TATA-Box Binding Protein O-GlcNAcylation at T114 Regulates Formation of the B-TFIID Complex and Is Critical for Metabolic Gene Regulation.

In eukaryotes, gene expression is performed by three RNA polymerases that are targeted to promoters by molecular complexes. A unique common factor, the TATA-box binding protein (TBP), is thought to serve as a platform to assemble pre-initiation complexes competent for transcription. Here, we describe a novel molecular mechanism of nutrient regulation of gene transcription by dynamic O-GlcNAcylation of TBP. We show that O-GlcNAcylation at T114 of TBP blocks its interaction with BTAF1, hence the formation of the B-TFIID complex, and its dynamic cycling on and off of DNA. Transcriptomic and metabolomic analyses of TBPT114A CRISPR/Cas9-edited cells showed that loss of O-GlcNAcylation at T114 increases TBP binding to BTAF1 and directly impacts expression of 408 genes. Lack of O-GlcNAcylation at T114 is associated with a striking reprogramming of cellular metabolism induced by a profound modification of the transcriptome, leading to gross alterations in lipid storage.

Legionella pneumophila usurps host cell lipids for vacuole expansion and bacterial growth.

Vacuolar pathogens reside in membrane-bound compartments within host cells. Maintaining the integrity of this compartment is paramount to bacterial survival and replication as it protects against certain host surveillance mechanisms that function to eradicate invading pathogens. Preserving this compartment during bacterial replication requires expansion of the vacuole membrane to accommodate the increasing number of bacteria, and yet, how this is accomplished remains largely unknown. Here, we show that the vacuolar pathogen Legionella pneumophila exploits multiple sources of host cell fatty acids, including inducing host cell fatty acid scavenging pathways, in order to promote expansion of the replication vacuole and bacteria growth. Conversely, when exogenous lipids are limited, the decrease in host lipid availability restricts expansion of the replication vacuole membrane, resulting in a higher density of bacteria within the vacuole. Modifying the architecture of the vacuole prioritizes bacterial growth by allowing the greatest number of bacteria to remain protected by the vacuole membrane despite limited resources for its expansion. However, this trade-off is not without risk, as it can lead to vacuole destabilization, which is detrimental to the pathogen. However, when host lipid resources become extremely scarce, for example by inhibiting host lipid scavenging, de novo biosynthetic pathways, and/or diverting host fatty acids to storage compartments, bacterial replication becomes severely impaired, indicating that host cell fatty acid availability also directly regulates L. pneumophila growth. Collectively, these data demonstrate dual roles for host cell fatty acids in replication vacuole expansion and bacterial proliferation, revealing the central functions for these molecules and their metabolic pathways in L. pneumophila pathogenesis.

Self-reported knowledge of tetrahydrocannabinol and cannabidiol concentration in cannabis products among cancer patients and survivors.

PURPOSE: Cannabis use may introduce risks and/or benefits among people living with cancer, depending on product type, composition, and nature of its use. Patient knowledge of tetrahydrocannabinol (THC) or cannabidiol (CBD) concentration could provide information for providers about cannabis use during and after treatment that may aide in risk and benefit assessments. This study aimed to examine knowledge of THC or CBD concentration among patients living with cancer who consume cannabis, and factors associated with knowledge of cannabinoid concentrations. METHODS: People living with cancer who consumed cannabis since their diagnosis (n = 343) completed an anonymous, mixed-mode survey. Questions assessed usual mode of delivery (MOD), knowledge of THC/CBD concentration, and how source of acquisition, current cannabis use, and source of instruction are associated with knowledge of THC/CBD concentration. Chi-square and separate binary logistic regression analyses were examined and weighted to reflect the Roswell Park patient population. RESULTS: Less than 20% of people living with cancer had knowledge of THC and CBD concentration for the cannabis products they consumed across all MOD (smoking- combustible products, vaping- vaporized products (e-cigarettes), edibles-eating or drinking it, and oral- taking by mouth (pills)). Source of acquisition (smoking-AOR:4.6, p < 0.01, vaping-AOR:5.8, p < 0.00, edibles-AOR:2.6, p < 0.04), current cannabis use (edibles-AOR:5.4, p < 0.01, vaping-AOR: 11.2, p < 0.00, and oral-AOR:9.3, p < 0.00), and source of instruction (vaping only AOR:4.2, p < 0.05) were found to be variables associated with higher knowledge of THC concentration. CONCLUSION: Self-reported knowledge of THC and CBD concentration statistically differed according to MOD, source of acquisition, source of instruction, and current cannabis use.

"You Can Do So Much Better Than What They Expect": An Arts-Based Engagement Ethnography on School Integration With Newcomer Youth.

Newcomer adolescents make up a large minority of Canada's population and their positive integration experiences with education systems across the country are critical for both their development and the country's long-term success. The current study examined newcomer adolescents' (n = 4, between 16 and 18 years old) integration experiences using an arts-based engagement ethnography to understand what influences their positive integration into the school system. Artifacts, interview, and focus group data were analyzed systematically using ethnographic research guidelines. Five structures were identified: (1) barriers to advancement at individual, school, and macro levels, (2) fluctuating relationship with cultural identity, (3) limited trust in systems, (4) resilience through independent learning, and (5) facilitating factors to positive integration experiences at the family and school level. In keeping with a relational developmental systems theory framework, each structure accounts for multiple inter- and intra-individual factors at multiple environmental levels. These findings outline considerations for systemic issues in academic institutions and offer suggestions for how institutions can better support newcomer adolescents.

Intracranial Relapse in Pediatric Sarcoma.

Advances in local control techniques, chemotherapy regimens, and imaging modalities have led to improvements in both morbidity and mortality in pediatric sarcoma patients. However, approximately one-third of patients develop disease relapse and intracranial metastasis was considered rare. The incidence of sarcoma brain metastasis is thought to have increased and is associated with grim outcomes. This was a retrospective study of 3 deidentified patient charts illustrating the possibility of the central nervous system as a potential site for pediatric sarcoma relapse and investigate the patterns of such relapses. We note this is the first report of infantile fibrosarcoma brain metastasis and a rare report of sarcoma lymph node metastasis. In addition, each patient was treated with targeted therapies, including entrectinib, Ruxolitnib, and pazopanib. Caregivers in cases 2 and 3 reported new-onset neurological manifestations before identification of new brain metastasis, indicating a lag in detection of new intracranial relapse in asymptomatic sarcoma patients. We suggest implementing a brief review of systems screening tool focused on concerning neurological manifestations to screen for new brain metastasis.

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.

Association between allergic sensitization and intestinal parasite infection in schoolchildren in Gqeberha, South Africa.

BACKGROUND: Inconsistent data exist regarding the influence of parasitic infection on the prevalence of allergic sensitization and disorders. OBJECTIVE: To investigate the impact of geohelminth and protozoan infections on sensitization patterns and allergic symptoms of children living in low-income communities in Gqeberha, South Africa. METHODS: In a cross-sectional study, 587 schoolchildren aged 8-12 years were recruited in June 2016 and screened for reactivity to common allergens by skin prick tests (SPTs) and for parasitic infections by stool examination. Additionally, questionnaires were completed to record allergic symptoms the children may have experienced. RESULTS: Positive SPTs were found in 237/587 children (40.4%), and about one-third of whom were polysensitized. Sensitizations were most frequently detected against the house dust mites (HDM) Dermatophagoides spp. (31.9%) and Blomia tropicalis (21.0%). Infections with geohelminths (Ascaris lumbricoides, Trichuris trichiura) were found in 26.8% and protozoan infections (Giardia intestinalis, Cryptosporidia spp.) in 13.9% of study participants. Mixed logistic regression analyses revealed negative associations between parasite infection and sensitization to Blomia tropicalis (OR: 0.54, 95% CI 0.33-0.89) and to Dermatophagoides spp. (OR 0.65, 95% CI 0.43-0.96), and between protozoan infection and allergic sensitization to any aeroallergen, although these associations were not significant when adjusted for false discovery. Geohelminth infection and intensity of geohelminth infection were both associated with reduced risk of polysensitization (OR 0.41, 95% CI 0.21-0.86), and this association remained significant with adjustment for false discovery. Reported respiratory symptoms were associated with HDM sensitization (ORs from 1.54 to 2.48), but not with parasite infection. CONCLUSIONS AND CLINICAL RELEVANCE: Our data suggest that geohelminth infection and high geohelminth infection intensity are associated with a reduced risk of polysensitization.

Choosing Wisely in Adult Hospital Medicine: Co-creation of New Recommendations for Improved Healthcare Value by Clinicians and Patient Advocates.

BACKGROUND: The American Board of Internal Medicine Foundation's Choosing Wisely campaign has resulted in a vast number of recommendations to reduce low-value care. Implementation of these recommendations, in conjunction with patient input, remains challenging. OBJECTIVE: To create updated Society of Hospital Medicine Adult Hospitalist Choosing Wisely recommendations that incorporate patient input from inception. DESIGN AND PARTICIPANTS: This was a multi-phase study conducted by the Society of Hospital Medicine's High Value Care Committee from July 2017 to January 2020 involving clinicians and patient advocates. APPROACH: Phase 1 involved gathering low-value care recommendations from patients and clinicians across the USA. Recommendations were reviewed by the committee in phase 2. Phase 3 involved a modified Delphi scoring in which 7 committee members and 7 patient advocates voted on recommendations based on strength of evidence, potential for patient harm, and relevance to either hospital medicine or patients. A patient-friendly script was developed to allow advocates to better understand the clinical recommendations. KEY RESULTS: A total of 1265 recommendations were submitted by clinicians and patients. After accounting for similar suggestions, 283 recommendations were categorized. Recommendations with more than 10 mentions were advanced to phase 3, leaving 22 recommendations for the committee and patient advocates to vote upon. Utilizing a 1-5 Likert scale, the top combined recommendations were reducing use of opioids (4.57), improving sleep (4.52), minimizing overuse of oxygen (4.52), reducing CK-MB use (4.50), appropriate venous thromboembolism prophylaxis (4.43), and decreasing daily chest x-rays (4.43). CONCLUSIONS: Specific voting categories, along with the use of patient-friendly language, allowed for the successful co-creation of recommendations.

Development of cerebral mitochondrial respiratory function is impaired by thyroid hormone deficiency before birth in a region-specific manner.

Thyroid hormones regulate adult metabolism partly through actions on mitochondrial oxidative phosphorylation (OXPHOS). They also affect neurological development of the brain, but their role in cerebral OXPHOS before birth remains largely unknown, despite the increase in cerebral energy demand during the neonatal period. Thus, this study examined prepartum development of cerebral OXPHOS in hypothyroid fetal sheep. Using respirometry, Complex I (CI), Complex II (CII), and combined CI&CII OXPHOS capacity were measured in the fetal cerebellum and cortex at 128 and 142 days of gestational age (dGA) after surgical thyroidectomy or sham operation at 105 dGA (term ~145 dGA). Mitochondrial electron transfer system (ETS) complexes, mRNA transcripts related to mitochondrial biogenesis and ATP production, and mitochondrial density were quantified using molecular techniques. Cerebral morphology was assessed by immunohistochemistry and stereology. In the cortex, hypothyroidism reduced CI-linked respiration and CI abundance at 128 dGA and 142 dGA, respectively, and caused upregulation of PGC1α (regulator of mitochondrial biogenesis) and thyroid hormone receptor ß at 128 dGA and 142 dGA, respectively. In contrast, in the cerebellum, hypothyroidism reduced CI&II- and CII-linked respiration at 128 dGA, with no significant effect on the ETS complexes. In addition, cerebellar glucocorticoid hormone receptor and adenine nucleotide translocase (ANT1) were downregulated at 128 dGA and 142 dGA, respectively. These alterations in mitochondrial function were accompanied by reduced myelination. The findings demonstrate the importance of thyroid hormones in the prepartum maturation of cerebral mitochondria and have implications for the etiology and treatment of the neurodevelopmental abnormalities associated with human prematurity and congenital hypothyroidism.

Increasing Cannabis Use Is Associated With Poorer Cigarette Smoking Cessation Outcomes: Findings From the ITC Four Country Smoking and Vaping Surveys, 2016-2018.

INTRODUCTION: Concurrent use of tobacco and cannabis may impede successful cigarette smoking cessation. This study examined whether changes in cannabis use frequency were associated with smoking cessation. AIMS AND METHODS: Nationally representative samples of adult cigarette smokers from Canada (n = 1455), the United States (n = 892), England (n = 1416), and Australia (n = 717) were surveyed in 2016 and 2018. In each year, smokers reported how often they used cannabis in the previous 12 months. Reports were compared to determine whether cannabis use increased, remained unchanged, or decreased. Smoking cessation outcomes, measured in 2018, were (1) any attempt to quit in the previous year, (2) currently quit, and (3) currently quit for at least 6 months. Weighted multivariable logistic regression estimated the association between changes in cannabis use and cessation outcomes. RESULTS: Cigarette smokers who increased their frequency of cannabis use were significantly less likely to be currently quit than noncannabis-using smokers (adjusted odds ratio (aOR) = 0.52, 95% CI = 0.31% to 0.86%); they were also less likely to have quit for at least 6 months (aOR = 0.30; 95% CI = 0.15% to 0.62%). CONCLUSIONS: Smokers who increase their frequency of cannabis use have poorer smoking cessation outcomes compared to noncannabis-using smokers. It will be important to monitor the impact of cannabis legalization on patterns of cannabis use, and whether this influences cigarette smoking cessation rates. IMPLICATIONS: Cigarette smokers who start using cannabis may be less likely to quit cigarettes compared with smokers who do not use cannabis at all. If smokers who also use cannabis are more likely to continue smoking, it is important to monitor these trends and understand the impact, if any, on smoking cessation in jurisdictions that have legalized cannabis for nonmedical use.

Characterizing Heated Tobacco Product Use Among Adult Cigarette Smokers and Nicotine Vaping Product Users in the 2018 ITC Four Country Smoking & Vaping Survey.

INTRODUCTION: Heated tobacco products (HTP) have diversified global tobacco markets, and user characteristics remain understudied. This study evaluated sociodemographic characteristics, nicotine-related perceptions, and behaviors of current HTP users within a sample of adult (18+ years) nicotine users across four countries. AIMS AND METHODS: Data were from current smokers or nicotine vaping product (NVP; known as "e-cigarettes") users from Canada, England, the United States, and Australia (n = 11 421) who participated in the 2018 ITC Four Country Smoking and Vaping Survey. Current (at-least-monthly) HTP users were characterized (n = 441), and weighted multivariable logistic regressions examined correlates of HTP use. RESULTS: Compared to nonusers, current HTP users were younger (mean age: 44.4 vs 31.0 years; p < .001) and had higher socioeconomic status (p < .001). A majority of current HTP users used HTPs nondaily (daily: 40.3% vs nondaily: 59.7%). Most HTP users concurrently used both cigarettes and NVPs (90.5%). Among concurrent cigarette-HTP-NVP users, 36.2% used all three products daily. Use of other combusted tobacco products (cigars, cigarillos, pipe, waterpipe/hookah), cannabis, and binge drinking were each associated with current HTP use. HTP use was more common among smokers intending to quit within 6 months or reporting a quit attempt in the past 18 months, and vapers who had experienced negative side effects. CONCLUSION: HTP users in this sample tended to be younger and more affluent. Most reported concurrent use of multiple nicotine products and other substances. Those cigarette smokers who used HTPs appeared more interested in smoking cessation, while some characteristics of concurrent HTP-NVP users were suggestive of dissatisfaction with NVPs. IMPLICATIONS: Few studies have scrutinized characteristics of HTP early adopters in emerging markets. Our results indicate that in 2018, characteristics of established nicotine users who adopted HTP use in four high-income Western countries mirror those of HTP users in East Asian markets (South Korea and Japan) where HTPs are popular. HTP users reported high levels of concurrent use of noncigarette-combusted tobacco products (e.g., cigars, pipe tobacco). These findings point to the need for future longitudinal studies of HTP use given the implications of those use patterns on the harm reduction potential of HTPs. HTP user characteristics may yield important information to consider in regulation of these products.

Assessing use of inhalable nicotine products within complex markets: the dilemma of heated tobacco products.

The introduction of electronic inhalable products, such as nicotine vaping products (NVPs) and heated tobacco products (HTPs), has further diversified the nicotine market landscape. This poses unique challenges in measuring self-reported nicotine use behaviours, which have been the hallmark of tobacco surveillance systems. This paper raises concerns of potential measurement error for electronic inhalable product use in surveys due to similarities in product design between NVPs and HTPs, as well as changing trends in cannabis administration. We identify several strategies for addressing this issue (eg, including descriptive preambles in surveys that differentiate product classes from one another; incorporating survey questions that probe beyond an initial question regarding product use). In the absence of comprehensive validation studies, caution is warranted when interpreting survey results that rely on self-reported HTP use.

Awareness, trial and use of heated tobacco products among adult cigarette smokers and e-cigarette users: findings from the 2018 ITC Four Country Smoking and Vaping Survey.

OBJECTIVE: To evaluate heated tobacco product (HTP) awareness, trial and current use among adult cigarette smokers and vaping product users in four countries with varying regulations governing HTP sales. DESIGN: Data came from Wave 2 of the ITC Four Country Smoking and Vaping Survey, collected from February to July 2018. Respondents were current and former smokers and/or users of vaping products (18 years or older) from Canada (CA; n=3778), England (EN; n=4848), the USA (US; n=2846) and Australia (AU; n=1515). At the time of the survey, only Canada and England permitted the sale of contemporary HTPs (eg, IQOS). RESULTS: Overall, 30.2% of respondents reported being aware of HTPs (CA=30.4%; EN=31.0%; US=30.2%; AU=27.4%; p=0.346), 2.4% had ever tried HTPs (CA=3.3%; EN=2.4%; US=2.0%; AU=0.9%; p=0.001) and 0.9% currently used HTPs at least monthly (CA=0.8%; EN=1.2%; US=0.7%; AU=0.2%; p<0.001). Trial and current use were higher among those who concurrently smoked and vaped (at least monthly) versus other nicotine use categories (trial: 10.9% v. 1.2%-2.0%, p<0.001; current use: 8.4% v. 0.1%-1.0%, p<0.001). In multivariable analyses, HTP awareness did not differ across countries, whereas odds of trial and current use were lower where HTPs were unavailable. Odds of HTP trial did not differ by regulatory environment when restricting analysis to HTP-aware concurrent smokers-vapers. CONCLUSION: Approximately one third of respondents were aware of HTPs, even in the USA and Australia, where contemporary HTPs were not yet on the market. Trial and use were uncommon, except among concurrent smokers-vapers. Restrictions on availability may have limited HTP use generally, but less so for concurrent smokers-vapers.

Consumer perceptions of legal cannabis products in Canada, 2019-2021: a repeat cross-sectional study.

BACKGROUND: Consumer perceptions of legal cannabis products may drive willingness to purchase from the illegal or legal market; however, little is known on this topic. The current study examined perceptions of legal products among Canadian cannabis consumers over a 3-year period following federal legalization of non-medical cannabis in 2018. METHODS: Data were analyzed from Canadian respondents in the International Cannabis Policy Study, a repeat cross-sectional survey conducted in 2019-2021. Respondents were 15,311 past 12-month cannabis consumers of legal age to purchase cannabis. Weighted logistic regression models examined the association between perceptions of legal cannabis and province of residence, and frequency of cannabis use over time. RESULTS: In 2021, cannabis consumers perceived legal cannabis to be safer to buy (54.0%), more convenient to buy (47.8%), more expensive (47.2%), safer to use (46.8%) and higher quality (29.3%) than illegal cannabis. Except for safety of purchasing, consumers had more favourable perceptions of legal cannabis in 2021 than 2019 across all outcomes. For example, consumers had higher odds of perceiving legal cannabis as more convenient to buy in 2021 than 2019 (AOR = 3.09, 95%CI: 2.65,3.60). More frequent consumers had less favourable perceptions of legal cannabis than less frequent consumers. CONCLUSIONS: Three years since legalization, Canadian cannabis consumers generally had increasingly favourable perceptions of legal vs. illegal products - except for price - with variation across the provinces and frequency of cannabis use. To achieve public health objectives of legalization, federal and provincial governments must ensure that legal cannabis products are preferred to illegal, without appealing to non-consumers.

Use of Inhaled Nicotine and Cannabis Products among Adults Who Vape Both Substances.

BACKGROUND: Co-occurring use (co-use) of nicotine and cannabis is common, and represents a broad range of use behaviors, including concurrent use, sequential use, and co-administration. Co-use has primarily been examined through the lens of smoked tobacco and cannabis. Little is known about those who co-use vaped nicotine and cannabis, and the degree to which specific co-use behaviors are associated, based on mode of use and/or substance. METHODS: We conducted an online pilot survey on use behaviors related to inhaled modes of nicotine and cannabis. The survey was administered to 112 concurrent vapers of these substances. Descriptive analyses examined sample characteristics and co-administered vaping and smoking behaviors. Logistic regressions examined associations in use behaviors by mode and substance. RESULTS: Participants who vaped nicotine and cannabis monthly also reported monthly smoking of cannabis (100%), and cigarettes (58%). Most exhibited moderate-to-high degrees of mental health and substance use problems requiring clinical intervention. Monthly concurrent use exhibited more differences by mode, and more similarities by substance. Specific sequential use practices showed mode-specific associations; with greater frequency of cigarette smoking and nicotine vaping. Co-administration was associated with more frequent tobacco and cannabis smoking. CONCLUSIONS: Those who regularly vape nicotine and cannabis tend to engage in some form of smoking. Different subsets of nicotine and cannabis co-use behaviors showed different associations with patterns of use and modes of drug delivery. Findings underscore the diversity of nicotine and cannabis use behaviors among co-users, and the importance of considering associations by both substance and mode of use.

The political economy of child servitude in Liberia, West Africa.

Child servitude is a form of economic exploitation of children around the world. We examine this phenomenon with local specificity, in Liberia, where it represents a perennial failure of the government to protect children, who are among its most vulnerable citizens. Despite its persistence and high prevalence, child servitude has not been the focus of academic research on Liberia. This paper explores the interplay of transmuted American chattel slavery and indigenous specific Liberian cultural practices of human subjugation against a backdrop of socio-economic inequalities, and their linkages to contemporary child servitude in postwar Liberia. We discuss the impacts of child servitude on victims and recommend policy measures to protect the rights of Liberian children. If postwar Liberia is to achieve its pro-poor developmental agenda, policies must be formulated that address child servitude and other forms of exploitation against Liberian children.

Hypergraph models of biological networks to identify genes critical to pathogenic viral response.

BACKGROUND: Representing biological networks as graphs is a powerful approach to reveal underlying patterns, signatures, and critical components from high-throughput biomolecular data. However, graphs do not natively capture the multi-way relationships present among genes and proteins in biological systems. Hypergraphs are generalizations of graphs that naturally model multi-way relationships and have shown promise in modeling systems such as protein complexes and metabolic reactions. In this paper we seek to understand how hypergraphs can more faithfully identify, and potentially predict, important genes based on complex relationships inferred from genomic expression data sets. RESULTS: We compiled a novel data set of transcriptional host response to pathogenic viral infections and formulated relationships between genes as a hypergraph where hyperedges represent significantly perturbed genes, and vertices represent individual biological samples with specific experimental conditions. We find that hypergraph betweenness centrality is a superior method for identification of genes important to viral response when compared with graph centrality. CONCLUSIONS: Our results demonstrate the utility of using hypergraphs to represent complex biological systems and highlight central important responses in common to a variety of highly pathogenic viruses.

How Does the Use of Flavored Nicotine Vaping Products Relate to Progression Toward Quitting Smoking? Findings From the 2016 and 2018 ITC 4CV Surveys.

INTRODUCTION: There is limited research on the role of flavors in nicotine vaping products (NVPs) in relation to smoking. We examined patterns of flavor use in NVPs in relation to progression toward quitting. AIMS AND METHODS: Data come from 886 concurrent users of NVPs (at least weekly) and cigarettes who were first surveyed in 2016 and then successfully recontacted in 2018 as part of the ITC 4CV Surveys conducted in Australia, Canada, England, and the United States. Participants were asked about their main vaping flavor categorized as: (1) tobacco or unflavored, (2) menthol or mint flavored, and (3) "sweet" flavors (eg, fruit or candy). We examined whether flavor was associated with progression toward quitting smoking between survey years. RESULTS: Overall, 11.1% of baseline concurrent users quit smoking by 2018. Compared with users of tobacco flavors, those vaping "sweet" flavors were more likely to quit smoking between surveys (13.8% vs. 9.6%; adjusted odds ratio [aOR] = 1.61, 95% confidence interval [CI] 1.01-2.58, p < .05), but those using menthol flavors were no more likely to quit smoking (8.3% vs. 9.6%, aOR = 0.87, 95% CI 0.43-1.47, p = .69). Among those who had quit smoking in 2018, 52.0% were still vaping, which was lower than the 65.8% among continuing smokers (aOR = 0.60, 95% CI 0.39-0.92, p = .02). Sweet flavor users were no more likely to continue vaping compared with tobacco flavor users, either for those continuing smoking or those having quit smoking by 2018. There was a net shift away from tobacco flavor among those who continued to vape at follow-up. CONCLUSIONS: Use of fruit and other sweet flavored e-liquids is positively related to smokers' transition away from cigarettes. IMPLICATIONS: With multiple jurisdictions considering limiting or banning the sale of flavored NVPs, it is important to consider how such policies may impact smokers using NVPs to transition away from cigarette smoking. Our results indicate that vapers who used sweet flavors were more likely to transition away from cigarette smoking and quit cigarette use, at least in the short term, compared with those who used tobacco or unflavored NVPs. Randomized clinical trials are needed to establish if the observed association between use of flavored e-liquids and smoking cessation is due to self-selection or is truly causal.

Exposure to Nicotine and Toxicants Among Dual Users of Tobacco Cigarettes and E-Cigarettes: Population Assessment of Tobacco and Health (PATH) Study, 2013-2014.

INTRODUCTION: Concurrent use of tobacco cigarettes and e-cigarettes ("dual use") is common among tobacco users. Little is known about differences in demographics and toxicant exposure among subsets of dual users. AIMS AND METHODS: We analyzed data from adult dual users (current every/some day users of tobacco cigarettes and e-cigarettes, n = 792) included in the PATH Study Wave 1 (2013-2014) and provided urine samples. Samples were analyzed for biomarkers of exposure to nicotine and selected toxicants (tobacco-specific nitrosamine NNK [NNAL], lead, cadmium, naphthalene [2-naphthol], pyrene [1-hydroxypyrene], acrylonitrile [CYMA], acrolein [CEMA], and acrylamide [AAMA]). Subsets of dual users were compared on demographic, behavioral, and biomarker measures to exclusive cigarette smokers (n = 2411) and exclusive e-cigarette users (n = 247). RESULTS: Most dual users were predominant cigarette smokers (70%), followed by daily dual users (13%), non-daily concurrent dual users (10%), and predominant vapers (7%). Dual users who smoked daily showed significantly higher biomarker concentrations compared with those who did not smoke daily. Patterns of e-cigarette use had little effect on toxicant exposure. Dual users with high toxicant exposure were generally older, female, and smoked more cigarettes per day. Dual users who had low levels of biomarkers of exposure were generally younger, male, and smoked non-daily. CONCLUSIONS: In 2013-2014, most dual users smoked cigarettes daily and used e-cigarettes occasionally. Cigarette smoking appears to be the primary driver of toxicant exposure among dual users, with little-to-no effect of e-cigarette use on biomarker levels. Results reinforce the need for dual users to stop smoking tobacco cigarettes to reduce toxicant exposure. IMPLICATIONS: With considerable dual use of tobacco cigarettes and e-cigarettes in the United States, it is important to understand differences in toxicant exposure among subsets of dual users, and how these differences align with user demographics. Findings suggest most dual users smoke daily and use e-cigarettes intermittently. Low exposure to toxicants was most common among younger users, males, and intermittent smokers; high exposure to toxicants was most common among older users, females, and heavier cigarette smokers. Results underscore the heterogeneity occurring within dual users, and the need to quit smoking cigarettes completely in order to reduce toxicant exposure.

Hypertension among South African children in disadvantaged areas and associations with physical activity, fitness, and cardiovascular risk markers: A cross-sectional study.

Childhood hypertension drives hypertension in later life; hence, assessing blood pressure in children is an important measure to determine current and future cardiovascular health. There is, however, a paucity of childhood blood pressure data, particularly for sub-Saharan Africa. This study explores blood pressure and associations with age, sex, socioeconomic status, physical activity, fitness, and cardiovascular risk markers. In the 'Disease, Activity and Schoolchildren's Health' (DASH) study, a cross-sectional analysis was conducted in disadvantaged neighbourhoods in the Eastern Cape province of South Africa. Assessments included blood pressure, accelerometer-measured physical activity, physical fitness, and cardiovascular risk markers. The study consisted of 785 children (383 boys, 402 girls, M = 12.4±0.9 years). Overall, 18% of the children were classified as hypertensive, while 20% were either overweight/obese, and almost four out of ten children did not meet global daily physical activity recommendations. Hypertensive children were more likely to be overweight/obese, χ2 (2,785) = 14.42, p < 0.01, but only if they did not meet physical activity recommendations, χ2 (2,295) = 11.93, p < 0.01. Considering the moderating effect which sufficient activity has on the relationship between hypertension and body weight, more emphasis should be placed on early primary health intervention and education strategies.