Molecular topography of an entire nervous system.

We have produced gene expression profiles of all 302 neurons of the C. elegans nervous system that match the single-cell resolution of its anatomy and wiring diagram. Our results suggest that individual neuron classes can be solely identified by combinatorial expression of specific gene families. For example, each neuron class expresses distinct codes of ∼23 neuropeptide genes and ∼36 neuropeptide receptors, delineating a complex and expansive "wireless" signaling network. To demonstrate the utility of this comprehensive gene expression catalog, we used computational approaches to (1) identify cis-regulatory elements for neuron-specific gene expression and (2) reveal adhesion proteins with potential roles in process placement and synaptic specificity. Our expression data are available at https://cengen.org and can be interrogated at the web application CengenApp. We expect that this neuron-specific directory of gene expression will spur investigations of underlying mechanisms that define anatomy, connectivity, and function throughout the C. elegans nervous system.

A multi-scale brain map derived from whole-brain volumetric reconstructions.

Animal nervous system organization is crucial for all body functions and its disruption can lead to severe cognitive and behavioural impairment1. This organization relies on features across scales-from the localization of synapses at the nanoscale, through neurons, which possess intricate neuronal morphologies that underpin circuit organization, to stereotyped connections between different regions of the brain2. The sheer complexity of this organ means that the feat of reconstructing and modelling the structure of a complete nervous system that is integrated across all of these scales has yet to be achieved. Here we present a complete structure-function model of the main neuropil in the nematode Caenorhabditis elegans-the nerve ring-which we derive by integrating the volumetric reconstructions from two animals with corresponding3 synaptic and gap-junctional connectomes. Whereas previously the nerve ring was considered to be a densely packed tract of neural processes, we uncover internal organization and show how local neighbourhoods spatially constrain and support the synaptic connectome. We find that the C. elegans connectome is not invariant, but that a precisely wired core circuit is embedded in a background of variable connectivity, and identify a candidate reference connectome for the core circuit. Using this reference, we propose a modular network architecture of the C. elegans brain that supports sensory computation and integration, sensorimotor convergence and brain-wide coordination. These findings reveal scalable and robust features of brain organization that may be universal across phyla.

Whole-animal connectomes of both Caenorhabditis elegans sexes.

Knowledge of connectivity in the nervous system is essential to understanding its function. Here we describe connectomes for both adult sexes of the nematode Caenorhabditis elegans, an important model organism for neuroscience research. We present quantitative connectivity matrices that encompass all connections from sensory input to end-organ output across the entire animal, information that is necessary to model behaviour. Serial electron microscopy reconstructions that are based on the analysis of both new and previously published electron micrographs update previous results and include data on the male head. The nervous system differs between sexes at multiple levels. Several sex-shared neurons that function in circuits for sexual behaviour are sexually dimorphic in structure and connectivity. Inputs from sex-specific circuitry to central circuitry reveal points at which sexual and non-sexual pathways converge. In sex-shared central pathways, a substantial number of connections differ in strength between the sexes. Quantitative connectomes that include all connections serve as the basis for understanding how complex, adaptive behavior is generated.

Widespread employment of conserved C. elegans homeobox genes in neuronal identity specification.

Homeobox genes are prominent regulators of neuronal identity, but the extent to which their function has been probed in animal nervous systems remains limited. In the nematode Caenorhabditis elegans, each individual neuron class is defined by the expression of unique combinations of homeobox genes, prompting the question of whether each neuron class indeed requires a homeobox gene for its proper identity specification. We present here progress in addressing this question by extending previous mutant analysis of homeobox gene family members and describing multiple examples of homeobox gene function in different parts of the C. elegans nervous system. To probe homeobox function, we make use of a number of reporter gene tools, including a novel multicolor reporter transgene, NeuroPAL, which permits simultaneous monitoring of the execution of multiple differentiation programs throughout the entire nervous system. Using these tools, we add to the previous characterization of homeobox gene function by identifying neuronal differentiation defects for 14 homeobox genes in 24 distinct neuron classes that are mostly unrelated by location, function and lineage history. 12 of these 24 neuron classes had no homeobox gene function ascribed to them before, while in the other 12 neuron classes, we extend the combinatorial code of transcription factors required for specifying terminal differentiation programs. Furthermore, we demonstrate that in a particular lineage, homeotic identity transformations occur upon loss of a homeobox gene and we show that these transformations are the result of changes in homeobox codes. Combining the present with past analyses, 113 of the 118 neuron classes of C. elegans are now known to require a homeobox gene for proper execution of terminal differentiation programs. Such broad deployment indicates that homeobox function in neuronal identity specification may be an ancestral feature of animal nervous systems.

Association between cigar use, with and without cigarettes, and incident diagnosed COPD: a longitudinal cohort study.

BACKGROUND: While regular cigar smoking is believed to carry similar health risks as regular cigarette smoking, the impact of cigar use, alone or in combination with cigarettes, on obstructive pulmonary disease (COPD) has not been well characterized. The purpose of this study was to examine the prospective association between exclusive and dual cigar and cigarette use and incident self-reported diagnosed COPD. METHODS: This study used data from Waves 1-5 (2013-2019) of the Population Assessment of Tobacco and Health (PATH) Study, a nationally representative survey of U.S. adults. Longitudinal data from adults aged 40 to 79 at Wave 1, without a pre-existing COPD diagnosis who participated at follow-up interview were analyzed. A time-varying current tobacco exposure, lagged by one wave and categorized as: (a) never/non-current use; (b) exclusive cigar use; (c) exclusive cigarette use; and (d) dual cigar/cigarette use. Multivariable models adjusted for demographics (age, sex, race or ethnicity, education), clinical risk factors (asthma, obesity), and smoking-related confounders (second-hand smoke exposure, other combustible tobacco product use, e-cigarette use, time since quitting, cigarette pack-years). The incidence of self-reported diagnosed COPD was estimated using discrete-time survival models, using a general linear modeling (GLM) approach with a binomial distribution and a complementary log-log link function. RESULTS: The analytic sample consisted of 9,556 adults with a mean (SD) age of 56 (10.4), who were predominately female (52.8%) and Non-Hispanic White (70.8%). A total of 906 respondents reported a diagnosis of COPD at follow-up. In the fully adjusted model, exclusive cigar use (adjusted hazard ratio (aHR) = 1.57, 95% CI: 0.77, 3.21) was not associated with increased COPD risk compared to non-use, while exclusive cigarette use (aHR = 1.48, 95% CI: 1.13, 1.93) and dual cigar/cigarette use (aHR = 1.88, 95% CI: 1.24, 2.85) were. CONCLUSIONS: Exclusive cigarette use and dual cigar/cigarette use were associated with diagnosed incident COPD. These results suggest that cigars, when used in combination with cigarettes, may be associated with poorer COPD health outcomes. Dual use may promote a higher likelihood of inhaling cigar smoke, and future research would benefit from examining whether inhalation of cigar smoke increases COPD risk.

Longitudinal association of exclusive and dual use of cigarettes and cigars with asthma exacerbation among US adults: a cohort study.

BACKGROUND: Cigar use among adults in the United States has remained relatively stable in the past decade and occupies a growing part of the tobacco marketplace as cigarette use has declined. While studies have established the detrimental respiratory health effects of cigarette use, the effects of cigar use need further characterization. In this study, we evaluate the prospective association between cigar use, with or without cigarettes, and asthma exacerbation. METHODS: We used data from Waves 1-5 (2013-2019) of the Population Assessment of Tobacco and Health Study to run generalized estimating equation models examining the association between time-varying, one-wave-lagged cigarette and cigar use and self-reported asthma exacerbation among US adults (18+). We defined our exposure as non-established (reference), former, exclusive cigarette, exclusive cigar, and dual use. We defined an asthma exacerbation event as a reported asthma attack in the past 12 months necessitating oral or injected steroid medication or asthma symptoms disrupting sleep at least once a week in the past 30 days. We adjusted for age, sex, race and ethnicity, household income, health insurance, established electronic nicotine delivery systems use, cigarette pack-years, secondhand smoke exposure, obesity, and baseline asthma exacerbation. RESULTS: Exclusive cigarette use (incidence rate ratio (IRR): 1.26, 95% confidence interval (CI): 1.03-1.54) and dual use (IRR: 1.41, 95% CI: 1.08-1.85) were associated with a higher rate of asthma exacerbation compared to non-established use, while former use (IRR: 1.01, 95% CI: 0.80-1.28) and exclusive cigar use (IRR: 0.70, 95% CI: 0.42-1.17) were not. CONCLUSION: We found no association between exclusive cigar use and self-reported asthma exacerbation. However, exclusive cigarette use and dual cigarette and cigar use were associated with higher incidence rates of self-reported asthma exacerbation compared to non-established use. Studies should evaluate strategies to improve cigarette and cigar smoking cessation among adults with asthma who continue to smoke.

The prevalence and mortality risks of PRISm and COPD in the United States from NHANES 2007-2012.

BACKGROUND: We estimated the prevalence and mortality risks of preserved ratio impaired spirometry (PRISm) and chronic obstructive pulmonary disease (COPD) in the US adult population. METHODS: We linked three waves of pre-bronchodilator spirometry data from the US National Health and Nutritional Examination Survey (2007-2012) with the National Death Index. The analytic sample included adults ages 20 to 79 without missing data on age, sex, height, BMI, race/ethnicity, and smoking status. We defined COPD (GOLD 1, 2, and 3-4) and PRISm using FEV1/FVC cut points by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). We compared the prevalence of GOLD stages and PRISm by covariates across the three waves. We estimated adjusted all-cause and cause-specific mortality risks by COPD stage and PRISm using all three waves combined. RESULTS: Prevalence of COPD and PRISm from 2007-2012 ranged from 13.1%-14.3% and 9.6%-10.2%, respectively. We found significant differences in prevalence by sex, age, smoking status, and race/ethnicity. Males had higher rates of COPD regardless of stage, while females had higher rates of PRISm. COPD prevalence increased with age, but not PRISm, which was highest among middle-aged individuals. Compared to current and never smokers, former smokers showed lower rates of PRISm but higher rates of GOLD 1. COPD prevalence was highest among non-Hispanic White individuals, and PRISm was notably higher among non-Hispanic Black individuals (range 31.4%-37.4%). We found associations between PRISm and all-cause mortality (hazard ratio [HR]: 2.3 95% CI: 1.9-2.9) and various cause-specific deaths (HR ranges: 2.0-5.3). We also found associations between GOLD 2 (HR: 2.1, 95% CI: 1.7-2.6) or higher (HR: 4.2, 95% CI: 2.7-6.5) and all-cause mortality. Cause-specific mortality risk varied within COPD stages but typically increased with higher GOLD stage. CONCLUSIONS: The prevalence of COPD and PRISm remained stable from 2007-2012. Greater attention should be paid to the potential impacts of PRISm due to its higher prevalence in minority groups and its associations with mortality across various causes including cancer.

A Longitudinal Analysis of Flavored Cigar Use and Cigar Smoking Cessation Among US Adults.

BACKGROUND: Flavorings in cigars increase their appeal, mask the harsh taste of tobacco, and may hinder successful cigar smoking cessation; however, limited evidence has examined whether flavors are associated with short- or long-term cigar smoking cessation. AIMS AND METHODS: Using restricted data from the Population Assessment of Tobacco and Health Study Waves 1-5, we examined whether flavored cigar use was associated with 30-day-plus and 1-year-plus cigar smoking cessation among US adults. Multivariable discrete-time survival models were fit to a nationally representative sample of US adult (18+) respondents who had a current, established cigar use, smoked five or more days in the past 30 days, and did not exclusively smoke traditional premium cigars at baseline. Models adjusted for age, sex, race and ethnicity, income, cigar and cigarette smoking intensity, and blunt use. RESULTS: At baseline, 44.6% of respondents (n = 674) were 18-34 years old, 75.0% were male, 56.7% were non-Hispanic White, 78.9% had household incomes of <$50,000, and 56.2% smoked flavored cigars. In fully adjusted models, flavored cigar use was associated with a lower risk of 30-day-plus (HR = 0.76, 95% CI = 0.60, 0.97) but not 1-year-plus cigar smoking cessation (HR = 0.81, 95% = 0.62, 1.05). CONCLUSIONS: We found that flavored cigar use was associated with a lower risk of short-term but not long-term cigar smoking cessation. More work is needed to understand the dynamics of cigar smoking transitions, including initiation, cessation, and relapse, particularly in larger cohorts and among those who exclusively use cigars or dual-use cigars and cigarettes. IMPLICATIONS: As local and some state jurisdictions continue to adopt partial or complete bans of flavored cigar products and the United States Food and Drug Administration considers a national ban of all characterizing flavors in cigars, there is a need for more longitudinal work examining the associations between flavorings in cigars and short and long-term cigar-smoking behaviors, including but not limited to initiation, cessation, intensity of use, and relapse, particularly in diverse cohorts.

Longitudinal associations between exclusive, dual and polytobacco use and respiratory illness among youth.

BACKGROUND: The health consequences of polytobacco use are not well understood. We evaluated prospective associations between exclusive, dual, and polytobacco use and diagnosed bronchitis, pneumonia, or chronic cough among US youth. METHODS: Data came from Waves 1-5 of the Population Assessment of Tobacco and Health Study. We categorized time-varying past 30-day tobacco use into seven categories: (1) non-current use; exclusive use of 2) cigarettes, 3) e-cigarettes, and 4) other combustible products (OC; pipes, hookah, and cigars); dual use of 5) e-cigarettes + cigarettes or e-cigarettes + OC, and 6) cigarettes + OC; and 7) polyuse of all three products. The outcome was parent-reported diagnosis of bronchitis, pneumonia, or chronic cough among youth. We conducted weighted multilevel Poisson models (person n = 17,517, 43,290 observations) to examine the longitudinal exposure-outcome relationship, adjusting for covariates: sex, age, race and ethnicity, parental education, body mass index, secondhand smoke exposure, and household use of combustible products. RESULTS: Compared to nonuse, exclusive cigarette use (Risk Ratio (RR) = 1.83, 95% CI 1.25-2.68), exclusive e-cigarette use (RR = 1.53, 95% CI 1.08-2.15), combustible product + e-cigarette dual use (RR = 1.90, 95% CI 1.18-3.04), cigarettes + OC dual use (RR = 1.96, 95% CI 1.11-3.48), and polytobacco use (RR = 3.06 95% CI 1.67-5.63) were associated with a higher risk of bronchitis, pneumonia, or chronic cough. In additional analyses, we found that the risk ratio for polytobacco use was higher compared to exclusive e-cigarette use (RR 2.01 CI 95% 1.02-3.95), but not higher compared to exclusive cigarette use (RR 1.67 CI 95% 0.85-3.28). CONCLUSION: We found that exclusive, dual, and poly tobacco use were all associated with higher risk of bronchitis, pneumonia, or chronic cough compared to non-current use.

The efficacy of 1-allyloxy-4-propoxybenzene (3c{3,6}) against Varroa destructor mites in honey bee colonies from Maryland, USA.

Varroa destructor Oud (Acari: Varroidae) is a harmful ectoparasite of Apis mellifera L. honey bees causing widespread colony losses in Europe and North America. To control populations of these mites, beekeepers have an arsenal of different treatments, including both chemical and nonchemical options. However, nonchemical treatments can be labor intensive, and Varroa has gained resistance to some conventional pesticides, and the use of other chemical treatments is restricted temporally (e.g., cannot be applied during periods of honey production). Thus, beekeepers require additional treatment options for controlling mite populations. The compound 1-allyloxy-4-propoxybenzene (3c{3,6}) is a diether previously shown to be a strong feeding deterrent against Lepidopteran larvae and a repellent against mosquitoes and showed promise as a novel acaricide from laboratory and early field trials. Here we test the effect of the compound, applied at 8 g/brood box on wooden release devices, on honey bees and Varroa in field honey bee colonies located in Maryland, USA, and using a thymol-based commercial product as a positive control. 3c{3,6} had minimal effect on honey bee colonies, but more tests are needed to determine whether it affected egg production by queens. Against Varroa3c{3,6} had an estimated efficacy of 78.5%, while the positive control thymol product showed an efficacy of 91.3%. 3c{3,6} is still in the development stage, and the dose or application method needs to be revisited.

Transferrin-mediated iron sequestration suggests a novel therapeutic strategy for controlling Nosema disease in the honey bee, Apis mellifera.

Nosemosis C, a Nosema disease caused by microsporidia parasite Nosema ceranae, is a significant disease burden of the European honey bee Apis mellifera which is one of the most economically important insect pollinators. Nevertheless, there is no effective treatment currently available for Nosema disease and the disease mechanisms underlying the pathological effects of N. ceranae infection in honey bees are poorly understood. Iron is an essential nutrient for growth and survival of hosts and pathogens alike. The iron tug-of-war between host and pathogen is a central battlefield at the host-pathogen interface which determines the outcome of an infection, however, has not been explored in honey bees. To fill the gap, we conducted a study to investigate the impact of N. ceranae infection on iron homeostasis in honey bees. The expression of transferrin, an iron binding and transporting protein that is one of the key players of iron homeostasis, in response to N. ceranae infection was analysed. Furthermore, the functional roles of transferrin in iron homeostasis and honey bee host immunity were characterized using an RNA interference (RNAi)-based method. The results showed that N. ceranae infection causes iron deficiency and upregulation of the A. mellifera transferrin (AmTsf) mRNA in honey bees, implying that higher expression of AmTsf allows N. ceranae to scavenge more iron from the host for its proliferation and survival. The suppressed expression levels of AmTsf via RNAi could lead to reduced N. ceranae transcription activity, alleviated iron loss, enhanced immunity, and improved survival of the infected bees. The intriguing multifunctionality of transferrin illustrated in this study is a significant contribution to the existing body of literature concerning iron homeostasis in insects. The uncovered functional role of transferrin on iron homeostasis, pathogen growth and honey bee's ability to mount immune responses may hold the key for the development of novel strategies to treat or prevent diseases in honey bees.

Longitudinal associations between exclusive, dual, and polytobacco use and asthma among US youth.

Little is known about the respiratory health effects of dual (two products) and polytobacco (three or more products) use among youth in the United States. Thus, we followed a longitudinal cohort of youth into adulthood using data from Waves 1-5 (2013-2019) of the Population Assessment of Tobacco and Health Study, examining incident asthma at each follow-up (Waves 2-5). We classified past 30-day tobacco use as 1) no products (never/former use), 2) exclusive cigarettes, 3) exclusive electronic nicotine delivery systems (ENDS), 4) exclusive other combustible (OC) tobacco products (cigars, hookah, pipe), 5) dual cigarettes/OC and ENDS, 6) dual cigarettes and OCs, and 7) polytobacco use (cigarettes, OCs, and ENDS). Using discrete time survival models, we analyzed the incidence of asthma across Waves 2-5, predicted by time-varying tobacco use lagged by one wave, and adjusted for potential baseline confounders. Asthma was reported by 574 of the 9141 respondents, with an average annual incidence of 1.44% (range 0.35% to 2.02%, Waves 2-5). In adjusted models, exclusive cigarette use (HR: 1.71, 95% CI: 1.11-2.64) and dual cigarette and OC use (HR: 2.78, 95% CI: 1.65-4.70) were associated with incident asthma compared to never/former use, while exclusive ENDS use (HR: 1.50, 95% CI: 0.92-2.44) and polytobacco use (HR: 1.95, 95% CI: 0.86-4.44) were not. To conclude, youth who use cigarettes with or without OCs had higher risk of incident asthma. Further longitudinal studies on the respiratory health effects of ENDS and dual/polytobacco use are needed as products continue to evolve.

The Longitudinal Association Between Cigarette Coupon Receipt and Short-term Smoking Cessation Among US Adults.

INTRODUCTION: To help offset the increased price of cigarettes and promote brand loyalty, tobacco companies distribute coupons, particularly to price-sensitive consumers. Few studies, however, have examined the longitudinal association between coupon receipt and smoking cessation. AIMS AND METHODS: Using adult data from waves 1-5 (2013-2019) of the Population Assessment of Tobacco and Health Study, we examined the longitudinal association between coupon receipt and short-term smoking cessation. Multivariable discrete-time survival models were fit to an unbalanced person-period dataset for adult respondents (≥18 years) with current established smoking status at baseline (person n = 9472, risk period n = 29 784). Short-term smoking cessation was measured as discontinued cigarette use (no past 30-day cigarette use at follow-up) and self-reported complete quitting. Coupon receipt was measured as a time-varying exposure, measured in the wave preceding the outcome. Tobacco dependence and time-varying cigarette use intensity were controlled as potential confounders. Effect modification by age, sex, race-ethnicity, and education was assessed by examining interaction terms. RESULTS: We found that adults who received a coupon were 19% less likely to quit smoking compared to adults who did not receive a coupon, adjusting for covariates (adjusted hazard rate [aHR]: 0.81, 95% CI: 0.74-0.89). None of the interaction terms were statistically significant, suggesting that the association between coupon receipt and short-term smoking cessation may not differ across the sociodemographic groups that we examined. CONCLUSIONS: Taken together, our results reveal that coupon receipt reduces the likelihood of short-term smoking cessation, and that this association does not differ by age, sex, race-ethnicity, or education. IMPLICATIONS (97/100): Tobacco companies distribute coupons for tobacco products to price-sensitive customers in the United States, and these coupons can be particularly effective in partly offsetting the impact of a tax increases and promoting brand loyalty. This study provides longitudinal evidence that coupon receipt is associated with a decrease in short-term smoking cessation among US adults who smoke cigarettes after adjusting for covariates and tobacco-related confounders. The findings from this study suggest that coupons are an effective tool for tobacco companies to prevent adults who smoke from quitting, and a national ban on coupons may help to facilitate smoking cessation.

Longitudinal Associations Between Exclusive and Dual Use of Electronic Nicotine Delivery Systems and Cigarettes and Self-Reported Incident Diagnosed Cardiovascular Disease Among Adults.

INTRODUCTION: The cardiovascular health effects of electronic nicotine delivery systems (ENDS) use are not well characterized, making it difficult to assess ENDS as a potential harm reduction tool for adults who use cigarettes. AIMS AND METHODS: Using waves 1-5 of the Population Assessment of Tobacco and Health Study (2013-2019), we analyzed the risk of self-reported incident diagnosed myocardial infarction (MI; 280 incident cases) and stroke (186 incident cases) associated with ENDS and/or cigarette use among adults aged 40 + using discrete time survival models. We employed a time-varying exposure lagged by one wave, defined as exclusive or dual established use of ENDS and/or cigarettes every day or some days, and controlled for demographics, clinical factors, and past smoking history. RESULTS: The analytic samples (MI = 11 031; stroke = 11 076) were predominantly female and non-Hispanic White with a mean age of 58 years. At baseline, 14.2% of respondents exclusively smoked cigarettes, 0.6% exclusively used ENDS, and 1.0% used both products. Incident MI and stroke were rare during follow-up (< 1% at each wave). Compared to no cigarette or ENDS use, exclusive cigarette use increased the risk of MI (aHR 1.99, 95% CI = 1.40-2.84) and stroke (aHR 2.26, 95% CI = 1.51-3.39), while exclusive ENDS use (MI: aHR 0.61, 95% CI = 0.12-3.04; stroke: aHR 1.74, 95% CI = 0.55-5.49) and dual use (MI: aHR 1.84, 95% CI = 0.64-5.30; stroke: aHR 1.12, 95% CI = 0.33-3.79) were not significantly associated with the risk of either outcome. CONCLUSIONS: Compared to non-use, exclusive cigarette use was associated with an increased risk of self-reported incident diagnosed cardiovascular disease over a 5-year period, while ENDS use was not associated with a statistically significant increase in the outcomes. IMPLICATIONS: Existing literature on the health effects of ENDS use has important limitations, including potential reverse causation and improper control for cigarette smoking. We accounted for these issues by using a prospective design and adjusting for current and former smoking status and cigarette pack-years. In this context, we did not find that ENDS use was associated with a statistically significant increase in self-reported incident diagnosed myocardial infarction or stroke over a 5-year period. While more studies are needed, this analysis provides an important foundation and key methodological considerations for future research on the health effects of ENDS use.

The longitudinal association between coupon receipt and established cigarette smoking initiation among young adults in USA.

INTRODUCTION: Tobacco companies frequently distribute coupons for their products. This marketing tactic may be particularly effective among young adults, who tend to be especially price-sensitive. Young adulthood is also a stage during which many individuals initiate established cigarette smoking and are especially vulnerable to the effects of tobacco marketing. METHODS: We used five waves of data from the US Population Assessment on Tobacco and Health Study (2013-2019) to assess the longitudinal relationship between cigarette coupon receipt and initiation of established cigarette smoking among young adults (18-24 years) who did not report current smoking and had smoked <100 cigarettes in their lifetime at baseline. Initiation of established cigarette smoking was defined as reporting current cigarette use and having smoked ≥100 cigarettes at follow-up. To test this relationship, we fit four discrete time survival models to an unbalanced person-period data set. The first model included our time-varying coupon receipt variable, which was lagged one wave. Subsequent models added sociodemographic, cigarette smoking exposure and other tobacco use variables. RESULTS: Adopting the model adjusting for sociodemographic variables, respondents who received a coupon were found to be more likely to initiate established cigarette smoking at follow-up (adjusted HR (aHR): 2.31, 95% CI 1.41 to 3.80). This relationship remained significant when controlling for all covariates in the fully adjusted model (aHR: 1.96, 95% CI 1.18 to 3.26). CONCLUSIONS: These findings show that receiving tobacco coupons may increase the likelihood that young adults will initiate established cigarette smoking, underscoring the need to address the effects of this tobacco marketing tactic.

Public health impact of a US ban on menthol in cigarettes and cigars: a simulation study.

INTRODUCTION: The US Food and Drug Administration most recently announced its intention to ban menthol cigarettes and cigars nationwide in April 2021. Implementation of the ban will require evidence that it would improve public health. This paper simulates the potential public health impact of a ban on menthol in cigarettes and cigars through its impacts on smoking initiation, smoking cessation and switching to nicotine vaping products (NVPs). METHODS: After calibrating an established US simulation model to reflect recent use trends in cigarette and NVP use, we extended the model to incorporate menthol and non-menthol cigarette use under a status quo scenario. Applying estimates from a recent expert elicitation on the behavioural impacts of a menthol ban, we developed a menthol ban scenario with the ban starting in 2021. We estimated the public health impact as the difference between smoking and vaping-attributable deaths and life-years lost in the status quo scenario and the menthol ban scenario from 2021 to 2060. RESULTS: As a result of the ban, overall smoking was estimated to decline by 15% as early as 2026 due to menthol smokers quitting both NVP and combustible use or switching to NVPs. These transitions are projected to reduce cumulative smoking and vaping-attributable deaths from 2021 to 2060 by 5% (650 000 in total) and reduce life-years lost by 8.8% (11.3 million). Sensitivity analyses showed appreciable public health benefits across different parameter specifications. CONCLUSIONS AND RELEVANCE: Our findings strongly support the implementation of a ban on menthol in cigarettes and cigars.

Executive functioning as mediator of the association between traumatic brain injury and prison bullying.

OBJECTIVE: This study examined whether executive functioning (EF) mediated the relationship between childhood traumatic brain injury (TBI) and engaging in bullying in prison (BP). PARTICIPANTS: A sample of male adults in custody in Uruguay (N = 236), drawn from five prisons. METHODS: Inmates filled out self-report questionnaires examining TBI (Head Injury Questionnaire), EF (Behavior Rating Inventory of Executive Function Adult, BRIEF-A) and bullying in prison (Direct and Indirect Prisoner Behavior Checklist - revised, SCALED, DIPC-SCALED-r). RESULTS: Findings showed that TBI was associated with prison bullying after controlling for age, level of education, socioeconomic status, and civil status. The mediation analysis indicated that the relationship between TBI and bullying was fully mediated via executive impairment, especially through the behavioral regulation component (mainly inhibition and emotional control). CONCLUSION: These findings suggested that compensating for EF difficulties in adult inmates with brain injuries might help to decrease the bullying in prison.

Family-Based Behavioral Treatment for Childhood Obesity Implemented in Pediatric Primary Care: A Randomized Clinical Trial.

Importance: Intensive behavioral interventions for childhood overweight and obesity are recommended by national guidelines, but are currently offered primarily in specialty clinics. Evidence is lacking on their effectiveness in pediatric primary care settings. Objective: To evaluate the effects of family-based treatment for overweight or obesity implemented in pediatric primary care on children and their parents and siblings. Design, Setting, and Participants: This randomized clinical trial in 4 US settings enrolled 452 children aged 6 to 12 years with overweight or obesity, their parents, and 106 siblings. Participants were assigned to undergo family-based treatment or usual care and were followed up for 24 months. The trial was conducted from November 2017 through August 2021. Interventions: Family-based treatment used a variety of behavioral techniques to develop healthy eating, physical activity, and parenting behaviors within families. The treatment goal was 26 sessions over a 24-month period with a coach trained in behavior change methods; the number of sessions was individualized based on family progress. Main Outcomes and Measures: The primary outcome was the child's change from baseline to 24 months in the percentage above the median body mass index (BMI) in the general US population normalized for age and sex. Secondary outcomes were the changes in this measure for siblings and in BMI for parents. Results: Among 452 enrolled child-parent dyads, 226 were randomized to undergo family-based treatment and 226 to undergo usual care (child mean [SD] age, 9.8 [1.9] years; 53% female; mean percentage above median BMI, 59.4% [n = 27.0]; 153 [27.2%] were Black and 258 [57.1%] were White); 106 siblings were included. At 24 months, children receiving family-based treatment had better weight outcomes than those receiving usual care based on the difference in change in percentage above median BMI (-6.21% [95% CI, -10.14% to -2.29%]). Longitudinal growth models found that children, parents, and siblings undergoing family-based treatment all had outcomes superior to usual care that were evident at 6 months and maintained through 24 months (0- to 24-month changes in percentage above median BMI for family-based treatment and usual care were 0.00% [95% CI, -2.20% to 2.20%] vs 6.48% [95% CI, 4.35%-8.61%] for children; -1.05% [95% CI, -3.79% to 1.69%] vs 2.92% [95% CI, 0.58%-5.26%] for parents; and 0.03% [95% CI, -3.03% to 3.10%] vs 5.35% [95% CI, 2.70%-8.00%] for siblings). Conclusions and Relevance: Family-based treatment for childhood overweight and obesity was successfully implemented in pediatric primary care settings and led to improved weight outcomes over 24 months for children and parents. Siblings who were not directly treated also had improved weight outcomes, suggesting that this treatment may offer a novel approach for families with multiple children. Trial Registration: ClinicalTrials.gov Identifier: NCT02873715.

Young people's online communication and its association with mental well-being: results from the 2019 student health and well-being survey.

BACKGROUND: Online communication has become an integral aspect of daily life for young people internationally. Very little research has examined whether the association between social media use and well-being depends on who young people engage with (i.e. real, or virtual friendships). METHODS: Data were drawn from a subsample of students (N = 38,736) who took part in the School Health Research Network (SHRN) 2019 Student Health and Well-being (SHW) survey. A series of multivariable regression models were used to assess the association between who adolescents were communicating with online and well-being, controlling for confounders: passive social media use; friendship quality; and cyberbullying. We also tested whether these associations were modified based on gender. RESULTS: Students are highly engaged on social networking sites, and these sites are used to communicate with existing friendship groups and develop virtual friendships. Frequent online communication with best friends (b = .340, p < .001) and bigger friendship groups (b = .397; p < .001) was associated with higher levels of well-being. However, the frequency of online contact with virtual friends made online was negatively and significantly associated with well-being (b = -.760; p < .001), with a larger negative association for girls than boys. CONCLUSIONS: Online communication with virtual friendship networks were associated with lower mental well-being, with stronger associations for girls than boys; however, frequent online communication with 'real' friends was associated with better well-being. Our results indicate the importance of considering the nature of adolescent online communication, rather than just its quantity, in developing interventions to improve adolescent well-being.

A longitudinal study of menthol cigarette use and smoking cessation among adult smokers in the US: Assessing the roles of racial disparities and E-cigarette use.

Using nationally representative longitudinal data from Wave 1 to Wave 4 of the Population Assessment of Tobacco and Health Study in the United States, we examined whether the association between menthol cigarette use and smoking cessation was modified by race/ethnicity and e-cigarette use. Multivariable discrete-time survival models were fit to an unbalanced person-period data set (person n = 7423, risk period n = 18,897) for adult respondents (ages 25+) who were current established cigarette smokers at baseline. We found that adults who smoke menthol cigarettes had lower odds of smoking cessation, but the effect was modified by race/ethnicity as non-Hispanic (NH) Black menthol smokers had lower odds of quitting smoking than NH White or Hispanic menthol smokers. We also found that e-cigarette use was associated with higher odds of smoking cessation among both menthol and non-menthol smokers, but the association was stronger among menthol smokers. Our results suggest that a menthol smoking ban may have a favorable impact on smoking cessation for NH Black adults. In addition, our results also suggest that a menthol smoking ban may be more effective if menthol smokers have access to e-cigarettes as a way to quit cigarette use.