Plasma IgG aggregates as biomarkers for multiple sclerosis.

We recently reported that multiple sclerosis (MS) plasma contains IgG aggregates and induces complement-dependent neuronal cytotoxicity (Zhou et al., 2023). Using ELISA, we report herein that plasma IgG levels in the aggregates can be used as biomarkers for MS. We enriched the IgG aggregates from samples of two cohorts (190 MS and 160 controls) by collecting flow-through after plasma binding to Protein A followed by detection of IgG subclass. We show that there are significantly higher levels of IgG1, IgG3, and total IgG antibodies in MS IgG aggregates, with an AUC >90%; higher levels of IgG1 distinguish secondary progressive MS from relapsing-remitting MS (AUC = 91%). Significantly, we provided the biological rationale for MS plasma IgG biomarkers by demonstrating the strong correlation between IgG antibodies and IgG aggregate-induced neuronal cytotoxicity. These non-invasive, simple IgG-based blood ELISA assays can be adapted into clinical practice for diagnosing MS and SPMS and monitoring treatment responses.

Exploring barriers and promoters of CRC screening use among agricultural operators: a pilot study of an application of concept mapping.

INTRODUCTION: The purpose of the study was to identify barriers and facilitators of colorectal cancer (CRC) screening use among agricultural operators in Nebraska, US. METHODS: The concept mapping approach was used to engage participants and enhance the generation of ideas and opinions regarding CRC screening. Two focus groups (seven women and seven men) were conducted. RESULTS: Among women, the cost domain was most agreed upon as important, followed by experiencing symptoms, awareness, and family. Among men, the important concepts related to CRC screening were family and friend support, feeling too young to get CRC, family or personal history of CRC, and lack of awareness of the need to be screened. Some gender differences regarding barriers were observed, such as women were more concerned about the cost of screening while men were far more concerned about the embarrassment associated with CRC screening. CONCLUSION: These findings will be crucial to developing educational materials to increase knowledge of risk factors for CRC and of CRC screening in the agricultural population.

Amylin, Aß42, and Amyloid in Varicella Zoster Virus Vasculopathy Cerebrospinal Fluid and Infected Vascular Cells.

BACKGROUND: Varicella zoster virus (VZV) vasculopathy is characterized by persistent arterial inflammation leading to stroke. Studies show that VZV induces amyloid formation that may aggravate vasculitis. Thus, we determined if VZV central nervous system infection produces amyloid. METHODS: Aß peptides, amylin, and amyloid were measured in cerebrospinal fluid (CSF) from 16 VZV vasculopathy subjects and 36 stroke controls. To determine if infection induced amyloid deposition, mock- and VZV-infected quiescent primary human perineurial cells (qHPNCs), present in vasculature, were analyzed for intracellular amyloidogenic transcripts/proteins and amyloid. Supernatants were assayed for amyloidogenic peptides and ability to induce amyloid formation. To determine amylin's function during infection, amylin was knocked down with small interfering RNA and viral complementary DNA (cDNA) was quantitated. RESULTS: Compared to controls, VZV vasculopathy CSF had increased amyloid that positively correlated with amylin and anti-VZV antibody levels; Aß40 was reduced and Aß42 unchanged. Intracellular amylin, Aß42, and amyloid were seen only in VZV-infected qHPNCs. VZV-infected supernatant formed amyloid fibrils following addition of amyloidogenic peptides. Amylin knockdown decreased viral cDNA. CONCLUSIONS: VZV infection increased levels of amyloidogenic peptides and amyloid in CSF and qHPNCs, indicating that VZV-induced amyloid deposition may contribute to persistent arterial inflammation in VZV vasculopathy. In addition, we identified a novel proviral function of amylin.

Occupational stress among farm and ranch operators in the midwestern United States.

BACKGROUND: This study used surveillance data from 2018 and 2020 to test the stability of work-related strain symptoms (high stress, sleep deprivation, exhaustion) with demographic factors, work characteristics, and musculoskeletal symptoms among farm and ranch operators in seven midwestern states of the United States. METHODS: Cross-sectional surveys were conducted among farm and ranch operators in 2018 (n = 4423) and 2020 (n = 3492). Operators were asked whether, in the past 12 months, they experienced extended work periods that resulted in high stress levels, sleep deprivation, exhaustion/fatigue, or other work-related strain symptoms. Covariates included personal and demographic factors, work characteristics, number of injuries, work-related health conditions, and exposures on the operation. Summary statistics were tabulated for explanatory and outcome variables. The classification (decision) tree approach was used to assess what variables would best separate operators with and without reported strain symptoms, based on a set of explanatory variables. Regularized regression was used to generate effect estimates between the work strain variables and explanatory variables. RESULTS: High stress level, sleep deprivation, and exhaustion were reported more frequently in 2018 than 2020. The classification tree reproduced the 2018 model using 2020 data with approximately 80% accuracy. The mean number of reported MSD symptoms increased slightly from 1.23 in 2018 to 1.41 in 2020. Older age, more time spent in farm work, higher gross farm income (GFI), and MSD symptoms in six body regions (ankles/feet, knees, lower back, neck, shoulders, wrists/hands) were associated with all three work strain symptoms. CONCLUSIONS: Musculoskeletal pain and discomfort was a strong predictor for stress, sleep deprivation, and exhaustion among farmers and ranchers. This finding indicates that reducing MSD pain and discomfort is beneficial for both physical and mental health.

Acute zoster plasma contains elevated amyloid, correlating with Aß42 and amylin levels, and is amyloidogenic.

Herpes zoster is associated with an increased dementia and neovascular macular degeneration risk and a decline in glycemic control in diabetes mellitus. Because amyloid is present and pathogenic in these diseases, we quantified amyloid, Aß40, Aß42, and amylin in 14 zoster and 10 control plasmas. Compared with controls, zoster plasma had significantly elevated amyloid that correlated with Aß42 and amylin levels and increased amyloid aggregation with addition of exogenous Aß42 or amylin. These results suggest that zoster plasma contains factor(s) that promotes aggregation of amyloidogenic peptides, potentially contributing to the toxic amyloid burden and explaining accelerated disease progression following zoster.

The Youth Firearm Risk and Safety Tool (Youth-FiRST): Psychometrics and Validation of a Gun Attitudes and Violence Exposure Assessment Tool.

This study reports on the development of a comprehensive assessment of exposure to guns and gun-related violence for evaluating the risk of gun-related trauma. Gun access, gun attitudes, gun safety education, and exposure to gun violence were measured. Participants were 630 youth, aged 2-17. Youth, ages 10-17, completed a self-report survey and caregivers of young children, ages 2-9, completed the survey as a proxy for that child. The youth were from urban (n = 286) and rural (n = 344) areas. Factor analysis, item response theory, and structural equation modeling were used. Two factors described access to guns, two factors described gun attitudes, and a single construct captured gun safety education. The gun violence exposure factor showed strong associations with trauma symptomatology. The individual constructs showed good psychometric properties and measurement noninvariance by urbanicity.

Gun Violence Exposure and Posttraumatic Symptoms Among Children and Youth.

Although statistics on youth homicide and injury from gun violence are available, little research has focused on how gun violence overlaps with other victimizations or on the psychological impact of gun violence on children. Pilot survey data were collected on the experiences of 630 U.S. children (age range: 2-17 years) from Boston, Philadelphia, and rural areas of eastern Tennessee. Youth aged 10-17 years completed a self-report survey on a wide range of gun violence exposures, and parents of younger children (aged 2-9 years) completed the survey as a proxy for that child. Direct gun violence exposure, witnessing gun violence, and hearing gunshots were all significantly associated with other forms of victimization, rs = .10-.38, p < .001. The findings suggest that youth who experience direct gun violence are often exposed to multiple violent contexts. For older youth (ages 10-17 years) polyvictimization was most strongly associated with posttraumatic symptoms, ß = .35, p < .001, although witnessing gun violence still uniquely predicted a higher level of symptoms, ß = .18, p < .01. For younger children (ages 2-9 years), hearing and witnessing gun violence were both related to posttraumatic symptoms, ß = .15, p < .01 for both, even after controlling for polyvictimization. Mental health professionals and trauma-informed services should be mindful that the traumatic impact of gun violence for children may not necessarily be attached to direct victimization experiences but may also result from simply seeing or hearing it in their neighborhoods.

Comparisons of Cocaine-Only, Opioid-Only, and Users of Both Substances in the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC).

BACKGROUND: Cocaine and opioid co-use is a notable public health concern, but little is known about correlates of this behavior. Most prior findings come from treatment samples and concern cocaine and heroin. Findings from a nationally representative sample involving primarily prescription opioid misuse would expand knowledge. METHODS: Past-12-month cocaine and/or opioid users in Wave 1 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) formed the sample (N = 839). Cocaine-only, opioid-only, and cocaine/opioid co-users were compared regarding sociodemographics, other substance involvement, psychiatric, and medical conditions/events. RESULTS: Opioid-only users were the largest group (n = 622), followed by cocaine-only (n = 144) and co-users (n = 73). The vast majority of opioid misuse was of prescription opioids (1.4% with past-12-month use of heroin). Notably, co-users did not differ from single drug users in frequency of use of either drug. Co-users did not have significantly greater incidence of any psychiatric conditions, medial conditions, or events. In preliminary analyses, co-users were more likely than either single use group to report several classes of other drug use. However, for most comparisons, opioid use did not add substantial risk beyond cocaine use. Differences on multiple sociodemographic variables suggested opioid-only users were at lowest risk of negative outcomes. These results may relate to a finding that opioid-only users were less likely to have sought treatment. CONCLUSIONS/IMPORTANCE: This sample of past-12-month cocaine and/or opioid users had greater involvement with other substances, more psychiatric and medical conditions compared to the general population. Co-users had greater involvement with other substances than opioid-only users in particular.

Characterization of air manganese exposure estimates for residents in two Ohio towns.

This study was conducted to derive receptor-specific outdoor exposure concentrations of total suspended particulate (TSP) and respirable (dae ≤ 10 µm) air manganese (air-Mn) for East Liverpool and Marietta (Ohio) in the absence of facility emissions data, but where long-term air measurements were available. Our "site-surface area emissions method" used U.S. Environmental Protection Agency's (EPA) AERMOD (AMS/EPA Regulatory Model) dispersion model and air measurement data to estimate concentrations for residential receptor sites in the two communities. Modeled concentrations were used to create ratios between receptor points and calibrated using measured data from local air monitoring stations. Estimated outdoor air-Mn concentrations were derived for individual study subjects in both towns. The mean estimated long-term air-Mn exposure levels for total suspended particulate were 0.35 µg/m³ (geometric mean [GM]) and 0.88 µg/m³ (arithmetic mean [AM]) in East Liverpool (range: 0.014-6.32 µg/m³) and 0.17 µg/m³ (GM) and 0.21 µg/m³ (AM) in Marietta (range: 0.03-1.61 µg/m³). Modeled results compared well with averaged ambient air measurements from local air monitoring stations. Exposure to respirable Mn particulate matter (PM10; PM <10 µm) was higher in Marietta residents.

Unbalanced estrogen metabolism in ovarian cancer.

Greater exposure to estrogens is a risk factor for ovarian cancer. To investigate the role of estrogens in ovarian cancer, a spot urine sample and a saliva sample were obtained from 33 women with ovarian cancer and 34 age-matched controls. Thirty-eight estrogen metabolites, conjugates and DNA adducts were analyzed in the urine samples using ultraperformance liquid chromatography/tandem mass spectrometry, and the ratio of adducts to metabolites and conjugates was calculated for each sample. The ratio of depurinating estrogen-DNA adducts to estrogen metabolites and conjugates was significantly higher in cases compared to controls (p < 0.0001), demonstrating high specificity and sensitivity. DNA was purified from the saliva samples and analyzed for genetic polymorphisms in the genes for two estrogen-metabolizing enzymes. Women with two low-activity alleles of catechol-O-methyltransferase plus one or two high-activity alleles of cytochrome P450 1B1 had higher levels of estrogen-DNA adducts and were more likely to have ovarian cancer. These findings indicate that estrogen metabolism is unbalanced in ovarian cancer and suggest that formation of estrogen-DNA adducts plays a critical role in the initiation of ovarian cancer.

A brief, critical review of research on impaired control over alcohol use and suggestions for future studies.

Impaired control, defined as "a breakdown of an intention to limit consumption" (Heather et al. J Stud Alcohol 1993; 54, 701), has historically been considered an important aspect of addiction. Despite recognition of its importance to addiction and potential value as an early indicator of problem drinking risk, we argue that impaired control over alcohol use has not received sufficient research attention. In an effort to spark further research, the present critical review offers brief discussion of the current state of knowledge regarding impaired control and avenues for future research. Three main research areas are addressed: (i) epidemiology; (ii) measurement issues; and (iii) potential mechanisms underlying relationships between impaired control and subsequent problem drinking. Measurement issues include complexities involved in self-report assessment of impaired control, development and validation of human and animal laboratory models, and impaired control's relationship to other constructs (i.e., impulsivity and other difficulties with self-control; symptoms of dependence such as craving). We discuss briefly 2 potential mechanisms that may help to explain why some drinkers experience impaired control while others do not: neurobiological dysfunction and family history/genetics. Suggestions for future research are focused on ways in which the impaired control construct may enhance prediction of who might be at particular risk of subsequent problem drinking and to facilitate intervention to reduce problem alcohol use.

Exploring wearable technology use and importance of health monitoring in the hazardous occupations of first responders and professional drivers.

OBJECTIVES: Hazardous materials (HAZMAT) pose risks to the health and safety of professionals involved with transportation and emergency responses. Two distinct occupational groups that encounter HAZMAT events are first responders and professional drivers. Wearable technology is a tool that can assist with monitoring the health of professionals involved in HAZMAT events. The aim of this study was to compare and evaluate the perceptions of first responders and professional drivers on wearable technology and attitudes toward health monitoring. METHODS: A survey was administered to first responders (n = 112) and professional drivers (n = 218). Statistical approaches included bivariate analysis, latent class analysis, logistic regression analysis, and path analysis for the variables of interest. RESULTS: There were significant differences between the groups in perceptions of the benefits of monitoring certain health indicators. Professional drivers were more likely to have a history of wearable technology use compared with first responders (odds ratio [OR] = 10.1; 95% CI, 4.42-22.9), reported greater exposure to HAZMAT (OR = 4.32; 95% CI, 2.24-8.32), and were more willing to have their health data monitored by someone other than themselves (OR = 9.27; 95% CI, 3.67-23.4). A multinomial regression model revealed that occupation was not a significant predictor of class preference for acceptance of monitoring specific health indicators. CONCLUSIONS: Occupation appeared to be important but further analysis uncovered that characteristics of individuals within the occupations were more salient to the use of wearable technology. HAZMAT exposure, someone else monitoring health data, and experience with wearable technology use were found to be important factors for perceptions about benefits of health monitoring with wearable technology.

Unbalanced estrogen metabolism in thyroid cancer.

Well-differentiated thyroid cancer most frequently occurs in premenopausal women. Greater exposure to estrogens may be a risk factor for thyroid cancer. To investigate the role of estrogens in thyroid cancer, a spot urine sample was obtained from 40 women with thyroid cancer and 40 age-matched controls. Thirty-eight estrogen metabolites, conjugates and DNA adducts were analyzed by using ultraperformance liquid chromatography/tandem mass spectrometry and the ratio of adducts to metabolites and conjugates was calculated for each sample. The ratio of depurinating estrogen-DNA adducts to estrogen metabolites and conjugates significantly differed between cases and controls (p < 0.0001), demonstrating high specificity and sensitivity. These findings indicate that estrogen metabolism is unbalanced in thyroid cancer and suggest that formation of estrogen-DNA adducts might play a role in the initiation of thyroid cancer.

Is school community readiness related to physical activity before and after the Ready for Recess intervention?

The purpose of this study was to determine: (i) the effect of schools' baseline community readiness (CR) on youth physical activity (PA) at recess prior to the Ready for Recess intervention; (ii) if changes in PA due to the intervention were explained by baseline CR and (iii) if specific components of the intervention altered an association between baseline CR and changes in youth PA. Methods that were employed included: six informants from each of 17 schools participated in CR interviews at baseline (N = 101). CR scores were calculated based on the CR model's nine stages. Direct observation was used to measure PA. Poisson models evaluated the association between baseline CR and PA. Results were that seven schools were in denial, eight in vague awareness and two in pre-planning stages. CR marginally predicted pre-intervention PA. When compared with youth at schools in denial, youth at schools in vague awareness and pre-planning demonstrated significant increases in moderate/vigorous PA. Ready for Recess strengthened this association. This is the first study to demonstrate that school CR may explain changes in PA at recess after a school-based PA intervention. Low CR levels may contraindicate interventions. Efforts to increase school CR a priori may be critical to increasing PA among youth.

Changes in community readiness among key school stakeholders after Ready for Recess.

School community readiness (CR) for health promotion efforts may be critical to the effectiveness of school-based interventions aimed at promoting youth physical activity and reducing childhood obesity. The purpose of this study was to: (i) identify key informants who scored highest on school CR at baseline and (ii) determine the effects of Ready for Recess on changes in CR among school key informants from baseline to post-intervention. Key informants (N = 98) across 17 schools participated in CR interviews. Interview questions focused on school CR for physical activity and childhood obesity efforts across six dimensions. At baseline, principals scored higher than teachers in overall readiness and knowledge of the issue and higher than recess staff and nurses in leadership. Leadership readiness decreased across key informants at post-intervention and principals demonstrated greater decreases when compared with recess staff. Baseline disparities between principals and other key informants suggest principals may have overestimated the readiness of staff implementing the intervention. Declines among principals indicate that they may not have been prepared to deliver adequate support to successfully implement the intervention. These results illuminate the importance of assessing/improving school readiness prior to interventions. The CR model may provide an opportunity to improve school-based physical activity interventions.

Injury, Musculoskeletal Symptoms, and Stress as a Function of Aging in Agricultural Operators in the Central United States.

BACKGROUND: Studies show conflicting evidence on the association of age and occupational injury in agriculture, and few studies have addressed the effect of age on work-related chronic conditions or preventive practices among farmers. METHODS: We examined the probability of injury, work-related stress, musculoskeletal symptoms (MSS), and preventive practices for MSS as a function of aging using surveillance data of 7,711 farm and ranch operators in the central United States. FINDINGS: Segmented regression analyses of men (85% of sample) indicated that the probability of all four outcomes increased up to a certain age and then decreased; the changepoints in years of age being 59.6 for injury, 55.4 for work-related stress, 59.6 for MSS, and 67.9 for MSS preventive practices. Female operators had an increasing trend for stress up to age 29.7, while they showed no changepoints across their age spectrum in the proportion of injury, MSS, and prevention techniques. CONCLUSION/APPLICATION TO PRACTICE: These findings emphasize the need for preventive efforts particularly among younger and middle-aged farmers and ranchers, and the need to modify work duties to match work abilities at older ages.

Agricultural Injuries: Risk Factors and Severity by Affected Body Part among US (Midwest) Farmers.

OBJECTIVES: Statistics from the United States Bureau of Labor Statistics indicate that agriculture consistently ranks as the most hazardous industry in the US. To identify specific targets for prevention, we investigated injury risk factor profiles separately for each injured body site. We also characterized the severity of agricultural injuries by injured body site using the type of medical care and lost work time due to injury. METHODS: We used the Central States Center for Agricultural Safety and Health (CS-CASH) surveillance data for 2018 to perform descriptive statistics and regression modeling. RESULTS: We found that 12% (513/4351) of the participants experienced one or more injuries in the previous 12 months. Compared to female operators, male operators had 3.53 (95% CI: 1.17-10.68) times higher odds of back injury. Operators in livestock production had 2.77 times (95% CI:1.12-6.82), 2.28 times (95% CI:1.25-4.14), and 1.69 times (95% CI:1.10-2.59) higher odds of injury to the chest/trunk, finger, and leg/knee/hip, respectively, compared to operators in crop or mixed production. After adjusting for age and gender, operators who worked full time (vs. part-time) on the farm/ranch had 2.11 times (95% CI:1.03-4.34) higher odds of back injury. Arm/shoulder and leg/knee/hip injuries were more frequent in older age groups. CONCLUSIONS: Prevention measures should be tailored considering specifically livestock producers with emphasis on trainings on proper livestock handling, such as being gentle, establishing routine, keeping distance, and avoiding sudden and loud noise when handling animals. Applying these techniques avoid startling the animals and reduce the risk of injuries.

County-level analysis on occupation and ecological determinants of child abuse and neglect rates employing elastic net regression.

BACKGROUND: Occupation is a known determinant of worker physical and behavioral health risk, yet most previous studies have focused on unemployment, underemployment, and job satisfaction to understand child maltreatment risk. OBJECTIVE: This county-level study (n = 278) investigated the association between occupation and child maltreatment rates and community well-being in California, Colorado, Minnesota, Oregon, and New Mexico. PARTICIPANTS AND SETTING: States were selected due to having comparable, publicly available county-level data on substantiated child abuse and neglect rates within a five-year span between 2015 and 2020. METHODS: Using US Census Bureau American Community Survey data, we collected percentages of the employed population among 13 occupations. Five additional community health indicators came from the County Health Rankings and Roadmaps. Elastic net linear regression was used for variable selection and because of explanatory variables' interrelationships. Linear regression was used to model individual industries positively associated with child abuse rates. RESULTS: The elastic net model selected ten important variables in explaining child maltreatment rates. Important occupational sectors were agriculture, forestry, fishing (AFF), manufacturing, wholesale, retail, finance, and education. Important community indicators included housing, injury deaths, and poor mental health days. Only AFF and retail showed greater child abuse rates with increasing percentages of the workforce in these occupations in unadjusted models (AFF: ß = 0.03 SE = 0.01, p = 0.02; Retail: ß = 0.09 SE = 0.04, p = 0.02). CONCLUSIONS: Our findings suggest group-level effects of counties with a larger AFF and retail presence experiencing higher child maltreatment rates. Given that numerous prior studies of county economies note the strong associations of certain employment types with cultural attitudes, educational opportunities, regional biases, and other unmeasured variables, future studies should incorporate individual level data in a multilevel framework.

Self-reported Quad Bike Use, Safety Behaviors, and Safety Awareness among Young Adults in U.S. and Canadian Agriculture.

The number of agricultural fatalities and injuries related to agricultural quad bike use has risen substantially in the last two decades. Safe engineering design features such as crush protection and roll bars have proven potential to lessen the burden of injury but have traditionally not been included in many quad bike safety training programs. The aim of this study was to survey more than 700 young adults working in U.S. and Canadian agriculture to examine self-reported quad bike safety behaviors and awareness of quad bike safety design engineering features. We found that U.S. males continue to be at higher risk for quad bike-rollover incidents when compared to other groups. Even when accounting for other factors such as age and country, we found that participants who reported youth occupational quad bike use (≤14 years old) were up to 200% more likely to allow extra riders and up to 489% more likely to not wear a helmet when compared to participants who reported beginning occupational quad bike use in adulthood. These findings support the Agricultural Youth Work Guideline (AYWG) for occupational quad bike use at age 16. Less than 20% of young adults working in agriculture were aware of safe design features such as wide frames, stability ratings, crush protection devices, and accessories made by the original equipment manufacturer. There is tremendous need to educate the future agricultural workforce about the importance of choosing quad bikes with safer design features.

Hierarchical Modeling of Psychosocial, Parental, and Environmental Factors for Susceptibility to Tobacco Product Use in 9-10-Year-Old Children.

PURPOSE: Tobacco use during early adolescence can harm brain development and cause adverse health outcomes. Identifying susceptibility in early adolescence before initiation presents an opportunity for tobacco use prevention. METHODS: Data were drawn from the Adolescent Brain and Cognitive Development study that enrolled 9-10-year-old children in 21 US cities between 2016 and 2018 at baseline. Separate nested hierarchical models were performed to incrementally examine the associations of sociodemographic factors, psychosocial influences, parental substance use, immediate social contacts, and perceived neighborhood safety with tobacco use susceptibility among never tobacco users (n = 10,449), overall and stratified by gender. RESULTS: A total of 16.6% of youths who have never used tobacco reported susceptibility to tobacco. Females (vs. males, adjusted odds ratio [AOR] [95% confidence interval {CI}] = 0.80 [0.70-0.91]), positive parental monitoring (AOR [95% CI] = 0.76 [0.66-0.87]) and positive school environment (AOR [95% CI] = 0.95 [0.93-0.98]) were associated with reduced susceptibility to tobacco use. Parental education level (high school, AOR [95% CI] = 1.52 [1.02-2.28]; bachelor's degree, AOR [95% CI] = 1.53 [1.03-2.28]; or postgraduate degree, AOR [95% CI] = 1.54 [1.03-2.3] vs. less than high school), youth substance ever use (AOR [95% CI] = 2.24 [1.95-2.58]), internalizing problems (AOR [95% CI] = 1.03 [1-1.06]), and high scores on negative urgency, lack of premeditation, lack of perseverance, sensation seeking, and positive urgency-impulsive behavior scale were associated with increased susceptibility to tobacco use. Stratified analysis showed that parent-perceived neighborhood safety was associated with reduced susceptibility to tobacco use among males but not among females (AOR [95% CI] = 0.89 [0.81-0.99]) vs. (AOR [95% CI] = 1.01 [0.9-1.13]). A positive school environment was associated with lower susceptibility to tobacco use among females but not among males. DISCUSSION: Parental, environmental, and psychosocial factors influence early childhood tobacco susceptibility. Family and school-based tobacco prevention programs should consider integrating these factors into primary school curricula to reduce youth tobacco susceptibility and later initiation.