Effect of dynamic exclusion and the use of FAIMS, DIA and MALDI-mass spectrometry imaging with ion mobility on amyloid protein identification.

Amyloidosis is a disease characterized by local and systemic extracellular deposition of amyloid protein fibrils where its excessive accumulation in tissues and resistance to degradation can lead to organ failure. Diagnosis is challenging because of approximately 36 different amyloid protein subtypes. Imaging methods like immunohistochemistry and the use of Congo red staining of amyloid proteins for laser capture microdissection combined with liquid chromatography tandem mass spectrometry (LMD/LC-MS/MS) are two diagnostic methods currently used depending on the expertise of the pathology laboratory. Here, we demonstrate a streamlined in situ amyloid peptide spatial mapping by Matrix Assisted Laser Desorption Ionization-Mass Spectrometry Imaging (MALDI-MSI) combined with Trapped Ion Mobility Spectrometry for potential transthyretin (ATTR) amyloidosis subtyping. While we utilized the standard LMD/LC-MS/MS workflow for amyloid subtyping of 31 specimens from different organs, we also evaluated the potential introduction in the MS workflow variations in data acquisition parameters like dynamic exclusion, or testing Data Dependent Acquisition combined with High-Field Asymmetric Waveform Ion Mobility Spectrometry (DDA FAIMS) versus Data Independent Acquisition (DIA) for enhanced amyloid protein identification at shorter acquisition times. We also demonstrate the use of Mascot's Error Tolerant Search and PEAKS de novo sequencing for the sequence variant analysis of amyloidosis specimens.

Exploring the cross-sectional association between the strength of school vaping policies and student vaping behaviours using data from the 2021-2022 COMPASS Study.

OBJECTIVES: Youth vaping is a concern in Canada. While school-level policies influence student behaviours, few studies have investigated the association between school vaping policies and student vaping. This study reviewed and scored the comprehensiveness of school vaping policies and investigated the association between school vaping policy scores and student vaping. METHODS: Online policy documents from n = 39 schools in Ontario, Alberta, and British Columbia, Canada, participating in the 2021-2022 wave of the COMPASS study were collected, reviewed, and scored for comprehensiveness (/39) using the School Tobacco Policy Index (STPI) rating form. The mean and range of scores for each domain of the STPI were calculated. School policy scores were linked to student vaping data from the COMPASS study. Multilevel logistic regression analyses identified the association between school vaping policy score and student lifetime and current (past 30-day) vaping. RESULTS: The mean total policy score was 10.2/39 (range 0‒24), and 28% of schools scored 0/39. The majority of school policies did not identify enforcement approaches or available preventive or cessation resources. Increasing STPI score was not associated with the odds of student lifetime or current vaping in multilevel logistic regression analyses. CONCLUSION: The STPI quickly identified components of school vaping policies that were missing. The overall score of most school vaping policies in our sample was low and most school vaping policies lacked many important components. Future studies should explore factors associated with adolescent vaping and identify effective prevention measures.

RéSUMé: OBJECTIFS: Le vapotage des jeunes est préoccupant au Canada. Les politiques scolaires influencent les comportements des élèves, mais il y a peu d'études sur l'association entre les politiques scolaires sur le vapotage et le vapotage des élèves. Nous avons passé en revue des politiques scolaires sur le vapotage et noté leur complétude, puis étudié l'association entre les notes attribuées aux politiques scolaires sur le vapotage et le vapotage des élèves. MéTHODE: Les documents de politique accessibles en ligne de n = 39 écoles de l'Ontario, de l'Alberta et de la Colombie-Britannique, au Canada, ayant participé au cycle 2021-2022 de l'étude COMPASS ont été collectés, passés en revue et notés selon leur complétude (/39) à l'aide du formulaire de notation de l'indice School Tobacco Policy Index (STPI). La moyenne et l'intervalle des notes attribuées pour chaque élément de l'indice STPI ont été calculés. Les notes des politiques scolaires ont été maillées aux données sur le vapotage des élèves de l'étude COMPASS. Des analyses de régression logistique multiniveaux ont repéré l'association entre les notes attribuées aux politiques scolaires sur le vapotage et le vapotage des élèves à un moment de leur vie et récemment (au cours des 30 jours précédents). RéSULTATS: La note totale moyenne attribuée aux politiques a été de 10,2/39 (intervalle : 0‒24), et 28 % des écoles ont obtenu une note de 0/39. La majorité des politiques scolaires ne mentionnaient pas d'approches ou de ressources de prévention et d'arrêt disponibles. Les notes STPI plus élevées n'étaient pas associées à la probabilité de vapotage récemment ou à un moment de la vie des élèves dans les analyses de régression logistique multiniveaux. CONCLUSION: L'indice STPI a rapidement repéré les lacunes dans les politiques scolaires sur le vapotage. La note globale de la plupart des politiques scolaires sur le vapotage de l'échantillon était faible, et il manquait d'importants éléments dans la plupart des politiques. Les études futures devraient explorer les facteurs associés au vapotage des adolescents et identifier des mesures de prévention efficaces.

Do sociodemographic risk profiles for adolescents engaging in weekly e-cigarette, cigarette, and dual product use differ?

BACKGROUND: E-cigarette use represents a contemporary mode of nicotine product use that may be changing the risk profile of participating adolescents. Understanding differences in sociodemographic characteristics of adolescents engaging in contemporary e-cigarette use and traditional cigarette use is important for effectively developing and targeting public health intervention programs. The objective of this study was to identify and compare sociodemographic risk profiles for exclusive e-cigarette use and dual-product use among a large sample of Canadian youth. METHODS: A survey of 46,666 secondary school students in the 2021-22 wave of the COMPASS study measured frequency of past month e-cigarette and cigarette use as well as age, sex, gender, racial or ethnic background, spending money, relative family affluence, and having one's own bedroom. Rates of cigarette-only, e-cigarette-only, and dual product use were calculated, and separate classification trees were run using the CART algorithm to identify sociodemographic risk profiles for weekly dual-product use and weekly e-cigarette-only use. RESULTS: Over 13% of adolescents used only e-cigarettes at least weekly, 3% engaged in weekly dual e-cigarette and cigarette use, and less than 0.5% used only cigarettes. Available spending money was a common predictor of dual-product and e-cigarette-only use. Gender diverse youth and youth with lower perceived family affluence were at higher risk for dual-product use, while white and multiethnic adolescents were at greater risk of e-cigarette-only use. Two high-risk profiles were identified for e-cigarette-only use and four high-risk profiles were identified for dual product use. CONCLUSIONS: This study used a novel modelling approach (CART) to identify combinations of sociodemographic characteristics that profile high-risk groups for exclusive e-cigarette and dual-product use. Unique risk profiles were identified, suggesting that e-cigarettes are attracting new demographics of adolescents who have not previously been considered as high-risk for traditional cigarette use.

The association between single and dual use of cannabis and alcohol and driving under the influence and riding with an impaired driver in a large sample of Canadian adolescents.

OBJECTIVE: Dual use of cannabis and alcohol has increased in adolescents, but limited research has examined how it relates to impaired driving or riding with an impaired driver (IDR) compared to single substance use. This study aimed to examine the odds of alcohol- and/or cannabis-IDR among adolescents based on their use of alcohol and/or cannabis, and whether associations differed by gender and age. METHODS: Cross-sectional survey data were used from a sample of 69,621 students attending 182 Canadian secondary schools in the 2021/22 school year. Multilevel logistic regression estimated the odds of exclusive alcohol-IDR, exclusive cannabis-IDR, and both alcohol and cannabis IDR (alcohol-cannabis-IDR). Substance use interactions with gender and age were tested. RESULTS: Overall, 14.7% of participants reported IDR; 7.5% reported exclusive alcohol-IDR, 3.2% reported exclusive cannabis-IDR, 4.0% reported alcohol-cannabis-IDR, and 7.4% were unsure if they had experienced IDR. The prevalence of IDR varied across substance use groups, 8.0% among nonuse, 21.9% among alcohol-only use, 35.9% among cannabis-only use, and 49.6% among dual use groups. Gender diverse, older, and students with lower socioeconomic status exhibited a higher likelihood of reporting alcohol-cannabis-IDR. Dual use was significantly associated with 9.5 times higher odds of alcohol-cannabis-IDR compared to alcohol-only use, and 3.0 times higher odds compared to cannabis-only use. Dual use was also associated with an increased likelihood of either alcohol- or cannabis-IDR. CONCLUSIONS: This study highlights that all students, regardless of substance use, are at risk of IDR, but students engaged in dual use of alcohol and cannabis face an elevated risk compared to both peers who do not use substances and those who use only a single substance. These findings emphasize the importance of targeted interventions that address the risks associated with IDR.

Development and validation of a deep learning-based microsatellite instability predictor from prostate cancer whole-slide images.

Microsatellite instability-high (MSI-H) is a tumor-agnostic biomarker for immune checkpoint inhibitor therapy. However, MSI status is not routinely tested in prostate cancer, in part due to low prevalence and assay cost. As such, prediction of MSI status from hematoxylin and eosin (H&E) stained whole-slide images (WSIs) could identify prostate cancer patients most likely to benefit from confirmatory testing to evaluate their eligibility for immunotherapy and need for Lynch syndrome testing. Prostate biopsies and surgical resections from prostate cancer patients referred to our institution were analyzed. MSI status was determined by next-generation sequencing. Patients sequenced before a cutoff date formed an algorithm development set (n = 4015, MSI-H 1.8%) and a paired validation set (n = 173, MSI-H 19.7%) that consisted of two serial sections from each sample, one stained and scanned internally and the other at an external site. Patients sequenced after the cutoff date formed a temporally independent validation set (n = 1350, MSI-H 2.3%). Attention-based multiple instance learning models were trained to predict MSI-H from H&E WSIs. The predictor achieved area under the receiver operating characteristic curve values of 0.78 (95% CI [0.69-0.86]), 0.72 (95% CI [0.63-0.81]), and 0.72 (95% CI [0.62-0.82]) on the internally prepared, externally prepared, and temporal validation sets, respectively, showing effective predictability and generalization to both external staining/scanning processes and temporally independent samples. While MSI-H status is significantly correlated with Gleason score, the model remained predictive within each Gleason score subgroup.

Exploring the association between the proximity to and density around schools of retailers selling IQOS products and youth use of heated tobacco products: evidence from the 2020-2021 COMPASS study. / Exploration de l'association entre la proximité et la densité des détaillants de produits IQOS autour des écoles et l'utilisation de produits de tabac chauffé chez les adolescents : données de l'étude COMPASS 2020-2021.

INTRODUCTION: Heated tobacco products (HTPs) are novel tobacco products that may appeal to youth. This study explored whether HTP retailer proximity and density to secondary schools were associated with youth use of HTPs in four Canadian provinces. METHODS: An online search between November 2020 and March 2021 identified retailers selling IQOS devices and HEETS (tobacco sticks used in IQOS) within 500 m, 1000 m and 1500 m radius circular buffer zones around high schools (N = 120) participating in the COMPASS study in 2020-2021. Retailer proximity/density data were linked to crosssectional student-level data (N = 40 636 students), and multilevel regression models examined the association between HTP retailer proximity and density and current HTP use, controlling for relevant covariates. RESULTS: While only 10.0% of schools had at least one retailer selling IQOS devices within 1000 m of the school, 65.0% of schools had at least one retailer selling HEETS. The school a student attended accounted for 23.7% of the variability in the likelihood of currently using an HTP. However, HTP retailer proximity to and density around schools were not significantly associated with the likelihood of students currently using HTPs. CONCLUSION: While the school a student attended accounted for a significant amount of variability in HTP use, these findings suggest that students may be obtaining HTPs through other, non-retail sources. Continued monitoring is warranted as HTP use among youth may change.

Medical School Curricula and the Role of Third-Party Resources in Medical Student Urology Education.

OBJECTIVE: To assess the quality and extent of the urology education provided to medical students both by third-party resources (TPRs) and by the curriculum provided by medical schools METHODS: TPRs were assessed by systematically comparing the content of the 4 most common resources (Anking, Pathoma, Uworld, and First Aid) to the American Urological Association's Medical Student Curriculum (AUA-MSC). Medical school curricula were assessed via a survey sent to the top-150 allopathic medical schools in the United States. The survey asked about clinical and pre-clinical exposure to urology received by medical students at their school. RESULTS: The TPRs for Step 1 together covered 73.3% of the AUA-MSC topics, and for Step 2 covered 81.9%. First Aid covered 49.5% of Step 1 topics and 58.4% of Step 2 topics, Uworld covered 58.6% and 67.9%, respectively, and Anking covered 61.8% and 58.8%, respectively. Pathoma covered 28.1% of Step 1 topics. Survey results showed that 33/39 (84.6%) of schools have required urology coursework in preclinical years, but only 3/39 (7.7%) have required urology rotations in the third or fourth years. Of those without required rotations, 35/36 (97.2%) indicated that they offer an elective rotation in urology. CONCLUSION: There is little emphasis placed on urology after the preclinical years of medical school, pointing to a need for greater exposure to these topics regardless of the student's selected specialty. This need stems from incomplete knowledge provided by TPRs compared to the AUA-MSC. Drawing attention to this gap can provide insight for those creating future iterations of medical curricula and shed light on areas in need of improvement, which would ultimately benefit both patients and providers.

Evaluating the One-Year Impact of School e-Cigarette Use Interventions among Current Youth e-Cigarette Users in the COMPASS Study, 2017/18-2018/19.

There is a lack of evidence for the impact of school-based e-cigarette interventions among current e-cigarette users. This natural experimental evaluation study evaluated the one-year impact of various school-based e-cigarette prevention/cessation programs among a sample of current youth e-cigarette users. The COMPASS study sample included n = 3586 current e-cigarette users from n = 90 schools with data collected between 2017 and 2019. Student e-cigarette use patterns were categorized as "escalated", "maintained", and "reduced" based on the change in past 30-day e-cigarette use between baseline and follow-up. Intervention schools added e-cigarette use "prevention", "cessation", or "protection" programs, while control schools did not make any changes. Logistic regression models identified how each category of added programs was associated with e-cigarette use patterns. About one quarter of schools added an e-cigarette use prevention/cessation program over one year. Student e-cigarette use patterns between control and intervention groups differed in proportion ranging from a decrease of 3.35% to an increase of 5.80%. Regression models did not identify any significant differences in the odds of escalating or reducing e-cigarette use in intervention relative to control schools. While many schools implemented new e-cigarette programs over one year, none of the interventions led to significant changes in e-cigarette escalation or reduction among current youth e-cigarette users. Additional studies are needed to evaluate the impact of e-cigarette interventions among current e-cigarette users.

Changes in Quantity Measures of Various Forms of Cannabis Consumption among Emerging Adults in Canada in Relation to Policy and Public Health Developments.

Limited research examines changes in quantities of various forms of smoked/vaped cannabis among regular consumers, including emerging adults (EAs; 18 to 29) in Canada. This information is particularly relevant in the current context of emerging cannabis behaviors among EAs related to political amendments (legalization of cannabis), vaping-related lung illnesses (EVALI), and unprecedented pandemics (COVID-19). This study investigated the impact of legalizing recreational cannabis use in Canada, the EVALI epidemic, and the COVID-19 pandemic on the quantity of smoked/vaped forms of cannabis in relation to gender differences. EAs retrospectively self-reported the quantity of herb, hash, concentrates, joint size, and the number of joints and vaping cartridges in relation to three consecutive developments: pre-legalization, post-legalization; pre-EVALI, post-EVALI, pre-COVID-19, and during COVID-19. The quantity of herb use significantly increased among heavy users, and vaping quantity significantly increased among light users. Overall, an increasing incremental trend was observed in the average quantity of cannabis forms used over time. Males consumed higher quantities of all cannabis forms than females. More males than females reported using concentrates (p < 0.05). These findings reveal unique aspects of the amount of various cannabis forms smoked/vaped in relation to gender and provides preliminary evidence of cannabis consumption behaviors in relation to changing social and cultural contexts.

What Is the Optimal Stenting Duration After Ureteroscopy and Stone Intervention? Impact of Dwell Time on Postoperative Emergency Department Visits.

PURPOSE: AUA stone management guidelines recommend stenting duration following ureteroscopy be minimized to reduce morbidity; stents with extraction strings may be used for this purpose. However, an animal study demonstrated that short dwell time results in suboptimal ureteral dilation, and a pilot clinical study showed this increases postprocedure events. Using real-world practice data we examined stent dwell time after ureteroscopy and its association with postoperative emergency department visits. MATERIALS AND METHODS: We used the Michigan Urological Surgery Improvement Collaborative registry to identify ureteroscopy and stenting procedures (2016-2019). Pre-stented cases were excluded. Stenting cohorts with and without strings were analyzed. Using multivariable logistic regression we evaluated the risk of an emergency department visit occurring on the day of, or day after, stent removal based on dwell time and string status. RESULTS: We identified 4,437 procedures; 1,690 (38%) had a string. Median dwell time was lower in patients with a string (5 vs 9 days). Ureteroscopy in younger patients, smaller stones, or renal stone location had a higher frequency of string use. The predicted probability of an emergency department visit was significantly greater in procedures with string, compared to without string, when dwell times were less than 5 days (P < .01) but were not statistically significant after. CONCLUSIONS: Patients who had ureteroscopy and stenting with a string have short dwell times. Patients are at increased risk of a postoperative emergency department visit around the time of stent removal if dwell time is ≤4 days. We recommended stenting duration of at least 5 days in nonpre-stented patients.

Phosphatidylinositol 4-kinase IIα is a glycogen synthase kinase 3-regulated interaction hub for activity-dependent bulk endocytosis.

Phosphatidylinositol 4-kinase IIα (PI4KIIα) generates essential phospholipids and is a cargo for endosomal adaptor proteins. Activity-dependent bulk endocytosis (ADBE) is the dominant synaptic vesicle endocytosis mode during high neuronal activity and is sustained by glycogen synthase kinase 3ß (GSK3ß) activity. We reveal the GSK3ß substrate PI4KIIα is essential for ADBE via its depletion in primary neuronal cultures. Kinase-dead PI4KIIα rescues ADBE in these neurons but not a phosphomimetic form mutated at the GSK3ß site, Ser-47. Ser-47 phosphomimetic peptides inhibit ADBE in a dominant-negative manner, confirming that Ser-47 phosphorylation is essential for ADBE. Phosphomimetic PI4KIIα interacts with a specific cohort of presynaptic molecules, two of which, AGAP2 and CAMKV, are also essential for ADBE when depleted in neurons. Thus, PI4KIIα is a GSK3ß-dependent interaction hub that silos essential ADBE molecules for liberation during neuronal activity.

Safety and Efficacy of Combined Resveratrol and Sirolimus in Lymphangioleiomyomatosis.

BACKGROUND: A critical need exists to develop remission-inducing therapies for lymphangioleiomyomatosis. RESEARCH QUESTION: Is the addition of resveratrol safe and more efficacious than sirolimus alone in patients with lymphangioleiomyomatosis? STUDY DESIGN AND METHODS: We conducted a phase 2, dose-escalating, open-label trial of resveratrol in patients with lymphangioleiomyomatosis receiving a stable regimen of sirolimus. Resveratrol was started at 250 mg/d and escalated every 8 weeks to maximum dose of 1,000 mg/d over 24 weeks. The primary outcome was ≥ 42% decline in serum vascular endothelial growth factor D (VEGF-D) levels on combined therapy compared with baseline VEGF-D levels on sirolimus. Secondary objectives included an assessment of the safety profile and the effect on lung function and health-related quality of life (HRQOL). Longitudinal change in outcome measures was assessed using linear mixed models. Adverse effects were tabulated using the National Cancer Institute's Common Terminology Criteria for Adverse Events version 4. RESULTS: Twenty-five patients with lymphangioleiomyomatosis with a median age of 51 years were enrolled. Pulmonary function parameters at study inclusion were: FEV1: median absolute, 1.72 L; 64% predicted; FVC: median absolute, 2.99 L; 96% predicted; and diffusing capacity of the lungs for carbon monoxide: median absolute, 14.68 mL/mm Hg/min; 37% predicted. The median serum VEGF-D value at baseline was 617 pg/mL. Patients entered the study with a median sirolimus dose of 2 mg/d with median trough level of 6.3 ng/mL. Despite some GI side effects, the addition of resveratrol was well tolerated. Although the primary outcome was not met, a statistically significant reduction in serum VEGF-D levels and improvement in HRQOL during the study was found. INTERPRETATION: The addition of resveratrol was safe and well tolerated in patients with lymphangioleiomyomatosis taking sirolimus and was associated with modest improvement in HRQOL. Larger controlled trials of this combination might be warranted to assess definitively the usefulness of resveratrol as an additive therapy in lymphangioleiomyomatosis. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03253913; URL: www. CLINICALTRIALS: gov.

Youth Vaping During the Early Stages of the COVID-19 Pandemic Period: Adjusted Annual Changes in Vaping Between the Pre-COVID and Initial COVID-Lockdown Waves of the COMPASS Study.

BACKGROUND: Adolescence is a critical period for vaping onset. The purpose of this article was to examine the effect of the early stages of the COVID-19 pandemic period on youth vaping. METHODS: We used 3-year linked data from the COMPASS study, including 7585 Canadian (Quebec, Ontario) adolescents from which 1949 completed all three survey waves (pre-COVID-19 [2018, 2019] and online [2020] during the early pandemic period [May-July 2020]) and provided vaping data. Structural equation modeling (SEM) and difference-in-difference (DD) models were used to estimate pre-COVID-19 to initial COVID-19 pandemic period change (2019-2020) in vaping (monthly, weekly, daily) compared with 2018-2019 change to adjust for age-related effects. Models were adjusted for age of entry into the cohort and sociodemographic characteristics. RESULTS: In the SEM and DD models, the proportion of youth who were monthly and weekly vaping increased from 2018 to 2019 but decreased from 2019 to 2020; daily vaping increased across all waves. However, for all vaping outcomes modeled, the expected increases from the pre-COVID-19 wave (2019) to the initial COVID-19 period wave (2020) were lesser relative to the changes seen across the 2018 to 2019 waves. CONCLUSION: The early stages of the COVID-19 pandemic period appear to be associated with a reduction in the proportion of youth who were monthly and weekly vapers in our adjusted longitudinal models. While daily vaping increased over this same period of time, the magnitude of the increase in our adjusted longitudinal models appears attenuated by the early stages of the pandemic. IMPLICATIONS: This large prospective study of youth that included pre-pandemic data is unique in that we were able to identify that the early stages of the COVID-19 pandemic period was associated with a reduction in the proportion of youth who were monthly and weekly vapers in our adjusted longitudinal models. Conversely, the proportion of youth who were daily vaping increased over this same period of time, but the magnitude of the increase appears smaller than expected during the early stages of the pandemic in our adjusted longitudinal models. This study provides novel robust evidence that the patterns of vaping most aligned with onset and progression (i.e., monthly and weekly use) appear attenuated during the initial pandemic period.

Hughes-Stovin Syndrome and the Acute Management of Recurrent Pulmonary Aneurysms.

Hughes-Stovin syndrome (HSS) is a rare autoimmune disease that is considered to be a variant of Behçet's disease. It typically presents with multiple venous thrombi, thrombophlebitis, as well as pulmonary and bronchial aneurysms. The disease is typically associated with high morbidity and mortality in those diagnosed. This case discusses a 28-year-old male with HSS complicated by venous cardiac emboli and a mechanical valve on chronic anticoagulation. Despite medical and surgical management, the patient experienced continued progression of his pulmonary aneurysms and excessive bleeding, eventually requiring lung transplantation.

Identifying changes in e-cigarette use among a longitudinal sample of Canadian youth e-cigarette users in the COMPASS cohort study, 2017/18-2018/19.

Objectives: There are few studies describing longitudinal changes in vaping patterns among current youth e-cigarette users. The objective of this study was to identify-one-year changes in e-cigarette use patterns among a longitudinal sample of Canadian youth e-cigarette users between 2017/18 and 2018/19. Methods: The longitudinal sample included n = 4,071 current (past 30-day) e-cigarette users in grades 9-11 attending schools in four Canadian provinces. Students reported the number of days they used e-cigarettes in the past 30 days in 2017/18 and 2018/19. Based on responses, students could have escalated, reduced, stopped, or maintained their level of vaping. The prevalence of each e-cigarette use pattern was identified across demographic characteristics and regression models identified significant predictors of each use pattern. Results: Over one year, 49.2% of current youth e-cigarette users escalated, 12.8% reduced, 20.2% stopped, and 17.8% maintained their frequency of e-cigarette use. Baseline e-cigarette use frequencies varied according to use pattern. Current youth e-cigarette users with higher baseline vaping frequencies had lower odds of escalating and stopping e-cigarette use and higher odds of reducing e-cigarette use relative to maintaining the same frequency of use. Conclusions: While about half of current youth e-cigarette users increased their frequency of e-cigarette use over a 1-year period, a significant number also decreased or stopped vaping at a time when the prevalence of youth e-cigarette use increased rapidly in Canada. There is a need for longitudinal data to monitor and evaluate changes to e-cigarette use patterns that may be in response to changing public health policies.

California School Staff Reports of Seeing Students Vaping at School and Disciplinary Actions.

Youth vaping is a concern and schools may use many approaches to discipline students caught vaping at school. This study identified the prevalence of school staff seeing vaping in schools and the measures used to discipline students. A state-wide sample of 7,938 staff from 255 middle and high schools reported whether they saw any students vaping at school in the last 30 days, whether they have caught any students vaping during class in the last semester, and what happened after catching a student vaping in class. Open-text responses were coded and themes were identified related to disciplinary approaches. 31.9% of staff reported seeing students vaping at school, and 11.9% of teachers reported catching a student vaping during class. Teachers described four categories of disciplinary approaches after catching students vaping in class: no consequences, punitive approaches, restorative approaches, and mixed approaches. Additional support is necessary to help schools address student vaping.

Clinical Significance of Hepsin and Underlying Signaling Pathways in Prostate Cancer.

The hepsin gene encodes a type II transmembrane serine protease. Previous studies have shown the overexpression of hepsin in prostate cancer, and the dysregulation of hepsin promotes cancer cell proliferation, migration, and metastasis in vitro and in vivo. The review incorporated with our work showed that hepsin expression levels were specifically increased in prostate cancer, and higher expression in metastatic tumors than in primary tumors was also observed. Moreover, increased expression was associated with poor outcomes for patients with prostate cancer. Using in silico protein-protein interaction prediction, mechanistic analysis showed that hepsin interacted with eight other oncogenic proteins, whose expression was significantly correlated with hepsin expression in prostate cancer. The oncogenic functions of hepsin are mainly linked to proteolytic activities that disrupt epithelial integrity and regulatorily interact with other genes to influence cell-proliferation, EMT/metastasis, inflammatory, and tyrosine-kinase-signaling pathways. Moreover, genomic amplifications of hepsin, not deletions or other alterations, were significantly associated with prostate cancer metastasis. Targeting hepsin using a specific inhibitor or antibodies significantly attenuates its oncogenic behaviors. Therefore, hepsin could be a novel biomarker and therapeutic target for prostate cancer.

Changes in Cannabis Consumption Among Emerging Adults in Relation to Policy and Public Health Developments.

Background: Rates of cannabis use appear to be highest among emerging adults (EA). Evidence suggests that cannabis smoking, as well as alternate methods of cannabis use (e.g., vaping, edibles) have become a prevalent mode of consumption among this population. Substance use or misuse peaks during emerging adulthood and may be influenced by extreme economic, social and community developments, such as policy changes, public health concerns, and significant global events such as pandemics. For instance, it is highly likely that cannabis consumption trends among at-risk populations were influenced by the legalization of recreational cannabis in Canada, the declaration of the "e-cigarette or vaping product use associated lung injury" or "EVALI" outbreak, and the "COVID-19" pandemic. ObjectivesWe aimed to examine self-reported changes in frequency of cannabis use among EA in Canada (N = 312): pre-legalization, post-legalization; pre-EVALI, post-EVALI; pre-COVID-19, since-COVID-19. ResultsThere was a gradual increase in average frequency of smoking and vaping cannabis across the six different time intervals from the pre-legalization period (2018) to the COVID-19 pandemic period (2020). Males reported higher frequencies of cannabis smoking and vaping compared to females. ConclusionsDespite health concerns and expectations that EVALI and COVID-19 events would lead to decreased consumption, our results suggest an average increase in smoking and vaping cannabis, although the most notable increase was after legalization. There are important sex differences in behavioral factors of cannabis use in EA, though it appears that the "gender-gap" in cannabis consumption is closing. These findings may facilitate the development of intervention programs for policy measures to address cannabis-attributable outcomes in the face of contextual factors that promote use, such as public emergencies or changes in policy landscapes.

Early adoption of heated tobacco products resembles that of e-cigarettes.

BACKGROUND: Heated tobacco products (HTP) generate nicotine-containing aerosol by heating tobacco rather than burning it. The US Food and Drug Administration (FDA) has recently authorised the sale of one HTP brand, iQOS, in the USA. This study examined the awareness, use and risk perceptions of HTP in the USA following FDA authorisation. METHODS: A national probability sample of 20 449 US adults completed an online survey between November 2019 and February 2020. In addition to assessing awareness and use of HTP, two ratios were calculated: the ratio of those who experimented with HTP given that they had heard about it (E/H) and the ratio of those who currently used HTP given experimentation (C/E). These ratios for HTP were compared against those for e-cigarettes from a similar national survey in 2012. RESULTS: Overall, 8.1% of respondents had heard of HTP. Only 0.55% had tried and 0.10% were current users. The rate of experimentation among those who heard about HTP and the rate of current use among experimenters were, however, similar to those for e-cigarettes in 2012: E/H and C/E for HTP were 6.8% and 18.2%, respectively; and 10.7% and 17.8%, respectively for e-cigarettes. The majority of respondents considered HTP either less harmful than (11.6%), or equally harmful as e-cigarettes (42.7%). CONCLUSIONS: Only a small fraction of US population in 2020 have tried any HTP. However, the similarity in early adoption rates following awareness, suggests that future adoption for HTP may be similar to that for e-cigarettes, if HTP are marketed more aggressively.

More support needed: Evaluating the impact of school e-cigarette prevention and cessation programs on e-cigarette initiation among a sample of Canadian secondary school students.

Given the recent increase in e-cigarette use among adolescents, there is a need to further explore how school programs are associated with e-cigarette initiation. The objective of this quasi-experimental study was to evaluate the impact of multiple school-based e-cigarette prevention and cessation programs on e-cigarette initiation among Canadian adolescents. This study used data from Year 6 (2017/18) and Year 7 (2018/19) of the COMPASS study in British Columbia, Alberta, Ontario, and Quebec, Canada. Students in grades 9 to 11 who had never tried e-cigarettes at baseline were included (n = 13,269). Schools (n = 88) reported whether they added programming that addressed e-cigarette or tobacco prevention or cessation. Generalized estimating equations were used to identify how added programs were associated with e-cigarette initiation at follow-up. At one-year follow-up (2018/19), 23% of schools added programs. Our evaluation results suggest that none of the activities taken by schools to prevent or reduce vaping among students significantly prevented vaping onset. In fact, female students at schools that reported adding a theme week had higher odds of e-cigarette initiation (OR 1.68 [95% CI 1.31-2.16]) and male students at schools that reported a cessation program had higher odds of e-cigarette initiation (OR 1.20 [95% CI 1.01-1.44]). These results suggest that schools may not know how to address e-cigarette use and that there can be risks to students if programs are not carefully implemented. Results point to the need for additional support to ensure that schools are taking evidence-based approaches that support all students.