Gene Expression Profile of Benign, Intermediate, and Malignant Spitz and Spitzoid Melanocytic Lesions.

Spitz and Spitzoid lesions represent one of the most challenging melanocytic neoplasms in dermatopathology. Nosologic classification has been more recently improved by the discovery of novel molecular drivers, particularly translocations. In the current study, we aimed to use an unbiased approach to explore the gene expression profile of a group of melanocytic Spitz and Spitzoid melanocytic lesions ranging from benign lesions to melanoma, including intermediate lesions such as SPARK nevi and atypical Spitz tumors/melanocytomas. Using unsupervised analysis of gene expression data, we found some distinct hierarchical clusters of lesions, including groups characterized by ALK and NTRK translocations. Few non-ALK translocated tumors demonstrated increased ALK expression, confirmed by immunohistochemistry. Spitz tumors with overlapping features of dysplastic nevi, so-called SPARK nevi, appear to have a common gene expression profile by hierarchical clustering. Finally, weighted gene correlation network analysis identified gene modules variably regulated in subtypes of these cases. Thus, gene expression profiling of Spitz and Spitzoid lesions represents a viable instrument for the characterization of these lesions.

User-Centered Development of a Patient Decision Aid for Choice of Early Abortion Method: Multi-Cycle Mixed Methods Study.

BACKGROUND: People seeking abortion in early pregnancy have the choice between medication and procedural options for care. The choice is preference-sensitive-there is no clinically superior option and the choice depends on what matters most to the individual patient. Patient decision aids (PtDAs) are shared decision-making tools that support people in making informed, values-aligned health care choices. OBJECTIVE: We aimed to develop and evaluate the usability of a web-based PtDA for the Canadian context, where abortion care is publicly funded and available without legal restriction. METHODS: We used a systematic, user-centered design approach guided by principles of integrated knowledge translation. We first developed a prototype using available evidence for abortion seekers' decisional needs and the risks, benefits, and consequences of each option. We then refined the prototype through think-aloud interviews with participants at risk of unintended pregnancy ("patient" participants). Interviews were audio-recorded and documented through field notes. Finally, we conducted a web-based survey of patients and health care professionals involved with abortion care, which included the System Usability Scale. We used content analysis to identify usability issues described in the field notes and open-ended survey questions, and descriptive statistics to summarize participant characteristics and close-ended survey responses. RESULTS: A total of 61 individuals participated in this study. Further, 11 patients participated in think-aloud interviews. Overall, the response to the PtDA was positive; however, the content analysis identified issues related to the design, language, and information about the process and experience of obtaining abortion care. In response, we adapted the PtDA into an interactive website and revised it to include consistent and plain language, additional information (eg, pain experience narratives), and links to additional resources on how to find an abortion health care professional. In total, 25 patients and 25 health care professionals completed the survey. The mean System Usability Scale score met the threshold for good usability among both patient and health care professional participants. Most participants felt that the PtDA was user-friendly (patients: n=25, 100%; health care professionals: n=22, 88%), was not missing information (patients: n=21, 84%; health care professionals: n=18, 72%), and that it was appropriate for patients to complete the PtDA before a consultation (patients: n=23, 92%; health care professionals: n=23, 92%). Open-ended responses focused on improving usability by reducing the length of the PtDA and making the website more mobile-friendly. CONCLUSIONS: We systematically designed the PtDA to address an unmet need to support informed, values-aligned decision-making about the method of abortion. The design process responded to a need identified by potential users and addressed unique sensitivities related to reproductive health decision-making.

The role of vaccination and environmental factors on outbreaks of high pathogenicity avian influenza H5N1 in Bangladesh.

High Pathogenicity Avian Influenza (HPAI) H5N1 outbreaks continue to wreak havoc on the global poultry industry and threaten the health of wild bird populations, with sporadic spillover in humans and other mammals, resulting in widespread calls to vaccinate poultry. Bangladesh has been vaccinating poultry since 2012, presenting a prime opportunity to study the effects of vaccination on HPAI H5N1circulation in both poultry and wild birds. We investigated the efficacy of vaccinating commercial poultry against HPAI H5N1 along with climatic and socio-economic factors considered potential drivers of HPAI H5N1 outbreak risk in Bangladesh. Using a multivariate modeling approach, we estimated that the rate of outbreaks was 18 times higher before compared to after vaccination, with winter months having a three times higher chance of outbreaks than summer months. Variables resulting in small but significant increases in outbreak rate were relatively low ambient temperatures for the time of year, literacy rate, chicken and duck density, crop density, and presence of highways; this may be attributable to low temperatures supporting viral survival outside the host, higher literacy driving reporting rate, density of the host reservoir, and spread of the virus through increased connectivity. Despite the substantial impact of vaccination on outbreaks, we note that HPAI H5N1 is still enzootic in Bangladesh; vaccinated poultry flocks have high rates of H5N1 prevalence, and spillover to wild birds has increased. Vaccination in Bangladesh thus bears the risk of supporting "silent spread," where the vaccine only provides protection against disease and not also infection. Our findings underscore that poultry vaccination can be part of holistic HPAI mitigation strategies when accompanied by monitoring to avoid silent spread.

Potential risk zones and climatic factors influencing the occurrence and persistence of avian influenza viruses in the environment of live bird markets in Bangladesh.

Live bird markets (LBMs) are critical for poultry trade in many developing countries that are regarded as hotspots for the prevalence and contamination of avian influenza viruses (AIV). Therefore, we conducted weekly longitudinal environmental surveillance in LBMs to determine annual cyclic patterns of AIV subtypes, environmental risk zones, and the role of climatic factors on the AIV presence and persistence in the environment of LBM in Bangladesh. From January 2018 to March 2020, we collected weekly fecal and offal swab samples from each LBM and tested using rRT-PCR for the M gene and subtyped for H5, H7, and H9. We used Generalized Estimating Equations (GEE) approaches to account for repeated observations over time to correlate the AIV prevalence and potential risk factors and the negative binomial and Poisson model to investigate the role of climatic factors on environmental contamination of AIV at the LBM. Over the study period, 37.8% of samples tested AIV positive, 18.8% for A/H5, and A/H9 was, for 15.4%. We found the circulation of H5, H9, and co-circulation of H5 and H9 in the environmental surfaces year-round. The Generalized Estimating Equations (GEE) model reveals a distinct seasonal pattern in transmitting AIV and H5. Specifically, certain summer months exhibited a substantial reduction of risk up to 70-90% and 93-94% for AIV and H5 contamination, respectively. The slaughtering zone showed a significantly higher risk of contamination with H5, with a three-fold increase in risk compared to bird-holding zones. From the negative binomial model, we found that climatic factors like temperature and relative humidity were also significantly associated with weekly AIV circulation. An increase in temperature and relative humidity decreases the risk of AIV circulation. Our study underscores the significance of longitudinal environmental surveillance for identifying potential risk zones to detect H5 and H9 virus co-circulation and seasonal transmission, as well as the imperative for immediate interventions to reduce AIV at LBMs in Bangladesh. We recommend adopting a One Health approach to integrated AIV surveillance across animal, human, and environmental interfaces in order to prevent the epidemic and pandemic of AIV.

Co-evolution of AR gene copy number and structural complexity in endocrine therapy resistant prostate cancer.

Androgen receptor (AR) inhibition is standard of care for advanced prostate cancer (PC). However, efficacy is limited by progression to castration-resistant PC (CRPC), usually due to AR re-activation via mechanisms that include AR amplification and structural rearrangement. These two classes of AR alterations often co-occur in CRPC tumors, but it is unclear whether this reflects intercellular or intracellular heterogeneity of AR. Resolving this is important for developing new therapies and predictive biomarkers. Here, we analyzed 41 CRPC tumors and 6 patient-derived xenografts (PDXs) using linked-read DNA-sequencing, and identified 7 tumors that developed complex, multiply-rearranged AR gene structures in conjunction with very high AR copy number. Analysis of PDX models by optical genome mapping and fluorescence in situ hybridization showed that AR residing on extrachromosomal DNA (ecDNA) was an underlying mechanism, and was associated with elevated levels and diversity of AR expression. This study identifies co-evolution of AR gene copy number and structural complexity via ecDNA as a mechanism associated with endocrine therapy resistance.

Dispensing mifepristone for medical abortion in Canada: Pharmacists' experiences of the first year.

Background: Mifepristone for medical abortion was first dispensed by community pharmacists in Canada directly to patients in January 2017. We asked about pharmacists' experiences over their first year dispensing mifepristone in order to evaluate the frequency of the new practice and assess availability in urban/rural pharmacies. Methods: From August to December 2019, we invited 433 community pharmacists who had completed a baseline survey at least 1 year prior to participate in a follow-up online survey. We summarized categorical data using counts and proportions and conducted a qualitative thematic analysis of open-ended responses. Results: Among 122 participants, 67.2% had dispensed the product, and 48.4% routinely stocked mifepristone. Pharmacists reported a mean of 26 and median of 3 (interquartile range, 1, 8) mifepristone prescriptions filled in their pharmacies in the previous year. Participants perceived that the benefits of making mifepristone available in pharmacies included increased abortion access for patients (n = 115; 94.3%), reduced pressure on the health care system (n = 104; 85.3%), increased rural and remote abortion access (n = 103; 84.4%) and increased interprofessional collaborations (n = 48; 39.3%). Few participants reported challenges to maintaining adequate stock of mifepristone, but these challenges included low demand (n = 24; 19.7%), short expiry dating (n = 12; 9.8%) and drug shortages (n = 8; 6.6%). The overwhelming majority, 96.7%, reported that their communities did not resist the provision of mifepristone by their pharmacy. Interpretation: Participating pharmacists reported many benefits and very few barriers to stocking and dispensing mifepristone. Both urban and rural communities responded positively to enhanced access to mifepristone in their community. Conclusions: Mifepristone is well accepted by pharmacists within the primary care system in Canada.

The financial burden of accessing care for people with scleroderma in Canada: a patient-oriented, cross-sectional survey.

BACKGROUND: Patients with scleroderma require a lifetime of treatment and frequent contacts with rheumatologists and other health care professionals. Although publicly funded health care systems in Canada cover many costs, patients may still face a substantial financial burden in accessing care. The purpose of this study was to quantify out-of-pocket costs borne by people with scleroderma in Canada and compare this burden for those living in large communities and smaller communities. METHODS: We analyzed responses to a Web-based survey of people living in Canada with scleroderma. Respondents reported annual out-of-pocket medical, travel and accommodation and other nonmedical costs (2019 Canadian dollars). We used descriptive statistics to describe travel distance and out-of-pocket costs. We used a 2-part model to estimate the impact on out-of-pocket costs of living in a large urban centre (≥ 100 000 population), compared with smaller urban centres or rural areas (< 100 000 population). We generated combined mean estimates from the 2-part models using predictive margins. RESULTS: The survey included 120 people in Canada with scleroderma. The mean, annual, total out-of-pocket costs were $3357 (standard deviation $5580). Respondents living in smaller urban centres and rural areas reported higher mean total costs ($4148, 95% confidence interval [CI] $3618-$4680) and travel or accommodation costs ($1084, 95% CI $804-$1364) than those in larger urban centres (total costs $2678, 95% CI $2252-$3104; travel or accommodation costs $332, 95% CI $207-$458). INTERPRETATION: Many patients with scleroderma incur considerable out-of-pocket costs, and this burden is exacerbated for those living in smaller urban centres and rural areas. Health care systems and providers should consider ways to alleviate this burden and support equitable access to care.

Experience of stigma and harassment among respondents to the 2019 Canadian abortion provider survey.

OBJECTIVE: We conducted a national survey to assess the experiences of stigma and harassment among physicians and nurse practitioners providing abortions and abortion service administrators in Canada. STUDY DESIGN: We conducted an exploratory, cross-sectional, national, anonymized, online survey between July and December 2020. Subsections of the survey explored stigma and harassment experienced by respondents, including the 35-item Revised Abortion Providers Stigma Scale and open-ended responses. We analyzed the quantitative data to generate descriptive statistics and employed a reflexive thematic analysis to interpret open-ended responses. RESULTS: Three hundred fifty-four participants started the stigma and harassment section of the survey. Among low-volume clinicians (<30 abortions/year, 60%, n = 180) 8% reported harassment; 21% among higher volume clinicians (≥30 abortions/year, 40%, n = 119) and 47% among administrators (n = 39), most commonly picketing. The mean stigma score was 67.8 (standard deviation 17.2; maximum score 175). Our qualitative analysis identified five themes characterizing perceptions of stigma and harassment: concerns related to harassment from picketing, protestors, and the public; wanting protestor "bubble zones"; aiming to be anonymous to avoid being a target; not providing an abortion service; but also witnessing a safe and positive practice environment. CONCLUSIONS: Being a low-volume clinician compared to higher volume clinician and administrator appears to be associated with less harassment. Clinicians providing abortion care in Canada reported mid-range abortion-related stigma scores, and expressed strong concerns that stigma interfered with their abortion provision. Our results indicate that further de-stigmatization and protection of abortion providers in Canada is needed through policy and practice interventions including bubble zones. IMPLICATIONS: While Canadian abortion care clinicians and administrators reported relatively low incidence of harassment, our results indicate that they are concerned about stigma and harassment. However, as this was an exploratory survey, these data may not be representative of all Canadian abortion providers. Our data identify a need to support abortion clinicians and to bolster protections for dedicated abortion services.

Prevalence and risk factors for avian influenza virus (H5 and H9) contamination in peri-urban and rural live bird markets in Bangladesh.

Avian influenza viruses (AIV) have been frequently detected in live bird markets (LBMs) around the world, primarily in urban areas, and have the ability to spillover to other species, including humans. Despite frequent detection of AIV in urban LBMs, the contamination of AIV on environmental surfaces in rural and peri-urban LBMs in Bangladesh is poorly documented. Therefore, we conducted this study to determine the prevalence of AIV subtypes within a subset of peri-urban and rural LBMs in Bangladesh and to further identify associated risk factors. Between 2017 and 2018, we collected faecal and offal samples from 200 stalls in 63 LBMs across four sub-districts. We tested the samples for the AIV matrix gene (M-gene) followed by H5, H7, and H9 subtypes using real-time reverse transcriptase-polymerase chain reaction (rRT-PCR). We performed a descriptive analysis of market cleanliness and sanitation practices in order to further elucidate the relationship between LBM biosecurity and AIV subtypes by species, sample types, and landscape. Subsequently, we conducted a univariate analysis and a generalized linear mixed model (GLMM) to determine the risk factors associated with AIV contamination at individual stalls within LBMs. Our findings indicate that practices related to hygiene and the circulation of AIV significantly differed between rural and peri-urban live bird markets. 42.5% (95% CI: 35.56-49.67) of stalls were positive for AIV. A/H5, A/H9, and A HA/Untyped were detected in 10.5% (95% CI: 6.62-15.60), 9% (95% CI: 5.42-13.85), and 24.0% (95% CI: 18.26-30.53) of stalls respectively, with no detection of A/H7. Significantly higher levels of AIV were found in the Sonali chicken strain compared to the exotic broiler, and in offal samples compared to fecal samples. In the GLMM analysis, we identified several significant risk factors associated with AIV contamination in LBMs at the stall level. These include: landscape (AOR: 3.02; 95% CI: 1.18-7.72), the number of chicken breeds present (AOR: 2.4; 95% CI: 1.01-5.67), source of birds (AOR: 2.35; 95% CI: 1.0-5.53), separation of sick birds (AOR: 3.04; 95% CI: 1.34-6.92), disposal of waste/dead birds (AOR: 3.16; 95% CI: 1.41-7.05), cleaning agent (AOR: 5.99; 95% CI: 2.26-15.82), access of dogs (AOR: 2.52; 95% CI: 1.12-5.7), wild birds observed on site (AOR: 2.31; 95% CI: 1.01-5.3). The study further revealed a substantial prevalence of AIV with H5 and H9 subtypes in peri-urban and rural LBMs. The inadequate biosecurity measures at poultry stalls in Bangladesh increase the risk of AIV transmission from poultry to humans. To prevent the spread of AIV to humans and wild birds, we suggest implementing regular surveillance at live bird markets and enhancing biosecurity practices in peri-urban and rural areas in Bangladesh.

Pregnancy intentions of young women in Canada in the era of climate change: a qualitative auto-photography study.

BACKGROUND: Climate change poses a global health risk through consequences such as sea level rise, wildfires, and increased air pollution. Children born today and in the future may be disproportionately affected by climate change. As a result, many young adults are rethinking having children. The impacts of the climate crisis on the decision-making of parents is an understudied area of research. This study aims to be one of the first to explore how climate change impacts the pregnancy intentions of young women in Canada and their perspectives towards childbearing. METHODS: We conducted auto-photography and qualitative interviews. Participants were recruited using social media, and were aged 18-25, nulliparous, assigned female at birth, and were either current or previous residents of British Columbia, Canada. We asked participants to take photos that responded to the question, "Show us how climate change impacts your decision to have a family," then complete a virtual, one-on-one interview during which photo-elicitation was employed to guide conversation about participants' decision-making related to childbearing and climate change. We subjected all transcribed interviews to qualitative thematic analysis. RESULTS: We conducted in-depth interviews with seven participants who discussed a total of 33 photographs. Analysis of participants' interviews and photographs identified themes of eco-anxiety, hesitancy towards having children, sense of loss, and a desire for systemic change. Participants experienced anxiety, grief, and loss when faced with thoughts of change associated with their environments. Climate change impacted all but two participants' childbearing decision making, which was found to be interrelated with social-environmental factors, such as cost of living. CONCLUSION: We aimed to identify the ways in which climate change may impact youth decisions to have a family. Further research on this topic is needed to understand the prevalence of this phenomenon, and to build such considerations into climate action policy and family planning tools used among young people.

Expectant Parents' Preferences for Teaching by Texting: Development and Usability Study of SmartMom.

BACKGROUND: Prenatal education encourages healthy behavioral choices and reduces rates of adverse birth outcomes. The use of mobile health (mHealth) technologies during pregnancy is increasing and changing how pregnant people acquire prenatal education. SmartMom is an evidence-based prenatal education SMS text messaging program that overcomes barriers to prenatal class attendance, including rural or remote location, cost, stigma among participants, lack of instructors, and cessation of classes during the COVID-19 pandemic. OBJECTIVE: We sought to explore perceived information needs and preferences for the content and structure of prenatal education mHealth programs among persons enrolled in or eligible to enroll in SmartMom. METHODS: This was a qualitative focus group study conducted as part of a development and usability study of the SmartMom program. Participants were older than 19 years of age, Canadian residents, fluent in English, and either currently pregnant or pregnant within the last year. We asked open-ended questions about information-seeking behaviors during pregnancy, the nature of the information that participants were seeking, how they wanted to receive information, and if SmartMom was meeting these needs. Focus groups took place via videoconference technology (Zoom) between August and December 2020. We used reflexive thematic analysis to identify themes that emerged from the data and the constant comparison method to compare initial coding to emerging themes. RESULTS: We conducted 6 semistructured focus groups with 16 participants. All participants reported living with a partner and owning a cell phone. The majority (n=13, 81%) used at least 1 app for prenatal education. Our analysis revealed that "having reliable information is the most important thing" (theme 1); pregnant people value inclusive, local, and strength-based information (theme 2); and SMS text messages are a simple, easy, and timely modality ("It was nice to have that [information] fed to you"; theme 3). Participants perceived that SmartMom SMS text messages met their needs for prenatal education and were more convenient than using apps. SmartMom's opt-in supplemental message streams, which allowed users to tailor the program to their needs, were viewed favorably. Participants also identified that prenatal education programs were not meeting the needs of diverse populations, such as Indigenous people and LGBTQIA2S+ (lesbian, gay, bisexual, transgender, queer and/or questioning, intersex, asexual, Two-Spirit plus) communities. CONCLUSIONS: The shift toward digital prenatal education, accelerated by the COVID-19 pandemic, has resulted in a plethora of web- or mobile technology-based programs, but few of these have been evaluated. Participants in our focus groups revealed concerns about the reliability and comprehensiveness of digital resources for prenatal education. The SmartMom SMS text messaging program was viewed as being evidence-based, providing comprehensive content without searching, and permitting tailoring to individual needs through opt-in message streams. Prenatal education must also meet the needs of diverse populations.

Can youth-engaged research facilitate equitable access to contraception in Canada? The qualitative study protocol for the Ask Us project.

INTRODUCTION: There is little to no evidence in Canada on the barriers that youth face when accessing contraception. We seek to identify the contraception access, experiences, beliefs, attitudes, knowledge, and needs of youth in Canada, from the perspectives of youth and youth service providers. METHODS AND ANALYSIS: This prospective, mixed-methods, integrated knowledge mobilisation study, the Ask Us project, will involve a national sample of youth, healthcare and social service providers, and policy makers recruited via a novel relational mapping and outreach approach led by youth. Phase I will centre the voices of youth and their service providers through in-depth one-on-one interviews. We will explore the factors influencing youth access to contraception, theoretically guided by Levesque's Access to Care framework. Phase II will focus on the cocreation and evaluation of knowledge translation products (youth stories) with youth, service providers, and policy makers. ETHICS AND DISSEMINATION: Ethical approval was received from the University of British Columbia's Research Ethics Board (H21-01091). Full open-access publication of the work will be sought in an international peer-reviewed journal. Findings will be disseminated to youth and service providers through social media, newsletters, and communities of practice, and to policy makers through invited evidence briefs and face-to-face presentations.

Abortion and contraception for incarcerated people: A scoping review.

BACKGROUND: Women experiencing incarceration have higher rates of unmet contraceptive needs and rates of abortion than the public. Incarceration presents multiple potential barriers to accessing abortion and contraception care, including prison security protocols, prison locations, lack of access to care providers, stigma, and low health literacy. The objective of this scoping review is to understand the extent and type of evidence in relation to contraception and abortion access for people experiencing criminalization and incarceration. METHODS: We used the Joanna Briggs Institute methodology for scoping reviews and include empirical research with people experiencing criminalization or incarceration and/or with prison staff; with respect to prescription contraception or abortion access, while in custody or after having experienced incarceration/criminalization. Databases searched include CINAHL, APA PsycInfo, Gender Studies, Medline (Ovid), Embase, Sociological Abstracts, and Social Services Abstracts. The search yielded 6096 titles of which 43 were included in the review. RESULTS: Our search yielded 43 studies published between 2001 and 2021 across six countries. The studies included qualitative, quantitative, and mixed methods designs. The main outcomes of interest included contraceptive use; attitudes towards abortion, contraception, and pregnancy; and barriers to care. Barriers identified included lack of onsite access to options, contraceptive coercion by providers, financial costs, and disruptions to medical coverage and insurance status which incarcerated. DISCUSSION: Evidence indicates that people in prison face significant barriers to maintaining continuity of contraceptive methods, abortion access, and reproductive health guidance. Some studies articulated participants felt judged when discussing contraception with prison-based health care providers. Geographic location, out-of-pocket payments, and trust in health care providers were reported as barriers to access. CONCLUSION: Incarceration presents considerable challenges to the access of contraception and abortion care. Future research should examine the interaction between institutional security policies and procedures on care seeking, the experiences of underserved and hyper-incarcerated groups, and the impact of being denied access to contraception and abortion and experiences of criminalization.

Co-designing a Sexual Health App With Immigrant Adolescents: Protocol for a Qualitative Community-Based Participatory Action Research Study.

BACKGROUND: Canada is one of the world's most ethnically diverse countries, with over 7 million individuals out of a population of 38 million being born in a foreign country. Immigrant adolescents (aged 10 to 19 years) make up a substantial proportion of newcomers to Canada. Religious and cultural practices can influence adolescents' sexual attitudes and behaviors, as well as the uptake of sexual and reproductive health (SRH) services among this population. Adolescence is a time to establish lifelong healthy behaviors. Research indicates an alarming gap in adolescents' SRH knowledge, yet there is limited research on the SRH needs of immigrant adolescents in Canada. OBJECTIVE: The purpose of this study is to actively engage with immigrant adolescents to develop, implement, and evaluate a mobile health (mHealth) intervention (ie, mobile app). The interactive mobile app will aim to deliver accurate and evidence-based SRH information to adolescents. METHODS: We will use community-based participatory action research to guide our study. This research project will be conducted in 4 stages based on user-centered co-design principles. In Stage 1 (Empathize), we will recruit and convene 3 adolescent advisory groups in Edmonton, Toronto, and Vancouver. Members will be engaged as coresearchers and receive training in qualitative and quantitative methodologies, sexual health, and the social determinants of health. In Stage 2 (Define and Ideate), we will explore SRH information and service needs through focus group discussions with immigrant adolescents. In Stage 3 (Prototype), we will collaborate with mobile developers to build and iteratively design the app with support from the adolescent advisory groups. Finally, in Stage 4 (Test), we will return to focus group settings to share the app prototype, gather feedback on usability, and refine and release the app. RESULTS: Recruitment and data collection will be completed by February 2023, and mobile app development will begin in March 2023. The mHealth app will be our core output and is expected to be released in the spring of 2024. CONCLUSIONS: Our study will advance the limited knowledge base on SRH and the information needs of immigrant adolescents in Canada as well as the science underpinning participatory action research methods with immigrant adolescents. This study will address gaps by exploring SRH priorities, health information needs, and innovative strategies to improve the SRH of immigrant adolescents. Engaging adolescents throughout the study will increase their involvement in SRH care decision-making, expand efficiencies in SRH care utilization, and ultimately improve adolescents' SRH outcomes. The app we develop will be transferable to all adolescent groups, is scalable in international contexts, and simultaneously leverages significant economies of scale. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/45389.

Barriers and enablers to nurse practitioner implementation of medication abortion in Canada: A qualitative study.

In this study we explored nurse practitioner-provided medication abortion in Canada and identified barriers and enablers to uptake and implementation. Between 2020-2021, we conducted 43 semi-structured interviews with 20 healthcare stakeholders and 23 nurse practitioners who both provided and did not provide medication abortion. Data were analyzed using interpretive description. We identified five overarching themes: 1) Access and use of ultrasound for gestational dating; 2) Advertising and anonymity of services; 3) Abortion as specialized or primary care; 4) Location and proximity to services; and 5) Education, mentorship, and peer support. Under certain conditions, ultrasound is not required for medication abortion, supporting nurse practitioner provision in the absence of access to this technology. Nurse practitioners felt a conflict between wanting to advertise their abortion services while also protecting their anonymity and that of their patients. Some nurse practitioners perceived medication abortion to be a low-resource, easy-to-provide service, while some not providing medication abortion continued to refer patients to specialized clinics. Some participants in rural areas felt unable to provide this service because they were too far from emergency services in the event of complications. Most nurse practitioners did not have any training in abortion care during their education and desired the support of a mentor experienced in abortion provision. Addressing factors that influence nurse practitioner provision of medication abortion will help to broaden access. Nurse practitioners are well-suited to provide medication abortion care but face multiple ongoing barriers to provision. We recommend the integration of medication abortion training into nurse practitioner education. Further, widespread communication from nursing organizations could inform nurse practitioners that medication abortion is within their scope of practice and facilitate public outreach campaigns to inform the public that this service exists and can be provided by nurse practitioners.

Nurse practitioners on 'the leading edge' of medication abortion care: A feminist qualitative approach.

AIMS: To explore nurse practitioners' experiences of medication abortion implementation in Canada and to identify ways to further support the implementation of medication abortion by nurse practitioners in Canada. DESIGN: A qualitative approach informed by feminist theory and integrated knowledge translation. METHODS: Qualitative interviews with stakeholders and nurse practitioners between January 2020 and May 2021. Data were analysed using critical feminist theory. RESULTS: Participants included 20 stakeholders, 16 nurse practitioner abortion providers, and seven nurse practitioners who did not provide abortions. We found that nurse practitioners conduct educational, communication and networking activities in the implementation of medication abortion in their communities. Nurse practitioners navigated resistance to abortion care in the health system from employers, colleagues and funders. Participants valued making abortion care more accessible to their patients and indicated that normalizing medication abortion in primary care was important to them. CONCLUSION: When trained in abortion care and supported by employers, nurse practitioners are leaders of abortion care in their communities and want to provide accessible, inclusive services to their patients. We recommend nursing curricula integrate abortion services in education, and that policymakers and health administrators partner with nurses, physicians, midwives, social workers and pharmacists, for comprehensive provincial/territorial sexual and reproductive health strategies for primary care. IMPACT: The findings from this study may inform future policy, health administration and curriculum decisions related to reproductive health, and raise awareness about the crucial role of nurse practitioners in abortion care and contributions to reproductive health equity. PATIENT OR PUBLIC CONTRIBUTION: This study focused on provider experiences. In-kind support was provided by Action Canada for Sexual Health & Rights, an organization that provides direct support and resources to the public and is committed to advocating on behalf of patients and the public seeking sexual and reproductive health services.

Nuclear corepressors NCOR1/NCOR2 regulate B cell development, maintain genomic integrity and prevent transformation.

The nuclear corepressors NCOR1 and NCOR2 interact with transcription factors involved in B cell development and potentially link these factors to alterations in chromatin structure and gene expression. Herein, we demonstrate that Ncor1/2 deletion limits B cell differentiation via impaired recombination, attenuates pre-BCR signaling and enhances STAT5-dependent transcription. Furthermore, NCOR1/2-deficient B cells exhibited derepression of EZH2-repressed gene modules, including the p53 pathway. These alterations resulted in aberrant Rag1 and Rag2 expression and accessibility. Whole-genome sequencing of Ncor1/2 DKO B cells identified increased number of structural variants with cryptic recombination signal sequences. Finally, deletion of Ncor1 alleles in mice facilitated leukemic transformation, whereas human leukemias with less NCOR1 correlated with worse survival. NCOR1/2 mutations in human leukemia correlated with increased RAG expression and number of structural variants. These studies illuminate how the corepressors NCOR1/2 regulate B cell differentiation and provide insights into how NCOR1/2 mutations may promote B cell transformation.

Pharmacist direct dispensing of mifepristone for medication abortion in Canada: a survey of community pharmacists.

INTRODUCTION: Pharmacists were acknowledged as the most appropriate healthcare professional to dispense mifepristone for medication abortion shortly after the prescription therapy became available in January 2017 in Canada. OBJECTIVE: We aimed to identify the facilitators and barriers for successful initiation and ongoing dispensing of mifepristone among community pharmacists across Canada. STUDY DESIGN: We surveyed community pharmacists from urban/rural practice settings across Canada by recruiting from January 2017 to January 2019 through pharmacist organisations, professional networks, at mifepristone training courses and at professional conferences. The Diffusion of Innovations theory informed the study design, thematic analysis and interpretation of findings. We summarised categorical data using counts and proportions, χ2 tests, Wilcoxon rank-sum and proportional odds logistic regression. RESULTS: Of the 433 responses from dispensing community pharmacists across 10/13 Canadian provinces and territories, 93.1% indicated they were willing and ready to dispense mifepristone. Key facilitators were access to a private consultation setting (91.4%), the motivation to increase accessibility for patients (87.5%) and to reduce pressure on the healthcare system (75.3%). The cost of the mifepristone/misoprostol product was an initial barrier, subsequently resolved by universal government subsidy. A few pharmacists mentioned liability, lack of prescribers or inadequate stock as barriers. CONCLUSIONS: Pharmacist respondents from across Canada reported being able and willing to dispense mifepristone and rarely mentioned barriers to stocking/dispensing the medication in the community pharmacy setting. The removal of initial regulatory obstacles to directly dispense mifepristone to patients facilitated the provision of medication abortion in the primary care setting.