Statement of Problem: Alkyl nitrites (poppers) are potent short-acting inhalants commonly used by men who have sex with men (MSM). Despite their association with HIV risk, their causal association and mechanism for HIV transmission is not well understood. The aims of this dissertation are to describe available literature on popper use in the U.S. in the context of HIV, identify research gaps, contribute to a better understanding of biological impacts of popper use on MSM with HIV, qualitatively describe contextual factors of popper use among young MSM with HIV, and provide recommendations for clinical care and future research.Methods: Chapter 1 - A scoping review on the use of poppers as a risk factor for people living with and at-risk for HIV in the U.S. was conducted using the Social Ecological Model to contextualize findings. Studies were included (N=89) if they reported results on non-clinical use of alkyl nitrites, were related to HIV or HIV risk, were published between 2001 and 2021, and were conducted in the U.S. Chapter 2 – Total HIV DNA from 90 stored peripheral blood mononuclear cells was measured. Non-parametric rank analysis of covariance (ANCOVA) was conducted on the dependent variable (HIV DNA), with group (popper use versus no popper use) as the independent variable and alcohol, tobacco, and cannabis use as covariates. Chapter 3 – In-depth, semi-structured interviews with 15 young MSM (18-30 years old) living with HIV were conducted to explore individual, social and environmental contexts of popper use influencing HIV care outcomes. Summary of Findings: Between 36% to 72% of MSM in the U.S. report lifetime popper use. Existing research supports the relationship between popper use and HIV risk, however the impact of popper use on the HIV care continuum remains unknown. Concurrent use of poppers and other drugs is common. Among MSM who use poppers, perceived risk of use is low and education is needed and desired. Clinicians caring for MSM and people with HIV are well situated to assess and address popper use. Implications for clinical care, public health, policy, and future research are discussed.

Objective: Much research has investigated the effect of adolescent substance use on neurocognitive abilities but the influence of neurocognition on later use behaviors has been relatively less studied, especially among youth who are already engaged in substance use. Hence, the goal of this dissertation project was to explore predictive associations of neurocognitive markers with substance use behaviors via the following 3 aims (Chapters).Methods: Chapter 1- A scoping review was conducted on the existing literature to synthesize current research on minimally reviewed neurocognitive domains and their predictive associations with substance use (hence papers on well-reviewed impulsivity facets were excluded). Secondary analyses were conducted in Chapters 2 and 3 with data from a longitudinal study for adolescents (Youth At Risk study) to investigate neurocognitive performance in late adolescence during maximum substance use, as predictors of changes in later use. Chapter 2- Hierarchical linear regression models with 4 neurocognitive abilities (inhibition/cognitive flexibility, visuospatial ability, verbal memory, working memory) predicting change in follow-up alcohol use (drinking days, average drinks per drinking day, peak drinks, binge episodes) were estimated while covarying for baseline age, follow-up duration, and sex. Chapter 3- To investigate relationships between neurocognition and cannabis and nicotine use, in addition to alcohol, hierarchical linear regression models predicting change in follow-up overall substance use frequency index scores and individual substance (alcohol, cannabis, nicotine) use outcomes were estimated. Follow-up analyses exploring this relationship within 3 groups of one-, co-, and tri-substance users were also conducted independently. Results: Our scoping review revealed a common theme where cognitive processing in constructs of working memory, attention, emotion regulation, and elevated reward circuit activity during decision-making in childhood and early adolescence predicted earlier onset, greater use escalation, and even development of substance use disorders in some instances. Findings from our 2 analytical aims suggest working memory, verbal memory, visuospatial ability, and inhibition/cognitive flexibility at maximum substance (alcohol, cannabis, and/or nicotine) use in late adolescence are useful as predictors of changes in later use behaviors. Conclusion: Our results have the potential to inform policies and intervention research on cognitive vulnerability markers in youth that predict substance use into adulthood.

Background: The coexistence of micronutrient deficiencies and obesity and their adverse effect on children’s development is understudied.

Aims: The aims of this dissertation were to: 1) describe the link between economic changes and child nutritional outcomes by linking indicators related to immediate and underlying determinants; 2) assess neurocognitive outcomes of response inhibition and accuracy to adolescents exposed to ‘iron deficiency/iron deficiency anemia (ID/IDA) in infancy’, ‘overweight/obesity (OW/OB) in adolescence’, or ‘both’ compared to those without these conditions; and 3) assess the adverse outcome of youth externalizing behavior problem exposed to ‘ID/IDA in infancy’, ‘OW/OB in adolescence’, or ‘both’ compared to those without these conditions.

Methods: Study 1 focuses on the economic growth and nutrition profiles of Brazil, Chile, and Mexico from 1990 to 2010. Estimates for all indicators were retrieved and reconstructed from data sources including the Ministry of Health of each country, the Organization of Economic, and Co-operation and Development and Food Agriculture Organization of the United Nations. Study 2 and 3 uses data from a longitudinal cohort study of Chilean infants who participated in a randomized controlled trial of iron to prevent iron deficiency anemia were used. The Stroop computerized task was used to assess individual's reaction times and accuracy. The Achenbach’s Youth Self Report was used to assess clinically meaningful externalizing behavior problem.

Results: Study 1, presents evidence indicating that economic growth affects child nutritional outcomes through several pathways. Study 2 found that the combination of poorer brain-circuit development during infancy due to ID/IDA and the inflammation of fat due to adolescent OW/OB may have additive effects on reaction times. Study 3 found that adolescents who experienced a two-hit insult of ID/IDA and OW/OB had a positive deviation from additivity (RERI=1.4; S=2.9; AP=40%) and multiplicativity (OR=1.7; 95% CI: 1.1, 2.7) on youth externalizing behavior problem.

Conclusion: The dual burden of nutritional disorders among children are closely linked to their economic growth and nutritional transition. The two-hit insult concept proved useful in understanding the additive and multiplicative effects of two independent nutritional insults and warrants further application.

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