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Technology-based gambling prevalence is not well understood since relevant questions are not included in health and disease surveillance studies. The current study sought to estimate the prevalence of internet-based and smartphone app-based gambling, along with casino gambling, in a sample of U.S. young adults and determine if gambling modality was associated with problem gambling symptoms or substance use. The 2022 Rhode Island Young Adult Survey included N = 1,022 students between the ages of 18 to 25 years old who had lived in Rhode Island, with n = 414 lifetime gamblers (40.5%) included in this study. Odds of gambling via a smartphone app and on the internet, respectively, were greater in heterosexual cis-males compared to heterosexual cis-females (OR[95%CI] = 3.14 [1.25,7.91]; OR[95%CI] = 6.30 [2.05,19.3]). Internet gambling amongst employed students was less common than among those who were not a student and not employed (OR[95%CI] = 0.25 [0.06,1.00]). Odds of problem gambling symptoms were higher among those who gambled via a smartphone app (OR[95%CI] = 3.23 [1.21,8.60]). All forms of gambling were associated with alcohol consumption, although the strength of the association was stronger in app and internet gamblers. Casino gamblers were more likely to be high risk marijuana and illicit drug users. The rising availability of app gambling coupled with its social, psychological, and cultural context may presents an alternative pathway to problem gambling. Bans on internet gambling and/or strict guidelines on the frequency of wagers and cash placed per wager, should be considered as viable methods to mitigate associated consequences., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Little is known about the consequences of substance-related advertising on driving under the influence of alcohol (DUIA) or cannabis (DUIC). This study seeks to estimate associations between substance-related digital advertising exposures and DUIA and DUIC in a sample of young adults., Method: The Rhode Island Young Adult Survey 2022 was a cross-sectional web-based survey of 1,022 adults ages 18-25 years. Analyses were conducted among lifetime alcohol users ( n = 824) and lifetime cannabis users ( n = 471). Prevalence of past-30-day digital ad exposure to alcohol and cannabis was assessed, as well as the prevalence of past-month DUIA and DUIC. Multivariable logistic regressions examined the association between digital ad exposure and substance use among lifetime users, and ad exposure and DUI among current users., Results: In all, 54.4% of participants reported past-30-day exposure to digital alcohol advertising, and 33.5% reported exposure to digital cannabis advertising. Exposure to social media alcohol advertising was associated with higher odds of DUIA after adjustment for sociodemographic variables (odds ratio [95% CI] = 2.14 [1.07, 4.28]) but not after accounting for frequency of use. Odds of DUIC remained significantly higher for those exposed to app-based cannabis advertising after adjusting for sociodemographic variables (odds ratio [95% CI] = 4.36 [1.76, 10.8]) and frequency of use (odds ratio [95% CI] = 3.96 [1.53, 10.2])., Conclusions: Since social media alcohol ad exposure may be indirectly linked with DUIA, and app-based cannabis ad exposure may be directly linked to frequency of use and DUIC, legislators should consider comprehensive substance-related ad regulations and bans., Competing Interests: The authors declare that they have no conflicts of interest.

Proteins with a pierced lasso topology (PLT) have a covalent loop created by a disulfide bond, and the backbone circles back to thread the loop. This threaded topology has unique features compared to knotted topologies; notably, the topology is controlled by the chemical environment and the covalent loop remains intact even when denatured. In this work, we use the hormone leptin as our model PLT system and study its folding using molecular dynamics simulations that employ a structure-based (Go̅-like) model. We find that the reduced protein has a two-state folding mechanism with a transition state ensemble (TSE) that can be characterized by the reaction coordinate Q , the fraction of native contacts formed. In contrast, the oxidized protein, which must thread part of the polypeptide chain through a covalent loop, has a folding process that is poorly characterized by Q . Instead, we find that a topological coordinate that monitors the residue crossing the loop can identify the TSE of oxidized leptin. By precisely identifying the predicted TSE, one may now reliably calculate theoretical phi-values for the PLT protein, thereby enabling a comparison with experimental measurements. We find the loop-threading constraint leads to noncanonical phi-values that are uniformly small because this PLT protein has a flat energy landscape through the TSE.

Youth who are lesbian, gay, bisexual, and who identify with other sexual orientations (LGB+) are at higher risk for illicit drug use and have higher rates of mental illness. The current study examined the prevalence of illicit drug use among LGB+ persons and assessed the moderating effect of mental illness. Cross-sectional data from the 2015, 2017, and 2019 Youth Risk Behavioral Surveillance System were aggregated. The outcome was any reported use of cocaine, inhalants, heroin, methamphetamines, ecstasy, or hallucinogens. The primary exposure was self-reported sexual orientation category (i.e., heterosexual, gay/lesbian, bisexual, not sure). Self-reported depressive symptoms were tested as a moderator. Logistic regression models assessed main and interactive effects. Gay or lesbian students [AOR=1.87 95%CI: 1.45,2.43], bisexual students [AOR=2.07 95%CI: 1.77,2.42], and those unsure of their sexual orientation [AOR=1.99 95%CI: 1.65,2.39] had increased odds of illicit drug use. Odds were higher among LGB+ youth who did not have depressive symptoms (p<0.001). Odds of illicit substance use was significantly greater in youth identifying as gay and lesbian, bisexual, and students who were not sure about their sexual orientation and among LGB+ youth without depressive symptoms. Targeted, but non-stigmatizing, prevention programs are needed., Competing Interests: Disclosure Statement The authors report no conflicts of interest.

Objective: Existing literature on driving under the influence during adolescence is sparse, especially for driving after the use of non-medical prescription drugs (DAP). This study examines the prevalence of driving after use of alcohol (DAA), cannabis (DAC), and DAP, and examines the role of several potential risk and protective factors., Methods: This was a secondary analysis of the 2022 Rhode Island Study Survey, a cross-sectional survey of middle and high school students. Separate multivariable regressions were conducted for each outcome among lifetime users for each substance, controlling for current substance use, individual-, perceived parental-, and perceived friend-substance use risk perception, age, sexual/gender minority (SGM) status, race, ethnicity, school level, and town poverty level., Results: Among lifetime users of alcohol ( n  = 3849), cannabis ( n  = 2289), and non-medical prescription drugs ( n  = 611), the prevalence of DAA, DAC, and DAP was 4.9, 14.3, and 16.9%, respectively. Current substance use, high individual risk perception, being nonwhite, and being Hispanic were risk factors for DAA while perceiving parent's risk perception as negative and being heterosexual cisgender-female were protective. Current substance use, negative individual risk perception, and being nonwhite were risk factors for DAC while perceiving parent's risk perception as negative and being in high school were protective. Current substance use and older age were risk factors for DAP while perceiving parent's risk perception as negative and perceiving friend's risk perception as negative were protective., Conclusions: Driving under the influence is a concern among adolescent substance users. Current substance use and perceived parental risk perception as negative are common risks and protective factors, respectively. Findings suggest substance-specific, heterogeneous interventions are needed. For example, interventions focusing on peer perceptions are most relevant for DAP, while shifting personal perceptions of harm are most relevant for DAC.

Aims: To estimate the use of home alcohol delivery and other methods of obtaining alcohol, rates of ID checking for home alcohol delivery purchases, and associations with alcohol-related consequences., Methods: Surveillance data from 784 lifetime drinkers participating in the 2022 Rhode Island Young Adult Survey were used. The method of obtaining alcohol (e.g. type of purchase, gifted, theft) was assessed. The Alcohol Use Disorders Identification Test, Brief Young Adults Alcohol Consequences Questionnaire, and a drinking and driving question were used to measure high-risk drinking behaviors, experiencing negative alcohol questions, and history of drinking and driving. Logistic regression models adjusting for sociodemographic variables were used to estimate main effects., Results: About 7.4% of the sample purchased alcohol through a home delivery or to-go purchase; 12.1% of participants who obtained alcohol this way never had their ID checked during the purchase attempt, and 10.2% of these purchases were completed by participants under the legal purchase age. Home delivery/to-go purchases were associated with high-risk drinking. Alcohol theft was associated with high-risk drinking, experiencing negative alcohol consequences, and drinking and driving., Conclusions: Home alcohol delivery and to-go purchases may provide an opportunity for underage access to alcohol, but their current use as a method of obtaining alcohol is rare. Stronger ID checking policies are needed. Alcohol theft was linked to several negative alcohol outcomes, and home-based preventive interventions should be considered., (© The Author(s) 2023. Medical Council on Alcohol and Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Depression and anxiety contribute to the burden of disease among college students. The current study determined if depressive and anxiety symptoms were more prevalent in first generation students and if social and emotional support moderated this relationship. Methods: Depressive and anxiety symptoms were measured in 432 U.S. college students via an online survey. Single items determined student generation status and available social support. The CES-D10 and GAD-7 measured depression and anxiety, respectively. Structural equation modeling was used to identify significant effects. Results:  First generation status was associated with increased cognitive-emotional ( p  = 0.036) and somatic ( p  = 0.013) anxiety symptoms, but not depression. High social and emotional support appeared to suppress somatic anxiety symptoms experienced by first generation students ( p  = 0.004). Conclusions: Greater anxiety symptoms in first generation students may be due to increased general and acculturative stress, although more research is needed. Large national surveys of college students should consider adding a question about first generation status.

Background: Numerous states in the USA have legalized sports betting due to recent legal decisions by the US Supreme Court. Here, sociodemographic correlates of current gambling and specific gambling activities associated with symptoms of gambling problems were identified., Methods: Cross-sectional data were obtained from the 2020 Rhode Island Young Adult Survey (RIYAS). RIYAS participants (n = 540) were a convenience sample of 18 to 25 year olds who lived in Rhode Island for at least part of 2020. Data were collected from May to October 2020. Four gambling activities were assessed (i.e. sports betting; betting on races; gaming tables at a casino; poker machines at a casino). Logistic regression models assessed main effects., Results: 22.4% engaged in one or more gambling activities. 11.5% of participants had any gambling problems. Odds of gambling activities were higher among men; Black, Indigenous, People of Color; older young adults; and essential workers. Odds of gambling problems were 2.4 times higher among participants who engaged with sports betting., Conclusions: Gambling activities are common among several population subgroups, and participation in sports betting may be a risk factor for the development of problem gambling. Comprehensive prevention policies are needed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: The purpose of the current study was to estimate prevalence of pornography use and addiction in Rhode Island young adults, identify sociodemographic disparities, and determine if use and addiction were associated with mental illness., Methods: Data from n=1022 participants of the Rhode Island Young Adult Survey were used. Pornography use and addiction, depression, anxiety, and suicide ideation were assessed. Multivariable logistic regressions controlled for age, social status, sex, gender, sexual orientation, and race/ethnicity., Results: 54% indicated pornography use; 6.2% met the criteria for addiction. Odds of pornography use were 5 times higher (95%CI=3.18,7.71), and addiction 13.4 times higher (95%CI=5.71,31.4) among heterosexual cis-males. Pornography addiction was associated with increased odds of depression (OR=1.92, 95%CI=1.04,3.49) and suicide ideation (OR=2.34, 95%CI=1.24,4.43)., Conclusions: Pornography use is highly prevalent, and addiction may be associated with mental illness. New screenings, media literacy training, and developing new therapeutic interventions should be considered.

Objectives: This study examined the association between loss of a loved one to COVID-19 and depression, anxiety and suicide ideation among Rhode Island young adults., Methods: The 2022 Rhode Island Young Adult Survey recruited 1,022 young adults aged 18-25 years who lived in Rhode Island. Logistic regression models were used to estimate the odds of depression, anxiety, and suicide ideation due to experiencing a loss due to COVID-19., Results: The odds of anxiety and suicide ideation were 57% (OR[95% CI] = 1.57 [1.13, 2.18]) and 79% (OR[95% CI] = 1.79 [1.19, 2.70]) greater among participants who lost a close friend or family member due to COVID-19., Conclusions: Losing a loved one to COVID-19 increases the risk of anxiety or suicide ideation among young adults in RI. Prevention measures such as screening for mental health symptoms and incorporating mental health awareness into college, university and workplace settings should be instituted.

Objectives: This study aimed to identify individual and relational risk factors for suicide ideation among students enrolled in 2- and 4-year colleges., Methods: A cross-sectional analysis was conducted using N=685 college students from the 2022 Rhode Island Young Adult Survey., Results: 13.7% (N = 94) reported suicide ideation, 7.6% (N = 52) reported making a suicide plan, and 3.2% (N = 22) reported at least one suicide attempt. Sexual and gender minorities had 300% (95%CI: 47%, 987%) increased odds relative to cisgender heterosexual males, students living on campus had 56% (95%CI: 79%, 10%) lower odds compared to those living off campus with a parent, and students with insomnia had 156% (57%, 320%) increased odds of suicide ideation., Conclusions: Interventions to 1) cultivate identity- affirming communities for sexual and gender minority students, 2) create a sense of belonging for students living off campus, and 3) improve sleep health are needed.

Objectives: This study examined the association between racial discrimination and depressive symptoms among Rhode Island young adults., Methods: The 2022 Rhode Island Young Adult Survey recruited 1,022 young adults aged 18-25 years who lived in Rhode Island for at least part of the year. Multivariable logistic regression for depressive symptoms controlled for sexual and gender identity, race/ethnicity, social status, age, employment, and student status., Results: 23.6% of young adults reported experiencing racial discrimination in childhood and/or adulthood. Odds of depressive symptoms increased for experiences of childhood racial discrimination (+70%; 95%CI: 14%, 155%) and any racial discrimination (+56%; 95%CI: 6%, 130%), but not for racial discrimination in adulthood (+38%; 95%CI: -8%, 108%)., Conclusions: Experiences of racial discrimination increase odds of depressive symptoms among young adults. Prevention measures such as universal screening for childhood adversity, incorporating antiracism education into all institutional settings, and continued nondiscrimination policy and enforcement should be employed.

Background: Smartphone addiction is a rising problem in the United States. The current study estimated the prevalence of smartphone addiction in Rhode Island young adults and its associations with mental illness., Methods: The 2022 Rhode Island Young Adult Survey measured smartphone addiction, depression, anxiety, and suicide ideation. Covariates included age, sex/gender minority status, race/ethnicity, and social status., Results: The prevalence of smartphone addiction was 34%. Odds of experiencing depression (OR[95%CI]=2.69 [2.05,3.52]), anxiety (OR[95%CI]=2.06 [1.58,2.69]), and suicide ideation (OR[95%CI]=1.55 [1.08,2.20]) were greater in participants with smartphone addiction. The relationship between smartphone addiction and depression was strongest in heterosexual cis-males (OR[95%CI] = 8.45 [3.53, 20.3])., Discussion: Smartphone addiction is prevalent among Rhode Island's young adults and may be associated with depression, anxiety, and suicide ideation. Heterosexual cis-males may be particularly vulnerable. Screening programs and interventions to reduce smartphone use for all young adults, and particularly young men, should be considered.

Objectives: This study examined sociodemographic disparities in traumatic brain injury (TBI), and the association between TBI and substance misuse among young adults in Rhode Island., Methods: Among this sample of N=1,022 from the 2022 Rhode Island Young Adult Survey, multivariable logistic regressions were used to examine both study objectives., Results: Black, Asian, and Hispanic young adults had 77% (95%CI: 26%, 93%), 79% (95%CI: 32%, 94%), and 58% (95%CI: 31%, 75%) lower odds of brain injury, respectively, compared to White, non-Hispanic young adults. Those having experienced brain injury were more likely to engage in hazardous alcohol use (p = 0.003), hazardous marijuana use (p < 0.001), and illicit drug use (p = 0.003), but not OTC or prescription drug misuse., Conclusions: There is a pressing need for integrated, large-scale, multidisciplinary programs with a well-trained workforce to address TBI and substance misuse in various medical settings for behavioral health and emergency care.

Objective: Research on COVID-19's effect on substance use is mixed, and few studies have focused on adolescents. We assessed whether implementation of the COVID-19 lockdown affected substance use and changed perceptions of psychoactive substance availability in middle and high school students., Methods: We assessed self-reported use and perceived availability of alcohol, tobacco cigarettes, electronic cigarettes, marijuana, synthetic marijuana, nonprescribed prescription drugs, and illicit drugs (heroin, inhalants) among middle and high school respondents aged 11-18 years to the Rhode Island Student Survey (N = 17 751). An administrative pause because of COVID-19 lockdowns allowed us to divide results into surveys completed before (January through March 2020; n = 13 259) and after (November 2020 through May 2021; n = 4492) the lockdown implementation. We determined the effects of the COVID-19 lockdown using logistic regression models, adjusting for age, gender/sexual orientation, middle/high school level, and city/town classification., Results: After the COVID-19 lockdown implementation, the odds of respondents using psychoactive substances decreased, with the largest decreases occurring for prescription drugs (odds ratio [OR] = 0.39; 95% CI, 0.28-0.54) and inhalants (OR = 0.37; 95% CI, 0.26-0.53). The odds of respondents perceiving difficulties in obtaining psychoactive substances significantly increased after lockdown implementation, with the largest increases occurring for prescription drugs (OR = 1.53; 95% CI, 1.39-1.69) and illicit drugs (OR = 1.65; 95% CI, 1.44-1.88)., Conclusions: COVID-19 lockdown implementation was associated with a decreased perception of availability of psychoactive substances and use of psychoactive substances. Decreases in substance use may be because of decreased perceived availability and increased parental support and oversight. Interventions that focus on parental oversight and strengthened policies to disrupt the licit and illicit drug markets are needed.

Background: Children with disabilities may be at increased risk for engaging in health risk behaviors compared to their peers without disabilities., Objective: This secondary analysis aims to assess if Individualized Education Program (IEP) status, a proxy for having a disability, is a risk factor for youth to engage in health risk behaviors such as alcohol use, marijuana use, other substance use, bullying or cyberbullying victimization, and sexual activity., Methods: Data from Connecticut Youth Risk Behavior Surveillance System (YRBSS) 2013, 2015, 2017, and 2019 were combined for a representative sample of 9243 students, 850 reporting having an IEP. Having a disability was measured by an item that asked if participants received special education services as part of an IEP. Logistic regression that accounted for the YRBSS sample design was used to assess main effects., Results: Having an IEP significantly predicted the likelihood of being bullied (OR = 1.81), cyberbullied (OR = 1.49), and other drug use (OR = 1.65), but did not predict engaging in sexual activity., Conclusions: Students with disabilities in CT, as defined by the receipt of special education services as specified on an IEP, are at increased risk to engage in health risk behaviors than are students without disabilities during their high school years. Further analyses and comparisons across sites, years, and type of disability are limited as there is no current item on the national YRBSS questionnaire that measures a participant's special education status or disability status., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Eps15-homology domain containing proteins (EHDs) are eukaryotic, dynamin-related ATPases involved in cellular membrane trafficking. They oligomerize on membranes into filaments that induce membrane tubulation. While EHD crystal structures in open and closed conformations were previously reported, little structural information is available for the membrane-bound oligomeric form. Consequently, mechanistic insights into the membrane remodeling mechanism have remained sparse. Here, by using cryo-electron tomography and subtomogram averaging, we determined structures of nucleotide-bound EHD4 filaments on membrane tubes of various diameters at an average resolution of 7.6 Å. Assembly of EHD4 is mediated via interfaces in the G-domain and the helical domain. The oligomerized EHD4 structure resembles the closed conformation, where the tips of the helical domains protrude into the membrane. The variation in filament geometry and tube radius suggests a spontaneous filament curvature of approximately 1/70 nm -1 . Combining the available structural and functional data, we suggest a model for EHD-mediated membrane remodeling., (© 2022. The Author(s).)

Mitochondrial cristae membranes are the oxidative phosphorylation sites in cells. Crista junctions (CJs) form the highly curved neck regions of cristae and are thought to function as selective entry gates into the cristae space. Little is known about how CJs are generated and maintained. We show that the central coiled-coil (CC) domain of the mitochondrial contact site and cristae organizing system subunit Mic60 forms an elongated, bow tie-shaped tetrameric assembly. Mic19 promotes Mic60 tetramerization via a conserved interface between the Mic60 mitofilin and Mic19 CHCH (CC-helix-CC-helix) domains. Dimerization of mitofilin domains exposes a crescent-shaped membrane-binding site with convex curvature tailored to interact with the curved CJ neck. Our study suggests that the Mic60-Mic19 subcomplex traverses CJs as a molecular strut, thereby controlling CJ architecture and function.

Objectives: Gambling is a prevalent behavior associated with numerous consequences. The purpose of the current study was to assess the prevalence of gambling and problem gambling in Rhode Island young adults and to identify sociodemographic correlates of gambling., Methods: Data from n=546 participants of the Rhode Island Young Adult Survey were used. Twelve types of gambling behaviors, and problem gambling, were assessed. Sociodemographic variables included age, race/ethnicity, gender, sexual orientation, social status, education, employment, and essential worker status., Results: The prevalence of any gambling was 62.3%, and odds of any gambling was 57% higher (95%CI = 1.08,2.27) among essential workers. The prevalence of problem gambling was 11.4%, and the odds were 3.6 times higher (95%CI = 1.32, 9.86) among persons who are transgender., Conclusions: The prevalence of gambling and problem gambling are high among Rhode Island's young adults. Implementing programmatic and regulatory measures to prevent and treat problem gambling are vital.

Objectives: There is limited data available specific to young adult tobacco use in Rhode Island. This study examines whether young adult cigarette and e-cigarette use varies by sociodemographics, mental health, and use of other substances., Methods: This cross-sectional web-based survey was administered during the COVID-19 pandemic, from May to October 2020., Results: A total of 12.9% of young adults reported current cigarette or e-cigarette use. Young adults who currently used cigarettes or e-cigarettes were more likely to be white, non-Hispanic, younger, and have depressive symptoms, a depression diagnosis, suicide ideation, engage in harmful drinking, alcohol dependence, current marijuana use, and frequent marijuana use., Conclusions: To address the needs of disproportionately affected young adults, steps must be taken to integrate comprehensive, barrier-free, widely promoted coverage of tobacco cessation treatment in all behavioral healthcare settings.

Objectives: Use of telehealth for behavioral health services has increased since the start of the COVID-19 pandemic. This study examines which young adults in Rhode Island were using these telehealth services and are interested in its use., Methods: This cross-sectional web-based survey was administered in the midst of the COVID-19 pandemic, from May to October 2020., Results: Results suggest sexual and gender minorities and those with low social status were more likely to access these services, highlighting its effectiveness at reaching disadvantaged young adults. Those with mental health symptoms were more likely to utilize telehealth, but those with substance use were not., Conclusions: There is a missed opportunity to target substance use telehealth services to this willing and interested population. Continued coverage and use of telehealth for mental health and substance use services is essential in breaking down barriers to care for young adults in Rhode Island.

Applying simulations with structure-based G o ¯ - like models has proven to be an effective strategy for investigating the factors that control biomolecular dynamics. The common element of these models is that some (or all) of the intra/inter-molecular interactions are explicitly defined to stabilize an experimentally determined structure. To facilitate the development and application of this broad class of models, we previously released the SMOG 2 software package. This suite allows one to easily customize and distribute structure-based (i.e., SMOG) models for any type of polymer-ligand system. The force fields generated by SMOG 2 may then be used to perform simulations in highly optimized MD packages, such as Gromacs, NAMD, LAMMPS, and OpenMM. Here, we describe extensions to the software and demonstrate the capabilities of the most recent version (SMOG v2.4.2). Changes include new tools that aid user-defined customization of force fields, as well as an interface with the OpenMM simulation libraries (OpenSMOG v1.1.0). The OpenSMOG module allows for arbitrary user-defined contact potentials and non-bonded potentials to be employed in SMOG models, without source-code modifications. To illustrate the utility of these advances, we present applications to systems with millions of atoms, long polymers and explicit ions, as well as models that include non-structure-based (e.g., AMBER-based) energetic terms. Examples include large-scale rearrangements of the SARS-CoV-2 Spike protein, the HIV-1 capsid with explicit ions, and crystallographic lattices of ribosomes and proteins. In summary, SMOG 2 and OpenSMOG provide robust support for researchers who seek to develop and apply structure-based models to large and/or intricate biomolecular systems., (© 2021 The Protein Society.)

Background: Exposure to alcohol marketing is positively associated with alcohol consumption. However, few research studies have tested alcohol marketing's effect on other alcohol-related outcomes. Consequently, the current study sought to identify associations between exposure to alcohol marketing and alcohol-related consequences in young adults. Methods: A secondary analysis of the 2020 Rhode Island Young Adult Survey was conducted. Participants were lifetime drinkers (n = 390) who were 18 to 25 years old and lived in Rhode Island for at least part of 2020. Past 30 day exposure to 6 forms of alcohol marketing was assessed. Alcohol consequences were measured using 8 items from the Brief Young Adult Alcohol Consequences Questionnaire. Logistic regression models were adjusted for AUDIT score, age, race/ethnicity, gender, sexual orientation, employment status, and enrollment in school. Results: 92.3% of participants reported past 30 days exposure to any form of alcohol marketing. 43.6% of participants reported experiencing any alcohol-related consequence. Exposure to any form of alcohol marketing was positively associated with experiencing alcohol-related consequences (OR[95% CI] = 3.35 [1.19, 9.44]). After disaggregation by marketing type, only television exposure remained significantly associated with alcohol-related consequences (OR[95% CI] = 1.85 [1.06, 3.24]). Conclusions: Exposure to alcohol advertising on television may be positively associated with experiencing negative alcohol consequences in young adults. If confirmed, the findings may renew interest in strengthening alcohol marketing guidelines and regulations.

This study documents disparities in the mental health burden of young adults in Rhode Island during the COVID-19 pandemic as it pertains to essential worker status, sexual orientation, gender identity, and childhood trauma. A cross-sectional web-based survey of young adults aged 18 to 25 years conducted between May and October of 2020 assessed anxiety symptoms, depressive symptoms, and thoughts of suicide. In fully adjusted regression models, (n =528 young adults) being an essential worker, a sexual minority, having lower relative SES, and having more adverse childhood experiences were significantly associated with negative mental health outcomes. In models adjusted for individual ACEs, exposure to mental illness in the household, physical violence between adults in the household, emotional abuse, and sexual abuse were independently associated with all three outcomes. Young adults most vulnerable and stigmatized in the community are also those who are most severely affected in terms of mental health.

Dynamin belongs to the large GTPase superfamily, and mediates the fission of vesicles during endocytosis. Dynamin molecules are recruited to the neck of budding vesicles to assemble into a helical collar and to constrict the underlying membrane. Two helical forms were observed: the one-start helix in the constricted state and the two-start helix in the super-constricted state. Here we report the cryoEM structure of a super-constricted two-start dynamin 1 filament at 3.74 Å resolution. The two strands are joined by the conserved GTPase dimeric interface. In comparison with the one-start structure, a rotation around Hinge 1 is observed, essential for communicating the chemical power of the GTPase domain and the mechanical force of the Stalk and PH domain onto the underlying membrane. The Stalk interfaces are well conserved and serve as fulcrums for adapting to changing curvatures. Relative to one-start, small rotations per interface accumulate to bring a drastic change in the helical pitch. Elasticity theory rationalizes the diversity of dynamin helical symmetries and suggests corresponding functional significance., (© 2021. The Author(s).)

Introduction: Alcohol advertising is prevalent on social media. The current study sought to identify effective message types to pair with social media alcohol ads to minimise purchase intentions associated with exposure., Methods: A 6 (within) × 5 (between) randomised controlled experiment was conducted with n = 723 US participants. Participants viewed six unique social media alcohol ads and were randomised to view one of four message types (i.e. pro-drinking comments, anti-drinking comments, industry responsibility messages and health warning labels) associated with the ads or the control (i.e. no messages). Purchase intentions were measured after each ad exposure. Significant main and interactive effects were determined by two-level, random intercept hierarchical linear models., Results: Purchase intentions were significantly lower among participants who viewed anti-drinking comments relative to the control (P = 0.022) and warning labels (P = 0.016). Purchase intentions were significantly greater among participants who viewed pro-drinking comments and had a family history of alcohol use (P = 0.032) and among those who viewed warning labels and were previously exposed to alcohol depictions through family and friends' social media posts (P = 0.033)., Discussion and Conclusions: Anti-drinking messages, written by social media users, may be effective at reducing alcohol purchase intentions when posted as social media comments. Current industry responsibility messages had no effect, and caution may be needed if warning labels are applied to ads in this medium., (© 2021 Australasian Professional Society on Alcohol and other Drugs.)

Dynamin oligomerizes into helical filaments on tubular membrane templates and, through constriction, cleaves them in a GTPase-driven way. Structural observations of GTP-dependent cross-bridges between neighboring filament turns have led to the suggestion that dynamin operates as a molecular ratchet motor. However, the proof of such mechanism remains absent. Particularly, it is not known whether a powerful enough stroke is produced and how the motor modules would cooperate in the constriction process. Here, we characterized the dynamin motor modules by single-molecule Förster resonance energy transfer (smFRET) and found strong nucleotide-dependent conformational preferences. Integrating smFRET with molecular dynamics simulations allowed us to estimate the forces generated in a power stroke. Subsequently, the quantitative force data and the measured kinetics of the GTPase cycle were incorporated into a model including both a dynamin filament, with explicit motor cross-bridges, and a realistic deformable membrane template. In our simulations, collective constriction of the membrane by dynamin motor modules, based on the ratchet mechanism, is directly reproduced and analyzed. Functional parallels between the dynamin system and actomyosin in the muscle are seen. Through concerted action of the motors, tight membrane constriction to the hemifission radius can be reached. Our experimental and computational study provides an example of how collective motor action in megadalton molecular assemblies can be approached and explicitly resolved., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Membrane remodeling and repair are essential for all cells. Proteins that perform these functions include Vipp1/IM30 in photosynthetic plastids, PspA in bacteria, and ESCRT-III in eukaryotes. Here, using a combination of evolutionary and structural analyses, we show that these protein families are homologous and share a common ancient evolutionary origin that likely predates the last universal common ancestor. This homology is evident in cryo-electron microscopy structures of Vipp1 rings from the cyanobacterium Nostoc punctiforme presented over a range of symmetries. Each ring is assembled from rungs that stack and progressively tilt to form dome-shaped curvature. Assembly is facilitated by hinges in the Vipp1 monomer, similar to those in ESCRT-III proteins, which allow the formation of flexible polymers. Rings have an inner lumen that is able to bind and deform membranes. Collectively, these data suggest conserved mechanistic principles that underlie Vipp1, PspA, and ESCRT-III-dependent membrane remodeling across all domains of life., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Alcohol marketing has proliferated on social media. When exposed to social media advertisements, users view comments written in response to the ad and user engagement metrics, in addition to the ad itself. Here, the independent effect of different types of comments on alcohol craving was assessed. Methods: In all, n  = 722 participants were randomized to view either no comments, pro-drinking comments, anti-drinking comments, warning labels, or industry responsibility messages associated with six alcohol ads. Alcohol cravings, measured using the Desires for Alcohol Questionnaire (DAQ), were assessed before and after ad exposure. Smoking urges were also assessed. The significance of main effects was determined using repeated-measures ANCOVA. Results: Warning labels significantly decreased scores on the desires and intentions to drink DAQ sub-scale ( p = .025) and decreased smoking urges ( p = .024). Pro-drinking comments significantly increased scores on the control of drinking sub-scale ( p = .006). Conclusions: The findings suggest that user-generated comments can influence the desire to drink and smoking urges, beyond the effects of ads themselves. If so, alcohol warning labels may decrease alcohol cravings when used in this way. Additionally, to limit the loss of control over drinking, the ability of social media users to post pro-drinking comments may need to be curtailed.

The study sought to determine participants' preferred methods for self-reporting biological sex, gender identity, and sexual orientation in national surveillance studies. An online, cross-sectional survey was conducted with n = 255 adults, 18 years old or older and currently living in the US. After completing a series of questions and question sets related to biological sex, gender identity, and sexual orientation, participants were asked which question or question set they preferred to use to identify their identifying characteristic. Two "no preference options," one stating that all the questions were good and another stating that all the questions were bad, were included as response options. A majority (53.8%) preferred "What sex were you at birth?" to identify their biological sex. A plurality (42.3%) preferred "Are you male, female, or transgender?" to identify their gender identify. For sexual orientation, there were no clear question preferences. Biological sex question preference significantly differed by age ( p = .001) and political affiliation ( p = .01). Gender identity question preference significantly differed by marital status ( p = .006) and political affiliation ( p = .005). The results suggest there may be disagreement in question preference in self-reporting biological sex, gender identity, and sexual orientation in surveillance systems. More research is needed.

Leptin is an important signaling hormone, mostly known for its role in energy expenditure and satiety. Furthermore, leptin plays a major role in other proteinopathies, such as cancer, marked hyperphagia, impaired immune function, and inflammation. In spite of its biological relevance in human health, there are no NMR resonance assignments of the human protein available, obscuring high-resolution characterization of the soluble protein and/or its conformational dynamics, suggested as being important for receptor interaction and biological activity. Here, we report the nearly complete backbone resonance assignments of human leptin. Chemical shift-based secondary structure prediction confirms that in solution leptin forms a four-helix bundle including a pierced lasso topology. The conformational dynamics, determined on several timescales, show that leptin is monomeric, has a rigid four-helix scaffold, and a dynamic domain, including a transiently formed helix. The dynamic domain is anchored to the helical scaffold by a secondary hydrophobic core, pinning down the long loops of leptin to the protein body, inducing motional restriction without a well-defined secondary or tertiary hydrogen bond stabilized structure. This dynamic region is well suited for and may be involved in functional allosteric dynamics upon receptor binding., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: Alcohol marketing has proliferated on digital media, such as websites, social media, and apps. A systematic review was conducted to examine studies of associations between exposure to digital alcohol marketing and alcohol consumption., Method: Eight electronic databases were searched for "alcohol" and "marketing" through 14 February 2017. Studies were included if exposure to digital alcohol marketing and alcohol consumption, or related attitudes and intentions, were assessed. Studies were excluded if they only measured exposure to alcohol depictions posted online by family and friends. Study quality was also assessed., Results: In all, 25 studies were included, including 2 randomized controlled trials, 15 cross-sectional studies, and 8 prospective cohort studies. There was a consistent finding across studies that participation and engagement with digital alcohol marketing--such as clicking on an alcohol ad, visiting an alcohol-branded website, liking or sharing an ad on social media, or downloading alcohol-branded content--was positively associated with alcohol use. The effects of simple exposure to digital alcohol advertising were inconclusive. Proper blinding of subjects, measuring exposures before the outcomes, and measuring the exposures multiple times would improve study quality., Conclusions: Although more research is needed, existing studies suggest that engagement with digital alcohol marketing is positively associated with increased alcohol consumption and increased binge or hazardous drinking behavior. Governments should consider implementing digital alcohol marketing regulations under the precautionary principle as the alcohol industry's self-regulated marketing codes are likely ineffective at protecting populations vulnerable to alcohol-related harm., Competing Interests: The authors declare they have no conflicts of interest.

Aims: Alcohol-attributable harm remains high worldwide, and alcohol use among adolescents is particularly concerning. The purpose of this study is to determine the effect of national alcohol control policies on adolescent alcohol use in low-, middle- and high-income countries and improve on previous cross-national attempts to estimate the impact of alcohol policy on this population., Methods: Data on adolescent (n = 277,110) alcohol consumption from 84 countries were pooled from the Global School-based Health Survey and the European School Survey Project on Alcohol and Other Drugs. Alcohol use measures included lifetime alcohol use, current (past 30 days) alcohol use and current (past 30 days) binge drinking. Information on national alcohol control policies was obtained from the World Health Organization's Global Information System on Alcohol and Health and scored for effectiveness. Main effects were estimated using two-level, random intercept hierarchical linear models, and the models were adjusted for sex and age of the participants, and pattern of drinking score, gross domestic product based on purchasing power parity and study at the country level., Results: Availability (OR [95% CI] = 0.991 [0.983, 0.999]), marketing (OR [95% CI] = 0.994 [0.988, 1.000]) and pricing (OR [95% CI] = 0.955 [0.918, 0.993]) policies were inversely associated with lifetime drinking status. Pricing policies were also inversely associated with current binge drinking status among current drinkers (OR [95% CI] = 0.939 [0.894, 0.986]). There were no associations between the included alcohol policies and current drinking status., Conclusions: Strong availability, marketing and pricing policies can significantly and practically impact adolescent alcohol consumption., (© The Author(s) 2019. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Peripheral membrane proteins with intrinsic curvature can act both as sensors of membrane curvature and shape modulators of the underlying membranes. A well-studied example of such proteins is the mechanochemical GTPase dynamin, which assembles into helical filaments around membrane tubes and catalyzes their scission in a GTPase-dependent manner. It is known that the dynamin coat alone, without GTP, can constrict membrane tubes to radii of ∼10 nm, indicating that the intrinsic shape and elasticity of dynamin filaments should play an important role in membrane remodeling. However, molecular and dynamic understanding of the process is lacking. Here, we develop a dynamical polymer-chain model for a helical elastic filament bound on a deformable membrane tube of conserved mass, accounting for thermal fluctuations in the filament and lipid flows in the membrane. The model is based on the locally cylindrical helix approximation for dynamin. We obtain the elastic parameters of the dynamin filament by molecular dynamics simulations of its tetrameric building block and also from coarse-grained structure-based simulations of a 17-dimer filament. The results show that the stiffness of dynamin is comparable to that of the membrane. We determine equilibrium shapes of the filament and the membrane and find that mostly the pitch of the filament, not its radius, is sensitive to variations in membrane tension and stiffness. The close correspondence between experimental estimates of the inner tube radius and those predicted by the model suggests that dynamin's "stalk" region is responsible for its GTP-independent membrane-shaping ability. The model paves the way for future mesoscopic modeling of dynamin with explicit motor function., (Copyright © 2019 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Balanced fusion and fission are key for the proper function and physiology of mitochondria 1,2 . Remodelling of the mitochondrial inner membrane is mediated by the dynamin-like protein mitochondrial genome maintenance 1 (Mgm1) in fungi or the related protein optic atrophy 1 (OPA1) in animals 3-5 . Mgm1 is required for the preservation of mitochondrial DNA in yeast 6 , whereas mutations in the OPA1 gene in humans are a common cause of autosomal dominant optic atrophy-a genetic disorder that affects the optic nerve 7,8 . Mgm1 and OPA1 are present in mitochondria as a membrane-integral long form and a short form that is soluble in the intermembrane space. Yeast strains that express temperature-sensitive mutants of Mgm1 9,10 or mammalian cells that lack OPA1 display fragmented mitochondria 11,12 , which suggests that Mgm1 and OPA1 have an important role in inner-membrane fusion. Consistently, only the mitochondrial outer membrane-not the inner membrane-fuses in the absence of functional Mgm1 13 . Mgm1 and OPA1 have also been shown to maintain proper cristae architecture 10,14 ; for example, OPA1 prevents the release of pro-apoptotic factors by tightening crista junctions 15 . Finally, the short form of OPA1 localizes to mitochondrial constriction sites, where it presumably promotes mitochondrial fission 16 . How Mgm1 and OPA1 perform their diverse functions in membrane fusion, scission and cristae organization is at present unknown. Here we present crystal and electron cryo-tomography structures of Mgm1 from Chaetomium thermophilum. Mgm1 consists of a GTPase (G) domain, a bundle signalling element domain, a stalk, and a paddle domain that contains a membrane-binding site. Biochemical and cell-based experiments demonstrate that the Mgm1 stalk mediates the assembly of bent tetramers into helical filaments. Electron cryo-tomography studies of Mgm1-decorated lipid tubes and fluorescence microscopy experiments on reconstituted membrane tubes indicate how the tetramers assemble on positively or negatively curved membranes. Our findings convey how Mgm1 and OPA1 filaments dynamically remodel the mitochondrial inner membrane.

With the broad accessibility of high-performance computing resources, the significance of a molecular dynamics simulation is now rarely limited by hardware and/or software availability. Rather, the scientific value of each calculation is determined by the principles that underlie the theoretical model. The current review addresses this topic in the context of simplified models applied to large-scale (∼20-100 Å) dynamics in the ribosome. Specifically, we focus on applications of the "SMOG" class of structure-based models, which can be used to simulate spontaneous (i.e. non-targeted) conformational rearrangements in complex molecular assemblies. Here, we aim to provide an entry-level assessment of the methods, which can help bridge conceptual and communication gaps between the experimental and computational communities. In addition, inspecting the strategies that have been deployed previously can provide guidelines for future computational investigations into the relationship between structure, energetics and dynamics in other assemblies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The alcohol industry recognizes children and pregnant women as population sub-groups vulnerable to the effects of alcohol marketing. Research indicates that heavy alcohol users are also potentially vulnerable to alcohol marketing. The purpose of the current study is to determine if sub-groups defined by psychological characteristics should be classified as potentially vulnerable as well., Methods: College students (n = 326) from two northeast schools were recruited to complete a survey containing questions on demographics, alcohol use, and psychological characteristics (alcohol expectancies, alcohol dependence, sensation seeking traits, and past delinquent behaviors). Additionally, after viewing each of five alcohol ads (4 television and 1 magazine), participants answered questions about their perceptions of alcohol consumption, responsible drinking, excessive drinking, and appeal of the ads. Main effects were assessed using hierarchical linear modeling, with adjustment for age, sex, race, ethnicity, and AUDIT score., Results: Alcohol expectancies (p < .001), particularly the social and physical pleasure and social expressiveness sub-scales, and sensation seeking traits (p = .002) were positively associated with alcohol ad appeal. Alcohol dependence symptoms, specifically impaired control and tolerance, were positively associated with perceptions of responsible drinking (p = .035), even though mean perceived number of drinks consumed met the definition of binge drinking., Conclusions: Individuals with positive alcohol expectancies, sensation seeking traits, and alcohol dependence may be vulnerable to alcohol advertising and marketing. Because alcohol advertising often contains content that can serve as a cue or reinforce to drink, specific regulations may be needed to prevent alcohol-related harm from occurring in these sub-populations.

Over the last 20 years, the application of structure-based (Gō-like) models has ranged from protein folding with coarse-grained models to all-atom representations of large-scale molecular assemblies. While there are many variants that may be employed, the common feature of these models is that some (or all) of the stabilizing energetic interactions are defined based on the knowledge of a particular experimentally obtained conformation. With the generality of this approach, there was a need for a versatile computational platform for designing and implementing this class of models. To this end, the SMOG 2 software package provides an easy-to-use interface, where the user has full control of the model parameters. This software allows the user to edit XML-formatted files in order to provide definitions of new structure-based models. SMOG 2 reads these "template" files and maps the interactions onto specific structures, which are provided in PDB format. The force field files produced by SMOG 2 may then be used to perform simulations with a variety of popular molecular dynamics suites. In this chapter, we describe some of the key features of the SMOG 2 package, while providing examples and strategies for applying these techniques to complex (often large-scale) molecular assemblies, such as the ribosome.

Objective: Social networking sites (SNSs) may influence the behavior of SNS users by exposing them to information about the number of other users who engaged with a SNS post (i.e., user engagement) and any comments left in response to a post (i.e., user-generated comments [UGCs]). The current study hypothesized that beer advertisements with higher user engagement levels and pro-drinking UGCs would be positively associated with the desire to drink and ad engagement. The effect of ad content in relation to regulatory compliance was also investigated., Method: A 2 (regulatory compliant vs. noncompliant) × 2 (low vs. high user engagement) × 2 (pro- vs. anti-alcohol UGC) mixed factorial experiment was used. A total of 120 young adults viewed two compliant and two noncompliant ads. Participants were randomized into four groups: ads with high or low user engagement values, which were paired with either pro- or anti-drinking UGCs. Dependent variables included desire to drink and engaging (i.e., Liking or Sharing) with the ad., Results: When associated with high user engagement values, the desire to drink was 3.5 times greater in the pro-drinking UGC group compared with the anti-drinking UGC group (odds ratio = 3.48, 95% CI [1.60, 7.55]). Ad engagement was 2.3 times greater among those exposed to pro-drinking UGCs (odds ratio = 2.30, 95% CI [1.09, 4.85])., Conclusions: Pro-drinking comments may increase the desire to drink and ad engagement, both of which may be predictive of future drinking behavior. Regulations are needed to limit the ability of SNS users to engage with alcohol ads.

Aims: The current study was conducted to investigate how changes in the content of a social media ad, user engagement values associated with the ad and user-generated comments (UGCs) associated with the ad can influence the appeal (i.e. source appeal, informational appeal and emotional appeal) of a social media ad., Short Summary: Facebook beer ads that violated the guidelines of a relevant marketing code were rated as more emotionally appealing compared to Facebook beer ads that did not violated the guidelines. Increased emotional appeal in beer advertising increases the probability that the ad will be remembered and influence future drinking occasions., Methods: A 2 (ad regulatory compliance: compliant vs. non-compliant) × 2 (user engagement: low vs. high) × 2 (UGC congruence: pro- vs anti-alcohol) mixed factorial experiment was conducted with 120 young adults, 21-24 years old. Each participant viewed four Facebook beer ads that were previously evaluated for thematic content and regulatory compliance. Participants were randomized to view either high or low user engagement values and either pro- or anti-drinking user-generated comments. After each ad exposure, ad appeal was assessed. Statistical analysis was conducted using hierarchical linear modeling. Models were adjusted for demographics, Alcohol Use Disorders Identification Test (AUDIT) scores and Facebook involvement., Results: Source appeal (P = 0.034) and informational appeal (P < 0.001) were significantly higher among ads that were compliant with existing advertising regulations. Emotional appeal was significantly higher among ads that were non-compliant (P = 0.004). The effect of user engagement and UGCs were non-significant (p's > 0.05). Additionally, AUDIT scores (p's < 0.01) and Facebook involvement scores (p's < 0.01) were positively associated with all forms of ad appeal., Conclusion: The appeal of Facebook beer ads may be primarily determined by ad content. Increased emotional appeal in advertising caused by non-compliant advertising may increase the probability that the ad will be remembered and influence future drinking occasions.

Influenza hemagglutinin (HA) mediates viral entry into host cells through a large-scale conformational rearrangement at low pH that leads to fusion of the viral and endosomal membranes. Crystallographic and biochemical data suggest that a loop-to-coiled-coil transition of the B-loop region of HA is important for driving this structural rearrangement. However, the microscopic picture for this proposed "spring-loaded" movement is missing. In this study, we focus on understanding the transition of the B loop and perform a set of all-atom molecular dynamics simulations of the full B-loop trimeric structure with the CHARMM36 force field. The free-energy profile constructed from our simulations describes a B loop that stably folds half of the postfusion coiled coil in tens of microseconds, but the full coiled coil is unfavorable. A buried hydrophilic residue, Thr59, is implicated in destabilizing the coiled coil. Interestingly, this conserved threonine is the only residue in the B loop that strictly differentiates between the group 1 and 2 HA molecules. Microsecond-scale constant temperature simulations revealed that kinetic traps in the structural switch of the B loop can be caused by nonnative, intramonomer, or intermonomer β-sheets. The addition of the A helix stabilized the postfusion state of the B loop, but introduced the possibility for further β-sheet structures. Overall, our results do not support a description of the B loop in group 2 HAs as a stiff spring, but, rather, it allows for more structural heterogeneity in the placement of the fusion peptides during the fusion process., Competing Interests: The authors declare no conflict of interest.

Dynamin-like proteins (DLPs) are large GTPases that restructure membrane. DLPs such as the mitofusins form heterotypic oligomers between isoform pairs that bridge and fuse opposing membranes. In bacteria, heterotypic oligomerisation may also be important for membrane remodelling as most DLP genes are paired within operons. How DLPs tether opposing membranes is unknown. Here we show the crystal structure of a DLP heterotypic pair from the pathogen Campylobacter jejuni. A 2:2 stoichiometric tetramer is observed where heterodimers, conjoined by a random coil linker, assemble back-to-back to form a tripartite DLP chain with extreme flexibility. In vitro, tetramerisation triggers GTPase activity and induces lipid binding. Liposomes are readily tethered and form tubes at high tetramer concentration. Our results provide a direct mechanism for the long-range binding and bridging of opposing membranes by a bacterial DLP pair. They also provide broad mechanistic and structural insights that are relevant to other heterotypic DLP complexes.

Background: Individuals who are particularly vulnerable to the influence of alcohol advertising, such as youth, need special protections, yet little research has been done to determine if other vulnerable groups exist. Secondary data analysis was conducted to determine if perceptions of alcohol advertising differ between groups based on their alcohol use and whether the definition of "vulnerable" should be expanded beyond demographic categories., Methods: Students (n = 326) from 2 U.S. colleges viewed 5 alcohol ads and rated them using a scale designed to detect violations of the alcohol industry's self-regulated marketing codes. Individuals with a history of excessive alcohol use, as measured by the Alcohol Use Disorders Identification Test (AUDIT), were considered potentially vulnerable to alcohol advertising and were compared against individuals without a history of excessive alcohol use. Hierarchical linear modeling was used to determine between-group differences in 4 dependent variables (ad appeal, perceived alcohol consumption, perceived excessive drinking, and perceived responsible drinking). All models were adjusted for age, race, ethnicity, sex, and parental alcohol use., Results: AUDIT risk categories were positively associated with ad appeal (p < 0.001), the amount of alcohol perceived to be consumed (p < 0.01), and perceptions of responsible drinking (p < 0.05). There was no significant associated with perceptions of excessive drinking., Conclusions: Individuals with a history of heavy alcohol use perceived greater alcohol consumption in alcohol ads but perceived this consumption, which often met the definition for binge drinking, to be responsible. Stricter regulations may be needed to protect heavy alcohol users from the effects of alcohol advertising.

Objective: To evaluate the impact of junk food broadcast marketing policies on nationwide junk food sales and identify policy characteristics effective in reducing sales., Methods: Country policy data (n = 79) were categorized in a thorough literature review and analysed using a repeated measures design against data on food sales per capita. Study conducted in United States, 2017., Results: Countries with junk food broadcast marketing policies saw a decrease in junk food sales per capita after implementation, while those without said policies saw an increase (p = 0.013). Countries with statutory policies saw a decrease in sales per capita, while those with only self-regulation saw an increase (p = 0.004). Audience restrictions (p = 0.024) and standardized nutrition criteria (p = 0.008) were policy characteristics significantly associated with a decrease in sales per capita., Conclusions: Utilizing a novel approach to evaluate junk food broadcast marketing policies, the study demonstrated that countries with statutory policies saw a significant decrease in junk food sales per capita not seen in countries with no or only self-regulatory policies. To effectively reduce exposure to child-targeted junk food marketing, governments should establish strong, comprehensive statutory regulations. Additionally, countries that implement junk food marketing policies can use food sales data to track policy effectiveness., (© 2018 World Obesity Federation.)

Objective: Current national responses to the monitoring and prevention of alcohol marketing to vulnerable populations, such as youth, typically rely on partial bans, co-regulation and industry self-regulation. Efforts to evaluate compliance with existing regulations are often cumbersome and resource intensive. We sought to develop a short questionnaire to assess compliance of alcohol advertising to existing alcohol industry self-regulated marketing codes., Methods: Questions for the Alcohol Marketing Assessment Rating Tool (AMART) were taken from a longer rating instrument that was originally developed to detect violations of a self-regulated alcohol marketing code. Secondary analysis of data from three studies of alcohol advertisements was performed to determine the reliability and validity of AMART at detecting code violations, using the longer form as the criterion. One sample was used as an exploratory set. Two samples were used to validate the questionnaire., Results: In the exploratory set, the reliability of AMART was considered near perfect (kappa = 0.92). Sensitivity was 97%, and specificity was 100%. Positive predictive value (PPV) was perfect and negative predictive value (NPV) was approximately 90%. In the validation sets, reliability was considered substantial to near perfect (kappa = 0.71-0.94). Specificity and PPV remained perfect, and NPV was 86%-90%., Conclusion: The AMART is a reliable tool to detect violations of a self-regulated marketing code in alcohol advertising. It significantly decreases the amount of resources needed to evaluate a finite number of advertisements., Competing Interests: Declaration of conflicting interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2018.)

The ribosome is a large ribonucleoprotein complex that is responsible for the production of proteins in all organisms. Accommodation is the process by which an incoming aminoacyl-tRNA (aa-tRNA) molecule binds the ribosomal A site, and its kinetics has been implicated in the accuracy of tRNA selection. In addition to rearrangements in the aa-tRNA molecule, the L11 stalk can undergo large-scale anisotropic motions during translation. To explore the potential impact of this protruding region on the rate of aa-tRNA accommodation, we used molecular dynamics simulations with a simplified model to evaluate the free energy as a function of aa-tRNA position. Specifically, these calculations describe the transition between A/T and elbow-accommodated (EA) configurations (∼20 Å displacement). We find that the free-energy barrier associated with elbow accommodation is proportional to the degree of mobility exhibited by the L11 stalk. That is, when L11 is more rigid, the free-energy barrier height is decreased. This effect arises from the ability of L11 to confine, and thereby destabilize, the A/T ensemble. In addition, when elongation factor Tu (EF-Tu) is present, the A/T ensemble is further destabilized in an L11-dependent manner. These results provide a framework that suggests how next-generation experiments may precisely control the dynamics of the ribosome.

Aims: The prevalence of alcohol advertising has been growing on social media platforms. The purpose of this study was to evaluate alcohol advertising on Facebook for regulatory compliance and thematic content., Methods: A total of 50 Budweiser and Bud Light ads posted on Facebook within 1 month of the 2015 NFL Super Bowl were evaluated for compliance with a self-regulated alcohol advertising code and for thematic content. An exploratory sensitivity/specificity analysis was conducted to determine if thematic content could predict code violations., Results: The code violation rate was 82%, with violations prevalent in guidelines prohibiting the association of alcohol with success (Guideline 5) and health benefits (Guideline 3). Overall, 21 thematic content areas were identified. Displaying the product (62%) and adventure/sensation seeking (52%) were the most prevalent. There was perfect specificity (100%) for 10 content areas for detecting any code violation (animals, negative emotions, positive emotions, games/contests/promotions, female characters, minorities, party, sexuality, night-time, sunrise) and high specificity (>80%) for 10 content areas for detecting violations of guidelines intended to protect minors (animals, negative emotions, famous people, friendship, games/contests/promotions, minorities, responsibility messages, sexuality, sunrise, video games)., Conclusions: The high prevalence of code violations indicates a failure of self-regulation to prevent potentially harmful content from appearing in alcohol advertising, including explicit code violations (e.g. sexuality). Routine violations indicate an unwillingness to restrict advertising content for public health purposes, and statutory restrictions may be necessary to sufficiently deter alcohol producers from repeatedly violating marketing codes., Short Summary: Violations of a self-regulated alcohol advertising code are prevalent in a sample of beer ads published on Facebook near the US National Football League's Super Bowl. Overall, 16 thematic content areas demonstrated high specificity for code violations. Alcohol advertising codes should be updated to expressly prohibit the use of such content., (© The Author 2017. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Focal adhesions are dynamic constructs at the leading edge of migrating cells, linking them to the extracellular matrix and enabling force sensing and transmission. The lifecycle of a focal adhesion is a highly coordinated process involving spatial and temporal variations of protein composition, interaction, and cellular tension. The assembly of focal adhesions requires the recruitment and activation of vinculin. Vinculin is present in the cytoplasm in an autoinhibited conformation in which its tail is held pincerlike by its head domains, further stabilized by two high-affinity head-tail interfaces. Vinculin has binding sites for talin and F-actin, but effective binding requires vinculin activation to release its head-tail associations. In migrating cells, it has been shown that the locations of vinculin activation coincide with areas of high cellular tension, and that the highest recorded tensions across vinculin are associated with adhesion assembly. Here, we use a structure-based model to investigate vinculin activation by talin modulated by tensile force generated by transient associations with F-actin. We show that vinculin activation may proceed from an intermediate state stabilized by partial talin-vinculin association. There is a low-force regime and a high-force regime where vinculin activation is dominated by two different pathways with distinct responses to force. Specifically, at zero or low forces, vinculin activation requires substantial destabilization of the main head-tail interface, which is rigid and undergoes very limited fluctuations, despite the other being relatively flexible. This pathway is not significantly affected by force; instead, higher forces favor an alternative pathway, which seeks to release the vinculin tail from its pincerlike head domains before destabilizing the head-tail interfaces. This pathway has a force-sensitive activation barrier and is significantly accelerated by force. Experimental data of vinculin during various stages of the focal adhesion lifecycle are consistent with the proposed force-regulated activation pathway., (Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.)