transmission are poorly understood, creating challenges to public health surveillance. We looked for evidence of POWV infection among candidate wildlife host species and ticks collected from mammals and birds in southern Ontario. Tissues (including blood) and ticks from trapped wild mammals were collected in the summers of 2015 and 2016. Ticks removed from dogs in 2015-2016 and wildlife diagnostic cases from 2011 to 2013 were also included. Tissue and tick (Ixodes spp.) homogenates were tested for POWV by reverse transcriptase-polymerase chain reaction (RT-PCR). In addition, sera from wild mammals were tested for antibodies to POWV, West Nile virus (WNV), and heartland virus (HRTV) by plaque reduction neutralization test. All 724 tissue samples were negative for POWV by RT-PCR. One of 53 pools of Ixodes cookei (among 98 total tick pools) was RT-PCR positive for deer tick virus (POWV) lineage. Antibodies to POWV and WNV were detected in 0.4% of 265 and 6.1% of 264 samples, respectively, and all of 219 serum samples tested negative for anti-HRTV antibodies. These results reveal low POWV detection rates in southern Ontario, while highlighting the challenges and need for continued efforts into understanding POWV epidemiology and targeted surveillance strategies.

Serological and molecular epidemiological outcomes after two decades of universal infant hepatitis B virus (HBV) vaccination in Nunavut, Canada.

Chronic hepatitis B virus (HBV) infection within the Canadian Arctic is considered endemic (>2% prevalence). Within the Arctic region of Nunavut, a vaccination program targeted at newborn infants was initiated approximately 20years ago, along with interim grade school catch-up programs, with the result that individuals born after 1980 are presumed vaccinated. This study investigates the effectiveness of these programs and is the first seroepidemiological survey to determine HBV prevalence in Nunavut in the post-vaccination era. Anonymized serum specimens scheduled for destruction following medical testing were collected between April 2013 and April 2014 from individuals granting consent. Specimens were tested for HBV antibodies, surface antigen (HBsAg), and HBV DNA to perform molecular characterization. Four thousand eight hundred and two specimens (13% of the population) were collected, with a resulting median age of 29years (range 1week to 93years). The prevalence of antibody to the HBV core protein was 9.4%; however, a 10-fold decrease in the rate of HBV exposure was noted among those born after 1980 compared to those born before (1.8% vs. 19.8%, p<0.01). HBsAg positivity was primarily documented in individuals born before 1980 (2.5%), although cases still occurred among the vaccine age cohort (0.3%). HBV subgenotype B5 (previously B6) was the most prevalent genotype observed (81.8%) indicating persistence of locally acquired infection. Vaccine-based antibody as the sole serological marker was evident in the vaccine age cohort, although the rate of decay with increasing age was much greater than predicted (less than 10% in those aged 5-19years). Nearly two decades after the advent of HBV vaccination in Nunavut, HBV prevalence has decreased to 1.2%, indicating non-endemic prevalence. However, the persistence of infection and a lower than expected prevalence of vaccine-based immunity in the vaccine age cohort will require further investigation to understand the causes and consequences.

Brevibacterium massiliense (Roux and Raoult 2009) is a later heterotypic synonym of Brevibacterium ravenspurgense (Mages, Frodl, Bernard and Funke 2009), using whole-genome sequence analysis as a comparative tool.

A patient strain derived from urine was found by 16S rRNA gene sequencing to be closely related (99.6 % identity) to sequences derived from both Brevibacterium ravenspurgense CCUG 56047T and Brevibacterium massilienseCCUG 53855T. Those species had been described during the same 11 month period in 2008-2009. Further characterization revealed that those isolates could not be readily distinguished from each other biochemically, by cellular fatty acids, antimicrobial susceptibility, MALDI-TOF MS, 16S rRNA gene sequencing or by whole-genome sequence (WGS) analyses. By WGS comparison, these isolates had an aerage nucleotide identity using blastn (ANIb) scores of 95.7 % or higher to each other, DNA G+C content in the range of 62.3 mol%-62.4 mol%, with genome sizes ranging from 2.28×106 to 2.41×106 bases. Based on these data, we propose that the name B. massiliense is a later heterotypic synonym of B. ravenspurgense and provide an emended description of B. ravenspurgense.

Corynebacterium lowii sp. nov. and Corynebacterium oculi sp. nov., derived from human clinical disease and an emended description of Corynebacterium mastitidis.

Strains of members of the genus Corynebacterium derived from ophthalmologic patients in Japan, Belgium and Switzerland and found to be closely related to-, but distinguishable from Corynebacterium mastitidis by 16S rRNA gene sequencing, were characterized using biochemical, chemotaxonomic, MALDI-TOF mass spectrometry and antimicrobial susceptibility methods and DNA-DNA hybridization as well as by whole-genome sequencing (WGS). Based on this investigation, we describe Corynebacterium lowii sp. nov. and Corynebacterium oculi sp. nov., derived from human ocular specimens, as well as emend the description of Corynebacterium mastitidis. Type strains for these species are: C. lowii R-50085T (=LMG 28276T =CCUG 65815T) and C. oculi R-50187T (=LMG 28277T =CCUG 65816T). DNA G+C content was found to be 62.2 % (by HPLC) and 62.8 % (by WGS) for C. lowii R-50085T, 64.1 % (HPLC) and 64.8 % (WGS) for C. oculi R-50187T and 67.8 % (HPLC) for C. mastitidis LMG 19040T [=S-8T =CCUG 38654T =CECT 4843T =CIP 105509T =DSM 44356T =IFO (NBRC)16160T =JCM 12269T].

Establishing diagnostic criteria for occult hepatitis B virus infections in community based populations.

Present diagnostic criteria for occult hepatitis B virus (HBV) infection requires blood or liver samples to test positive for at least two HBV DNA targets in hepatitis B surface antigen (HBsAg) negative individuals. These criteria were derived from studies involving referred or selected patient populations. The objective of the present study was to determine whether the present definition of occult HBV infection also applies within a nonselected community based population. HBV DNA testing was performed in 1,007 HBsAg negative sera by real time PCR with primer sets targeting the Enhancer I (ENHI), precore/core and surface/polymerase (S) genomic regions. Real time PCR positive cases were analyzed further by nested PCR. The results were then correlated with serologic findings among HBV DNA negative and occult positive individuals. Fifty-five sera (5.5%) were positive for at least one of the three genomic regions. Positive results with at least two primer/probe sets (thereby satisfying present diagnostic criteria for occult HBV infection) were identified in 8 (0.8%) samples (3 ENHI plus S, 2 ENHI plus precore/core and 3 having positive results with all three primer/probe sets). The prevalence of HBV serologic markers in samples that tested positive for only one primer set were similar to those of HBV DNA negative matched controls, thereby arguing against their representing occult infection. The results of this study suggest that the present diagnostic criteria for occult HBV infection are also appropriate for population based studies. However, further studies are required to confirm that impression.

Noise performance of phase-insensitive frequency multicasting in parametric mixer with finite dispersion.

Noise performance of dual-pump, multi-sideband parametric mixer operated in phase-insensitive mode is investigated theoretically and experimentally. It is shown that, in case when a large number of multicasting idlers are generated, the noise performance is strictly dictated by the dispersion characteristics of the mixer. We find that the sideband noise performance is significantly degraded in anomalous dispersion region permitting nonlinear noise amplification. In contrast, in normal dispersion region, the noise performance converges to the level of four-sideband parametric process, rather than deteriorates with increased sideband creation. Low noise generation mandates precise dispersion-induced phase mismatch among pump and sideband waves in order to control the noise coupling. We measure the noise performance improvement for a many-sideband, multi-stage mixer by incorporating new design technique.

Interaction of aspirin (acetylsalicylic acid) with lipid membranes.

We studied the interaction of Aspirin (acetylsalicylic acid) with lipid membranes using x-ray diffraction for bilayers containing up to 50 mol% of aspirin. From 2D x-ray intensity maps that cover large areas of reciprocal space we determined the position of the ASA molecules in the phospholipid bilayers and the molecular arrangement of the molecules in the plane of the membranes. We present direct experimental evidence that ASA molecules participate in saturated lipid bilayers of DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) and preferably reside in the head group region of the membrane. Up to 50 mol% ASA molecules can be dissolved in this type of bilayer before the lateral membrane organization is disturbed and the membranes are found to form an ordered, 2D crystal-like structure. Furthermore, ASA and cholesterol were found to co-exist in saturated lipid bilayers, with the ASA molecules residing in the head group region and the cholesterol molecules participating in the hydrophobic membrane core.