Is Childhood Adversity Before Age 5 Associated with Adolescent and Young Adult Substance Use? Findings from a U.S. Prospective Cohort Study.

OBJECTIVE: Growing research suggests that adversity experienced early in life can affect young children's development, with implications for health-related outcomes years later. This study explored long-term associations between early life adversity before age 5 (ELA) and later substance use outcomes, and racial and ethnic differences in associations. METHOD: Data are from children born 1984-2000 to female participants in the U.S. National Longitudinal Study of Youth-1979 cohort (N = 4582 children nested within 2683 mothers, with 1.4-1.8 outcome observations on average for each child in each age period). ELA at ages 0-4 was measured through home observations and maternal surveys, and included high parental conflict and maternal hazardous drinking/drug use (threat-related exposures), and low cognitive stimulation, low emotional support, and household poverty (deprivation-related exposures). Alcohol and cannabis use frequency were measured in biennial adolescent and young adult surveys through 2016. Analyses involved multilevel regression and interactions accounting for demographics, birth cohort, and family history of alcoholism. RESULTS: ELA-threat exposure was associated with greater alcohol and cannabis use frequency in mid-adolescence and at ages 22-25 and 26-32 [exp(ß^)'s = 1.05 to 1.13, p's < 0.05]. Associations of ELA-deprivation with substance use were either null or negative. There were pronounced racial and ethnic inequities in ELA exposure but no evidence of racial and ethnic differences in associations between ELA and later substance use. CONCLUSIONS: Broadening substance use research to focus on early childhood conditions appears warranted. Studies that identify intervening pathways to outcomes could inform early, targeted substance use prevention. Efforts are needed to eliminate racial and ethnic inequities in early life conditions.

Protective effects of ethnic enclaves: Testing pathways to alcohol use and use disorders in Mexican American young adults.

Ethnic enclave residence is associated with decreased risk for drinking and related problems, but less is known about the mechanisms that explain this association. Informed by theories of social control, we used a multilevel framework to examine whether negative attitudes toward drinking mediated associations between ethnic enclave residence (i.e., neighborhood linguistic isolation) and alcohol outcomes among Mexican American young adults (N = 628) in Southern California. Model 1 assessed mediation effects in the pathways from linguistic isolation to current drinking and alcohol use disorder (AUD). Model 2 adjusted for parental drinking attitudes and neighborhood alcohol availability. There were differential associations by gender in direct effects of linguistic isolation and negative drinking attitudes on both drinking and AUD. Among women only, linguistic isolation was related to greater abstinence and decreased AUD after accounting for social control proxies of parent attitudes and alcohol availability. Young adults' own drinking attitudes did not mediate relationships between linguistic isolation and alcohol outcomes. This study offers evidence on the importance of disaggregating Hispanic national groups by gender to uncover social mechanisms within ethnic enclave settings for tailored supports in reducing risk of drinking and alcohol-related harms.

Risky drinking and other drug use in adults with chronic conditions in the United States: differential associations by race/ethnicity.

Co-use of multiple drugs may prolong or increase heavy drinking, even for individuals with health conditions adversely affected by it. Patterns of alcohol and drug use may vary across racial/ethnic groups, with differential implications for health. This study examines racial/ethnic differences in the associations between risky drinking and other drug use in adults with diabetes, hypertension, heart disease, or cancer. Multiple logistic regression modeling, stratified by condition, was performed using a nationally representative sample of adults drawn from the 2015 to 2019 National Survey on Drug and Health. The outcome was risky drinking (consuming more than 7/14 drinks weekly). Other drugs considered were tobacco, marijuana, illicit drugs, and non-medical prescription drugs. Covariates included age, sex, education, income, marital/cohabitation status, health insurance coverage, and self-rated health status. Each drug category was positively associated with risky drinking across all four conditions. Racial/ethnic minority adults were less likely than White adults to engage in risky drinking, with this pattern most consistent for those with hypertension. Other drug use in minority adults (i.e. tobacco and illicit drug use in Black and Hispanic adults, and marijuana and prescription drug use in Asian adults) was associated with disproportionately greater odds of risky drinking compared with White adults. This pattern was more prominent for those with a heart condition, and not found for those with cancer. Future interventions might address co-use of alcohol and other drugs in adults with chronic conditions, with special attention to racial/ethnic minority adults.

Synthesis and in vitro antiprotozoal evaluation of novel metronidazole-Schiff base hybrids.

Herein we report the synthesis of 21 novel small molecules inspired by metronidazole and Schiff base compounds. The compounds were evaluated against Trichomonas vaginalis and cross-screened against other pathogenic protozoans of clinical relevance. Most of these compounds were potent against T. vaginalis, exhibiting IC50 values < 5 µM. Compound 20, the most active compound against T. vaginalis, exhibited an IC50 value of 3.4 µM. A few compounds also exhibited activity against Plasmodium falciparum and Trypanosomal brucei brucei, with compound 6 exhibiting an IC50 value of 0.7 µM against P. falciparum and compound 22 exhibiting an IC50 value of 1.4 µM against T.b. brucei. Compound 22 is a broad-spectrum antiprotozoal agent, showing activities against all three pathogenic protozoans under investigation.

Ethnic enclaves and ethnoburbs: Are there differences in associations with juvenile offense type among Asian Americans?

Little is known about the neighborhood context of offending for Asian American youth. The current study differentiates between coethnic neighborhood types and considers if residence in ethnoburbs-a more recently conceptualized coethnic neighborhood-is associated with more serious arrests (for substance, property, weapon, or violent offenses). Asian youth in ethnic enclaves had lower odds of a violence arrest relative to youth in non-coethnic neighborhoods. Youth in ethnoburbs had greater odds of a weapons arrest, but this association is attenuated after adjusting for individual-level covariates. Implications for future research include exploring mechanisms for place-based targeted intervention strategies.

Associations of clustered health risk behaviors with diabetes and hypertension in White, Black, Hispanic, and Asian American adults.

BACKGROUND: The clustering of Big Four contributors to morbidity and mortality-alcohol misuse, smoking, poor diet, and physical inactivity-may further elevate chronic health risk, but there is limited information about their specific combinations and associated health risks for racial/ethnic minority groups. We aimed to examine patterns of clustering in risk behaviors for White, Black, Hispanic, and Asian American adults and their associations with diabetes and hypertension. As these behaviors may be socioeconomically-patterned, we also examined associations between clustering and socioeconomic status (SES). METHODS: Latent class analyses and multinomial and logistic regressions were conducted using a nationally-representative sample of United States (US) adults ages 40-70 (N = 35,322) from Waves 2 (2004-2005) and 3 (2012-2013) of the National Epidemiologic Survey on Alcohol and Related Conditions. Obesity was used as a proxy for unhealthy diet. The outcomes were diabetes and hypertension. RESULTS: A relatively-healthy-lifestyle class was found only among White adults. Common patterns of unhealthy clustering were found across groups with some variations: the obese-inactive class among White, Black, and Hispanic adults (and the inactive class among Asian adults); the obese-inactive-smoking class among White, Black, and Hispanic adults; the smoking-risky-drinking class among White and Hispanic adults; and the smoking-risky-drinking-inactive class among Black and Asian adults. Positive associations of unhealthier clustering (having a greater number of risk behaviors) with lower SES (i.e., family income and education) and with health conditions were more consistent for Whites than for other groups. For racial minority groups, lower education than income was more consistently associated with unhealthy clusters. The associations between unhealthier clustering and diabetes and hypertension were less clear for Blacks and Asians than for Whites, with no significant association observed for Hispanics. CONCLUSION: Concerted efforts to address clustered risk behaviors in most US adults, particularly in racial/ethnic minority groups given the high prevalence of unhealthy clustering, are warranted.

Age of onset and alcohol and cannabis use disorders among Mexican American young adults: Robust substance-specific effects of early use as a risk factor.

We investigated the substance-specific and cross-substance risk associated with early onset (before age 15) of drunkenness and cannabis use in the subsequent development of alcohol (AUD) and cannabis use disorder (CUD) in Mexican American young adults. Survival analyses employed Cox proportional hazards models for AUD and CUD, separately. In cross-risk analyses, we modeled estimates for those participants reporting lifetime use of both substances. Early onset of drunkenness and early onset of cannabis use were associated with shorter time to AUD and CUD, respectively, even after accounting for psychiatric disorders. While there were no cross-risk associations, adjusting for psychiatric disorders and early onset cannabis use attenuated the association of early drunkenness with AUD.

Alcohol Consumption, Cardiovascular-Related Conditions, and ALDH2*2 Ethnic Group Prevalence in Asian Americans.

BACKGROUND: Little is known about the relationships between alcohol consumption and cardiovascular disease (CVD) and related chronic conditions in Asian Americans and how such risk relationships vary among their subgroups. We examine these relationships in Asian Americans and their moderation by ethnic prevalence of a variant the aldehyde dehydrogenase gene: ALDH2*2. METHODS: Multiple logistic regression modeling was performed using a nationally representative sample of Asian-American adults aged 30 to 70 (n = 1,720) from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) Waves 2 (2004 to 2005) and 3 (2012 to 2013). Outcomes considered were diabetes, hypertension, high cholesterol, CVD, any of the 3 conditions (i.e., diabetes, high cholesterol, and CVD) documented to have a J-shaped relationship with drinking (CVDRC3), and any of the CVD-related conditions (ANYCVD). Demographic and socioeconomic characteristics, health insurance coverage, and other lifestyle risk factors (smoking and obesity/overweight) were adjusted. Analyses were stratified by gender. RESULTS: Alcohol consumption level was positively associated only with hypertension in Asian males, with consuming 7 to 14 drinks per week associated with more than double the risk of lifetime abstinence. For females, alcohol consumption had a dose-response relationship with high cholesterol and CVDRC3. Membership in the higher ALDH2*2 ethnic group overall was associated with lower risk of CVD-related conditions. However, compared to abstainers in lower ALDH2*2 group, females in the higher ALDH2*2 group who consumed more than 7 drinks per week had a higher risk of diabetes, hypertension, CVDRC3, and ANYCVD. CONCLUSIONS: Asian Americans may have increased risk of CVD-related conditions at relatively low alcohol consumption levels. Among Asian-American females, in particular, any amount of drinking may increase risk for high cholesterol or any of the CVD-related conditions previously documented to have a curvilinear relationship with drinking. These risks may be particularly elevated for those in ethnic groups with a high prevalence of ALDH2*2.

Drinking and Neighborhood Contexts of Alcohol's Harms from Others.

AIMS: Negative consequences of alcohol (or secondhand effects) extend beyond drinkers to affect other people, including both known others (friends, family members, spouses/partners) and strangers. Secondhand effects of alcohol manifest across various social environments, including the places where people drink and the neighborhoods where they live. These neighborhoods are characterized by different levels of alcohol availability and degrees of residential social cohesion. Hence, social environments may confer risk or protect from harms from others' drinking. The current study explores: (a) how drinking venues and neighborhood contexts relate to harms from other people's drinking (both known others and strangers), and (b) whether these associations vary by gender. METHODS: Using pooled data from the National Alcohol Survey and National Alcohol's Harms to Others Survey (N = 5425), we regressed harms from various drinking others on social environment characteristics (drinking venues, alcohol availability and social cohesion) for the full sample and separately by gender. We used the false discovery rate method to adjust for multiple testing. RESULTS: Overall, greater neighborhood social cohesion was associated with lower odds of harm from drinking others and, specifically, harm from drinking strangers. The effect of social cohesion was most pronounced for men. CONCLUSIONS: Social cohesion was the most salient neighborhood factor associated with reduced alcohol-related harms from strangers. Directions for future research and policies to mitigate these harms are discussed.

Intersections Of Neighborhood Co-Ethnic Density and Nativity Status On Heavy Drinking In a General Population Sample Of US Latinos and Asians.

AIMS: Greater neighborhood co-ethnic density (living in proximity with people sharing an ethnicity) and being foreign-born each can protect against risky drinking, but little is known about whether these two factors interact. Using a representative sample of Latinos and Asians from California, USA, we investigate main and interactive effects of neighborhood co-ethnic density and nativity status in relation to heavy episodic drinking (HED). METHODS: This study uses the California Health Interview Survey (N = 30,203) linked with neighborhood data to investigate associations of co-ethnic density and nativity status with HED. Co-ethnic density was based on matching each respondent's ethnicity to the proportion of residents of the corresponding group in their Census tract. Using weighted logistic regression, we first examined main effects of neighborhood co-ethnic density and respondent nativity status on HED. Next, we assessed the interaction of co-ethnic density and nativity status. Finally, we estimated nativity-stratified models to investigate variation in effects of co-ethnic density. RESULTS: Co-ethnic density was not associated with HED for the full sample, but US-born nativity status was associated with increased odds of past-year HED. The interaction model showed co-ethnic density and nativity had synergistic effects, whereby greater levels of neighborhood co-ethnic density buffered risk associated with being US-born. Further, greater neighborhood co-ethnic density was associated with reduced odds of HED for US-born respondents, but it was not associated with HED for foreign-born respondents. CONCLUSIONS: Protective effects of high neighborhood co-ethnic density on HED are stronger for US-born than for foreign-born Latinos and Asians in California.

Investigation of the immunogenicity of Zika glycan loop.

BACKGROUND: Zika virus (ZIKV) is a major human pathogen and member of the Flavivirus genus. Previous studies have identified neutralizing antibodies from Zika patients that bind to quaternary epitopes across neighboring envelope (E) proteins, called E dimer epitopes (EDE). An asparagine-linked glycan on the "glycan loop" (GL) of the ZIKV envelope protein protects the functionally important "fusion loop" on the opposite E subunit in the dimer, and EDE antibodies have been shown to bind to both of these loops. Human EDE antibodies have been divided into two subclasses based on how they bind to the glycan loop region: EDE1 antibodies do not require glycosylation for binding, while EDE2 antibodies strongly rely on the glycan for binding. METHODS: ZIKV GL was expressed on tobacco mosaic virus nanoparticles. Mice were immunized with GL or full-length monomeric E and the immune response was analyzed by testing the ability of sera and monoclonal antibodies to bind to GL and to neutralize ZIKV in in vitro cellular assay. RESULTS: We report here the existence of ZIKV moderately neutralizing antibodies that bind to E monomers through epitopes that include the glycan loop. We show that sera from human Zika patients contain antibodies capable of binding to the unglycosylated glycan loop in the absence of the rest of the envelope protein. Furthermore, mice were inoculated with recombinant E monomers and produced neutralizing antibodies that either recognize unglycosylated glycan loop or require glycan for their binding to monomeric E. We demonstrate that both types of antibodies neutralize ZIKV to some extent in a cellular virus neutralization assay. CONCLUSIONS: Analogous to the existing EDE antibody nomenclature, we propose a new classification for antibodies that bind to E monomer epitopes (EME): EME1 and EME2 for those that do not require and those that do require glycan for binding to E, respectively.

The Inhibitory Activity of Anthraquinones against Pathogenic Protozoa, Bacteria, and Fungi and the Relationship to Structure.

Plant-derived anthraquinones were evaluated in cell assays for their inhibitory activities against the parasitic protozoa Trichomonas vaginalis human strain G3 that causes the sexually transmitted disease trichomoniasis in women, Tritrichomonas foetus bovine strain D1 that causes sexually transmitted diseases in farm animals (bulls, cows, and pigs), Tritrichomonas foetus-like strain C1 that causes diarrhea in domestic animals (cats and dogs), and bacteria and fungi. The anthraquinones assessed for their inhibitory activity were anthraquinone, aloe-emodin (1,8-dihydroxy-3-hydroxymethylanthraquinone), anthrarufin (1,5-dihydroxyanthraquinone), chrysazin (1,8-dihydroxyanthraquinone), emodin (1,3,8-trihydroxy-6-methylanthraquinone), purpurin (1,2,4-trihydroxyanthraquinone), and rhein (1,8-dihydroxy-3-carboxyanthraquinone). Their activities were determined in terms of IC50 values, defined as the concentration that inhibits 50% of the cells under the test conditions and calculated from linear dose response plots for the parasitic protozoa, and zone of inhibition for bacteria and fungi, respectively. The results show that the different substituents on the anthraquinone ring seem to influence the relative potency. Analysis of the structure-activity relationships in protozoa indicates that the aloe-emodin and chrysazin with the highest biological activities merit further study for their potential to help treat the diseases in women and domestic and farm animals. Emodin also exhibited antifungal activity against Candida albicans. The suggested mechanism of action and the additional reported beneficial biological properties of anthraquinones suggest that they have the potential to ameliorate a broad spectrum of human diseases.

Justice involvement and girls' sexual health: Directions for policy and practice.

Arrested girls in the United States (US) are often diverted from detention through referrals to juvenile specialty courts (e.g., juvenile drug court), community-based diversion programs, or pre-adjudicated probation services. Limited research suggests that sexual and reproductive health needs for diverted, or court-involved, non-incarcerated (CINI) girls are similar to that of their detained counterparts. Despite the US justice system's emphasis on diverting youth from detention, research and programmatic efforts to improve sexual and reproductive health outcomes has primarily focused on detained girls. Policy and programming for CINI girls is scant and thus warrants further attention. This report details the immediate sexual and reproductive health needs of CINI girls. We discuss implications of current health care policies and practices for this population and conclude with recommendations for research focused on improving access to sexual and reproductive health care.

Organometallic Conjugates of the Drug Sulfadoxine for Combatting Antimicrobial Resistance.

Fourteen novel arene RuII , and cyclopentadienyl (Cpx ) RhIII and IrIII complexes containing an N,N'-chelated pyridylimino- or quinolylimino ligand functionalized with the antimalarial drug sulfadoxine have been synthesized and characterized, including three by X-ray crystallography. The rhodium and iridium complexes exhibited potent antiplasmodial activity with IC50 values of 0.10-2.0 µm in either all, or one of the three Plasmodium falciparum assays (3D7 chloroquine sensitive, Dd2 chloroquine resistant and NF54 sexual late stage gametocytes) but were only moderately active towards Trichomonas vaginalis. They were active in both the asexual blood stage and the sexual late stage gametocyte assays, whereas the clinical parent drug, sulfadoxine, was inactive. Five complexes were moderately active against Mycobacterium tuberculosis (IC50 <6.3 µm), while sulfadoxine showed no antitubercular activity. An increase in the size of both the Cpx ligand and the aromatic imino substituent increased hydrophobicity, which resulted in an increase in antiplasmodial activity.

Cinnamoyl-Oxaborole Amides: Synthesis and Their in Vitro Biological Activity.

Due to the increased interest in their application in the treatment of infectious diseases, boron-containing compounds have received a significant coverage in the literature. Herein, a small set of novel cinnamoly-oxaborole amides were synthesized and screened against nagana Trypanosoma brucei brucei for antitrypanosomal activity. Compound 5g emerged as a new hit with an in vitro IC50 value of 0.086 µM against T. b. brucei without obvious inhibitory activity against HeLa cell lines. The same series was also screened against other human pathogens, including Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), for which moderate to weak activity (10 to >125 µM) was observed. Similarly, these compounds exhibited moderate activity against the human protozoal pathogen Trichomonas vaginalis with no observed effect on common microbiome bacterial species. The cross-species inhibitory activity presents the possibility of these compounds serving as broad-spectrum antibiotics for these prevalent three human pathogens.

The exocyst is required for trypanosome invasion and the repair of mechanical plasma membrane wounds.

The process of host cell invasion by Trypanosoma cruzi shares mechanistic elements with plasma membrane injury and repair. Both processes require Ca(2+)-triggered exocytosis of lysosomes, exocytosis of acid sphingomyelinase and formation of ceramide-enriched endocytic compartments. T. cruzi invades at peripheral sites, suggesting a need for spatial regulation of membrane traffic. Here, we show that Exo70 and Sec8 (also known as EXOC7 and EXOC4, respectively), components of the exocyst complex, accumulate in nascent T. cruzi vacuoles and at sites of mechanical wounding. Exo70 or Sec8 depletion inhibits T. cruzi invasion and Ca(2+)-dependent resealing of mechanical wounds, but does not affect the repair of smaller lesions caused by pore-forming toxins. Thus, T. cruzi invasion and mechanical lesion repair share a unique requirement for the exocyst, consistent with a dependence on targeted membrane delivery.

Phytochemical-rich foods inhibit the growth of pathogenic trichomonads.

BACKGROUND: Plants produce secondary metabolites that often possess widespread bioactivity, and are then known as phytochemicals. We previously determined that several phytochemical-rich food-derived preparations were active against pathogenic foodborne bacteria. Trichomonads produce disease (trichomoniasis) in humans and in certain animals. Trichomonads are increasingly becoming resistant to conventional modes of treatment. It is of interest to test bioactive, natural compounds for efficacy against these pathogens. METHODS: Using a cell assay, black tea, green tea, grape, pomegranate, and jujube extracts, as well as whole dried jujube were tested against three trichomonads: Trichomonas vaginalis strain G3 (found in humans), Tritrichomonas foetus strain D1 (found in cattle), and Tritrichomonas foetus-like organism strain C1 (found in cats). The most effective of the test substances was subsequently tested against two metronidazole-resistant Trichomonas vaginalis strains, and on normal mucosal flora. RESULTS: Black tea extract inhibited all the tested trichomonads, but was most effective against the T. vaginalis organisms. Inhibition by black tea was correlated with the total and individual theaflavin content of the two tea extracts determined by HPLC. Metronidazole-resistant Trichomonas vaginalis strains were also inhibited by the black tea extract. The response of the organisms to the remaining preparations was variable and unique. We observed no effect of the black tea extract on common normal flora bacteria. CONCLUSIONS: The results suggest that the black tea, and to a lesser degree green tea, grape seed, and pomegranate extracts might present possible natural alternative therapeutic agents to treat Trichomonas vaginalis infections in humans and the related trichomonad infections in animals, without negatively affecting the normal flora.

From Medical to Recreational Marijuana Sales: Marijuana Outlets and Crime in an Era of Changing Marijuana Legislation.

A movement from medical to recreational marijuana use allows for a larger base of potential users who have easier access to marijuana, because they do not have to visit a physician before using marijuana. This study examines whether changes in the density of marijuana outlets were related to violent, property, and marijuana-specific crimes in Denver, CO during a time in which marijuana outlets began selling marijuana for recreational, and not just medical, use. We collected data on locations of crimes, marijuana outlets and covariates for 481 Census block groups over 34 months (N = 16,354 space-time units). A Bayesian Poisson space-time model assessed statistical relationships between independent measures and crime counts within "local" Census block groups. We examined spatial "lag" effects to assess whether crimes in Census block groups adjacent to locations of outlets were also affected. Independent of the effects of covariates, densities of marijuana outlets were unrelated to property and violent crimes in local areas. However, the density of marijuana outlets in spatially adjacent areas was positively related to property crime in spatially adjacent areas over time. Further, the density of marijuana outlets in local and spatially adjacent blocks groups was related to higher rates of marijuana-specific crime. This study suggests that the effects of the availability of marijuana outlets on crime do not necessarily occur within the specific areas within which these outlets are located, but may occur in adjacent areas. Thus studies assessing the effects of these outlets in local areas alone may risk underestimating their true effects.

Where Are the Beds? Housing Locations for Transition Age Youth Exiting Public Systems.

Transition age youth (TAY) from the child welfare and juvenile justice systems experience high rates of homelessness, but little is known about the neighborhoods to which they return after they exit these systems. This exploratory study investigates whether housing options are located in areas where TAY exit public systems and if the characteristics of areas surrounding these facilities support their transition to adulthood. Results show that housing is not related to areas where TAY exit public systems. Further, supportive housing and shelter density is related to low-income areas. Implications for practice and policy on housing locations for TAY are discussed.

YfbA, a Yersinia pestis regulator required for colonization and biofilm formation in the gut of cat fleas.

For transmission to new hosts, Yersinia pestis, the causative agent of plague, replicates as biofilm in the foregut of fleas that feed on plague-infected animals or humans. Y. pestis biofilm formation has been studied in the rat flea; however, little is known about the cat flea, a species that may bridge zoonotic and anthroponotic plague cycles. Here, we show that Y. pestis infects and replicates as a biofilm in the foregut of cat fleas in a manner requiring hmsFR, two determinants for extracellular biofilm matrix. Examining a library of transposon insertion mutants, we identified the LysR-type transcriptional regulator YfbA, which is essential for Y. pestis colonization and biofilm formation in cat fleas.