Peptidoglycan fragment release and NOD activation by commensal Neisseria species from humans and other animals.

Neisseria gonorrhoeae, a human restricted pathogen, releases inflammatory peptidoglycan (PG) fragments that contribute to the pathophysiology of pelvic inflammatory disease. The genus Neisseria is also home to multiple species of human- or animal-associated Neisseria that form part of the normal microbiota. Here we characterized PG release from the human-associated nonpathogenic species Neisseria lactamica and Neisseria mucosa and animal-associated Neisseria from macaques and wild mice. An N. mucosa strain and an N. lactamica strain were found to release limited amounts of the proinflammatory monomeric PG fragments. However, a single amino acid difference in the PG fragment permease AmpG resulted in increased PG fragment release in a second N. lactamica strain examined. Neisseria isolated from macaques also showed substantial release of PG monomers. The mouse colonizer Neisseria musculi exhibited PG fragment release similar to that seen in N. gonorrhoeae with PG monomers being the predominant fragments released. All the human-associated species were able to stimulate NOD1 and NOD2 responses. N. musculi was a poor inducer of mouse NOD1, but ldcA mutation increased this response. The ability to genetically manipulate N. musculi and examine effects of different PG fragments or differing amounts of PG fragments during mouse colonization will lead to a better understanding of the roles of PG in Neisseria infections. Overall, we found that only some nonpathogenic Neisseria have diminished release of proinflammatory PG fragments, and there are differences even within a species as to types and amounts of PG fragments released.

Systematic Screening and Assessment of Hospital-Based Youth Violence Prevention Programs.

Youth violence is a preventable public health issue. Few hospital-based programs intentionally focus on youth violence prevention. This project aimed to describe the Systematic Screening and Assessment (SSA) methodology used to identify existing hospital-based youth violence prevention (HBYVP) programs ready for future rigorous evaluation. To identify promising HBYVP programs currently in use and assess readiness for evaluation, data from the 2017 American Hospital Association (AHA) Annual Survey of Hospitals was used to identify hospitals with Level I-III trauma centers with reported HBYVP programs. Information for each program was gathered via environmental scan and key informant interviews. A total of 383 hospital-based violence prevention programs were identified. Two review panels were conducted with violence prevention experts to identify characteristics of programs suitable for an evaluability assessment (EA). Fifteen programs focused on youth (10-24 years old) and were identified to be promising and evaluable. Three of the 15 programs were determined to have the infrastructure and readiness necessary for rigorous evaluation. Lessons learned and best practices for SSA project success included use of streamlined outreach efforts that provide program staff with informative and culturally tailored project materials outlining information about the problem, project goals, proposed SSA activities, and altruistic benefit to the community at the initial point of contact. In addition, success of review panels was attributed to use of software to streamline panelist review processes and use of evaluation and data analysis subject matter experts to serve as panel facilitators. Communities experiencing high youth violence burden and hospitals serving these communities can improve health outcomes among youth by implementing and evaluating tailored HBYVP programs.

Mutation of mltG increases peptidoglycan fragment release, cell size, and antibiotic susceptibility in Neisseria gonorrhoeae.

IMPORTANCE: Neisseria gonorrhoeae is unusual in that the bacteria release larger amounts of cell wall material as they grow as compared to related bacteria, and the released cell wall fragments induce inflammation that leads to tissue damage in infected people. The study of MltG revealed the importance of this enzyme for controlling cell wall growth, cell wall fragment production, and bacterial cell size and suggests a role for MltG in a cell wall synthesis and degradation complex. The increased antibiotic sensitivities of mltG mutants suggest that an antimicrobial drug inhibiting MltG would be useful in combination therapy to restore the sensitivity of the bacteria to cell wall targeting antibiotics to which the bacteria are currently resistant.

Addressing Accessibility Within the Church: Perspectives of People with Disabilities.

People with disabilities often lack full access to corporate worship and participation in their faith communities. Yet many church leaders experience uncertainty about the steps they should take to remove barriers and widen the welcome for members of their community who are impacted by disability. This study examined the recommendations of people with disabilities regarding how churches should pursue greater accessibility. We interviewed 37 Christians who were members of a local church in Tennessee and who experienced various disabilities (i.e., visual impairments, intellectual disability, autism, physical disabilities, hearing impairments). Their guidance coalesced around nine primary actions: advocating, reflecting, asking, researching, equipping, embracing, proacting, including, and praying. We address key implications for churches striving to be inclusive of people with and without disabilities, as well as offer recommendations for future research.

Minimally Invasive Radical Hysterectomy for Cervical Cancer: A Systematic Review and Meta-analysis.

OBJECTIVE: To compare recurrence rate, progression-free survival (PFS), and overall survival for early-stage cervical cancer after minimally invasive (MIS) vs abdominal radical hysterectomy. DATA SOURCES: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Library databases. METHODS OF STUDY SELECTION: We identified studies from 1990 to 2020 that included women with stage I or higher cervical cancer treated with primary radical hysterectomy and compared recurrence and/or PFS and overall survival with MIS vs abdominal radical hysterectomy. (The review protocol was registered with the International Prospective Register of Systematic Reviews: CRD4202173600). TABULATION, INTEGRATION, AND RESULTS: We performed random-effects meta-analyses overall and by length of follow-up. Fifty articles on 40 cohort studies and 1 randomized controlled trial that included 22 593 women with cervical cancer met the inclusion criteria. Twenty percent of the studies had <36 months of follow-up, and 24% had more than 60 months of follow-up. The odds of PFS were worse for women undergoing MIS radical hysterectomy (odds ratio 1.54; 95% CI [confidence interval], 1.24-1.94; 14 studies). When limited to studies with longer follow-up, the odds of PFS were progressively worse with MIS radical hysterectomy (HR [hazard ratio] 1.48 for >36 months; 95% CI, 1.21-1.82; 10 studies; HR 1.69 for >48 months; 95% CI, 1.26-2.27; 5 studies; and HR 2.020 for >60 months; 95% CI, 1.36-3.001; 3 studies). For overall survival, the odds were not significantly different for MIS vs abdominal hysterectomy (odds ratio 0.94; 95% CI, 0.66-1.35; 14 studies) (HR 0.99 for >36 months; 95% CI, 0.66-1.48; 9 studies; HR 1.05 for >48 months; 95% CI, 0.57-1.94; 4 studies; and HR 1.35 for >60 months; 95% CI, 0.73-2.51; 3 studies). CONCLUSION: In our meta-analysis of 50 studies, MIS radical hysterectomy was associated with worse PFS than open radical hysterectomy for early-stage cervical cancer. The emergence of this finding with longer follow-up highlights the importance of long-term, high-quality studies to guide cancer and surgical treatments.

Key Informants Discuss Cancer Care Research for Trans and Gender Diverse People.

The aim was to explore issues in relation to accessing cancer care for the Australian trans and gender diverse community through key informant interviews to inform a larger study on the topic. Semi-structured interviews were conducted with key informants who either had clinical and/or research experience with trans and gender diverse populations or were members of the community who act as advocates (total n = 14). Participants had diverse genders, including three transwomen, one transman, three non-binary people, six cis woman and one cis man. Thematic analysis was used to analyse the transcripts. Four themes were identified in the data: 'More Important Issues' than Cancer Concern, Experiences of Cancer Care, Barriers to Cancer Care and (Potential) Facilitating Factors to Access Cancer Care. The findings show the inconsistencies in awareness of cancer in the trans and gender diverse population, both within the community itself and in healthcare. There are issues concerning underutilization of screening services, healthcare workers lacking knowledge and an invisibility within organizations and systems. Education is needed in cancer care, as are partnerships with community organizations, inclusive policies, improved data collection on gender, targeted health promotion and research.

Racial Equity in Academic Success: The Role of School Climate and Social Emotional Learning.

Many schools and school districts have put significant effort into improving school climate and the social emotional learning (SEL) of students, as they have been shown to be related to improved academic success. Yet, little is known about whether these efforts will contribute to or ameliorate racial differences in academic outcomes. In a series of structural equation models adjusting for school clustering, this study examined mediating and moderating effects of student perceptions of school climate and their own SEL on race differences in self-reported grades. Asian and Latinx students reported slightly more positive perceived school climate while Multiracial students reported significantly less positive perceived school climate compared to White students. Compared to their White peers, all racial groups reported lower levels of SEL. Significant but small indirect standardized effects of race on grades through social emotional competence but not school climate suggest that SEL partially mediates the relationship of race with grades. The association of SEL with grades was significantly stronger for White students compared to other racial groups; the standardized effect size of the association was nearly twice as large for White students as for Black and Native students.

General and Specific Predictors of Comorbid Substance Use and Internalizing Problems from Adolescence to Age 33.

The current study examines the continuity in comorbidity between substance use and internalizing mental health problems from adolescence to adulthood and investigates the general and specific predictors of comorbidity across development. Participants were drawn from the Seattle Social Development Project (N = 808), a gender-balanced, ethnically diverse longitudinal panel. Structural equation modeling was used to examine risk factors for comorbid substance use and internalizing problems in family and peer social environments; substance use- and mental health-specific social environments (family tobacco, alcohol, and marijuana use; family history of depression); and individual risk factors (behavioral disinhibition). Latent factors were created for comorbid substance use and mental health problems at ages 13-14 and comorbidity of substance abuse and dependence symptoms and mental health disorder symptoms at ages 30-33 and included indicators of anxiety, depression, alcohol, tobacco, and marijuana problems. Comorbid problems in adolescence predicted later comorbidity of disorders in adulthood. In addition, family tobacco environment and behavioral disinhibition predicted adolescent comorbidity, while family history of depression was associated with adult comorbidity. Finally, family and peer substance use in adolescence predicted substance use (alcohol, tobacco, and marijuana) both in adolescence and adulthood. The pattern of results suggests that comorbidity in adolescence continues into adulthood and is predicted by both general and behavior-specific environmental experiences during adolescence. Findings clarify the etiology of comorbid internalizing and substance use problems and suggest potential preventive intervention targets in adolescence to curb the development of comorbidity in adulthood.

"Everybody is an Artist": Arts-based Education and Formerly Incarcerated Young Black Men's Academic and Social-Emotional Development in an Alternative School.

Although arts-based programming is shown to positively influence the development of youth exposed to adversity, little is known about the influence these programs have on formerly incarcerated emerging adult Black men enrolled in an alternative school. With educational resilience as a guiding framework, this qualitative case study explored the ways in which an arts-based program in the context of an alternative school designed for formerly incarcerated young people facilitates emerging adult Black men's academic and social-emotional development. Data collection consisted of observations and interviews with school personnel and formerly incarcerated Black male students. Analysis and interpretation included a range of inductive techniques (coding, constant comparisons, and memoing). Results indicate that offering arts-based activities fostered an environment where students could build caring and supportive relationships with peers and school personnel. Instructional practices that integrated music and poetry provided meaningful opportunities for the young men to participate, which appeared to enhance their motivation and attitudes (self, others, learning, and school) and academic self-efficacy, and lessen their psychological and emotional distress. Study findings provide insights into how an arts-based program in an alternative school can improve healthy development and academic achievement among formerly incarcerated young Black men transitioning into adulthood.

Young Adult Unemployment and Later Depression and Anxiety: Does Childhood Neighborhood Matter?

Young adulthood represents a developmental period with disproportionately heightened risk of losing a job. Young adult unemployment has been linked to increased mental health problems, at least in the short term. However, their possible long-term impacts, often referred as "scarring effects," have been understudied, possibly underestimating the magnitude of mental health burden that young adult unemployment generates. This longitudinal study examined whether duration of unemployment during young adulthood is associated with later mental health disorders, after accounting for mental and behavioral health problems in childhood. Furthermore, the current study investigated whether childhood neighborhood characteristics affect this association and if so, in what specific functional ways. Data were drawn from a longitudinal study of developmental outcomes in a community sample in Seattle. Data collection began in 1985 when study participants were elementary students and involved yearly assessments in childhood and adolescence (ages 10-16) and then biennial or triennial assessments (ages 18-39; N = 677 at age 39; 47% European American, 26% African American, 22% Asian American, and 5% Native American; 49% female). The current study findings suggest that duration of unemployment across young adulthood increased mental health problems at age 39, regardless of gender. Childhood neighborhood characteristics, particularly their positive aspect, exerted independent impacts on adult mental health problems beyond unemployment experiences across young adulthood. The current findings indicate a needed shift in service profiles for unemployed young adults-a comprehensive approach that not only facilitates reemployment but also addresses mental health needs to help them to cope with job loss. Further, the present study findings suggest that childhood neighborhoods, particularly positive features such as positive neighborhood involvement, may represent concrete and malleable prevention targets that can curb mental health problems early in life.

Cervical cerclage for singleton pregnant patients on vaginal progesterone with progressive cervical shortening.

BACKGROUND: Premature cervical ripening plays a significant role in spontaneous preterm birth. Vaginal progesterone is the recommended treatment in singleton pregnancy with incidental short cervix. There is lack of evidence on whether it is beneficial to reinforce the cervix with cerclage when the cervical length becomes progressively shortened <10 mm while on vaginal progesterone. OBJECTIVE: Our aims are to determine whether cerclage with vaginal progesterone will: (1) reduce the overall spontaneous preterm birth rate, (2) prolong pregnancy latency, and (3) improve neonatal outcomes compared to vaginal progesterone alone. STUDY DESIGN: This was a retrospective cohort study at the University of Illinois at Chicago of all women with singleton pregnancy on vaginal progesterone for incidental short cervix, cervical length <20 mm. Only those with progressive cervical length shortening <10 mm who delivered at the University of Illinois at Chicago from January 2013 through December 2016 were included. The decision to perform cerclage was based on individual physician preference. Demographic data; information on serial cervical length status; medical, obstetric, and social history; cerclage vs no cerclage; and neonatal outcomes were compared. RESULTS: A total of 310 women with incidental short cervix on vaginal progesterone were identified, and of these, 75 had progressive shortening cervical length <10 mm and met inclusion criteria. Among the women with extremely shortened cervical length <10 mm, 36 women (48%) had cervical cerclage plus vaginal progesterone, and 39 women (52%) continued on vaginal progesterone alone. The baseline characteristics, mean cervical length (5.06 vs 5.52 mm), and mean gestational age at diagnosis of extreme short cervix (21.5 vs 21.3 weeks) were similar between women who received cerclage vs those who did not, respectively. The mean gestational age at delivery was significantly greater for those with cerclage (34 weeks and 3 days vs 27 weeks and 2 days; P < .001). The rate of spontaneous preterm birth at <37, 35, 32, 28, and 24 weeks were significantly lower in the cerclage group: 44.1% vs 84.2%, 38.2% vs 81.6%, 23.5% vs 78.9%, 14.7% vs 63.2%, and 11.8% vs 39.5%, respectively. The rate of spontaneous preterm birth <37 weeks remained significant after controlling for confounders (relative risk, 0.11; 95% confidence interval, 0.03-0.41; P < .001). The average pregnancy latency was 14 weeks in the cerclage combined with vaginal progesterone group compared to vaginal progesterone alone group. Neonatal intensive care unit admission and development of respiratory distress syndrome were significantly lower in the cerclage group compared to vaginal progesterone alone group: 13 (36.1%) vs 23 (65.7%) (relative risk, 0.55; 95% confidence interval, 0.34-0.90; P = .018) and 8 (22.2%) vs 17 (43.6%) (relative risk, 0.59; 95% confidence interval, 0.29-0.90; P = .027), respectively. Neonates of women with cerclage were also significantly less likely to develop necrotizing enterocolitis or experience neonatal death. CONCLUSION: Our study showed that cerclage plus vaginal progesterone in women with extremely shortened cervix significantly decreased overall spontaneous preterm birth rates, prolonged pregnancy latency by 2-fold, and decreased the overall neonatal morbidity and mortality.

High Glucose Induces Reactivation of Latent Kaposi's Sarcoma-Associated Herpesvirus.

A high prevalence of Kaposi's sarcoma (KS) is seen in diabetic patients. It is unknown if the physiological conditions of diabetes contribute to KS development. We found elevated levels of viral lytic gene expression when Kaposi's sarcoma-associated herpesvirus (KSHV)-infected cells were cultured in high-glucose medium. To demonstrate the association between high glucose levels and KSHV replication, we xenografted telomerase-immortalized human umbilical vein endothelial cells that are infected with KSHV (TIVE-KSHV cells) into hyperglycemic and normal nude mice. The injected cells expressed significantly higher levels of KSHV lytic genes in hyperglycemic mice than in normal mice. We further demonstrated that high glucose levels induced the production of hydrogen peroxide (H2O2), which downregulated silent information regulator 1 (SIRT1), a class III histone deacetylase (HDAC), resulting in the epigenetic transactivation of KSHV lytic genes. These results suggest that high blood glucose levels in diabetic patients contribute to the development of KS by promoting KSHV lytic replication and infection. IMPORTANCE Multiple epidemiological studies have reported a higher prevalence of classic KS in diabetic patients. By using both in vitro and in vivo models, we demonstrated an association between high glucose levels and KSHV lytic replication. High glucose levels induce oxidative stress and the production of H2O2, which mediates the reactivation of latent KSHV through multiple mechanisms. Our results provide the first experimental evidence and mechanistic support for the association of classic KS with diabetes.

The Relationship Between Marijuana and Conventional Cigarette Smoking Behavior from Early Adolescence to Adulthood.

Longitudinal analyses investigated (a) the co-occurrence of marijuana use and conventional cigarette smoking within time and (b) bidirectional associations between marijuana and conventional cigarette use in three developmental periods: adolescence, young adulthood, and adulthood. A cross-lag model was used to examine the bidirectional model of marijuana and conventional cigarette smoking frequency from ages 13 to 33 years. The bidirectional model accounted for gender, school-age economic disadvantage, childhood attention problems, and race. Marijuana use and conventional cigarette smoking were associated within time in decreasing magnitude and increased cigarette smoking predicted increased marijuana use during adolescence. A reciprocal relationship was found in the transition from young adulthood to adulthood, such that increased conventional cigarette smoking at age 24 years uniquely predicted increased marijuana use at age 27 years, and increased marijuana use at age 24 years uniquely predicted more frequent conventional cigarette smoking at age 27 years, even after accounting for other factors. The association between marijuana and cigarette smoking was found to developmentally vary in the current study. Results suggest that conventional cigarette smoking prevention efforts in adolescence and young adulthood could potentially lower the public health impact of both conventional cigarette smoking and marijuana use. Findings point to the importance of universal conventional cigarette smoking prevention efforts among adolescents as a way to decrease later marijuana use and suggest that a prevention effort focused on young adults as they transition to adulthood would lower the use of both cigarette and marijuana use.

Exploitation of the complement system by oncogenic Kaposi's sarcoma-associated herpesvirus for cell survival and persistent infection.

During evolution, herpesviruses have developed numerous, and often very ingenious, strategies to counteract efficient host immunity. Specifically, Kaposi's sarcoma-associated herpesvirus (KSHV) eludes host immunity by undergoing a dormant stage, called latency wherein it expresses a minimal number of viral proteins to evade host immune activation. Here, we show that during latency, KSHV hijacks the complement pathway to promote cell survival. We detected strong deposition of complement membrane attack complex C5b-9 and the complement component C3 activated product C3b on Kaposi's sarcoma spindle tumor cells, and on human endothelial cells latently infected by KSHV, TIME-KSHV and TIVE-LTC, but not on their respective uninfected control cells, TIME and TIVE. We further showed that complement activation in latently KSHV-infected cells was mediated by the alternative complement pathway through down-regulation of cell surface complement regulatory proteins CD55 and CD59. Interestingly, complement activation caused minimal cell death but promoted the survival of latently KSHV-infected cells grown in medium depleted of growth factors. We found that complement activation increased STAT3 tyrosine phosphorylation (Y705) of KSHV-infected cells, which was required for the enhanced cell survival. Furthermore, overexpression of either CD55 or CD59 in latently KSHV-infected cells was sufficient to inhibit complement activation, prevent STAT3 Y705 phosphorylation and abolish the enhanced survival of cells cultured in growth factor-depleted condition. Together, these results demonstrate a novel mechanism by which an oncogenic virus subverts and exploits the host innate immune system to promote viral persistent infection.

Validity of Single-Item Screening for Limited Health Literacy in English and Spanish Speakers.

OBJECTIVES: To evaluate 3 single-item screening measures for limited health literacy in a community-based population of English and Spanish speakers. METHODS: We recruited 324 English and 314 Spanish speakers from a community research registry in Dallas, Texas, enrolled between 2009 and 2012. We used 3 screening measures: (1) How would you rate your ability to read?; (2) How confident are you filling out medical forms by yourself?; and (3) How often do you have someone help you read hospital materials? In analyses stratified by language, we used area under the receiver operating characteristic (AUROC) curves to compare each item with the validated 40-item Short Test of Functional Health Literacy in Adults. RESULTS: For English speakers, no difference was seen among the items. For Spanish speakers, "ability to read" identified inadequate literacy better than "help reading hospital materials" (AUROC curve = 0.76 vs 0.65; P = .019). CONCLUSIONS: The "ability to read" item performed the best, supporting use as a screening tool in safety-net systems caring for diverse populations. Future studies should investigate how to implement brief measures in safety-net settings and whether highlighting health literacy level influences providers' communication practices and patient outcomes.

Understanding the interplay of individual and social-developmental factors in the progression of substance use and mental health from childhood to adulthood.

This study examines the interplay between individual and social-developmental factors in the development of positive functioning, substance use problems, and mental health problems. This interplay is nested within positive and negative developmental cascades that span childhood, adolescence, the transition to adulthood, and adulthood. Data are drawn from the Seattle Social Development Project, a gender-balanced, ethnically diverse community sample of 808 participants interviewed 12 times from ages 10 to 33. Path modeling showed short- and long-term cascading effects of positive social environments, family history of depression, and substance-using social environments throughout development. Positive family social environments set a template for future partner social environment interaction and had positive influences on proximal individual functioning, both in the next developmental period and long term. Family history of depression adversely affected mental health functioning throughout adulthood. Family substance use began a cascade of substance-specific social environments across development, which was the pathway through which increasing severity of substance use problems flowed. The model also indicated that adolescent, but not adult, individual functioning influenced selection into positive social environments, and significant cross-domain effects were found in which substance-using social environments affected subsequent mental health.

The Relationship between Interpersonal Violence Victimization and Smoking Behavior across Time and by Gender.

The current study examined relationships between interpersonal violence victimization and smoking from childhood to adulthood. Data were from a community-based longitudinal study (N = 808) spanning ages 10 - 33. Cross-lag path analysis was used to model concurrent, directional, and reciprocal effects. Results indicate that childhood physical abuse predicted smoking and partner violence in young adulthood; partner violence and smoking were reciprocally related in the transition from young-adulthood to adulthood. Gender differences in this relationship were not detected. Social work prevention efforts focused on interpersonal violence and interventions targeting smoking cessation may be critical factors for reducing both issues.

KSHV microRNAs mediate cellular transformation and tumorigenesis by redundantly targeting cell growth and survival pathways.

Kaposi's sarcoma-associated herpesvirus (KSHV) is causally linked to several human cancers, including Kaposi's sarcoma, primary effusion lymphoma and multicentric Castleman's disease, malignancies commonly found in HIV-infected patients. While KSHV encodes diverse functional products, its mechanism of oncogenesis remains unknown. In this study, we determined the roles KSHV microRNAs (miRs) in cellular transformation and tumorigenesis using a recently developed KSHV-induced cellular transformation system of primary rat mesenchymal precursor cells. A mutant with a cluster of 10 precursor miRs (pre-miRs) deleted failed to transform primary cells, and instead, caused cell cycle arrest and apoptosis. Remarkably, the oncogenicity of the mutant virus was fully restored by genetic complementation with the miR cluster or several individual pre-miRs, which rescued cell cycle progression and inhibited apoptosis in part by redundantly targeting IκBα and the NF-κB pathway. Genomic analysis identified common targets of KSHV miRs in diverse pathways with several cancer-related pathways preferentially targeted. These works define for the first time an essential viral determinant for KSHV-induced oncogenesis and identify NF-κB as a critical pathway targeted by the viral miRs. Our results illustrate a common theme of shared functions with hierarchical order among the KSHV miRs.

Progression of Comorbid Depression and Substance Use among Racially Diverse Adults.

Comorbidity of depression and substance abuse is common and a major public health burden. Studies of this form of comorbidity in racial and ethnic minoritized (REM) populations are minimal and have mixed findings. The present study examined the effect of general risk factors (family bonding, supervision, involvement, peer delinquency), depression risk factors (caregiver depression), and substance use risk factors (adult family members, sibling, and peer substance use) in early adolescence (~ ages 13-14) on comorbid depression and substance use in later adolescence (~ ages 15-17) and adulthood (~ ages 29-31) and continuity in comorbidity from adolescence to adulthood. Longitudinal data on 1000 Black (n = 680) Hispanic (n = 170) and White (n = 150) individuals came from the Rochester Youth Development Study. Participants were interviewed 14 times over 17 years beginning in 1988. General risk factors predicted comorbidity across racial/ethnic groups. Substance specific risk predicted comorbidity among Black and Hispanic individuals whereas depression specific risk was predictive among White individuals. Adolescent comorbidity predicted comorbidity in adulthood across race. These findings highlight the importance of substance use intervention for racial and ethnic minoritized individuals and mental health risk factors in Whites. The continuity of comorbidity from adolescence to adulthood highlights the importance of targeting adolescents for intervention to prevent long-term manifestation of this form of comorbidity and its associated consequences.