Assessing Trends in Internalizing Symptoms among Racialized and Minoritized Adolescents: Results from the Monitoring the Future Survey 2005-2020.

Depressive symptoms have rapidly accelerated among recent US adolescent birth cohorts, yet there remains little understanding of trends among racialized and minoritized groups. These groups may experience depressive symptoms due to the deleterious effects of structural racism. Using 2005-2020 Monitoring the Future survey data, we examine all racialized groups using within-group analyses to observe trends in high depressive symptoms across cohorts. Generally, across racialized groups and ages, the odds of high depressive symptoms increased in recent birth cohorts. For example, among 15-16-year-old students racialized as American Indian or Alaska Native and Black-Hispanic/Latine, the 2003-2006 birth cohort had 3.08 (95% CI: 2.00, 4.76) and 6.95 (95% CI: 2.70, 17.88) times higher odds, respectively, of high depressive symptoms compared to the 1987-1990 birth cohorts. Moreover, in a given year 15-16-year-olds generally experienced the highest depressive symptoms compared to 13-14 and 17-18-year-olds, suggesting that age-effects peaked during mid-adolescence. Depressive symptoms increased among US adolescents by birth cohort, within all racialized and minoritized groups assessed. Public health efforts to reduce disparities may consider barriers such as structural racism that may impact the mental health of racialized/minoritized adolescents while increasing access to culturally competent mental health providers and school-based services.

Adolescent simultaneous use of alcohol and marijuana by trends in cigarette and nicotine vaping from 2000 to 2020.

BACKGROUND: Simultaneous alcohol and marijuana (SAM) use is associated with adverse consequences for youth. While SAM use is overall declining among youth, prior studies indicate increasing marijuana use among US adolescents who ever used cigarettes, suggesting possible moderation of the alcohol-marijuana relationship by cigarette use. METHODS: We included 43,845 12-th grade students participating in Monitoring the Future data (2000-2020). A 5-level alcohol/marijuana measure was used, including past-year SAM, alcohol-only, marijuana-only, non-simultaneous alcohol and marijuana, or no use. Multinomial logistic regressions estimated associations between time periods (categorized based on sample size: 2000-2005, 2006-2009, 2010-2014, 2015-2020) and the 5-level alcohol/marijuana measure. Models adjusted for sex, race, parental education and survey mode and included interactions of time periods and lifetime cigarette or vaped nicotine use. RESULTS: While overall SAM among 12th graders decreased from 23.65% to 18.31% between 2000 and 2020, SAM increased among students who never used cigarettes or vaped nicotine (from 5.42% to 7.03%). Among students who ever used cigarettes or vaped nicotine, SAM increased from 39.2% in 2000-2005-44.1% in 2010-2014 then declined to 37.8% in 2015-2020. Adjusted models controlling for demographics indicated that among students with no lifetime cigarette or vaped nicotine use, students in 2015-2020 had 1.40 (95% C.I. 1.15-1.71) times the odds of SAM, and 5.43 (95% C.I. 3.63-8.12) times the odds of marijuana-only (i.e., no alcohol use) compared to students who used neither in 2000-2005. Alcohol-only declined over time in both students who ever and never used cigarettes or nicotine vape products. CONCLUSION: Paradoxically, while SAM declined in the overall adolescent US population, the prevalence of SAM increased among students who have never smoked cigarettes or vaped nicotine. This effect arises because of a substantial decline in the prevalence of cigarette smoking; smoking is a risk factor for SAM, and fewer students smoke. Increases in vaping are offsetting these changes, however. Preventing adolescent use of cigarettes and nicotine vaped products could have extended benefits for other substance use, including SAM.

Alcohol or Drug Self-Help Use Among Adults in the United States: Age, Period, and Cohort Effects Between 2002 and 2018.

In the context of an ongoing and worsening drug overdose epidemic in the USA, increases in free support services like self-help groups may be expected. We estimated differences in self-help use by age, period, or cohort among people who may have needed treatment. We included N = 92,002 adults from the 2002-2018 National Surveys on Drug Use and Health who met past-year DSM-IV substance use disorder criteria or received alcohol/drug treatment in any location. We used hierarchical age-period-cohort (HAPC) modeling to estimate average age-period-cohort associations with self-help. Level-1 covariates included age, race and ethnicity, household income, and sex. We quantified level-2 variance components using the median odds ratio (MOR). We found small positive HAPC period effects for alcohol/drug self-help that were driven by alcohol-specific effects. Birth cohort differences were observed starting at age 48. Younger birth cohorts, especially among Black adults, were less likely to report self-help use than older birth cohorts. MOR was consistently elevated for cohort effects (MOR = 1.17; covariance parameter: 0.15; 95% CI [0.11, 0.23]) but not for period effects. Overall, self-help use did not increase in the context of substantial treatment needs and worsening overdose racialized disparities. Instead, cohort effects explained trends in alcohol/drug self-help. Findings could indicate that younger birth cohorts may need additional supports, especially services tailored for Black and Hispanic people. Supplementary Information: The online version contains supplementary material available at 10.1007/s11469-023-01012-2.

Trends in Racial-Ethnic Disparities in Adult Mental Health Treatment Use From 2005 to 2019.

OBJECTIVE: Although U.S. mental health treatment rates increased in the 2000s, gaps in treatment among racial-ethnic groups grew. Little is known, however, about national trends after 2012, when treatment access increased overall. This study assessed trends in racial-ethnic disparities in past-year treatment rates among people with a major depressive episode, serious psychological distress, or serious mental illness. METHODS: National Survey on Drug Use and Health (2005-2019) data of adults with a past-year major depressive episode (N=49,791) or serious psychological distress (N=89,233) and of adults with past-year serious mental illness (N=24,944; 2008-2019) were analyzed. Linear risk regressions were used to model trends in past-year use of mental health treatment and included an interaction term between survey year and race-ethnicity. RESULTS: Treatment use prevalence (2005-2019) among marginalized individuals with a major depressive episode remained lower than that among White people. The magnitude of the disparity in treatment use between White and Hispanic people with major depressive episode decreased slightly (percentage-point difference=-25.1% to -14.9%), whereas the disparity in treatment use between White people and American Indian/Alaska Native people with serious mental illness increased significantly (percentage-point difference=23.4% to -12.2%), from 2005 to 2019. The magnitude of the disparities for other marginalized racial-ethnic groups did not meaningfully change. CONCLUSIONS: Racial-ethnic disparities in past-year mental health treatment use have persisted. Efforts to reduce disparities should consider structural barriers that hinder treatment use among marginalized groups.

Age, Period, and Cohort Trends in Perceived Mental Health Treatment Need and Differences by Mental Health Severity in the United States, 2008-2019.

Identifying age, period, and cohort trends in perceived mental health treatment need over time by mental illness severity is important to identify where to focus early intervention efforts. We included adults who did not report receiving past-year mental health treatment in the 2008-2019 National Survey on Drug Use and Health (N = 364,676). Hierarchical age-period-cohort models were used to assess perceived mental health treatment need, adjusting for demographics stratified by mental illness severity (none, any but not severe [AMI], severe [SMI]). Median odds ratios estimated cohort and period variance. Cohort effects explained a significant portion of the variance over time; period effects were minimal. Perceived mental health treatment need was highest among adults with AMI from recent birth cohorts (2000-2002: ß = 1.12; 95% CI = 0.96, 1.28). Efforts are needed to address increases in perceived mental health treatment need in younger birth cohorts, such as removing structural barriers (e.g., healthcare system barriers).

Temporal trends in alcohol, cannabis, and simultaneous use among 12th-grade U.S. adolescents from 2000 to 2020: Differences by sex, parental education, and race and ethnicity.

BACKGROUND: Simultaneous use of alcohol and cannabis to enhance each other's effect can cause potential harm. Time trends are diverging in adolescent use of alcohol, which is declining, and cannabis, which is increasing among certain subgroups. However, little is known about trends in their simultaneous and non-simultaneous use. Racial and socioeconomic disparities are emerging in cannabis use, which may portend consequences to public health. METHODS: The 2000 to 2020 Monitoring the Future surveys included approximately 38,000 U.S. 12th-grade students with information on simultaneous use and pertinent demographic factors. A 5-level alcohol/cannabis measure included past-year simultaneous use (i.e., alcohol and cannabis use at the same time), non-simultaneous alcohol and cannabis use, alcohol-use-only, cannabis-use-only, and no use. Multinomial logistic regressions estimated associations (adjusted relative risk ratios; aRRR) with time period (2000 to 2004, 2005 to 2009, 2010 to 2014, 2015 to 2020). Models were adjusted and included interactions with sex, race/ethnicity, and parental education. RESULTS: Between 2000 and 2020, simultaneous alcohol/cannabis use among 12th graders decreased from 24.4% to 18.7%. From 2015 to 2020 compared to 2000 to 2004, the odds of simultaneous use (adjusted relative risk ratio (aRRR) vs. no use = 0.57, 95% CI [0.50, 0.66]) and alcohol-use-only (aRRR = 0.55, 95% CI [0.49, 0.61]) decreased, while cannabis-use-only odds increased (aRRR = 2.59, 95% CI [1.87, 3.59]). Notably, the prevalence of cannabis-use-only more than doubled from 2011 to 2019. The odds of simultaneous use, alcohol-use-only, and non-simultaneous use of alcohol and cannabis declined more rapidly among males than females, whereas the odds for cannabis-use-only increased faster for females than males. Increases in cannabis-use-only were faster for non-white adolescents. CONCLUSION: Simultaneous use of alcohol and cannabis is declining among U.S. adolescents, but the decline is slower among females than males. Declines in simultaneous use are largely concomitant with historical declines in alcohol use, indicating that a continued focus on reducing alcohol use among adolescents and young adults has extended benefits to other adolescent substance use. However, cannabis use without any reported past-year alcohol use more than doubled in the last decade, a concerning trend.

Age, Period, and Cohort Effects of Internalizing Symptoms Among US Students and the Influence of Self-Reported Frequency of Attaining 7 or More Hours of Sleep: Results From the Monitoring the Future Survey 1991-2019.

Adolescent internalizing symptoms have increased since 2010, whereas adequate sleep has declined for several decades. It remains unclear how self-reported sleep attainment has affected internalizing-symptoms trends. Using 1991-2019 data from the Monitoring the Future Study (n ~ 390,000), we estimated age-period-cohort effects in adolescent internalizing symptoms (e.g., loneliness, self-esteem, self-derogation, depressive affect) and the association with yearly prevalence of a survey-assessed, self-reported measure of attaining ≥7 hours of sleep most nights. We focused our main analysis on loneliness and used median odds ratios to measure variance in loneliness associated with period differences. We observed limited signals for cohort effects and modeled only period effects. The feeling of loneliness increased by 0.83% per year; adolescents in 2019 had 0.68 (95% CI: 0.49, 0.87) increased log odds of loneliness compared with the mean, which was consistent by race/ethnicity and parental education. Girls experienced steeper increases in loneliness than boys (P < 0.0001). The period-effect median odds ratio for loneliness was 1.16 (variance = 0.09; 95% CI: 0.06, 0.17) before adjustment for self-reported frequency of getting ≥7 hours sleep versus 1.07 (variance = 0.02; 95% CI: 0.01, 0.03) after adjustment. Adolescents across cohorts are experiencing worsening internalizing symptoms. Self-reported frequency of <7 hours sleep partially explains increases in loneliness, indicating the need for feasibility trials to study the effect of increasing sleep attainment on internalizing symptoms.

A Systematic Review of Simulation Models to Track and Address the Opioid Crisis.

The opioid overdose crisis is driven by an intersecting set of social, structural, and economic forces. Simulation models are a tool to help us understand and address thiscomplex, dynamic, and nonlinear social phenomenon. We conducted a systematic review of the literature on simulation models of opioid use and overdose up to September 2019. We extracted modeling types, target populations, interventions, and findings; created a database of model parameters used for model calibration; and evaluated study transparency and reproducibility. Of the 1,398 articles screened, we identified 88 eligible articles. The most frequent types of models were compartmental (36%), Markov (20%), system dynamics (16%), and agent-based models (16%). Intervention cost-effectiveness was evaluated in 40% of the studies, and 39% focused on services for people with opioid use disorder (OUD). In 61% of the eligible articles, authors discussed calibrating their models to empirical data, and in 31%, validation approaches used in the modeling process were discussed. From the 63 studies that provided model parameters, we extracted the data sources on opioid use, OUD, OUD treatment, cessation or relapse, emergency medical services, and death parameters. From this database, potential model inputs can be identified and models can be compared with prior work. Simulation models should be used to tackle key methodological challenges, including the potential for bias in the choice of parameter inputs, investment in model calibration and validation, and transparency in the assumptions and mechanics of simulation models to facilitate reproducibility.

Contraceptive discontinuation and switching in urban Istanbul region in Turkey.

OBJECTIVE: To evaluate rates of contraceptive discontinuation and method switching and examine their determinants in Istanbul, Turkey, because discontinuation of modern contraception leading to unintended pregnancy is a public health concern. METHODS: We conducted a cross-sectional household survey between March and June 2018 among 4224 married women of reproductive age (16-44 years). Information on contraceptive use and discontinuation for the 31 months preceding the survey was recorded in a monthly calendar. Using single and multiple decrement life-table methods, we calculated the overall discontinuation and the cause-specific discontinuation rates. RESULTS: The 12-month overall discontinuation rate was 12.32%. Intrauterine devices had the lowest discontinuation rate (7.12%). The most common reasons for discontinuation were the desire to become pregnant (6.56%) and method failure (2.76%). One in three episodes of discontinuation was not followed by method switching (32.16%). Age, education, and the method type were predictive of contraceptive discontinuation. CONCLUSION: To reduce method failure, women should be provided with information about method effectiveness, correct use of methods, and what to do if they anticipate their method failed (e.g., emergency contraception). Programs should focus on improving knowledge about discontinuation and method failure. Contraceptive counseling should also emphasize timely switching to an effective method after discontinuation.

Trends in cannabis use and attitudes toward legalization and use among Australians from 2001-2016: an age-period-cohort analysis.

BACKGROUND AND AIMS: Changes in cannabis legalization and availability in Australia necessitate monitoring use and attitudes. We estimated age-period-cohort effects of past-year cannabis use and attitudes toward criminalization and legalization. DESIGN: Analysis of six waves of the Australian National Drug Strategy Household Survey (NDSHS) every 3 years (2001-2016). SETTING AND PARTICIPANTS: The study was nationally representative of Australian households using multistage random sampling, totaling 145 168 respondents 18-79 years old. Data were collected using telephone, face-to-face, and drop-and-collect. Sample sizes per analysis varied based on data availability (~107 000-127 000 per model). MEASUREMENTS: Six waves of data for past-year cannabis use (by sex and education), attitudes toward criminalization and legalization. FINDINGS: Past-year cannabis use decreased in young adults ages 18-35 from 2001-2016 (25.1%-18.6%) and increased in middle adults ages 36-55 (8.6%-10.1%) and older adults ages 56-79 (0.6%-3.0%). We observed a positive period effect and negative cohort effect for recent cohorts for past-year use (e.g. 1955 cohort had 1.41 (95% CI: [1.11, 1.70]) increased log odds vs. 1998 cohort had -2.86 (95% CI: [-3.17, -2.55]) increased log odds) compared with the mean across years. Results were consistent by sex and varied by education. We observed a negative period effect for criminalization favorability (0.14 (95% CI: [0.003, 0.28]) increased log odds in 2001 vs. -0.31 (95% CI: [-0.45, -0.17]) increased log odds in 2016) and positive cohort effect for recent cohorts. Last, we observed a positive period effect for legalization support (-0.03 (95% CI: [-0.20, 0.14]) increased log odds in 2001 vs. 0.38 (95% CI: [0.22, 0.55]) increased log odds in 2016) and negative cohort effect for recent cohorts. CONCLUSION: Cannabis use appears to be increasing in Australia among adults over 35, while decreasing among adolescents and young adults. Legalization support also appears to have been increasing since 2007, signaling discordance between use and attitudes among adolescents and young adults, and potentially predicting increases in use over time.

An Application of the List Experiment to Estimate Abortion Prevalence in Karachi, Pakistan.

CONTEXT: Abortion is particularly difficult to measure, especially in legally restrictive settings such as Pakistan. The List Experiment-a technique for measuring sensitive health behaviors indirectly-may minimize respondents' underreporting of abortion due to stigma or legal restrictions, but has not been previously applied to estimate abortion prevalence in Pakistan. METHODS: A sample of 4,159 married women of reproductive age were recruited from two communities of Karachi in 2018. Participants completed a survey that included a double list experiment to measure lifetime abortion prevalence, as well as direct questions about abortion and other background characteristics. Data were used to calculate direct and indirect estimates of abortion prevalence for the overall sample and by sociodemographic characteristics, as well as to test for a design effect. Regression analyses were conducted to examine associations between characteristics and abortion reporting from direct questioning and the list experiment. RESULTS: The estimate of abortion prevalence from the list experiment was 16%; the estimate from the direct question was 8%. No evidence of a design effect was found. Abortion reporting was associated with most selected characteristics in the regression model for direct questioning, but with few in the list experiment models. CONCLUSIONS: That the estimate of abortion prevalence in Karachi generated from the list experiment was twice that generated from direct questioning suggests that the indirect method reduced underreporting, and may have utility to estimate abortion in similar settings and to improve the accuracy of data collecting for other sensitive health topics.

RESUMEN Contexto: El aborto es particularmente difícil de medir, especialmente en entornos legalmente restringidos, como en Pakistán. El Experimento de Lista­una técnica para medir de manera indirecta comportamientos de salud sensibles­podría minimizar el hecho de que las personas encuestadas subnotifiquen el número de abortos debido al estigma o a restricciones legales; sin embargo, esta técnica no ha sido aplicada previamente para estimar la prevalencia del aborto en Pakistán. Métodos: En 2018, se reclutó una muestra de 4,159 mujeres casadas en edad reproductiva, provenientes de dos comunidades de Karachi. Las participantes completaron una encuesta que incluyó un experimento de lista doble para medir la prevalencia de aborto, así como preguntas directas sobre el aborto y otras características del contexto. Los datos se usaron para calcular estimaciones directas e indirectas de la prevalencia de aborto en la muestra en general y por características sociodemográficas, así como para probar el efecto de diseño. Se realizaron análisis de regresión para examinar las asociaciones entre las características y los abortos reportados a partir de las preguntas directas y el experimento de lista. Resultados: La estimación de la prevalencia de aborto del experimento de lista fue del 16%; la estimación a partir de la pregunta directa fue del 8%. No se encontró evidencia de un efecto de diseño. La notificación del número de abortos se asoció con la mayoría de las características seleccionadas en el modelo de regresión para la pregunta directa, pero con pocas características en los modelos de experimento de lista. Conclusiones: El hecho de que la estimación de la prevalencia de aborto en Karachi generada a partir del experimento de lista fue el doble que la obtenida a partir de preguntas directas, sugiere que el método indirecto reduce la subnotificación. El experimento de lista podría ser útil para estimar el aborto en entornos similares y para mejorar la precisión de la recolección de datos sobre otros temas sensibles de salud.

RÉSUMÉ Contexte: Il est extrêmement difficile de mesurer la prévalence de l'avortement, en particulier dans les contextes soumis à des lois restrictives, comme le Pakistan. La technique de mesure indirecte de comportements de santé sensibles « List Experiment ¼ peut minimiser la sous-déclaration de l'avortement pour raisons de stigmatisation ou de restrictions légales, mais elle n'a pas précédemment été utilisée pour estimer la prévalence de l'avortement au Pakistan. Méthodes: Un échantillon de 4 159 femmes mariées en âge de procréer a été recruté dans deux communautés de Karachi en 2018. Les participantes ont répondu à une enquête menée par double approche List Experiment pour mesurer la prévalence de l'avortement et qui comprenait aussi des questions directes sur l'avortement et d'autres caractéristiques socioculturelles. Les données ont servi à calculer les estimations directes et indirectes de la prévalence de l'avortement pour l'échantillon global et par caractéristiques sociodémographiques, ainsi qu'à tester l'effet du plan de sondage. Les associations entre les caractéristiques et la déclaration de l'avortement dans le questionnaire direct et la List Experiment ont été examinées par analyses de régression. Résultats: L'estimation de la prévalence de l'avortement selon la mesure List Experiment était de 16%; sur la base du questionnaire direct, elle était de 8%. Aucun signe d'effet de plan de sondage n'a été observé. La déclaration de l'avortement était associée à la plupart des caractéristiques sélectionnées dans le modèle de régression pour le questionnaire direct, mais à quelques-unes seulement dans les modèles de l'outil List Experiment. Conclusions: Le fait que l'estimation de la prévalence de l'avortement à Karachi générée d'après la List Experiment s'est révélée le double de celle produite par le questionnaire direct laisse entendre que la méthode indirecte réduit la sous-déclaration. La mesure List Experiment peut être utile à l'estimation de l'avortement dans des contextes similaires et pour améliorer l'exactitude des données collectées sur d'autres sujets de santé sensibles.

Impact of home-based family planning counselling and referral on modern contraceptive use in Karachi, Pakistan: a retrospective, cross-sectional matched control study.

OBJECTIVES: To assess: (1) the impact of a reproductive health program on modern contraceptive use from baseline to program close; (2) the sustained impact from baseline to follow-up 36 months later; and (3) the exposure-adjusted impact at program close and follow-up. DESIGN: Retrospective, cross-sectional matched control study. SETTING: Karachi, Pakistan. PARTICIPANTS: 2561 married women aged 16-49 years. INTERVENTIONS: The Willows Program, a community-based family planning counselling and referral program implemented from 2013 to 2015. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was community-level modern contraceptive prevalence rate (mCPR), measured for January 2013 (baseline), June 2015 (program close) and at follow-up 36 months later. A secondary outcome was exposure-adjusted mCPR (among women reporting a family planning home visit) at program close and at follow-up. RESULTS: There was no significant effect on community-level mCPR at program close (2.4 percentage point increase in intervention over comparison; 95% CI -2.2 to 7.0) or at follow-up (1.9 percentage point decrease; 95% CI -6.7 to 2.8). Only 18% of women in the intervention area reported receiving a family planning visit in the preceding 5 years. Among those reporting a visit, we observed a significant 10.3 percentage point increase (95% CI 4.6 to 15.9) from baseline to close, and a non-significant 2.0 percentage point increase (95% CI -3.8 to 7.8) from baseline to follow-up, relative to matched women in the comparison area. The cost per new modern method user was US$1089, while the cost per user-year during the intervention period was US$455. CONCLUSIONS: The program had a positive short-term effect on women who received a family planning visit; however, this effect was not sustained. Program coverage was low and did not significantly increase community-level family planning use. Findings highlight the need to increase community coverage of high-quality counselling and contextually relevant interventions for family planning demand generation.

Associations between digital technology and substance use among U.S. adolescents: Results from the 2018 Monitoring the Future survey.

OBJECTIVE: Social media and other digital technology use facilitate connection among adolescents, but also may reinforce norms and substance-related content from peers and advertisers. We use nationally representative data to examine the association between digital technology and past 30-day use of alcohol, cannabis, and vaping. METHODS: Data were drawn from the 2018 Monitoring the Future survey of US adolescents (N = 44,482). Poisson regressions estimated the association between hours/day of technology use and past 30-day use of alcohol, cannabis, and vaping adjusting for grade, sociodemographics, and other past-year drug use. RESULTS: Across grades, mean hours of social media/day was 3.06 (standard deviation = 2.90), past 30-day alcohol, cannabis, flavor vaping, cannabis vaping, and nicotine vaping were 15.7 %, 12.6 %, 10.6 %, 4.9 %, and 11.2 %, respectively. Digital technology use that required interaction with others was associated with increased risk of past 30-day drinking, cannabis use, and vaping. For example, social media 3+ hours/day was associated with past 30-day drinking (adjusted relative risk [aRR]: 1.99, 95 % CI: 1.65, 2.41). The magnitude of association was consistent across texting, phone calls, and video chatting, which were all more strongly associated with substance use than with activities that do not require interaction such as gaming and watching videos. CONCLUSION: Digital technology that facilitates interaction among adolescents, such as texting and social media, is associated with past substance use. Magnitudes of association are consistent across substances, supporting the hypothesis that networks of adolescents are social drivers of substance use, rather than the technology itself.

Longitudinal association of biomarkers of pesticide exposure with cardiovascular disease risk factors in youth with diabetes.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death among individuals with diabetes, but little is known about the role of exposures to environmental chemicals such as pesticides in the early development of CVD risk in this population. OBJECTIVES: To describe changes over time in concentrations of pesticide biomarkers among youth with diabetes in the United States and to estimate the longitudinal association between these concentrations and established risk factors for CVD. METHODS: Pesticide biomarkers were quantified in urine and serum samples from 87 youth with diabetes participating in the multi-center SEARCH cohort study. Samples were obtained around the time of diagnosis (baseline visit, between 2006 and 2010) and, on average, 5.4 years later (follow-up visit, between 2012 and 2015). We calculated geometric mean (95% CI) pesticide biomarker concentrations. Eight CVD risk factors were measured at these two time points: body mass index (BMI) z-score, HbA1c, insulin sensitivity, fasting C-peptide (FCP), LDL cholesterol, HDL cholesterol, total cholesterol, and triglycerides. Linear regression models were used to estimate the associations between each pesticide biomarker at baseline and each CVD risk factor at follow-up, adjusting for baseline health outcome, elapsed time between baseline and follow up, sex, age, race/ethnicity, and diabetes type. RESULTS: Participants were, on average, 14.2 years old at their baseline visit, and most were diagnosed with type 1 diabetes (57.5%). 4-nitrophenol, 3-phenoxybenzoic acid, 2,4-dichlorophenoxyacetic acid (2,4-D), 3,5,6-trichloro-2-pyridinol, 2,2-bis(4-chlorophenyl)-1,1-dichloroethene, and hexachlorobenzene were detected in a majority of participants at both time points. Participants in the highest quartile of 2,4-D and 4-nitrophenol at baseline had HbA1c levels at follow-up that were 1.05 percentage points (95% CI: -0.40, 2.51) and 1.27 percentage points (0.22, 2.75) higher, respectively, than participants in the lowest quartile of these pesticide biomarkers at baseline. These participants also had lower log FCP levels (indicating reduced beta-cell function) compared to participants in the lowest quartile at baseline: beta (95% CI) for log FCP of -0.64 (-1.17, -0.11) for 2,4-D and -0.39 (-0.96, 0.18) for 4-nitrophenol. In other words, participants in the highest quartile of 2,4-D had a 47.3% lower FCP level compared to participants in the lowest quartile, and those in the highest quartile of 4-nitrophenol had a 32.3% lower FCP level than those in the lowest quartile. Participants with trans-nonachlor concentrations in the highest quartile at baseline had HbA1c levels that were 1.45 percentage points (-0.11, 3.01) higher and log FCP levels that were -0.28 (-0.84, 0.28) lower than participants in the lowest quartile at baseline, that is to say, participants in the highest quartile of trans-nonachlor had a 24.4% lower FCP level than those in the lowest quartile. While not all of these results were statistically significant, potentially due to the small same size, clinically, there appears to be quantitative differences. No associations were observed between any pesticide biomarker at baseline with BMI z-score or insulin sensitivity at follow-up. CONCLUSIONS: Exposure to select pesticides may be associated with impaired beta-cell function and poorer glycemic control among youth with diabetes.

Elongation factor Ts directly facilitates the formation and disassembly of the Escherichia coli elongation factor Tu·GTP·aminoacyl-tRNA ternary complex.

BACKGROUND: Aminoacyl-tRNA (aa-tRNA) enters the ribosome in a ternary complex with the G-protein elongation factor Tu (EF-Tu) and GTP. RESULTS: EF-Tu·GTP·aa-tRNA ternary complex formation and decay rates are accelerated in the presence of the nucleotide exchange factor elongation factor Ts (EF-Ts). CONCLUSION: EF-Ts directly facilitates the formation and disassociation of ternary complex. SIGNIFICANCE: This system demonstrates a novel function of EF-Ts. Aminoacyl-tRNA enters the translating ribosome in a ternary complex with elongation factor Tu (EF-Tu) and GTP. Here, we describe bulk steady state and pre-steady state fluorescence methods that enabled us to quantitatively explore the kinetic features of Escherichia coli ternary complex formation and decay. The data obtained suggest that both processes are controlled by a nucleotide-dependent, rate-determining conformational change in EF-Tu. Unexpectedly, we found that this conformational change is accelerated by elongation factor Ts (EF-Ts), the guanosine nucleotide exchange factor for EF-Tu. Notably, EF-Ts attenuates the affinity of EF-Tu for GTP and destabilizes ternary complex in the presence of non-hydrolyzable GTP analogs. These results suggest that EF-Ts serves an unanticipated role in the cell of actively regulating the abundance and stability of ternary complex in a manner that contributes to rapid and faithful protein synthesis.