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IntroductionThere is a complex relationship between housing status and substance use, where substance use reduces housing opportunities and being unhoused increases reasons to use substances, and the associated risks and stigma. MethodsIn this descriptive analysis of people without housing who died of accidental substance-related acute toxicity in Canada, we used death investigation data from a national chart review study of substance-related acute toxicity deaths in 2016 and 2017 to compare sociodemographic factors, health histories, circumstances of death and substances contributing to death of people who were unhoused and people not identified as unhoused, using Pearson chi-square test. The demographic distribution of people who died of acute toxicity was compared with the 2016 Nationally Coordinated Point-In-Time Count of Homelessness in Canadian Communities and the 2016 Census. ResultsPeople without housing were substantially overrepresented among those who died of acute toxicity in 2016 and 2017 (8.9% versus $lt;1% of the overall population). The acute toxicity event leading to death of people without housing occurred more often in an outdoor setting (24%); an opioid and/or stimulant was identified as contributing to their death more frequently (68%–82%; both contributed in 59% of their deaths); and they were more frequently discharged from an institution in the month before their death (7%). ConclusionWe identified several potential opportunities to reduce acute toxicity deaths among people who are unhoused, including during contacts with health care and other institutions, through harm reduction supports for opioid and stimulant use, and by creating safer environments for people without housing.

AbstractThe acute toxicity (sometimes called “overdose” or “poisoning”) crisis has affected Canadians from all walks of life and of all ages—children, youth, adults including older adults have died.

IntroductionIl existe une relation complexe entre le statut résidentiel et la consommation de substances. En effet, la consommation de substances réduit les perspectives de logement et le fait d’être sans logement augmente les raisons de consommer des substances ainsi que les risques et la stigmatisation qui y sont associés. MéthodologieDans cette analyse descriptive des personnes sans logement qui ont perdu la vie en raison d’une intoxication aiguë accidentelle liée à une substance au Canada, nous avons utilisé les données relatives aux enquêtes sur les décès tirées d’une étude nationale d’examen des dossiers concernant les décès par intoxication aiguë due à une substance en 2016 et 2017, afin de comparer les facteurs sociodémographiques, les antécédents médicaux, les circonstances du décès et les substances ayant contribué au décès des personnes sans logement et des personnes non identifiées comme sans logement, au moyen du test du khi carré de Pearson. Nous avons comparé le profil démographique des personnes décédées d’une intoxication aiguë aux données du Dénombrement ponctuel coordonné de l’itinérance dans les collectivités canadiennes de 2016 et du Recensement de 2016. RésultatsLes personnes sans logement étaient nettement surreprésentées parmi les personnes décédées d’une intoxication aiguë en 2016 et 2017 (8,9 % contre moins de 1 % de la population générale). L’intoxication aiguë ayant entraîné le décès des personnes sans logement a eu lieu plus souvent à l’extérieur (24 %); un opioïde ou un stimulant a plus fréquemment contribué à leur décès (68 % à 82 %; les deux substances ont été responsables de 59 % des décès) et ces personnes avaient plus souvent été libérées d’un établissement correctionnel ou été autorisées à sortir d’un établissement de soins de santé au cours du mois précédant leur décès (7 %). ConclusionNous présentons plusieurs possibilités de réduire les décès attribuables à une intoxication aiguë chez les personnes sans logement, notamment lors de la prise de contact avec les services de santé et d’autres établissements, par des mesures de soutien à la réduction des méfaits liés à la consommation d’opioïdes et de stimulants ainsi que par la création d’environnements plus sûrs pour les personnes sans logement.

RésuméLa crise des intoxications aiguës (parfois appelées « surdoses » ou « empoisonnements ») touche la population canadienne à toutes les étapes de vie, que ce soit les jeunes, les adultes ou les aînés.

Abstract Background Evidence suggests that women who are incarcerated desire access to contraception while incarcerated, and that this need is not currently being met. Our objective in this study was to explore the perspectives and experiences of women in prisons regarding contraception and contraception access using data from focus groups with women in a provincial prison. We analyzed focus group data collected in a provincial prison in Ontario, Canada using content analysis and a constructivist epistemology. Results We conducted three focus groups, each approximately one hour in length. Discussions revolved around (1) knowledge and decision making about contraception, (2) accessing contraception, and (3) ideas for increasing access to contraception in the prison setting. Decision making about contraception was mainly related to concerns about side effects, consistent access to care, impacts on future fertility, and autonomy around decision-making. Participants discussed a wide range of experiences with contraception. Ideas for increasing access to contraception included information sessions, inclusion of discussions about contraception as a component of admission and release planning, and time spent in prison as a crucial juncture for decision-making about contraception. Conclusions More qualitative research is needed to better understand the needs of women in prisons related to contraception. The findings of this study suggest that programs should focus on consistency and continuity of access to care, education opportunities, and integration of discussions about contraception into official admission and release procedures.

Abstract Chronic antibody mediated rejection (AMR) is the major cause of solid organ graft rejection. Th17 contributes to AMR through the secretion of IL17A, IL21 and IL22. These cytokines promote neutrophilic infiltration, B cell proliferation and donor specific antibodies (DSAs) production. In the current study we investigated the role of Th17 in transplant sensitization. Additionally, we investigated the therapeutic potential of novel inverse agonists of the retinoic acid receptor-related orphan receptor gamma t (RORγt) in the treatment of skin allograft rejection in sensitized mice. Our results show that RORγt inverse agonists reduce cytokine production in human Th17 cells in vitro. In mice, we demonstrate that the RORγt inverse agonist TF-S14 reduces Th17 signature cytokines in vitro and in vivo and leads to blocking neutrophilic infiltration to skin allografts, inhibition of the B-cell differentiation, and the reduction of de novo IgG3 DSAs production. Finally, we show that TF-S14 prolongs the survival of a total mismatch grafts in sensitized mice. In conclusion, RORγt inverse agonists offer a therapeutic intervention through a novel mechanism to treat rejection in highly sensitized patients.

Worldwide, there is a lack of systematically collected health data on people who are incarcerated. Our objective in this paper was to describe a process model of formative work for a project to strengthen health surveillance for people incarcerated under a Canadian prison authority. We have developed project structures and processes, and we are evaluating project partnerships. To inform prison health surveillance foci, we are conducting a review of literature on best practices, a qualitative study to understand stakeholders’ needs and priorities, and mapping work to understand available prison health-related data. Developing and implementing prison health surveillance is gradual and developmental, necessitating time to build relationships and obtain approvals. The needs and interests of knowledge users should be prioritized, but there may be challenges to achieving a coherent vision due to feasibility and differing needs and objectives of various stakeholders. Developing collaborative relationships could help bridge this gap.

IntroductionSubstance-related acute toxicity deaths (ATDs) are a public health crisis in Canada. Youth are often at higher risk for substance use due to social, environmental and structural factors. The objectives of this study were to understand the characteristics of youth (aged 12–24 years) dying of accidental acute toxicity in Canada and examine the substances contributing to and circumstances surrounding youth ATDs. MethodsData from a national chart review study of coroner and medical examiner data on ATDs that occurred in Canada between 2016 and 2017 were used to conduct descriptive analyses with proportions, mortality rates and proportionate mortality rates. Where possible, youth in the chart review study were compared with youth in the general population and youth who died of all causes, using census data. ResultsOf the 732 youth who died of accidental acute toxicity in 2016–2017, most (94%) were aged 18 to 24 years. Youth aged 20 to 24 who were unemployed, unhoused or living in collective housing were overrepresented among accidental ATDs. Many of the youth aged 12 to 24 who died of accidental acute toxicity had a documented history of substance use. Fentanyl, cocaine and methamphetamine were the most common substances contributing to death, and 38% of the deaths were witnessed or potentially witnessed. ConclusionThe findings of this study point to the need for early prevention and harm reduction strategies and programs that address mental health, exposure to trauma, unemployment and housing instability to reduce the harms of substance use on Canadian youth.

IntroductionLes décès attribuables à une intoxication aiguë due à une substance sont à l’origine d’une crise de santé publique au Canada. Les jeunes courent souvent un risque accru de consommation de substances en raison de facteurs sociaux, environnementaux et structurels. Les objectifs de cette étude étaient de comprendre les caractéristiques des jeunes (12 à 24 ans) qui décèdent en raison d’une intoxication aiguë accidentelle au Canada ainsi que d’analyser les substances qui contribuent aux décès par intoxication aiguë chez les jeunes et les circonstances entourant ces décès. MéthodologieNous avons utilisé les données d’une étude nationale portant sur l’examen des dossiers des données de coroners et de médecins légistes concernant les décès par intoxication aiguë survenus au Canada en 2016 et 2017 afin de réaliser des analyses descriptives à partir des proportions, des taux de décès et des taux proportionnels de décès. Dans la mesure du possible, les jeunes faisant partie de l’étude sur l’examen des dossiers ont été comparés, au moyen de données de recensement, aux jeunes dans la population générale et aux jeunes décédés toutes causes confondues. RésultatsSur les 732 jeunes décédés par intoxication aiguë accidentelle en 2016-2017, la plupart (94 %) avaient entre 18 et 24 ans. Les jeunes de 20 à 24 ans sans emploi et vivant dans un logement collectif ou sans domicile étaient surreprésentés parmi les décès accidentels par intoxication aiguë. Parmi les jeunes de 12 à 24 ans décédés en raison d’une intoxication aiguë accidentelle, beaucoup avaient des antécédents documentés de consommation de substances. Le fentanyl, la cocaïne et la méthamphétamine ont été les substances ayant le plus fréquemment contribué aux décès, et 38 % des décès ont eu lieu en présence d’un témoin ou potentiellement en présence d’un témoin. ConclusionLes résultats de cette étude soulignent la nécessité de mettre en place des mesures de prévention précoce, des stratégies de réduction des méfaits et des programmes portant sur la santé mentale, l’exposition à un événement traumatisant ainsi que le chômage et l’instabilité résidentielle, afin de réduire les méfaits de la consommation de substances chez les jeunes Canadiens.

Latino boys' motivational beliefs in STEM remain under-examined in the literature, especially during middle school when building a strong STEM trajectory is critical for future success in STEM. The current study used Expectancy-Value Theory to analyze how Latino boys interpreted their expectancies and values in order to better understand their motivational beliefs. Furthermore, Critical Race Theory was incorporated to help identify the structural inequalities and familial motivational mechanisms that Latino boys perceived to play a role in their STEM persistence. A total of 89, predominantly low-income, Latino boys in middle school participated in focus groups. We analyzed the focus group data using deductive content analysis to examine students' expectancies and values and a hybrid inductive and deductive approach to examine perceived barriers and family motivators. The results illustrated boys' interpretations of their expectancies and subjective task values (i.e., utility, attainment, interest, and cost values) as contributors to their choices and persistence in STEM. Moreover, although boys perceived inequalities in STEM schooling, families served as primary motivators for students to pursue STEM. The results of this study have important implications for middle school educators who are facilitators of students' achievement motivation and engagement in STEM.

The nerve terminal and muscle membrane compose the neuromuscular junction. After opening the voltage-gated calcium channels, action potentials from the motor axons provoke a cascade for the acetylcholine release from synaptic vesicles to the synaptic cleft, where it binds to its receptor at the muscle membrane for depolarization. Low amplitude compound muscle action potential typically presents in presynaptic disorders, increasing by more than 100% after a 10-second effort in the Lambert-Eaton myasthenic syndrome and less in botulism. Needle electromyography may show myopathic motor unit action potentials and morphological instability (“jiggle”) due to impulse blocking. Low-frequency repetitive nerve stimulation (RNS) is helpful in postsynaptic disorders, such as myasthenia gravis and most congenital myasthenic syndromes, where the number of functioning acetylcholine receptors is reduced. Low-frequency RNS with a decrement >10% is abnormal when comparing the 4th to the first compound muscle action potential amplitude. High-frequency RNS is helpful in presynaptic disorders like Lambert-Eaton myasthenic syndrome, botulism, and some rare congenital myasthenic syndromes. The high-frequency RNS releases more calcium, increasing the acetylcholine with a compound muscle action potential increment. Concentric needle records apparent single-fiber action potentials (spikes). A voluntary activation measures the jitter between spikes from two endplates. An electrical activation measures the jitter of one spike (one endplate). The jitter is the most sensitive test for detecting a neuromuscular junction dysfunction. Most neuromuscular junction disorders are responsive to treatment.

The treatment of displaced intra-articular calcaneal fractures is not standardized, as many surgeons prefer not to perform surgery, considering a high rate of cutaneous complications associated with the usual extensile lateral approach. The Calcanail® represents a percutaneous osteosynthesis device that is biomechanically more stable than multiple screws or locking plates. While it effectively restores the height and axis of the hindfoot, it appears to be less reliable in achieving articular reduction of the thalamic surface in cases of mixed fractures. Therefore, we developed a new technique suitable for comminuted mixed fractures, using the Calcanail® device with an arthroscopically guided closed reduction internal fixation of the thalamic surface.

Background: There is little research with people who experience intellectual/developmental disabilities and imprisonment. Methods: The study linked health and correctional data to examine prevalence of intellectual/developmental disabilities and health and correctional characteristics among adults experiencing their first federal incarceration between 1 January 2002 and 31 December 2011 (n = 9278) and two non-incarcerated groups (n = 10,086,802). Results: The prevalence of intellectual/developmental disabilities was 2.1% in the incarcerated group and 0.9% in the non-incarcerated group. Before incarceration, those with, versus without, intellectual/developmental disabilities were at greater risk of traumatic brain injury, mental illness, and substance use disorders. While incarcerated, those with intellectual/developmental disabilities were more likely to incur serious institutional disciplinary charges. Post-incarceration, persons with intellectual/developmental disabilities were at greater risk of emergency department visits, and psychiatric and acute hospitalizations, than the non-incarcerated groups. Conclusions: People with intellectual/developmental disabilities are overrepresented in Canadian federal correctional institutions. The authors offer strategies to support people prior to, during, and post-incarceration.

ABSTRACT Transcription factors (TFs) play key roles in cellular regulation and are critical in the control of drug resistance in the fungal pathogen Candida albicans. We found that activation of the transcription factor C4_02500C_A (Adr1) conferred significant resistance against fluconazole. In Saccharomyces cerevisiae, Adr1 is a carbon-source-responsive zinc-finger transcription factor required for transcription of the glucose-repressed gene ADH1 and of genes required for ethanol, glycerol, and fatty acid utilization. Motif scanning of promoter elements suggests that Adr1 may be rewired in fungi and govern the ergosterol synthesis pathway in C. albicans. Because previous studies have identified the zinc-cluster transcription factor Upc2 as a regulator of the ergosterol pathway in both fungi, we examined the relationship between Adr1 and Upc2 in sterol biosynthesis in C. albicans. Phenotypic profiles of either ADR1 or UPC2 modulation in C. albicans showed differential growth in the presence of fluconazole; either adr1 or upc2 homozygous deletion results in sensitivity to the drug, while their activation generates a fluconazole-resistant strain. The rewiring from ergosterol synthesis to fatty acid metabolism involved all members of the Adr1 regulon except the alcohol dehydrogenase Adh1, which remains under Adr1 control in both circuits and may have been driven by the lifestyle of S. cerevisiae, which requires the ability to both tolerate and process high concentrations of ethanol. Importance Research often relies on well-studied orthologs within related species, with researchers using a well-studied gene or protein to allow prediction of the function of the ortholog. In the opportunistic pathogen Candida albicans, orthologs are usually compared with Saccharomyces cerevisiae, and this approach has been very fruitful. Many transcription factors (TFs) do similar jobs in the two species, but many do not, and typically changes in function are driven not by modifications in the structures of the TFs themselves but in the connections between the transcription factors and their regulated genes. This strategy of changing TF function has been termed transcription factor rewiring. In this study, we specifically looked for rewired transcription factors, or Candida-specific TFs, that might play a role in drug resistance. We investigated 30 transcription factors that were potentially rewired or were specific to the Candida clade. We found that the Adr1 transcription factor conferred resistance to drugs like fluconazole, amphotericin B, and terbinafine when activated. Adr1 is known for fatty acid and glycerol utilization in Saccharomyces, but our study reveals that it has been rewired and is connected to ergosterol biosynthesis in Candida albicans.

In the United States, Latin@s remain underrepresented in the STEM workforce despite being a growing population in postsecondary institutions and across the country. Mentorship is needed to foster agency and leadership to build more Latin@ representation in STEM. In this study, we used a focus group and interviews to examine the mentee and mentor experiences of five Latin@ college students enrolled in a Hispanic-serving institution and participating in a STEM mentoring program for youth. We applied a community cultural wealth framework to describe participants' mentoring experiences and the practices that help Latin@s navigate the pre-K-20+ STEM pipeline. Mentoring Latin@s in STEM necessitates a culturally affirming approach that acknowledges community wealth and the ways students overcome institutional barriers.

A critical race theory framework was used to examine the role of music listening practices in the academic and social contexts of Latino college students enrolled at a predominantly White institution. An inductive thematic analysis examined themes in participants' open-ended responses. Awareness of their Latino identity in music and the use of digital music players served to construct sonic counterspaces, an affirming auditory realm that is comprised of emotional, psychological, and physical space activated through intentional listening practices. Sonic counterspaces facilitated their academic experience and helped them navigate negative social encounters.

Introduction: Ligament balancing is essential to the functional outcome of total knee arthroplasty (TKA). The optimal method of alignment remains a controversial issue. The primary objective was to compare the clinical outcomes of TKA between functional and adjusted mechanical alignment techniques. The secondary objectives were to compare bone resection, robotic alignment, and radiological assessment. Materials and methods: This was a retrospective case-control series comparing TKA performed with functional alignment (FA) and adjusted mechanical alignment (aMA). Sixty-four FA subjects were matched with 64 aMA controls. These two groups were matched for age, gender, body mass index (BMI), surgeon, and type of frontal deformity. Both surgical procedures were performed using the MAKO® haptic robotic system. Functional scores (Forgotten Joint Score (FJS), Knee Society Score (KSS), and Oxford Knee Score (OKS)) were measured at the final postoperative follow-up. A radiographic evaluation was performed at the same time. Results: Mean FJS were respectively 63.4 ± 25.1 [0–100] and 51.2 ± 31.8 [0–100] in FA versus aMA group (p = 0.034). Mean OKS were respectively 40.8 ± 6.3 [21–48] and 34.9 ± 11.8 [3–48] in FA versus aMA group (p = 0.027). Mean KSS were respectively 184.9 ± 17.0 [126–200] and 175.6 ± 23.1 [102–200] in FA versus aMA group (p = 0.02). The main residual symptom was “none” for 73.0% versus 57.8%, “instability” for 6.4% versus 21.9%, “Pain” for 19.1% versus 12.5%, and “effusion” for 1.6% and 7.8% respectively for FA and aMA group (p = 0.016). There were 4 complications in the FA group versus 5 in the aMA group (p > 0.999). Mean postoperative hip-knee-ankle (HKA) robotic assessment were respectively 177.3° ± 2.0 [172–180] and 178.2° ± 2.0 [173–180] for FA and aMA group (p = 0.018). The median difference between HKA robotic and HKA radiological was −3.0° (IQR = 3.0; p

Less than half of adolescent mothers graduate from high school and fewer obtain a post-secondary degree. The purpose of this study is to understand how Latina mothers who experienced childbirth during adolescence transition to parenthood and higher education. We conducted 13 in-depth interviews with Latina mothers enrolled in higher education. We found that Latina mothers' persistence in higher education is influenced by psychosocial factors, initial commitments, academic and social experiences in college, and final commitments.

IntroductionMore than 30 million adults are released from incarceration globally each year. Many experience complex physical and mental health problems, and are at markedly increased risk of preventable mortality. Despite this, evidence regarding the global epidemiology of mortality following release from incarceration is insufficient to inform the development of targeted, evidence-based responses. Many previous studies have suffered from inadequate power and poor precision, and even large studies have limited capacity to disaggregate data by specific causes of death, sub-populations or time since release to answer questions of clinical and public health relevance.ObjectivesTo comprehensively document the incidence, timing, causes and risk factors for mortality in adults released from prison.MethodsWe created the Mortality After Release from Incarceration Consortium (MARIC), a multi-disciplinary collaboration representing 29 cohorts of adults who have experienced incarceration from 11 countries. Findings across cohorts will be analysed using a two-step, individual participant data meta-analysis methodology.ResultsThe combined sample includes 1,337,993 individuals (89% male), with 75,795 deaths recorded over 9,191,393 person-years of follow-up.ConclusionsThe consortium represents an important advancement in the field, bringing international attention to this problem. It will provide internationally relevant evidence to guide policymakers and clinicians in reducing preventable deaths in this marginalized population.Key wordsMortality; incarceration; prison; release; individual participant data meta-analysis; consortium; cohort.

Abstract Opioid agonist treatment (OAT) is the primary intervention for opioid use disorder (OUD) in Canada and the USA. Yet, a number of barriers contribute to sub-optimal treatment uptake and retention, including daily-supervised medication administration. Thus, clients are eventually granted access to take-home OAT doses (i.e., ‘carries’) to reduce this burden. However, this decision is based on physician discretion and whether patients can demonstrate stability in various life domains, many of which are inextricably linked to the social determinants of health (SDOH). Current Canadian and USA OAT carry guidance documents are not standardized and do not take the SDOH into consideration, resulting in the potential for inequitable access to OAT carries, which may be the case particularly among marginalized populations such as individuals with OUD who have been released from custody. This perspective article posits that current OAT guidelines contribute to inequities in access to OAT carries, and that these inequities likely result in disproportionately low coverage for OUD treatment among some high-risk groups, including individuals on release from incarceration in particular. Relevant impacts of COVID-19 and related policy changes are considered, and suggestions and recommendations to amend current OAT guidance documents are provided.

Objectives To describe mortality due to opioid toxicity among people who experienced incarceration in Ontario between 2015 and 2020, during the fentanyl-dominant era.Design In this retrospective cohort study, we linked Ontario coronial data on opioid toxicity deaths between 2015 and 2020 with correctional data for adults incarcerated in Ontario provincial correctional facilities.Setting Ontario, Canada.Participants Whole population data.Main outcomes and measures The primary outcome was opioid toxicity death and the exposure was any incarceration in a provincial correctional facility between 2015 and 2020. We calculated crude death rates and age-standardised mortality ratios (SMR).Results Between 2015 and 2020, 8460 people died from opioid toxicity in Ontario. Of those, 2207 (26.1%) were exposed to incarceration during the study period. Among those exposed to incarceration during the study period (n=1 29 152), 1.7% died from opioid toxicity during this period. Crude opioid toxicity death rates per 10 000 persons years were 43.6 (95% CI=41.8 to 45.5) for those exposed to incarceration and 0.95 (95% CI=0.93 to 0.97) for those not exposed. Compared with those not exposed, the SMR for people exposed to incarceration was 31.2 (95% CI=29.8 to 32.6), and differed by sex, at 28.1 (95% CI=26.7 to 29.5) for males and 77.7 (95% CI=69.6 to 85.9) for females. For those exposed to incarceration who died from opioid toxicity, 10.6% died within 14 days of release and the risk was highest between days 4 and 7 postrelease, at 288.1 per 10 000 person years (95% CI=227.8 to 348.1).Conclusions The risk of opioid toxicity death is many times higher for people who experience incarceration compared with others in Ontario. Risk is markedly elevated in the week after release, and women who experience incarceration have a substantially higher SMR than men who experience incarceration. Initiatives to prevent deaths should consider programmes and policies in correctional facilities to address high risk on release.