Exposure Among Middle and High School Students to Warning Labels on E-Cigarette Packages Before and After an FDA Requirement, 2018-2019.

Introduction: Beginning August 10, 2018, a US Food and Drug Administration (FDA) rule required all e-cigarette packages to have a health warning. We examined exposure among middle and high school students to e-cigarette warnings before and after the compliance date of the FDA's deeming rule, a rule allowing the FDA to regulate e-cigarettes, cigars, and other products. Methods: We analyzed data from middle and high school students participating in the 2018 and 2019 National Youth Tobacco Survey. We generated weighted prevalence estimates for any exposure ("rarely," "sometimes," "most of the time," or "always") and high exposure ("most of the time" or "always") to warnings. We used independent 2-sided t tests to examine differences in exposure between 2018 and 2019 and χ2 tests to examine differences in any exposure and high exposure by demographic characteristics and tobacco use behaviors in 2019. Analyses excluded respondents who reported they had not seen an e-cigarette package. Results: In 2019, 68.0% (vs 67.7% in 2018) of students reported any past 30-day exposure to e-cigarette warning labels and 35.0% (vs 28.7% in 2018) reported high exposure; we observed differences in the proportion of students reporting any and high exposure to warning labels across demographic characteristics and tobacco use behaviors. From 2018 to 2019, report of any and high exposure to e-cigarette warning labels increased among students who currently used any tobacco product and e-cigarettes. We observed increases in high exposure to e-cigarette warning labels overall, and among male students, female students, non-Hispanic White students, and middle and high school students. Conclusion: After implementation of the health warnings per the FDA's deeming rule, the percentage of current tobacco users and e-cigarette users among middle and high school students who reported any and high exposure to e-cigarette warning labels increased. Continued monitoring of reactions can inform if warnings are achieving their regulatory goal.

Changes in Availability of ENDS: 2019-2020, U.S.

INTRODUCTION: Events during 2019 and 2020, such as the outbreak of e-cigarette, or vaping, product use‒associated lung injury; manufacturer product withdrawals; federal regulations; and coronavirus disease 2019, potentially affected the retail availability of ENDS in the U.S. Measuring changes in ENDS availability informs the understanding of the ENDS marketplace and contextualizes sales trends. METHODS: Joinpoint regression was used to estimate slope changes in the number of available ENDS in 2019 and 2020 and considered correspondence with tobacco marketplace events. Availability, the weekly number of unique universal product codes with nonzero sales, was derived from NielsenIQ scanner data. U.S. ENDS availability was modeled overall and by subproduct and flavor category within subproduct: mint, menthol, tobacco flavored, and undetermined. RESULTS: ENDS availability increased by 66% from January 2019 to December 2020. Availability decreased by 43% among prefilled cartridges and increased by 511% among disposables, both led by flavored varieties. During January 2020-February 2020, prefilled cartridge availability decreased by 23.71 universal product codes per week. During July 2020-August 2020, disposable availability increased by 27.90 universal product codes per week, led by flavored products. CONCLUSIONS: ENDS availability increased during 2019 through 2020, led by a rise in flavored disposables. Multiple slope changes in ENDS availability occurred, many coinciding with tobacco marketplace events. The slope of ENDS explicitly prioritized for federal enforcement (i.e., flavored prefilled cartridges) notably decreased in early 2020 and, soon thereafter, the slope of ENDS not explicitly prioritized for enforcement (e.g., flavored disposables) notably increased, suggesting an association with U.S. Food and Drug Administration's prioritized enforcement guidance.

Youth Access to Tobacco Products in the United States, 2016-2018.

OBJECTIVES: In 2018, approximately 4.9 million US middle and high school students reported past 30-day use of any tobacco product. This study describes how and where youth obtained tobacco products and whether refusal of sale occurred during 2016-2018. METHODS: Data from 3 annual waves (2016-2018) of the National Youth Tobacco Survey, a school-based survey of US youth in grades 6-12, were analyzed among current (past 30-day) tobacco product users aged 9 to 17 years. RESULTS: During 2016-2018, youth tobacco product users most commonly obtained tobacco products from social sources. Although the percentage of users who reported buying tobacco products significantly decreased from 2016 to 2018 (2016: 15.6%; 2018: 11.4%), no significant differences in the prevalence of being refused sale were observed (2016: 24.7%; 2018: 25.5%). CONCLUSIONS: Whereas the number of youth users who report buying tobacco products has declined, sales of tobacco products to youth remain a public health concern, as only one in 4 youth who attempted to buy were refused sale in 2018. Monitoring youth tobacco product purchases, retailer compliance check inspections, and retailer penalties for sales to minors remain important for reducing youth access at retail sources.

Association Between Receptivity to Tobacco Advertising and Progression to Tobacco Use in Youth and Young Adults in the PATH Study.

Importance: Cigarette marketing contributes to initiation of cigarette smoking among young people, which has led to restrictions on use of cigarette advertising. However, little is known about other tobacco advertising and progression to tobacco use in youth and young adults. Objective: To investigate whether receptivity to tobacco advertising among youth and young adults is associated with progression (being a susceptible never user or ever user) to use of the product advertised, as well as conventional cigarette smoking. Design, Setting, and Participants: The Population Assessment of Tobacco and Health (PATH) Study at wave 1 (2013-2014) and 1-year follow-up at wave 2 (2014-2015) was conducted in a US population-based sample of never tobacco users aged 12 to 24 years from wave 1 of the PATH Study (N = 10 989). Household interviews using audio computer-assisted self-interviews were conducted. Exposures: Advertising for conventional cigarettes, electronic cigarettes (e-cigarettes), cigars, and smokeless tobacco products at wave 1. Main Outcomes and Measures: Progression to susceptibility or ever tobacco use at 1-year follow-up in wave 2. Results: Of the 10 989 participants (5410 male [weighted percentage, 48.3%]; 5579 female [weighted percentage, 51.7%]), receptivity to any tobacco advertising at wave 1 was high for those aged 12 to 14 years (44.0%; 95% confidence limit [CL], 42.6%-45.4%) but highest for those aged 18 to 21 years (68.7%; 95% CL, 64.9%-72.2%). e-Cigarette advertising had the highest receptivity among all age groups. For those aged 12 to 17 years, susceptibility to use a product at wave 1 was significantly associated with product use at wave 2 for conventional cigarettes, e-cigarettes, cigars, and smokeless tobacco products. Among committed never users aged 12 to 17 years at wave 1, any receptivity was associated with progression toward use of the product at wave 2 (conventional cigarettes: adjusted odds ratio [AOR], 1.43; 95% CL, 1.23-1.65; e-cigarettes: AOR, 1.62; 95% CL, 1.41-1.85; cigars: AOR, 2.01; 95% CL, 1.62-2.49; and smokeless [males only]: AOR, 1.42; 95% CL, 1.07-1.89) and with use of the product (conventional cigarettes: AOR, 1.54; 95% CL, 1.03-2.32; e-cigarettes: AOR, 1.45; 95% CL, 1.19-1.75; cigars: AOR, 2.07; 95% CL, 1.26-3.40). Compared with those not receptive to any product advertising, receptivity to e-cigarette advertising, but not to cigarette advertising, was independently associated with those aged 12 to 21 years having used a cigarette at wave 2 (AOR, 1.60; 95% CL, 1.08-2.38). Conclusions and Relevance: Receptivity to tobacco advertising was significantly associated with progression toward use in adolescents. Receptivity was highest for e-cigarette advertising and was associated with trying a cigarette.

Monitoring harm perceptions of smokeless tobacco products among U.S. adults: Health Information National Trends Survey 2012, 2014, 2015.

INTRODUCTION: Changes to the U.S. smokeless tobacco landscape in recent years include a change to health warnings on packages, the implementation of bans in some stadiums, and the launch of a federal youth prevention campaign. It is unclear whether such changes have impacted consumer beliefs about smokeless tobacco. This study examines relative harm perceptions of smokeless tobacco compared to cigarettes among adults and assesses changes in smokeless tobacco harm perceptions over time. METHODS: We analyzed data from three cycles (2012, 2014, 2015) of the Health Information National Trends Survey (HINTS). Using 2015 data, we assessed bivariate associations between smokeless tobacco harm perceptions and tobacco use, beliefs, information seeking, and demographics. Using 2012, 2014, and 2015 data, we assessed whether smokeless tobacco harm perceptions changed over time within demographic groups using chi-square tests. We then used a weighted multinomial logistic regression to assess the association between smokeless tobacco perceptions and survey year, adjusting for covariates. RESULTS: When asked whether smokeless tobacco products are less harmful than cigarettes, the majority of respondents across cycles said "no." The percent of respondents who selected this response option decreased over time. Findings showed significant differences in relative harm perceptions of smokeless tobacco versus cigarettes for specific demographic subgroups. Among subgroups, these shifts did not occur with a discernible pattern. CONCLUSIONS: Understanding factors associated with perceptions of smokeless tobacco can inform tobacco control efforts. Additional monitoring of these trends may provide researchers with a deeper understanding of how and why smokeless tobacco harm perceptions change.

Protein interaction screening identifies SH3RF1 as a new regulator of FAT1 protein levels.

Mutations and ectopic FAT1 cadherin expression are implicated in a broad spectrum of diseases ranging from developmental disorders to cancer. The regulation of FAT1 and its downstream signalling pathways remain incompletely understood. We hypothesized that identification of additional proteins interacting with the FAT1 cytoplasmic tail would further delineate its regulation and function. A yeast two-hybrid library screen carried out against the juxtamembrane region of the cytoplasmic tail of FAT1 identified the E3 ubiquitin-protein ligase SH3RF1 as the most frequently recovered protein-binding partner. Ablating SH3RF1 using siRNA increased cellular FAT1 protein levels and stabilized expression at the cell surface, while overexpression of SH3RF1 reduced FAT1 levels. We conclude that SH3RF1 acts as a negative post-translational regulator of FAT1 levels.

SETD7 Controls Intestinal Regeneration and Tumorigenesis by Regulating Wnt/ß-Catenin and Hippo/YAP Signaling.

Intestinal tumorigenesis is a result of mutations in signaling pathways that control cellular proliferation, differentiation, and survival. Mutations in the Wnt/ß-catenin pathway are associated with the majority of intestinal cancers, while dysregulation of the Hippo/Yes-Associated Protein (YAP) pathway is an emerging regulator of intestinal tumorigenesis. In addition, these closely related pathways play a central role during intestinal regeneration. We have previously shown that methylation of the Hippo transducer YAP by the lysine methyltransferase SETD7 controls its subcellular localization and function. We now show that SETD7 is required for Wnt-driven intestinal tumorigenesis and regeneration. Mechanistically, SETD7 is part of a complex containing YAP, AXIN1, and ß-catenin, and SETD7-dependent methylation of YAP facilitates Wnt-induced nuclear accumulation of ß-catenin. Collectively, these results define a methyltransferase-dependent regulatory mechanism that links the Wnt/ß-catenin and Hippo/YAP pathways during intestinal regeneration and tumorigenesis.

Smoke-free multiunit housing: a review of the scientific literature.

OBJECTIVE: Multiunit housing (MUH) residents are susceptible to secondhand smoke (SHS) exposure, which can transfer between living units. This review summarises existing scientific literature relevant to smoke-free MUH, discusses knowledge gaps and provides recommendations for future research to inform public health action. DATA SOURCES: We conducted a systematic search of peer-reviewed articles using three databases: EBSCOhost CINAHL, PubMed and Web of Science. STUDY SELECTION: Article titles, abstracts and text were reviewed to ascertain three inclusion criteria: (1) English language; (2) conducted in the USA; (3) reported on baseline data, development, implementation or evaluation of smoke-free MUH. DATA EXTRACTION: We used a multistep process to identify eligible articles: (1) two reviewers separately evaluated article titles; (2) two reviewers separately evaluated abstracts and (3) one reviewer read each article and determined inclusion eligibility. DATA SYNTHESIS: We identified and included 35 articles published during 2001-2014, grouped based on broad themes: MUH resident (n=16); MUH operator (n=6); environmental monitoring and biomarkers (n=9); economic (n=2); legal (n=3); and implementation process and policy impact (n=8). Studies with multiple themes were included in all relevant groups. CONCLUSIONS: Existing literature has focused on self-reported, cross-sectional studies of MUH residents and operators; some studies of environmental markers, biomarkers and economic indicators have also been conducted. Future research on smoke-free MUH policy compliance and enforcement, and on the impact of these policies on smoking behaviours and health outcomes, could further inform public health planning, policy and practice. Despite these gaps, the current literature provides sufficient evidence for action to eliminate SHS exposure in MUH.

Podocalyxin enhances breast tumor growth and metastasis and is a target for monoclonal antibody therapy.

INTRODUCTION: Podocalyxin (gene name PODXL) is a CD34-related sialomucin implicated in the regulation of cell adhesion, migration and polarity. Upregulated expression of podocalyxin is linked to poor patient survival in epithelial cancers. However, it is not known if podocalyxin has a functional role in tumor progression. METHODS: We silenced podocalyxin expression in the aggressive basal-like human (MDA-MB-231) and mouse (4T1) breast cancer cell lines and also overexpressed podocalyxin in the more benign human breast cancer cell line, MCF7. We evaluated how podocalyxin affects tumorsphere formation in vitro and compared the ability of podocalyxin-deficient and podocalyxin-replete cell lines to form tumors and metastasize using xenogenic or syngeneic transplant models in mice. Finally, in an effort to develop therapeutic treatments for systemic cancers, we generated a series of antihuman podocalyxin antibodies and screened these for their ability to inhibit tumor progression in xenografted mice. RESULTS: Although deletion of podocalyxin does not alter gross cell morphology and growth under standard (adherent) culture conditions, expression of PODXL is required for efficient formation of tumorspheres in vitro. Correspondingly, silencing podocalyxin resulted in attenuated primary tumor growth and invasiveness in mice and severely impaired the formation of distant metastases. Likewise, in competitive tumor engraftment assays where we injected a 50:50 mixture of control and shPODXL (short-hairpin RNA targeting PODXL)-expressing cells, we found that podocalyxin-deficient cells exhibited a striking decrease in the ability to form clonal tumors in the lung, liver and bone marrow. Finally, to validate podocalyxin as a viable target for immunotherapy, we screened a series of novel antihuman podocalyxin antibodies for their ability to inhibit tumor progression in vivo. One of these antibodies, PODOC1, potently blocked tumor growth and metastasis. CONCLUSIONS: We show that podocalyxin plays a key role in the formation of primary tumors and distant tumor metastasis. In addition, we validate podocalyxin as potential target for monoclonal antibody therapy to inhibit primary tumor growth and systemic dissemination.

Mast cells in human health and disease.

Mast cells are primarily known for their role in defense against pathogens, particularly bacteria; neutralization of venom toxins; and for triggering allergic responses and anaphylaxis. In addition to these direct effector functions, activated mast cells rapidly recruit other innate and adaptive immune cells and can participate in "tuning" the immune response. In this review we touch briefly on these important functions and then focus on some of the less-appreciated roles of mast cells in human disease including cancer, autoimmune inflammation, organ transplant, and fibrosis. Although it is difficult to formally assign causal roles to mast cells in human disease, we offer a general review of data that correlate the presence and activation of mast cells with exacerbated inflammation and disease progression. Conversely, in some restricted contexts, mast cells may offer protective roles. For example, the presence of mast cells in some malignant or cardiovascular diseases is associated with favorable prognosis. In these cases, specific localization of mast cells within the tissue and whether they express chymase or tryptase (or both) are diagnostically important considerations. Finally, we review experimental animal models that imply a causal role for mast cells in disease and discuss important caveats and controversies of these findings.

Measurement of mast cell surface molecules by high-throughput immunophenotyping using transcription (HIT).

Here we describe the application of a highly multiplexed proteomic assay, called HIT (high-throughput immunophenotyping using transcription), to analyze human mast cell surface antigens at rest and during stimulation. HIT allows analysis of up to 100 analytes, including surface antigens and intracellular phosphoproteins, transcription factors, and cytokines, in a single experiment. Briefly, anti-mouse monovalent Fab fragments are covalently conjugated with barcoded oligonucleotides to generate a panel of conjugates. The oligonucleotide-Fab fragment conjugates are bound to monoclonal primary antibodies, creating a cocktail of up to 48 unique barcoded primary antibodies. As few as 100,000 mast cells are stained with the cocktail and the barcodes of the bound primary antibodies are amplified by in vitro transcription with fluorescently labeled NTPs. The resulting barcoded transcripts are quantified using a microarray spotted with oligonucleotides that are complementary to the barcoded transcripts. Differences in levels of the barcoded transcripts correlate well with actual protein levels and are capable of detecting stimulation-dependent changes in protein levels. HIT is an invaluable, broad-spectrum approach for characterizing mast cell surface antigens, signaling molecules, transcription factors, and cytokines.

The component model of infrastructure: a practical approach to understanding public health program infrastructure.

Functioning program infrastructure is necessary for achieving public health outcomes. It is what supports program capacity, implementation, and sustainability. The public health program infrastructure model presented in this article is grounded in data from a broader evaluation of 18 state tobacco control programs and previous work. The newly developed Component Model of Infrastructure (CMI) addresses the limitations of a previous model and contains 5 core components (multilevel leadership, managed resources, engaged data, responsive plans and planning, networked partnerships) and 3 supporting components (strategic understanding, operations, contextual influences). The CMI is a practical, implementation-focused model applicable across public health programs, enabling linkages to capacity, sustainability, and outcome measurement.

Consideration of an applied model of public health program infrastructure.

Systemic infrastructure is key to public health achievements. Individual public health program infrastructure feeds into this larger system. Although program infrastructure is rarely defined, it needs to be operationalized for effective implementation and evaluation. The Ecological Model of Infrastructure (EMI) is one approach to defining program infrastructure. The EMI consists of 5 core (Leadership, Partnerships, State Plans, Engaged Data, and Managed Resources) and 2 supporting (Strategic Understanding and Tactical Action) elements that are enveloped in a program's context. We conducted a literature search across public health programs to determine support for the EMI. Four of the core elements were consistently addressed, and the other EMI elements were intermittently addressed. The EMI provides an initial and partial model for understanding program infrastructure, but additional work is needed to identify evidence-based indicators of infrastructure elements that can be used to measure success and link infrastructure to public health outcomes, capacity, and sustainability.

Developing Your Evaluation Plans: A Critical Component of Public Health Program Infrastructure.

A program's infrastructure is often cited as critical to public health success. The Component Model of Infrastructure (CMI) identifies evaluation as essential under the core component of engaged data. An evaluation plan is a written document that describes how to monitor and evaluate a program, as well as how to use evaluation results for program improvement and decision making. The evaluation plan clarifies how to describe what the program did, how it worked, and why outcomes matter. We use the Centers for Disease Control and Prevention's (CDC) "Framework for Program Evaluation in Public Health" as a guide for developing an evaluation plan. Just as using a roadmap facilitates progress on a long journey, a well-written evaluation plan can clarify the direction your evaluation takes and facilitate achievement of the evaluation's objectives.

Barriers to mental health treatment services for low-income African American women whose children receive behavioral health services: an ethnographic investigation.

Despite the prevalence of mental illness among low-income African American women, only a limited number seek and/or accept help from mental health service delivery systems. A qualitative analysis of 64 ethnographic interviews of low-income African American women whose children receive behavioral health services was completed to assess what barriers to care were reported for the women themselves. These African American women were interviewed as part of a larger study seeking to determine why mothers seek mental health treatment for their children, but not themselves, after many of the women (n = 32) met the baseline criteria for anxiety and/or depression. Our finding revealed that (1) the fear of losing their children, (2) economic stressors, (3) role strain, (4) perceptions of the system, and (5) violence and survival are key factors to consider when engaging low-income African American women in mental health treatment services. These factors have a negative influence on help seeking that should be considered for eliminating disparities in access to and utilization of mental health services.

Identification of low-level degradants from low dose tablets.

A multifaceted approach was successfully used to identify three of four unknown degradants in degraded low dose tablets. Accelerated solvent extraction (ASE) was found to be an invaluable tool in this multifaceted approach. ASE was capable of extracting four individual degradants of an active pharmaceutical component from 10 tablets into 15 mL of solvent with approximately 100% recovery for each degradant. Using ASE instead of manual extraction led to the extraction and isolation of the degradants in 1 day instead of 7 days. One of the degradants was extracted by ASE, isolated by semi-prep HPLC, and identified by LC-MS and NMR spectroscopy. The structures of two of the remaining three degradants were confirmed by synthesis of authentic samples, while the fourth degradant is yet to be identified.