Search

The objective of this research is to evaluate the impact of a treatment program specialized with criminalized addicts. In all, 119 criminalized addicts were admitted to the experimental procedure (specialized treatment) while 30 were admitted to a comparison group (general treatment). Both groups were contacted at five, eight, and eleven month intervals following the onset of the treatment process. Results showed that both groups improved. Those admitted to the unspecialized treatment improved earlier (in the first five months) than clients referred to the specialized treatment facility, however, after eight months, the improvement was similar for both groups. [ABSTRACT FROM AUTHOR]

The bulk of studies pertaining to addiction among delinquents have been conducted on male subjects. However, the few studies examining female inmates show that a significant proportion of them present an addictive disorder. Furthermore, the HIV infection rate is higher among these women than among incarcerated men. This study attempts to verify if women presenting a combination of criminal and addictive behaviors are at a higher risk of developing an earlier and a more severe delinquency than other delinquent women. Another goal is to determine whether women showing this comorbidity present a higher incidence of HIV-related risk behaviors. The study was conducted on a sample of 210 women from the Montreal detention center. It shows that addicted inmates present earlier onsets of both drug use and criminal behaviors compared to other female inmates. Addicted women also exhibit significantly more HIV-related risky behaviors, both in their drug use and in their sexual practices. [ABSTRACT FROM AUTHOR]

International co-operation treaties exist for decades, as well as the international drug traffic. However, they did not yet succeed in efficiently fighting international drug trafficking. This paper reviews the history of international traffic and illustrate the discussion with known examples like those of Colombia and Afghanistan

Abstract Background An important challenge in conducting social research of specific relevance to harm reduction programs is locating hidden populations of consumers of substances like cannabis who typically report few adverse or unwanted consequences of their use. Much of the deviant, pathologized perception of drug users is historically derived from, and empirically supported, by a research emphasis on gaining ready access to users in drug treatment or in prison populations with higher incidence of problems of dependence and misuse. Because they are less visible, responsible recreational users of illicit drugs have been more difficult to study. Methods This article investigates Respondent Driven Sampling (RDS) as a method of recruiting experienced marijuana users representative of users in the general population. Based on sampling conducted in a multi-city study (Halifax, Montreal, Toronto, and Vancouver), and compared to samples gathered using other research methods, we assess the strengths and weaknesses of RDS recruitment as a means of gaining access to illicit substance users who experience few harmful consequences of their use. Demographic characteristics of the sample in Toronto are compared with those of users in a recent household survey and a pilot study of Toronto where the latter utilized nonrandom self-selection of respondents. Results A modified approach to RDS was necessary to attain the target sample size in all four cities (i.e., 40 'users' from each site). The final sample in Toronto was largely similar, however, to marijuana users in a random household survey that was carried out in the same city. Whereas well-educated, married, whites and females in the survey were all somewhat overrepresented, the two samples, overall, were more alike than different with respect to economic status and employment. Furthermore, comparison with a self-selected sample suggests that (even modified) RDS recruitment is a cost-effective way of gathering respondents who are more representative of users in the general population than nonrandom methods of recruitment ordinarily produce. Conclusions Research on marijuana use, and other forms of drug use hidden in the general population of adults, is important for informing and extending harm reduction beyond its current emphasis on 'at-risk' populations. Expanding harm reduction in a normalizing context, through innovative research on users often overlooked, further challenges assumptions about reducing harm through prohibition of drug use and urges consideration of alternative policies such as decriminalization and legal regulation.

For many years, clinicians, especially those working in rehabilitation centers for alcohol and drug users, have been preoccupied with clients presenting with dual diagnosis: substance abuse and legal problems. Comparative analyses of three groups of addicted men, 553 offenders and 499 nonoffenders in treatment for addiction problems and 103 addicted inmates were made to ascertain the biopsychosocial profile of these persons. Results showed that dual-diagnosis clients experienced more severe biopsychosocial problems than the nonoffending group of subjects. Offenders in prison experienced more social maladjustment than offenders in drug addiction treatment, they were less preoccupied by their drug consumption, and less motivated to change. Implications for treatment are discussed. [ABSTRACT FROM AUTHOR]

Major histocompatibility complex class I (MHC I) molecules present peptides to CD8+ T-cells for immunosurveillance of infection and cancer. Recent studies indicate lineage-specific heterogeneity in MHC I expression. While respiratory diseases rank among the leading causes of mortality, studies in mice have shown that lung epithelial cells (LECs) express the lowest levels of MHC I in the lung. This study aims to answer three questions: (i) Do human LECs express low levels of MHC I? (ii) Is LEC MHC I expression modulated in chronic respiratory diseases? (iii) Which factors regulate MHC I levels in human LECs? We analyzed human LECs from parenchymal explants using single-cell RNA sequencing and immunostaining. We confirmed low constitutive MHC I expression in human LECs, with significant upregulation in chronic respiratory diseases. We observed a sexual dimorphism, with males having higher MHC I levels under steady-state conditions, likely due to differential redox balance. Our study unveils the complex interplay between MHC I expression, sex, and respiratory disease. Since MHC I upregulation contributes to the development of immunopathologies in other models, we propose that it may have a similar impact on chronic lung disease., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Introduction: Modifying risk perceptions related to driving after cannabis use (DACU) could deter individuals from enacting this behavior, as low-risk perception is associated with DACU engagement. This study identified sociodemographic characteristics, substance use, other driving behaviors, peer norms, and psychological characteristics that are associated with lower risk perception regarding DACU., Methods: Canadian drivers aged 17-35 who have used cannabis in the past year (n = 1,467) completed an online questionnaire. A multivariate linear regression model allowed for identifying variables associated with the low-risk perception of DACU (i.e. believing it to be safe as one's driving ability is not impaired by cannabis or by being high)., Results: Lower risk perception of DACU was associated with identifying as male, weekly to daily cannabis use, engagement in DACU, general risky driving behaviors, being a passenger of a driver who engages in DACU, number of friends who engage in DACU, and peer approval of DACU. Having driven under the influence of alcohol, living in urban areas, having received traffic tickets in the past three years, and declaring past-week irritability and cognitive problems were associated with holding a higher risk perception related to DACU., Discussion: Road education and prevention programs should target attitudes and perceptions regarding risks shaped by sociocultural norms and past risky driving experiences. They need to reach out more specifically to drivers with the identified characteristics associated with the low-risk perception of DACU. These interventions can potentially help reduce the rate of individuals who engage in this behavior., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Transposable elements (TEs) are repetitive sequences representing ~45% of the human and mouse genomes and are highly expressed by medullary thymic epithelial cells (mTECs). In this study, we investigated the role of TEs on T-cell development in the thymus. We performed multiomic analyses of TEs in human and mouse thymic cells to elucidate their role in T-cell development. We report that TE expression in the human thymus is high and shows extensive age- and cell lineage-related variations. TE expression correlates with multiple transcription factors in all cell types of the human thymus. Two cell types express particularly broad TE repertoires: mTECs and plasmacytoid dendritic cells (pDCs). In mTECs, transcriptomic data suggest that TEs interact with transcription factors essential for mTEC development and function (e.g., PAX1 and REL), and immunopeptidomic data showed that TEs generate MHC-I-associated peptides implicated in thymocyte education. Notably, AIRE, FEZF2, and CHD4 regulate small yet non-redundant sets of TEs in murine mTECs. Human thymic pDCs homogenously express large numbers of TEs that likely form dsRNA, which can activate innate immune receptors, potentially explaining why thymic pDCs constitutively secrete IFN ɑ/β. This study highlights the diversity of interactions between TEs and the adaptive immune system. TEs are genetic parasites, and the two thymic cell types most affected by TEs (mTEcs and pDCs) are essential to establishing central T-cell tolerance. Therefore, we propose that orchestrating TE expression in thymic cells is critical to prevent autoimmunity in vertebrates., Competing Interests: JL, CL, AT, KV, LH, SB, CC, JH, ÉB, JL, CD, PG, JL, ER, SL, PT, CP No competing interests declared, (© 2023, Larouche et al.)

Pregnancy causes abrupt thymic atrophy. This atrophy is characterized by a severe decrease in the number of all thymocyte subsets and qualitative (but not quantitative) changes in thymic epithelial cells (TECs). Pregnancy-related thymic involution is triggered by progesterone-induced functional changes affecting mainly cortical TECs (cTECs). Remarkably, this severe involution is rapidly corrected following parturition. We postulated that understanding the mechanisms of pregnancy-related thymic changes could provide novel insights into signaling pathways regulating TEC function. When we analyzed genes whose expression in TECs was modified during late pregnancy, we found a strong enrichment in genes bearing KLF4 transcription factor binding motifs. We, therefore, engineered a Psmb11-iCre : Klf4 lox/lox mouse model to study the impact of TEC-specific Klf4 deletion in steady-state conditions and during late pregnancy. Under steady-state conditions, Klf4 deletion had a minimal effect on TEC subsets and did not affect thymic architecture. However, pregnancy-induced thymic involution was much more pronounced in pregnant females lacking Klf4 expression in TECs. These mice displayed a substantial ablation of TECs with a more pronounced loss of thymocytes. Transcriptomic and phenotypic analyses of Klf4 -/- TECs revealed that Klf4 is essential for preserving TEC's integrity and mitigating thymic involution during late pregnancy.Klf4 is essential for preserving TEC's integrity and mitigating thymic involution during late pregnancy., Competing Interests: Author MD-L was employed by the companies ExCell Thera, Inc. and Piercing Star Technologies. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Depoërs, Dumont-Lagacé, Trinh, Houques, Côté, Larouche, Brochu and Perreault.)

Lung infections are a perennial leading cause of death worldwide. The lung epithelium comprises three main cell types: alveolar type I (AT1), alveolar type II (AT2), and bronchiolar cells. Constitutively, these three cell types express extremely low amounts of surface MHC class I (MHC I) molecules, that is, <1% of levels found on medullary thymic epithelial cells (ECs). We report that inhalation of the TLR4 ligand LPS upregulates cell surface MHC I by ∼25-fold on the three subtypes of mouse lung ECs. This upregulation is dependent on Nlrc5 , Stat1 , and Stat2 and caused by a concerted production of the three IFN families. It is nevertheless hampered, particularly in AT1 cells, by the limited expression of genes instrumental in the peptide loading of MHC I molecules. Genes involved in production and response to cytokines and chemokines were selectively induced in AT1 cells. However, discrete gene subsets were selectively downregulated in AT2 or bronchiolar cells following LPS inhalation. Genes downregulated in AT2 cells were linked to cell differentiation and cell proliferation, and those repressed in bronchiolar cells were primarily involved in cilium function. Our study shows a delicate balance between the expression of transcripts maintaining lung epithelium integrity and transcripts involved in Ag presentation in primary lung ECs., (Copyright © 2022 by The American Association of Immunologists, Inc.)

Young adults that drive after cannabis use (DACU) may not share all the same characteristics. This study aimed to identify typologies of Canadians who engage in DACU. About 910 cannabis users with a driver's license (17-35 years old) who have engaged in DACU completed an online questionnaire. Two-step cluster analysis identified four subgroups, based on driving-related behaviors, cannabis use and related problems, and psychological distress. Complementary comparative analysis among the identified subgroups was performed as external validation. The identified subgroups were: (1) frequent cannabis users who regularly DACU; (2) individuals with generalized deviance with diverse risky road behaviors and high levels of psychological distress; (3) alcohol and drug-impaired drivers who were also heavy frequent drinkers; and (4) well-adjusted youths with mild depressive-anxious symptoms. Individuals who engaged in DACU were not a homogenous group. When required, prevention and treatment need to be tailored according to the different profiles., (© 2022 John Wiley & Sons Ltd.)

This study aimed to identify and compare major areas of met and unmet needs reported by 455 homeless or recently housed individuals recruited from emergency shelters, temporary housing, and permanent housing in Quebec (Canada). Mixed methods, guided by the Maslow framework, were used. Basic needs were the strongest needs category identified, followed by health and social services (an emergent category), and safety; very few participants expressed needs in the higher-order categories of love and belonging, self-esteem, and self-actualization. The only significant differences between the three housing groups occurred in basic needs met, which favored permanent housing residents. Safety was the only category where individuals reported more unmet than met needs. The study results suggested that increased overall access to and continuity of care with family physicians, MD or SUD clinicians and community organizations for social integration should be provided to help better these individuals. Case management, stigma prevention, supported employment programs, peer support and day centers should particularly be more widely implemented as interventions that may promote a higher incidence of met needs in specific needs categories., Competing Interests: The authors have declared that no competing interests exist.

Regulation of MHC class I (MHC I) expression has been studied almost exclusively in hematolymphoid cells. We report that thymic epithelial cells (TECs), particularly the medullary TECs, constitutively express up to 100-fold more cell surface MHC I proteins than epithelial cells (ECs) from the skin, colon, and lung. Differential abundance of cell surface MHC I in primary ECs is regulated via transcription of MHC I and of genes implicated in the generation of MHC I-binding peptides. Superior MHC I expression in TECs is unaffected by deletion of Ifnar1 or Ifngr1 , but is lessened by deletion of Aire , Ifnlr1 , Stat1 , or Nlrc5 , and is driven mainly by type III IFN produced by medullary TECs. Ifnlr1 -/- mice show impaired negative selection of CD8 thymocytes and, at 9 mo of age, present autoimmune manifestations. Our study shows unanticipated variation in MHC I expression by ECs from various sites and provides compelling evidence that superior expression of MHC I in TECs is crucial for proper thymocyte education., (Copyright © 2020 by The American Association of Immunologists, Inc.)

During gestation, sex hormones cause a significant thymic involution which enhances fertility. This thymic involution is rapidly corrected following parturition. As thymic epithelial cells (TECs) are responsible for the regulation of thymopoiesis, we analyzed the sequential phenotypic and transcriptomic changes in TECs during the postpartum period in order to identify mechanisms triggering postpartum thymic regeneration. In particular, we performed flow cytometry analyses and deep RNA-sequencing on purified TEC subsets at several time points before and after parturition. We report that pregnancy-induced involution is not caused by loss of TECs since their number does not change during or after pregnancy. However, during pregnancy, we observed a significant depletion of all thymocyte subsets downstream of the double-negative 1 (DN1) differentiation stage. Variations in thymocyte numbers correlated with conspicuous changes in the transcriptome of cortical TECs (cTECs). The transcriptomic changes affected predominantly cTEC expression of Foxn1 , its targets and several genes that are essential for thymopoiesis. By contrast, medullary TECs (mTECs) showed very little transcriptomic changes in the early postpartum regenerative phase, but seemed to respond to the expansion of single-positive (SP) thymocytes in the late phase of regeneration. Together, these results show that postpartum thymic regeneration is orchestrated by variations in expression of a well-defined subset of cTEC genes, that occur very early after parturition., (Copyright © 2020 Dumont-Lagacé, Daouda, Depoërs, Zumer, Benslimane, Brochu, Harrington, Lemieux and Perreault.)

Endothelial cells have multifaceted interactions with the immune system, both as initiators and targets of immune responses. In vivo, apoptotic endothelial cells release two types of extracellular vesicles upon caspase-3 activation: apoptotic bodies and exosome-like nanovesicles (ApoExos). Only ApoExos are immunogenic: their injection causes inflammation and autoimmunity in mice. Based on deep sequencing of total RNA, we report that apoptotic bodies and ApoExos are loaded with divergent RNA cargos that are not released by healthy endothelial cells. Apoptotic bodies, like endothelial cells, contain mainly ribosomal RNA whereas ApoExos essentially contain non-ribosomal non-coding RNAs. Endogenous retroelements, bearing viral-like features, represented half of total ApoExos RNA content. ApoExos also contained several copies of unedited Alu repeats and large amounts of non-coding RNAs with a demonstrated role in autoimmunity such as U1 RNA and Y RNA. Moreover, ApoExos RNAs had a unique nucleotide composition and secondary structure characterized by strong enrichment in U-rich motifs and unstably folded RNAs. Globally, ApoExos were therefore loaded with RNAs that can stimulate a variety of RIG-I-like receptors and endosomal TLRs. Hence, apoptotic endothelial cells selectively sort in ApoExos a diversified repertoire of immunostimulatory "self RNAs" that are tailor-made for initiation of innate immune responses and autoimmunity.

T cell development depends on sequential interactions of thymocytes with cortical thymic epithelial cells (cTECs) and medullary thymic epithelial cells. PSMB11 is a catalytic proteasomal subunit present exclusively in cTECs. Because proteasomes regulate transcriptional activity, we asked whether PSMB11 might affect gene expression in cTECs. We report that PSMB11 regulates the expression of 850 cTEC genes that modulate lymphostromal interactions primarily via the WNT signaling pathway. cTECs from Psmb11 -/- mice 1) acquire features of medullary thymic epithelial cells and 2) retain CD8 thymocytes in the thymic cortex, thereby impairing phase 2 of positive selection, 3) perturbing CD8 T cell development, and 4) causing dramatic oxidative stress leading to apoptosis of CD8 thymocytes. Deletion of Psmb11 also causes major oxidative stress in CD4 thymocytes. However, CD4 thymocytes do not undergo apoptosis because, unlike CD8 thymocytes, they upregulate expression of chaperones and inhibitors of apoptosis. We conclude that PSMB11 has pervasive effects on both CD4 and CD8 thymocytes via regulation of gene expression in cTECs., (Copyright © 2019 by The American Association of Immunologists, Inc.)