Maltreatment, psychiatric symptoms and human immunodeficiency virus/sexual transmitted infection risk behavior among youth with alcohol and other drug use problems: A person-centered analysis

Multi-problem youth undergoing treatment for substance use problems are at high behavioral risk for exposure to sexually transmitted infections (STIs), including human immunodeficiency virus (HIV). Specific risk factors include childhood adversities such as maltreatment experiences and subsequent forms of psychopathology. The current study used a person-centered analytical approach to examine how childhood maltreatment experiences were related to patterns of psychiatric symptoms and HIV/STI risk behaviors in a sample of adolescents (N = 408) receiving treatment services. Data were collected in face-to-face interviews at two community-based facilities. Descriptive statistics and Latent Profile Analysis (LPA) were used to (a) classify adolescents into groups based on past year psychiatric symptoms, and (b) examine relations between class membership and forms of childhood maltreatment experiences, as well as past year sexual risk behavior (SRB). ^ LPA results indicated significant heterogeneity in psychiatric symptoms among the participants. The three classes generated via the optimal LPA solution included: (a) a low psychiatric symptoms class, (b) a high alcohol symptoms class and (c) a high internalizing symptoms class. Class membership was associated significantly with adolescents’ self-reported scores for childhood sexual abuse and emotional neglect. ANOVAs documented significant differences in mean scores for multiple indices of SRB indices by class membership, demonstrating differential risk for HIV/STI exposure across classes. The two classes characterized by elevated psychiatric symptom profiles and more severe maltreatment histories were at increased behavioral risk for HIV/STI exposure, compared to the low psychiatric symptoms class. The high internalizing symptoms class reported the highest scores for most of the indices of SRB assessed. The heterogeneity of psychiatric symptom patterns documented in the current study has important implications for HIV/STI prevention programs implemented with multi-problem youth. The results highlight complex relations between childhood maltreatment experiences, psychopathology and multiple forms of health risk behavior among adolescents. The results underscore the importance of further integration between substance abuse treatment and HIV/STI risk reduction efforts to improve morbidity and mortality among vulnerable youth. ^

The 4-aza-S-ribosyl-L-homocysteine derivatives and the related gamma-lactam and azahemiacetal analogs: Synthesis, inhibition and quorum sensing activity

Quorum sensing (QS) is a population-dependent signaling process bacteria use to control multiple processes including virulence, critical for establishing infection. There are two major pathways of QS systems. Type 1 is species specific or intra-species communication in which N-acylhomoserine lactones (Gram-negative bacteria) or oligopeptides (Gram-positive bacteria) are employed as signaling molecules (autoinducer one). Type 2 is inter-species communication in which S-4,5-dihydroxy-2,3-pentanedione (DPD) or its borate esters are used as signaling molecules. The DPD is biosynthesized by LuxS enzyme from S-ribosylhomocysteine (SRH). Recent increase in prevalence of bacterial strains resistant to antibiotics emphasizes the need for the development of new generation of antibacterial agents. Interruption of QS by small molecules is one of the viable options as it does not affect bacterial growth but only virulence, leading to less incidence of microbial resistance. Thus, in this work, inhibitors of both N-acylhomoserine lactone (AHL) mediated intra-species and LuxS enzyme, involved in inter-species QS are targeted. The γ-lactam and their reduced cyclic azahemiacetal analogs, bearing the additional alkylthiomethyl substituent, were designed and synthesized targeting AHL mediated QS systems in P. aeruginosa and Vibrio harveyi. The γ-lactams with nonylthio or dodecylthio chains acted as inhibitors of las signaling in P. aeruginosa with moderate potency. The cyclic azahemiacetal with shorter propylthio or hexylthio substituent were found to strongly inhibit both las and rhl signaling in P. aeruginosa at higher concentrations. However, lactam and their azahemiacetal analogs were found to be inactive in V. harveyi QS systems. The 4-aza-S-ribosyl-L-homocysteine (4-aza-SRH) analogs and 2-deoxy-2-substituted-S-ribosyl-L-homocysteine analogs were designed and synthesized targeting Bacillus subtilis LuxS enzyme. The 4-aza-SRH analogs in which oxygen in ribose ring is replaced by nitrogen were further modified at anomeric position to produce pyrrolidine, lactam, nitrone, imine and hemiaminal analogs. Pyrrolidine and lactam analogs which lack anomeric hydroxyl, acted as competitive inhibitors of LuxS enzyme with KI value of 49 and 37 µM respectively. The 2,3-dideoxy lactam analogs were devoid of activity. Such findings attested the significance of hydroxyl groups for LuxS binding and activity. Hemiaminal analog of SRH was found to be a time-dependent inhibitor with IC50 value of 60 µM.

Syndemic health disparities and resilience processes related to HIV transmission risk among African American/Black men in south Florida

Rates of HIV infection continue to climb among minority populations and men who have sex with men (MSM), with African American/Black MSM being especially impacted. Numerous studies have found HIV transmission risk to be associated with many health and social disparities resulting from larger environmental and structural forces. Using anthropological and social environment-based theories of resilience that focus on individual agency and larger social and environmental structures, this dissertation employed a mixed methods design to investigate resilience processes among African American/Black MSM.^ Quantitative analyses compared African American/Black (N=108) and Caucasian/White (N=250) MSM who participated in a previously conducted randomized controlled trial (RCT) of sexual and substance use risk reduction interventions. At RCT study entry, using past 90 day recall periods, there were no differences in unprotected sex frequency, however African American/Black MSM reported higher frequencies of days high (P<0.000), and drugs and sex used in combination (P<0.000), and substance dependence (P<0.000) and lower levels of social support (P<0.024) compared to Caucasian/White MSM. At 12- month follow-up, multi-level statistical models found that African American/Black MSM reduced their frequencies of days high and unprotected sex at greater rates than Caucasian/White MSM (P<0.001).^ Qualitative data collected among a sub-sample of African American/Black MSM from the RCT (N=21) described the men's experiences of living with multiple health and social disparities and the importance of RCT study assessments in facilitating reductions in risk behaviors. A cross-case analysis showed different resilience processes undertaken by men who experienced low socioeconomic status, little family support, and homophobia (N=16) compared to those who did not (N=5).^ The dissertation concludes that resilience processes to HIV transmission risk and related health and social disparities among African American/Black MSM varies and are dependent on specific social environmental factors, including social relationships, structural homophobia, and access to social, economic, and cultural capital. Men define for themselves what it means to be resilient within their social environment. These conclusions suggest that both individual and structural-level resilience-based HIV prevention interventions are needed.^

Maltreatment, Psychiatric Symptoms and Human Immunodeficiency Virus/Sexual Transmitted Infection Risk Behavior Among Youth with Alcohol and Other Drug Use Problems: A Person-Centered Analysis

Multi-problem youth undergoing treatment for substance use problems are at high behavioral risk for exposure to sexually transmitted infections (STIs), including human immunodeficiency virus (HIV). Specific risk factors include childhood adversities such as maltreatment experiences and subsequent forms of psychopathology. The current study used a person-centered analytical approach to examine how childhood maltreatment experiences were related to patterns of psychiatric symptoms and HIV/STI risk behaviors in a sample of adolescents (N = 408) receiving treatment services. Data were collected in face-to-face interviews at two community-based facilities. Descriptive statistics and Latent Profile Analysis (LPA) were used to (a) classify adolescents into groups based on past year psychiatric symptoms, and (b) examine relations between class membership and forms of childhood maltreatment experiences, as well as past year sexual risk behavior (SRB). LPA results indicated significant heterogeneity in psychiatric symptoms among the participants. The three classes generated via the optimal LPA solution included: (a) a low psychiatric symptoms class, (b) a high alcohol symptoms class and (c) a high internalizing symptoms class. Class membership was associated significantly with adolescents’ self-reported scores for childhood sexual abuse and emotional neglect. ANOVAs documented significant differences in mean scores for multiple indices of SRB indices by class membership, demonstrating differential risk for HIV/STI exposure across classes. The two classes characterized by elevated psychiatric symptom profiles and more severe maltreatment histories were at increased behavioral risk for HIV/STI exposure, compared to the low psychiatric symptoms class. The high internalizing symptoms class reported the highest scores for most of the indices of SRB assessed. The heterogeneity of psychiatric symptom patterns documented in the current study has important implications for HIV/STI prevention programs implemented with multi-problem youth. The results highlight complex relations between childhood maltreatment experiences, psychopathology and multiple forms of health risk behavior among adolescents. The results underscore the importance of further integration between substance abuse treatment and HIV/STI risk reduction efforts to improve morbidity and mortality among vulnerable youth.

Syndemic Health Disparities and Resilience Processes Related to HIV Transmission Risk among African American/Black Men in South Florida

Rates of HIV infection continue to climb among minority populations and men who have sex with men (MSM), with African American/Black MSM being especially impacted. Numerous studies have found HIV transmission risk to be associated with many health and social disparities resulting from larger environmental and structural forces. Using anthropological and social environment-based theories of resilience that focus on individual agency and larger social and environmental structures, this dissertation employed a mixed methods design to investigate resilience processes among African American/Black MSM. Quantitative analyses compared African American/Black (N=108) and Caucasian/White (N=250) MSM who participated in a previously conducted randomized controlled trial (RCT) of sexual and substance use risk reduction interventions. At RCT study entry, using past 90 day recall periods, there were no differences in unprotected sex frequency, however African American/Black MSM reported higher frequencies of days high (P Qualitative data collected among a sub-sample of African American/Black MSM from the RCT (N=21) described the men’s experiences of living with multiple health and social disparities and the importance of RCT study assessments in facilitating reductions in risk behaviors. A cross-case analysis showed different resilience processes undertaken by men who experienced low socioeconomic status, little family support, and homophobia (N=16) compared to those who did not (N=5). The dissertation concludes that resilience processes to HIV transmission risk and related health and social disparities among African American/Black MSM varies and are dependent on specific social environmental factors, including social relationships, structural homophobia, and access to social, economic, and cultural capital. Men define for themselves what it means to be resilient within their social environment. These conclusions suggest that both individual and structural-level resilience-based HIV prevention interventions are needed.