The Effects of poly-GA and poly-PR C9orf72 Dipeptide Repeats on Sleep Patterns in Drosophila melanogaster.

C9orf72 is the most common familial gene associated with amyotrophic lateral sclerosis (ALS). Dipeptide repeats (DPRs) encoded by an expanded nucleotide repeat sequence in the C9orf72 gene were found in the sleep-related neurons of patients, indicating a role of DPRs in ALS-associated sleep disruptions. Poly-GA or poly-PR DPRs were expressed in male Drosophila melanogaster to study their effect on sleep . Poly-PR expression caused sleep disruptions while poly-GA expression did not. This study validates the use of Drosophila as an in vivo model system for exploring the roles of DPRs in perturbing the underlying molecular mechanisms in sleep regulation.

Support for nicotine reduction in cigarettes: findings from the 2016 and 2020 ITC Four Country Smoking and Vaping Surveys.

INTRODUCTION: The USA and New Zealand have sought to establish a product standard to set a maximum nicotine level for cigarettes to reduce their addictiveness. This study examined support for very low nicotine cigarettes (VLNCs) in Australia, Canada, England and the USA between 2016 and 2020. METHODS: Repeated cross-sectional data were analysed from participants who currently smoke, formerly smoked or vaped and/or currently vape in the 2016 (n=11 150) and/or 2020 (n=5432) International Tobacco Control (ITC) Four Country Smoking and Vaping Survey. Respondents were asked if they would support a law that reduces the amount of nicotine in cigarettes to make them less addictive. Adjusted and weighted logistic regression analyses estimated the prevalence and predictors of support, such as country, age, sex, education, income, race and smoking/vaping status for VLNCs (support vs oppose/do not know). RESULTS: A majority of respondents supported a VLNC law, with support highest in Canada (69%; 2016 and 2020 combined), followed by England (61%), Australia (60%) and the USA (58%). Overall, support decreased from 62% in 2016 to 59% in 2020 (p=0.004), which did not differ by country. Levels of support differed by smoking/vaping status, where those who exclusively smoked daily showed the lowest level of support (59%) and those who exclusively vaped non-daily had the highest level of support (72%). CONCLUSION: More than half of respondents in all four countries-including those who smoked daily-supported a hypothetical VLNC standard to render cigarettes less addictive. It is important to examine if support is sustained after policies are implemented.

C9orf72 proline-arginine dipeptide repeats disrupt the proteasome and perturb proteolytic activities.

The hexanucleotide G4C2 repeat expansion in C9orf72 is the most frequent genetic cause of familial amyotrophic lateral sclerosis (ALS). Aberrant translation of this hexanucleotide sequence leads to production of 5 dipeptide repeats (DPRs). One of these DPRs is proline-arginine (polyPR), which is found in C9orf72-expanded ALS (C9ALS) patient brain tissue and is neurotoxic across multiple model systems. PolyPR was previously reported to bind and impair proteasomes in vitro. Nevertheless, the clinical relevance of the polyPR-proteasome interaction and its functional consequences in vivo are yet to be established. Here, we aim to confirm and functionally characterize polyPR-induced impairment of proteolysis in C9ALS patient tissue and an in vivo model system. Confocal microscopy and immunofluorescence studies on both human and Drosophila melanogaster brain tissues revealed sequestration of proteasomes by polyPR into inclusion-like bodies. Co-immunoprecipitation in D. melanogaster showed that polyPR strongly binds to the proteasome. In vivo, functional evidence for proteasome impairment is further shown by the accumulation of ubiquitinated proteins along with lysosomal accumulation and hyper-acidification, which can be rescued by a small-molecule proteasomal enhancer. Together, we provide the first clinical report of polyPR-proteasome interactions and offer in vivo evidence proposing polyPR-induced proteolytic dysfunction as a pathogenic mechanism in C9ALS.

Vaccination in Kidney Transplant Candidates.

Background: Kidney transplant (KT) candidates have historically low immunization rates against recommended vaccines. A retrospective single-center study of contemporary KT candidates was conducted to assess vaccination rates and vaccine uptake. Methods: All KT candidates ≥18 y evaluated between January 1, 2020, and December 31, 2020, were retrospectively reviewed for history of prior vaccination against tetanus, diphtheria, and pertussis; 13-valent pneumococcal conjugate vaccine; 23-valent pneumococcal polysaccharide vaccine; and recombinant zoster vaccine. Positive hepatitis A IgG total, hepatitis B surface antibody, measles, mumps, rubella, and varicella IgG were assessed as surrogate markers of immunity. Vaccine uptake among vaccine-eligible candidates was also assessed. Results: Among 150 KT candidates, the rate of prior vaccination against tetanus, diphtheria, and pertussis; 13-valent pneumococcal conjugate vaccine; 23-valent pneumococcal polysaccharide vaccine; and recombinant zoster vaccine (latter among patients ≥50 y) was found to be as low as 11%. Hepatitis A IgG total, hepatitis B surface antibody, measles, mumps, rubella, and varicella IgG seropositivity rates were 30%, 66%, 88%, 78%, 90%, and 96%, respectively. Only 7 (5%) of 150 patients had complete immunization or seropositivity. Five (3%) of 143 vaccine-eligible patients declined vaccination. Hepatitis A vaccine declination was relatively common with 15 (16%) of 94 vaccine-eligible patients declining it. Conclusions: KT candidates have low baseline rates of prior immunization/seropositivity against most recommended vaccines. Overall vaccine uptake among eligible candidates was high.

It's addiction at this Point": A qualitative examination of youth E-cigarette use trajectory in the United States.

E-cigarettes (electronic cigarettes) have been the most used tobacco product among US youth since 2014, reaching a plateau during the COVID-19 pandemic. Youth e-cigarette use is associated with negative health consequences such as impaired cognitive functioning. For many, the COVID-19 pandemic altered social interactions, harm perceptions, and product availability. This changed the frequency and locations in which youth use e-cigarettes. To better understand youth e-cigarette use, we need more information on factors that can alter e-cigarette use, specifically, how the pandemic changed e-cigarette use among youth. In 2020-2021, we conducted online, individual interviews with 19 youth (aged 13-17) e-cigarette users living in the US to explore how COVID-19 impacted their e-cigarette use. Youth described a progression of e-cigarette use from initial experimentation, regular social use, and ultimately to nicotine addiction demonstrated by individual use in isolation. Many youth initiated e-cigarette use due to influences by friends or family members. Youth discussed progression to social use, with social interactions as an important reason for use and an avenue for expanding one's knowledge of e-cigarettes. After a period of time, youth began to recognize that the social interactions mattered less, suggesting to them that they had become addicted. This realization became more apparent during COVID-19, which changed how youth used e-cigarettes, especially around where use was occurring, health concerns, and use behavior and frequency. In our interviews, youth trajectory began with an initiation with family and friends, progressed to social use, and eventually developed to addiction, at which point social use was no longer the primary motivation for e-cigarette use. Understanding the trajectory of e-cigarette use will allow for effective interventions that reduce harm to youth from e-cigarette use.

"I Get the Flavors and It Makes Me Love Vaping More": How and Why Youth Users Modify Electronic Nicotine Delivery Systems.

INTRODUCTION: Youth in the United States are using electronic nicotine delivery systems (ENDS) at a high rate. Modifications to ENDS by youth can introduce additional health hazards which have not been previously considered. To better understand these risks, we need more information on what these modifications are, the motivations behind them, and the sources of information on modifications. AIMS AND METHODS: Utilizing a trained moderator, in 2020-2021, we conducted one-on-one interviews with 19 youth ENDS users aged 16-17 living in the United States and analyzed their responses using a qualitative description approach. RESULTS: The most prominent modification was to the e-liquid; youth indicated they mixed e-juices to create new flavors and added substances not intended for vaping, including illicit drugs such as cannabis and cocaine. Few youths from our sample were interested in achieving a specific nicotine level to vape, and modifications to the battery, coil and wick were less frequently mentioned. Some of these modifications were motivated by a desire to achieve specific experiences with their device. At other times, modifications were made due to necessity because of limited access to ENDS devices and supplies. YouTube and peers were the main sources of information about modifying. CONCLUSIONS: Youth are making modifications that are both intended and unintended by the manufacturer. Adding illicit drugs and other substances not made for vaping is of particular concern. Understanding how youth modify ENDS and how that changes their use is important to guide regulatory policy intended to reduce harm to youth from ENDS use. IMPLICATIONS: Youth from our study indicated that they make modifications to the ENDS devices, specifically to the e-liquid. These modifications are both intended by the manufacturer, such as changing the e-liquid and replacing coils, and unintended, such as adding substances not meant for vaping. Future policies aimed at reducing youth ENDS use should consider mandating better safeguards against modifications that appeal to youth.

Evaluation of a health system's implementation of a monkeypox care model under the RE-AIM framework.

Objective: Emerging infectious diseases challenge healthcare systems to implement new models of care. We aim to evaluate the rapid implementation of a new care model for monkeypox in our health system. Design: This is a retrospective case series evaluation under the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework of implementation of a testing and care model for monkeypox in a large, integrated health system. Methods: Atrium Health implemented education of providers, testing protocols, and management of potential monkeypox cases using electronic health record (EHR) data capabilities, telehealth, and collaboration between multiple disciplines. The first 4 weeks of care model implementation were evaluated under the RE-AIM framework. Results: One hundred fifty-three patients were tested for monkeypox by 117 unique providers at urgent care, emergency departments, and infectious disease clinics in our healthcare system between 18 July 2022 and 14 August 2022. Fifty-eight monkeypox cases were identified, compared with 198 cases in the state during the time period, a disproportionate number compared with the health system service area, and 52 patients were assessed for need for tecovirimat treatment. The number of tests performed and providers sending tests increased during the study period. Conclusion: Implementation of a dedicated care model leveraging EHR data support, telehealth, and cross-disciplinary collaboration led to more effective identification and management of emerging infectious diseases and is important for public health. Plain Language Summary: Impact of care model implementation on monkeypox New infectious diseases challenge health systems to implement new care practices. Our health system responded to this challenge by implementing a care model for education, testing, and clinical care of monkeypox patients. We analyzed results from implementing the model. We were able to identify a disproportionate number of monkeypox cases compared with the rest of our state by using our model to educate medical providers, encourage testing, and ensure patients had access to best disease care. Implementation of care models for testing and management of new diseases will improve patient care and public health.

Severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infections occurring in healthcare workers after booster vaccination: A comparison of delta versus omicron variants.

In this study, we used genomic sequencing to identify variants of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) in healthcare workers with coronavirus disease 2019 (COVID-19) after receiving a booster vaccination. We compared symptoms, comorbidities, exposure risks, and vaccine history between the variants. Postbooster COVID-19 cases increased as the SARS-CoV-2 omicron variant predominated.

Global monkeypox case hospitalisation rates: A rapid systematic review and meta-analysis.

Background: Estimates of the case hospitalization rate and case fatality rate when hospital care is available for monkeypox (MPX) infections have not been well defined. This rapid systematic review and meta-analysis aimed to estimate the case hospitalisation rate and case fatality rate where hospital care is available. Methods: We systematically searched PubMed, Embase, the Lancet Preprints, and MedRxiv for studies published between Jan 1, 1950 and Aug 2, 2022. We included documents which contained both the number of cases and associated hospitalisations of MPX infections. From eligible studies we extracted the country, the year of the study, the study design type, the clade of MPX, the participant characteristics, transmission type, any treatments used, number of cases (including suspected, probable, or laboratory confirmed diagnosis), number of hospitalizations, hospitalized patient outcomes, and case definition. Case hospitalization rate (CHR) was defined as the proportion of cases that were admitted to hospital care while case fatality rate (CFR) was defined as the proportion of cases that died. CHR and CFR were analysed in a fully Bayesian meta-analytic framework using random effects models, including sub-group analysis with heterogeneity assessed using I2. Findings: Of the 259 unique documents identified, 19 studies were eligible for inclusion. Included studies represented 7553 reported cases among which there were 555 hospitalizations. Of the 7540 cases for which outcomes were available, there were 15 recorded deaths. The median age of cases was 35 years (interquartile range 28-38, n = 2010) and primarily male (7339/7489, 98%) in studies where age or sex were available. Combined CHR was estimated to be 14.1% (95% credible interval, 7.5-25.0, I2 97.4%), with a high degree of heterogeneity. Further analysis by outbreak period indicates CHRs of 49.8% (28.2-74.0, I2 81.4%), 21.7% (7.2-52.1, I2 57.7%), and 5.8% (3.2-9.4, I2 92.4%) during the pre-2017, 2017-2021, and 2022 outbreaks, respectively, again with high levels of heterogeneity. CFR was estimated to be 0.03% (0.0-0.44, I2 99.9%), with evidence of large heterogeneity between the studies. Interpretation: There is limited data for MPX hospitalization rates in countries where MPX has been traditionally non-endemic until the current outbreak. Due to substantial heterogeneity, caution is needed when interpreting these findings. Health care organizations should be cognizant of the potential increase in healthcare utilization. Rapid identification of infection and use of appropriate therapies such as antivirals play a role reducing the CHR and associated CFR. Funding: None.

Citric Acid-Derived Carbon Quantum Dots Attenuate Paraquat-Induced Neuronal Compromise In Vitro and In Vivo.

The potent environmental herbicide and weedicide paraquat is linked to neuromotor defects and Parkinson's disease (PD). We have evaluated the neuroprotective role of citric acid-sourced carbon quantum dots (Cit-CQDs) on paraquat-insulted human neuroblastoma-derived SH-SY5Y cell lines and on a paraquat-exposed nematode (Caenorhabditis elegans). Our data reveal that Cit-CQDs are able to scavenge free radicals in test tube assays and mitigate paraquat-elevated reactive oxygen species (ROS) levels in SH-SY5Y cells. Furthermore, Cit-CQDs protect the cell line from paraquat, which otherwise elicits cell death. Cit-CQDs-challenged nematodes demonstrate enhanced survival rates 72 h post-paraquat exposure compared to controls. Paraquat ablates dopamine (DA) neurons, which results in compromised locomotor function in nematodes. However, the neurons remained intact when the nematodes were incubated with Cit-CQDs prior to neurotoxicant exposure. The collective data suggest Cit-CQDs offer neuroprotection for cell lines and organisms from xenotoxicant-associated neuronal injury and death. The study suggests Cit-CQDs as a potentially viable green chemistry-synthesized, biobased nanomaterial for intervention in neurodegenerative disorders.

Gelatin-derived carbon quantum dots mitigate herbicide-induced neurotoxic effects in vitro and in vivo.

The herbicide and viologen, N, N'-dimethyl-4,4'-bipyridinium dichloride (Paraquat) is known to be toxic to neuronal cells by a multifactorial process involving an elevation in the levels of reactive oxygen species (ROS), the triggering of amyloid-protein aggregation and their accumulation, collectively leading to neuronal dyshomeostasis. We demonstrate that green-chemistry-synthesized sustainable gelatin-derived carbon quantum dots (CQDs) mitigate paraquat-induced neurotoxic outcomes and resultant compromise in organismal mortality. Gelatin-derived CQDs were found to possess antioxidant properties and ameliorated ROS elevation in paraquat-insulted neuroblastoma-derived SHSY-5Y cells, protecting them from herbicide-induced cell death. These CQDs also increased lifespan in paraquat-compromised Caenorhabditis elegans and herbicide-mediated dopamine neuron ablation. Collectively, the data underscore the ability of this sustainably synthesized, environmentally friendly biocompatible nanomaterial to protect cell lines and organisms against neurotoxic outcomes. The study findings strategically position this relatively novel nanoscopic carbon quantum framework for further testing in vertebrate trials of neurotoxic insult.

General and Device-Specific Reasons for ENDS Use: A Qualitative Study with Adult ENDS Users.

BACKGROUND: A scientific consensus on the public health impact of electronic nicotine delivery systems (ENDS) remains elusive. This is partly due to the wide variation in product characteristics often lumped together under one category. Research is needed to better understand what ENDS device type characteristics motivate their use by adults. METHODS: Nine focus groups of 32 current ENDS users who were 18+ years old, had used ENDS in the previous 30 days, and had been using ENDS for more than two months were held either in person or online between February and June 2020. RESULTS: Participants' reasons for their choice of ENDS characteristics included both general, applying to all ENDS products, and specific, relating to particular ENDS devices. Health benefits and the lack of offensive odor were commonly identified as important reasons for using ENDS in general. Flavor and product discreteness were both general and device-specific determinants of ENDS use. Conversely, nicotine delivery, cloud size, battery properties, aesthetics, ease of use, and cost were device-specific drivers of participants' choice. CONCLUSIONS: The reasons that adults choose to use ENDS are complex and sometimes related to both ENDS as a category and as specific ENDS product types. Regulations and public communication campaigns should reflect their ultimate objective and consider both general and specific motivations when attempting to achieve public health objectives.

Disparities among smokers during the COVID-19 pandemic: Examination of COVID-19-related worries by sociodemographic factors in a U.S. Nationally representative survey.

Low-socioeconomic status (SES) and certain racial/ethnic minority groups disproportionately experience tobacco-related disease and death. Underserved populations of smokers may be at disproportionate risk for elevated stress and worry related to basic needs and healthcare during the pandemic, which could impede smoking cessation and exacerbate health disparities. This study examined whether experiences with stress and worry among smokers during the COVID-19 pandemic differed by sociodemographic factors, and whether these factors predicted serious psychological distress (SPD). Data came from an October-November 2020 U.S. national representative survey of 1,223 current cigarette smokers. Analyses examined associations between sociodemographic factors with COVID-19-related worries and past-month SPD. Worry in most domains (e.g., food, housing, finances, healthcare) was more prevalent among participants with less than high school education, income less than $30,000, and those who were unemployed. Women and participants aged 30-44, with income less than $30,000, with less than high school education, not working/disabled, or on Medicaid were more likely to experience SPD. Examined separately, each COVID-19 worry predicted higher likelihood of SPD. In adjusted models, COVID-19 worries about finances (aOR = 2.3) and isolation/loneliness (aOR = 3.0) uniquely predicted SPD. Among U.S. adult smokers during the COVID-19 pandemic, those with lower SES indicated disproportionately high worry about access to basic needs and were more likely to experience SPD. Policies and interventions that address basic needs and mental health among marginalized populations of tobacco users are needed.

"It's Cool, Modifying and All, but I Don't Want Anything Blowing Up on Me:" A Focus Group Study of Motivations to Modify Electronic Nicotine Delivery Systems (ENDS).

INTRODUCTION: Modifications to electronic nicoti ne delivery systems (ENDS) can pose health risks to users. This study explored users' motivations for modifying ENDS devices and how perceived risks of modifications influenced modification behaviors as product availability and device characteristics changed over time. METHOD: We conducted nine focus groups (February-June 2020) with 32 current ENDS users (18+, used ENDS in the past 30 days, and had been using ENDS for more than 2 months). RESULTS: Participants primarily modified ENDS devices to improve their experiences, such as experimenting with flavor, controlling nicotine levels, or using cannabis products with ENDS. Another reason for modifying was routine maintenance to ensure a satisfactory experience, including maintaining coils and keeping batteries charged. The broader availability of ENDS products shifted modification behaviors over time, with newer devices making some modifications (e.g., coil replacement) easier and making more intricate modifications (e.g., building coil from scratch) less common. Participants were aware of modification dangers and cited perceived risk as the reason for avoiding certain modifications, such as battery alterations. CONCLUSIONS: Modifications of ENDS are ongoing and evolving among users and should be considered by the Food and Drug Administration (FDA) and other regulatory decision-makers as product authorization reviews are conducted and product standards are developed.

"You have to vape to make it through": E-cigarette Outcome Expectancies among Youth and Parents.

Objectives: Outcome expectancies are central to explaining health behavior and have been shown to predict tobacco use. Research on outcome expectancies for e-cigarette use among youth is scarce but increasingly important given the growing rates of use, particularly of high-nicotine pod devices and the recent outbreak of e-cigarette related lung disease. Methods: In 2019, we conducted 3 focus groups with middle school youth (N=25), 5 with high school youth (N=38), and 4 with parents (N=27). Youth and parents were not related and groups included both users and non-users. Participants discussed reasons for e-cigarette use and bad and good things that might happen to a person who vapes. Results: Participants described positive and negative psychoactive/sensory, social, and health-related outcome expectancies. Both youth and parents mentioned stress relief and appearing older as positive outcome expectancies, and e-cigarette flavors, acting rebellious, and structural opportunities as other reasons for initiating e-cigarette use. Social consequences and health outcomes were negative outcome expectancies deterring use. Conclusions: Regulations and public communication campaigns can counteract the positive outcome expectancies (flavor regulation, providing stress reduction tips) and capitalize on negative ones (communicating negative health outcomes) to decrease youth e-cigarette use.

Which tobacco control policies do smokers support? Findings from the International Tobacco Control Four Country Smoking and Vaping Survey.

As governments consider policy action to reduce smoking, a key factor in creating political will is the level of public support, particularly among smokers who are most affected by the policies. The goal of this paper is to assess and compare the level of support in Canada, the United States, England, and Australia for five smoking control policies: 1) banning menthol in cigarettes, 2) banning cigarette additives, 3) reducing nicotine in cigarettes to make them less addictive, 4) raising the minimum age to purchase cigarettes to 21 years and older, and 5) requiring pictorial warning labels on cigarette packs (examined in the US only). Data for these analyses come from 8165 daily cigarette smokers who responded to the 2016 International Tobacco Control Four Country Smoking and Vaping Survey. In all countries, the highest level of support was for raising the legal age for purchase to 21 years and older (62-70%) and reducing the nicotine content of cigarettes to make them less addictive (57-70%). Smokers who were less dependent on cigarettes and those expressing interest in quitting were more likely to support all policies. When asked how they would respond to a nicotine reduction policy, the most common response given was to try the non-nicotine cigarettes to see how they liked them (42-48%), with the next most common response being to quit smoking entirely (16-24%). The high level of support for these proposed policies among daily smokers provides important evidence for policymakers to counteract claims that such policies would be unpopular.

Prescription stimulant use among young adult college students: Who uses, why, and what are the consequences?

OBJECTIVE: To examine prescription stimulant use among college students, particularly use with versus without prescriptions or attention deficit hyperactive disorder (attention-deficit/hyperactivitydisorder (ADHD)) diagnoses. Participants: Data were drawn from a diverse sample of college students from seven colleges/universities in Georgia participating. Methods: Measures assessed ADHD-specific factors, prescription stimulant use, access, motives, side effects, and covariates. Results: Of the 219 students reporting prescription stimulant use (average age 20.72 years, 54.8% female, 82.1% White), 45.7% did not have prescriptions or ADHD diagnoses. Correlates of use without prescriptions/diagnoses included lower parental education, attending private school, not having depression- or anxiety-related diagnoses, and past 30-day marijuana and tobacco use. Those without prescriptions/diagnoses were more likely to use to stay awake longer, to have more enjoyable time, and to party longer; they also reported fewer adverse side effects. Conclusions: Campuses should educate students about ADHD, facilitate screening and treatment, and emphasize adverse consequences of recreational use.

"Don't do vape, bro!" A qualitative study of youth's and parents' reactions to e-cigarette prevention advertisements.

INTRODUCTION: Growing rates of e-cigarette use among youth have reached epidemic proportions. Media messages have been deployed to counteract this trend, but their evaluations are lacking. We assessed youth's and parents' reactions to various existing e-cigarette prevention messages. METHODS: In 2019, 12 focus groups were conducted with youth (n = 63) and parents (n = 27). Participants discussed their reactions to 9 existing messages with various topics. RESULTS: Information on chemicals in e-cigarettes was seen as new and scary, but unknown chemical names created confusion. Youth appreciated novel ways to visualize health effects of e-cigarettes (parasites in the body) and nicotine's effect on behavior (mood swings), but they cautioned that some of these effects (irritability) are not always caused by nicotine. Some participants did not know if e-cigarette companies were "Big Tobacco." Some found it hard to argue with the financial costs of vaping, but others did not think they were too great. Participants recommended messages featuring testimonials from diverse adolescents and messages aimed at youth who are struggling with addiction to e-cigarettes. CONCLUSION: Messages would be particularly effective if they featured real youth and did not look like adults created them for youth. Another area that is currently not covered in media messages is talking to youth who are using e-cigarettes and might be already addicted but do not know where to turn for help. These adolescents need to be referred to resources for cessation.

Longitudinal changes in alcohol use and binge-drinking among young-adult college students: Analyses of predictors across system levels.

BACKGROUND: Longitudinal research regarding young-adult college student alcohol use behaviors is needed to identify risk factors and inform interventions, particularly with regard to binge-drinking. METHODS: Data from 3,418 US college students (aged 18-25) in a two-year, six-wave panel study (64.6% female, 63.4% White) were used to examine alcohol use and binge-drinking trajectories, as well as predictors of differing trajectories across individual (sociodemographics, depressive symptoms, ADHD symptoms, early-onset substance use), interpersonal (adverse childhood events, social support, parental substance use), and community factors (college type, rural/urban). RESULTS: Baseline alcohol use was associated with being White, higher parental education, early-onset use of alcohol, cigarettes, and marijuana, greater social support, parental alcohol use, attending private institutions, and rurality (p's < 0.01). Greater alcohol use over time was predicted by being White and attending private institutions (p's < 0.01). Multivariable regression indicated that predictors of binge-drinking at any assessment included older age, sexual minority, greater ADHD symptoms, early-onset substance use, parental alcohol use, attending private institutions, and rurality (p's < 0.01). GMM indicated 4 binge-drinking trajectory classes: Dabblers (89.94% of the sample), Slow decelerators (7.35%), Accelerators (1.86%), and Fast decelerators (0.84%). Fast and Slow decelerators were older; Dabblers and Fast decelerators were more likely female; Accelerators reported more depressive symptoms; Dabblers were less likely early-onset substance users; and those from rural settings were more likely Slow decelerators vs. Dabblers (p's < 0.05). CONCLUSIONS: Intervention efforts should be informed by data regarding those most likely to drink, binge-drink, and escalate use (e.g., Whites, men, early-onset users, parental use, private college students, rural).