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Rationale: Chronic infection with Stenotrophomonas maltophilia in persons with cystic fibrosis (pwCF) has been linked to an increased risk of pulmonary exacerbations and lung function decline. We sought to establish whether baseline sputum microbiome associates with risk of S. maltophilia incident infection and persistence in pwCF., Methods: pwCF experiencing incident S. maltophilia infections attending the Calgary Adult CF Clinic from 2010-2018 were compared with S. maltophilia -negative sex, age (+/-2 years), and birth-cohort-matched controls. Infection outcomes were classified as persistent (when the pathogen was recovered in ≥50% of cultures in the subsequent year) or transient. We assessed microbial communities from prospectively biobanked sputum using V3-V4 16S ribosomal RNA (rRNA) gene sequencing, in the year preceding (Pre) ( n  = 57), at (At) ( n  = 22), and after (Post) ( n  = 31) incident infection. We verified relative abundance data using S. maltophilia -specific qPCR and 16S rRNA-targeted qPCR to assess bioburden. Strains were typed using pulse-field gel electrophoresis., Results: Twenty-five pwCF with incident S. maltophilia (56% female, median 29 years, median FEV 1 61%) with 33 total episodes were compared with 56 uninfected pwCF controls. Demographics and clinical characteristics were similar between cohorts. Among those with incident S. maltophilia infection, sputum communities did not cluster based on infection timeline (Pre, At, Post). Communities differed between the infection cohort and controls ( n  = 56) based on Shannon Diversity Index (SDI, p  = 0.04) and clustered based on Aitchison distance (PERMANOVA, p  = 0.01) prior to infection. At the time of incident S. maltophilia isolation, communities did not differ in SDI but clustered based on Aitchison distance (PERMANOVA, p  = 0.03) in those that ultimately developed persistent infection versus those that were transient. S. maltophilia abundance within sputum was increased in samples from patients (Pre) relative to controls, measuring both relative ( p  = 0.004) and absolute ( p  = 0.001). Furthermore, S. maltophilia abundance was increased in sputum at incident infection in those who ultimately developed persistent infection relative to those with transient infection, measured relatively ( p  = 0.04) or absolute ( p  = 0.04), respectively., Conclusion: Microbial community composition of CF sputum associates with S. maltophilia infection acquisition as well as infection outcome. Our study suggests sputum microbiome may serve as a surrogate for identifying infection risk and persistence risk., Competing Interests: The 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 © 2024 Bowron, Acosta, Thornton, Carpentero, Waddell, Bharadwaj, Ebbert, Castañeda-Mogollón, Conly, Rabin, Surette and Parkins.)

One in three grade 7 to 12 students in Canada report trying vaping or e-cigarettes. Despite consequences like nicotine addiction, impaired brain development, increased respiratory symptoms, and association with an increased risk of COVID-19 diagnosis, 48% of youth believe occasional vaping has little to no risk. There is a clear need for youth to learn about vaping consequences. We developed and piloted a novel free interactive educational program on vaping risks which has been used by over 800 grade 7 to 9 students. In post-program surveys, students reported a subjective increase in knowledge about the health consequences of vaping., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AH discloses a microgrant received from Health Canada’s Substance Use and Addictions Program used to fund development of the SOLVE Mystery Toolkit. ED discloses membership in the advocacy group Stop Addicting Adolescents to Vaping and E-Cigarettes, and a monetary compensation for presenting the SOLVE Mystery Toolkit at a teachers conference with all compensation directly used to fund toolkit expenses. KE discloses Cystic Fibrosis Canada Clinical Fellowship Funding for 2020. AG declares grants (Canadian Institutes of Health Research, Canadian Cardiovascular Society, Alberta Innovates, Campus Alberta Neurosciences, Sunnybrook Research Institute INOVAIT Program), consulting fees (MD Analytics, CTC Communications Corp, MyMedicalPanel, Atheneum, Deep Bench), honoraria (Fig. 1, Canadian Association of Neuroscience Nurses), meeting travel support (American Academy of Neurology, Association of Indian Neurologists in America, American Heart Association, University of Calgary), a patent (provisional US 63/024,239), editorial board memberships (Neurology: Clinical Practice, Neurology, Stroke) and ownership of stocks (SnapDx, TheRounds.com). JL and SS have no conflicts of interest to disclose., (© 2022 The Authors.)

The Tobacco and Vaping Products Act (Canada, 1997) (the " TVPA ") aims to protect the health of young persons by restricting access to vaping products. We studied whether the TVPA achieves this goal by sending young 'secret shoppers' to 120 shops in Calgary, Edmonton, and Red Deer to attempt to buy nicotine-based vaping-initiation products, and by asking minors to purchase the same product online. We used three 'improper' shop scenarios: 1. a minor or minors; 2. a young adult with no or invalid identification ("ID"); and 3. a young adult with valid ID but clearly buying for an accompanying minor. Of total vendors, 42.5% (51/120) were willing to sell to the young people (p < .001). Most vendors requested ID in all scenarios (97/120, 80.8%). Of these, 28 vendors (28.9% of those requesting ID), were still willing to sell the product. All vendors who did not request ID (23/120, 19.2%) were willing to sell; vape shops were more likely than convenience stores not to request ID (25.4% v. 13.1%). In five online purchase attempts, 60% of deliverers did not meet the TVPA's ID verification requirements. The TVPA does not require packages to reveal their contents; one parent inadvertently signed for the parcel. To prevent youth access, the TVPA should require: a minimum nicotine product purchase age of 21, positive obligations on vendors to request ID, prohibition of sales to adults buying for minors, and that manufacturers disclose the product on posted or delivered parcels. The TVPA should be strictly enforced., (© 2020 The Authors.)

Cell-cell interactions play crucial roles in the maintenance of tissue homeostasis, a loss of which often leads to varying diseases, including cancer. Here, we report that uncontrolled PI3K activity within oocytes irreversibly transforms granulosa cells (GC), causing GC tumors (GCT) through perturbed local cell communication. Previously, we reported reproductive phenotypes of transgenic mice, in which expression of constitutively active mutant PI3K was induced in primordial oocytes by Gdf9-iCre. The transgenic mice (Cre(+)) demonstrated severe ovarian phenotypes, including the overgrowth of excess ovarian follicles and anovulation. Surprisingly, the Cre(+) mice became cachectic by postnatal day 80 due to bilateral GCT. Although GCT cells proliferated independently of oocytes, local interactions with mutant PI3K-positive oocytes during early folliculogenesis were essential for the GC transformation. Growing GCT cells expressed high levels of inhibin βA and nuclear SMAD3, and the proliferation rate was positively correlated with a high activin A to inhibin A ratio. These results suggested that the tumor cells stimulated their growth through an activin A autocrine signaling pathway, a hypothesis confirmed by activin A secretion in cultured GCT cells, which proliferated in response. Although communication between the oocyte and surrounding somatic cells is critical for the normal development of ovarian follicles, perturbations in oocyte-GC communication during early folliculogenesis can induce GCT by activating an autocrine growth circuit program in GC. Cancer Res; 76(13); 3851-61. ©2016 AACR., Competing Interests: The authors disclose no potential conflicts of interest., (©2016 American Association for Cancer Research.)

During embryonic development, mouse female germ cells enter meiosis in an anterior-to-posterior wave believed to be driven by retinoic acid. It has been proposed that ovarian follicle formation and activation follow the same general wave of meiotic progression; however, the precise anatomic specification of these processes has not been delineated. Here, we created a mouse line using Mvh, Gdf9, and Zp3 promoters to drive distinct temporal expression of three fluorescent proteins in the oocytes and to identify where the first follicle cohort develops. The fluorescent profile revealed that the first growing follicles consistently appeared in a specific region of the ovary, the anterior-dorsal region, which led us to analyze if meiotic onset occurred earlier in the dorsal ovarian region. Surprisingly, in addition to the anterior-to-posterior wave, we observed an early meiotic entry in the ventral region of the ovary. This additional anatomic stratification of meiosis contrasts with the localization of the initial follicle formation and activation in the dorsal region of the ovary. Therefore, our study suggests that the specification of cortical and medullar areas in the ventral and dorsal regions on the ovary, rather than the onset of meiosis, impacts where the first follicle activation event occurs., (© 2015 by the Society for the Study of Reproduction, Inc.)

In this study, we explored the effects of oocytic phosphoinositide 3-kinase (PI3K) activation on folliculogensis by generating transgenic mice, in which the oocyte-specific Cre-recombinase induces the expression of constitutively active mutant PI3K during the formation of primordial follicles. The ovaries of neonatal transgenic (Cre+) mice showed significantly reduced apoptosis in follicles, which resulted in an excess number of follicles per ovary. Thus, the elevation of phosphatidylinositol (3,4,5)-trisphosphate levels within oocytes promotes the survival of follicles during neonatal development. Despite the increase in AKT phosphorylation, primordial follicles in neonatal Cre+ mice remained dormant demonstrating a nuclear accumulation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). These primordial follicles containing a high level of nuclear PTEN persisted in postpubertal females, suggesting that PTEN is the dominant factor in the maintenance of female reproductive lifespan through the regulation of primordial follicle recruitment. Although the oocytic PI3K activity and PTEN levels were elevated, the activation of primordial follicles and the subsequent accumulation of antral follicles with developmentally competent oocytes progressed normally in prepubertal Cre+ mice. However, mature Cre+ female mice were anovulatory. Because postnatal day 50 Cre+ mice released cumulus-oocyte complexes with developmentally competent oocytes in response to super-ovulation treatment, the anovulatory phenotype was not due to follicular defects but rather endocrine abnormalities, which were likely caused by the excess number of overgrown follicles. Our current study has elucidated the critical role of oocytic PI3K activity in follicular function, as well as the presence of a PTEN-mediated mechanism in the prevention of immature follicle activation.