Progress toward a vaccine for extraintestinal pathogenic E. coli (ExPEC) II: efficacy of a toxin-autotransporter dual antigen approach.

Extraintestinal pathogenic Escherichia coli (ExPEC) is a leading cause of worldwide morbidity and mortality, the top cause of antimicrobial-resistant (AMR) infections, and the most frequent cause of life-threatening sepsis and urinary tract infections (UTI) in adults. The development of an effective and universal vaccine is complicated by this pathogen's pan-genome, its ability to mix and match virulence factors and AMR genes via horizontal gene transfer, an inability to decipher commensal from pathogens, and its intimate association and co-evolution with mammals. Using a pan virulome analysis of >20,000 sequenced E. coli strains, we identified the secreted cytolysin α-hemolysin (HlyA) as a high priority target for vaccine exploration studies. We demonstrate that a catalytically inactive pure form of HlyA, expressed in an autologous host using its own secretion system, is highly immunogenic in a murine host, protects against several forms of ExPEC infection (including lethal bacteremia), and significantly lowers bacterial burdens in multiple organ systems. Interestingly, the combination of a previously reported autotransporter (SinH) with HlyA was notably effective, inducing near complete protection against lethal challenge, including commonly used infection strains ST73 (CFT073) and ST95 (UTI89), as well as a mixture of 10 of the most highly virulent sequence types and strains from our clinical collection. Both HlyA and HlyA-SinH combinations also afforded some protection against UTI89 colonization in a murine UTI model. These findings suggest recombinant, inactive hemolysin and/or its combination with SinH warrant investigation in the development of an E. coli vaccine against invasive disease.

Ethnic Discrimination and Self-rated Health among Hispanic Emerging Adults: Examining the Moderating Effects of Self-esteem and Resilience.

Exposure to ethnic discrimination has been conceptualized as a sociocultural stressor that is associated with lower self-rated health. However, this association remains understudied among Hispanics and less is known about constructs that may mitigate the effects of ethnic discrimination on self-rated health. Accordingly, this study aimed to (a) examine the association between ethnic discrimination and self-rated health among Hispanic emerging adults (ages 18-25), and (b) examine the extent to which self-esteem and resilience may moderate this association. A convenience sample of 200 Hispanic emerging adults from Arizona (n=99) and Florida (n=101) was recruited to complete a cross-sectional survey. Data were analyzed using hierarchical multiple regression and moderation analyses. Results indicate that higher ethnic discrimination was associated with lower self-rated health. Moderation analyses indicated that self-esteem functioned as a moderator that weakened the association between ethnic discrimination and self-rated health; however, resilience did not function similarly as a moderator. This study adds to the limited literature on ethnic discrimination and self-rated health among Hispanics and highlights that psychological factors, such as enhancing self-esteem, may help buffer the adverse effects of ethnic discrimination on health outcomes.

Substance use among Latino international and domestic college students.

While the United States hosts the greatest number of international students in the world, Latino international students remain understudied, especially in regards to substance use. The present study tests differences between Latino international and Latino domestic undergraduates in how they use alcohol, cigarette, and illicit drugs. Participants (N = 786 students, 386 international and 400 domestic, 65% female, mean age = 21.2 years) were a subsample of Latino students surveyed in the 2009 American College Health Association's revised National College Health Assessment (ACHA-NCHA II). Results indicate that Latino international students reported more alcohol use than Latino domestic students, but had similar use of cigarettes and illicit drugs. Among international students, gender, participation in Greek life, cigarette use, marijuana use, and year in school were associated with alcohol use. Similarly, gender, cigarette use, and marijuana use were significantly related to international students' binge drinking. Prevention and research implications are discussed.

Elevated cholesterol among African American adults: the role of fatalistic attitudes about health.

Objectives: Cardiovascular disease (CVD) affects 47% of African-American adults (AAs) in the United States. Elevated cholesterol, the greatest risk factor for CVD, is highly prevalent among AAs, potentially as the result of engagement in behavioral risk factors. Religiosity has been associated with a beneficial effect in health promoting behaviors, yet findings have been mixed depending on methods employed. Religious health fatalism, defined as 'the belief that health outcomes are inevitable and/or determined by God', is a more specific domain of a religiosity that needs further exploration through scientific research. The purpose of the current study is to examine the relationship between RHFQ subscales and self-reported lifetime history of elevated cholesterol. Methods: Participants (n = 135) were recruited from a large, predominately African American church. A multiple logistic regression model was used to test whether the three subscales of the Religious Health Fatalism Questionnaire (RHFQ) were cross-sectional predictors of self-reported lifetime history of elevated cholesterol. Sets of variables were entered into a stepwise logistic regression model with the first set (Block 1) including significant demographic variables and religiosity (i.e. sex, age, level of education, employment status and scores on the Lukwago Religiosity Scale score [LRS]. The three RHFQ subscales were entered into Block 2 as our predictors of interest. Results: After adjusting for covariates, the likelihood of elevated cholesterol increased significantly (OR = 3.21, 95% CI = 1.81-5.69, p < .001) as Helpless Inevitability (RHFQ subscale) scores increased. Conclusions: A greater degree of Helpless Inevitability was found to be significantly associated with self-reported elevated cholesterol level. Future research is needed to further understand the complex interplay of factors associated with religiosity and fatalism that contribute to increased risk of elevated cholesterol among AAs.

Gender as a Moderator of Descriptive Norms and Substance Use among Latino College Students.

This study addresses gaps in the literature by testing gender differences in the associations between substance use norms and substance use among Latino college students. Secondary data analysis was conducted using data from the 2009 National College Health Assessment. Participants selected for this study were 4,336 Latino undergraduates. Linear mixed modeling was used to test gender as a moderator of the relationship between alcohol use norms and alcohol use as well as marijuana use norms and marijuana use. Results indicated that the strength of the relationships between norms and substance use was stronger for males than for females. Substance use rates and gender roles differ for Latinos and Latinas and may partially account for the stronger relationship between these constructs for males. Implications for future research and prevention are discussed.

School Factors and Alcohol Use: The Moderating Effect of Nativity in a National Sample of Latino Adolescents.

BACKGROUND: School is an important developmental context for adolescents and may be related to adolescent alcohol use. Less is known as to whether the relationships between school factors and alcohol use differ between Latino youth born outside of the United States versus those born in the United States. OBJECTIVE: The aim of this study is to test nativity as a moderator of the relationship between school factors and alcohol use among Latino adolescents. METHODS: This study used data from Waves I and II of the National Longitudinal Study of Adolescent Health (Add Health) to test nativity as a moderator of the relationship between school factors and alcohol use in a subsample of Latino adolescents. RESULTS: Results found that during adolescence, nativity moderates the relationship between school connectedness and Wave I alcohol use. For those born outside of the United States, school connectedness was not related to alcohol use. Significant main effects emerged for grades in school and truancy. Better grades were associated with less alcohol use, while truancy was associated with greater alcohol use. The longitudinal relationships between school factors and Wave II alcohol use were not statistically significant. CONCLUSIONS: School connectedness is a contemporaneous risk factor for alcohol use among those born in the United States. Prevention efforts that address school contextual factors may be important for all Latino students to reduce engagement in alcohol use and optimize well-being.

Smoking Status and Substance Use Treatment Outcomes Among Spanish Speakers Enrolled in Substance Abuse Treatment.

OBJECTIVE: Smoking is highly prevalent among individuals with drug and alcohol disorders. Concurrent tobacco dependence treatment during substance use disorder (SUD) treatment is supported, yet the association between SUD treatment outcomes and smoking status has been understudied in minorities, including Latinos. METHOD: Participants were 322 Spanish-speaking Latinos enrolled in a SUD treatment study in 5 U.S. cities. Logistic regression examined associations between baseline smoking status and treatment outcomes for nontobacco substance use at follow-up. Covariates included age, gender, level of education, marital status, treatment group, and mandated treatment status. RESULTS: Results indicated smokers had a reduced likelihood of abstinence for all nontobacco substances (p = .001) and their primary drug of use (p = .007). CONCLUSIONS: Findings contribute to the growing literature indicating a possible beneficial effect of smoking cessation services on SUD treatment, specifically among Latinos. Further research is needed to identify ideal smoking cessation treatments for Latinos.

Alcohol Use Severity Among Hispanic Emerging Adults in Higher Education: Understanding the Effect of Cultural Congruity.

BACKGROUND: Identifying and understanding determinants of alcohol use behavior among Hispanic college students is an increasingly important public health issue, particularly during emerging adulthood. Studies examining ethnocultural determinants of alcohol use behavior among Hispanic college students have focused on direct associations with cultural orientation (e.g., acculturation and enculturation); yet there is a need for research that accounts for the complex interplay of other culturally relevant sociocultural factors. OBJECTIVES: This study examined associations of behavioral acculturation, behavioral enculturation, and cultural congruity (perception of cultural fit between the values of the academic environment and the student's personal values) with alcohol use severity (AUS); and tested if gender moderated those associations. METHODS: A hierarchical linear regression and moderation analysis were conducted on a sample of 167 Hispanic emerging adults (ages 18-25) enrolled in college. RESULTS: All predictor variables entered in the regression model accounted for 20.9% of the variance in AUS. After controlling for demographic variables and depressive symptoms, behavioral acculturation and enculturation did not have a statistically significant association with AUS. Further, gender did not moderate either of these associations. Conversely, greater cultural congruity was associated with lower reports of AUS. A moderation analysis suggested that cultural congruity predicted lower reports of AUS among men, but not among women. CONCLUSIONS: This was the first known study to examine the association of cultural congruity with alcohol use. Findings highlight the value of examining contextual factors of culture and moving beyond reductive measures of cultural orientation.

Enrollment in Hispanic Serving Institutions as a Moderator of the Relationship Between Drinking Norms and Quantity of Alcohol Use Among Hispanic College Students.

BACKGROUND: Hispanic college students represent a growing proportion of the college population. Studies have found that an individual's perception of the drinking of others is linked to one's own personal use and that college students frequently overestimate the drinking of their peers. The current study builds on previous college student drinking literature by examining the influence that attending a Hispanic-serving institution (HSI) has on the personal alcohol use and perception of peers' drinking norms among Hispanic college students. METHODS: This secondary data analysis utilized data from the American College Health Association's National College Health Assessment. Participants were self-identified Hispanics between the ages of 18 and 25 (N = 4336). RESULTS: Results indicated that there was a significant interaction between attending an HSI and the perception of the number of drinks of a typical student. Specifically, the perception of others' drinking was more strongly linked to personal drinking for students in non-Hispanic serving institutions. CONCLUSIONS: The protective effect of attending a Hispanic-serving institution may be related to a more culturally affirming college environment.

Public religiosity, religious importance, and substance use among Latino emerging adults.

OBJECTIVE: This study examined the relationship between religiosity (religious importance and public religion) and substance use (binge drinking and marijuana use) among Latino emerging adults. METHOD: Study utilized data (N = 2,442; 51.9% male) from wave 3 of the National Longitudinal Study of Adolescent Health (Add Health). RESULTS: Only public religion was found to be a protective factor for both binge drinking and marijuana use. CONCLUSION: The study results suggest the potential for public forms of religion, such as attendance to services and activities, to act as a protective factor for substance use.

Vaccines against extraintestinal pathogenic Escherichia coli (ExPEC): progress and challenges.

The emergence of antimicrobial resistance (AMR) is a principal global health crisis projected to cause 10 million deaths annually worldwide by 2050. While the Gram-negative bacteria Escherichia coli is commonly found as a commensal microbe in the human gut, some strains are dangerously pathogenic, contributing to the highest AMR-associated mortality. Strains of E. coli that can translocate from the gastrointestinal tract to distal sites, called extraintestinal E. coli (ExPEC), are particularly problematic and predominantly afflict women, the elderly, and immunocompromised populations. Despite nearly 40 years of clinical trials, there is still no vaccine against ExPEC. One reason for this is the remarkable diversity in the ExPEC pangenome across pathotypes, clades, and strains, with hundreds of genes associated with pathogenesis including toxins, adhesins, and nutrient acquisition systems. Further, ExPEC is intimately associated with human mucosal surfaces and has evolved creative strategies to avoid the immune system. This review summarizes previous and ongoing preclinical and clinical ExPEC vaccine research efforts to help identify key gaps in knowledge and remaining challenges.

Relationships between Child Emotional and Behavioral Symptoms and Caregiver Strain and Parenting Stress.

Children with emotional and behavioral disturbance often have difficulties in multiple symptom domains. This study investigates the relationships between child symptoms and caregiver strain and parenting stress among 177 youth and their caregivers participating in a school-based system of care. Youth were grouped by symptom domain and included those with low scores on both internalizing and externalizing symptoms, those with only high internalizing symptoms, those with only high externalizing symptoms, and those with high symptoms levels in both internalizing and externalizing domains. Results revealed significant group differences on measures of caregiver strain and parenting stress. Caregivers of youth with symptoms in both internalizing and externalizing domains reported the highest levels of strain and stress; however, there was some variation in group differences by caregiver outcome. The results of this study emphasize the importance of not only providing services for youth, but also providing support services for their caregivers.

Functional Genomics of Gastrointestinal Escherichia coli Isolated from Patients with Cancer and Diarrhea.

We describe the epidemiology and clinical characteristics of 29 patients with cancer and diarrhea in whom Enteroaggregative Escherichia coli (EAEC) was initially identified by GI BioFire panel multiplex. E. coli strains were successfully isolated from fecal cultures in 14 of 29 patients. Six of the 14 strains were identified as EAEC and 8 belonged to other diverse E. coli groups of unknown pathogenesis. We investigated these strains by their adherence to human intestinal organoids, cytotoxic responses, antibiotic resistance profile, full sequencing of their genomes, and annotation of their functional virulome. Interestingly, we discovered novel and enhanced adherence and aggregative patterns for several diarrheagenic pathotypes that were not previously seen when co-cultured with immortalized cell lines. EAEC isolates displayed exceptional adherence and aggregation to human colonoids compared not only to diverse GI E. coli , but also compared to prototype strains of other diarrheagenic E. coli . Some of the diverse E. coli strains that could not be classified as a conventional pathotype also showed an enhanced aggregative and cytotoxic response. Notably, we found a high carriage rate of antibiotic resistance genes in both EAEC strains and diverse GI E. coli isolates and observed a positive correlation between adherence to colonoids and the number of metal acquisition genes carried in both EAEC and the diverse E. coli strains. This work indicates that E. coli from cancer patients constitute strains of remarkable pathotypic and genomic divergence, including strains of unknown disease etiology with unique virulomes. Future studies will allow for the opportunity to re-define E. coli pathotypes with greater diagnostic accuracy and into more clinically relevant groupings.

Mental health problems, legal involvement, and smoking during pregnancy.

The current study examined predictors of past 30-day cigarette use among a US nationally representative sample of pregnant women over the age of 18 (N = 1,782). The study consisted of secondary data analysis of the 2005-2007 survey years of the National Survey on Drug Use and Health (NSDUH). Logistic regression analyses indicated that low-income women, those who experienced mental health problems in the past year, and women who experienced legal problems were more likely to smoke during pregnancy. Limitations to the study as well as implications for future research are discussed.

Academics and substance use among Latino adolescents: results from a national study.

This study investigated the relationship between academic factors and past-year alcohol, cigarette, and marijuana use in an adolescent sample of Latinos. Secondary data analysis was conducted using a subsample of Latino adolescents (N=2,593) from the 2006 National Survey on Drug Use and Health. School connectedness and parental involvement in school were protective across all substances. Fighting in school increased the risk for use of all substances, and failing grades increased the risk for alcohol and marijuana use. Implications for prevention include the development of prevention programs that aim to increase students' connection to school and increase parental involvement.

Parental Concerns About Students' Transition Into College: Substance Use and Sexual Assault.

Parents play an important role in the development of their college-bound children, including engagement in risk behaviors and associated consequences. Still, few studies have investigated parental concerns about their children's transition into college. The aim of this study was to describe parental concerns about substance use and sexual assault and to test differences between parents of sons and parents of daughters in their levels of concern and communication. Data are from 450 parents of incoming students to a large, midwestern university. Parents responded to questions regarding their concerns about substance use and sexual assault. Results found that parents of sons are more concerned about substance use while parents of daughters are more concerned about sexual assault. Parents of daughters also communicate more about sexual assault than parents of sons. Finally, there was a positive relationship between relationship quality and communication about sexual assault. Implications for future research and the development of parent-based prevention are explored.

Metabolic profiling reveals nutrient preferences during carbon utilization in Bacillus species.

The genus Bacillus includes species with diverse natural histories, including free-living nonpathogenic heterotrophs such as B. subtilis and host-dependent pathogens such as B. anthracis (the etiological agent of the disease anthrax) and B. cereus, a cause of food poisoning. Although highly similar genotypically, the ecological niches of these three species are mutually exclusive, which raises the untested hypothesis that their metabolism has speciated along a nutritional tract. Here, we developed a pipeline for quantitative total assessment of the use of diverse sources of carbon for general metabolism to better appreciate the "culinary preferences" of three distinct Bacillus species, as well as related Staphylococcus aureus. We show that each species has widely varying metabolic ability to utilize diverse sources of carbon that correlated to their ecological niches. This approach was applied to the growth and survival of B. anthracis in a blood-like environment and find metabolism shifts from sugar to amino acids as the preferred source of energy. Finally, various nutrients in broth and host-like environments are identified that may promote or interfere with bacterial metabolism during infection.

Race, psychosocial characteristics, and treatment outcomes among individuals undergoing treatment for cannabis use disorder: A latent profile analysis based on preferred method of using cannabis.

INTRODUCTION: There are a wide variety of methods for using combustible cannabis which may impact an individual's pattern of use as well as their response to cannabis use disorder (CUD) treatment. Previous research has noted racial/ethnic differences in cannabis users' preferred method of use. METHOD: The current study examined data from a randomized placebo-controlled trial of a pharmacological intervention for adults with CUD. Latent profile analysis classified participants (N = 302) based on their primary method of combustible cannabis use. RESULTS: A four profile solution emerged which identified participants who demonstrated 1) Primarily Joint (n = 50), 2) Primarily Blunt (n = 106), 3) Mixed MoU (n = 30), and 4) Primarily Pipe (i.e., pipe or bong; n = 116) use. Profiles were compared on socio-demographic characteristics and racial differences were found among the four latent profiles as well as differences in their level of use. Cannabis users with a preference for joints were more likely to be White as compared to other racial groups. In contrast, a greater proportion of participants with a preference for blunts were African American. The Primarily Joint profile was found to have the highest cannabis relapse rate at 1-month follow-up (94%) which was significantly greater than the Mixed MoU (74%, x2 = 5.06, p < .05) and Primarily Pipe (78%, x2 = 9.24, p < .01) profiles. Interestingly, there was no difference in 1-Month Follow-up cannabis relapse rates between the Primarily Joint and Blunt profiles (87%, x2 = 9.24, p > .05). CONCLUSIONS: Findings suggest that treatment-seeking individuals who primarily use joints or blunts may face unique challenges that may impact cannabis abstinence. Along with other cannabis-related characteristics, an individual's preferred method of use may represent an important factor to consider in the treatment of CUD.

Psychosocial intervention utilization and substance abuse treatment outcomes in a multisite sample of individuals who use opioids.

BACKGROUND: There are several relatively safe and effective FDA-approved medications for Opioid Use Disorder (OUD). Despite the existence of these medications, the rate of returning to opioid use after treatment is relatively high, underscoring the need for continued enhancement of treatments. Adjunctive psychosocial interventions paired with medication have been shown to improve OUD treatment outcomes. However, studies have yet to conclusively examine the distinct effects of the most widely utilized psychosocial treatment modalities. The current study will investigate the relationship between individual counseling, group therapy, and 12-Step participation and illicit opioid abstinence at the end of treatment, 1 and 3 months after treatment. METHOD: A secondary analysis was conducted with data from a sample of 570 individuals diagnosed with OUD who were recruited from eight substance abuse treatment centers in the United States. Participants were enrolled in a two-group randomized, controlled trial testing buprenorphine-naloxone versus extended-release naltrexone for OUD. A two-level hierarchical linear growth model was used to examine the effects of individual counseling, group therapy, and 12-Step participation on illicit opioid abstinence (urinanalyses) 1- and 3-months post-treatment. RESULTS: Hours of individual counseling and 12-Step participation significantly predicted abstinence at follow-up (p < .001, b = -0.59, 95% CI [0.42, 0.74]; p < .01, b = -0.05, 95% CI [0.92, 0.98]). There was a significant interaction between individual counseling and 12-Step participation (p < .01, b = -0.06, 95% CI [1.02, 1.10]). Additionally, participant age and employment status were significant predictors of illicit opioid abstinence (p < .01, b = -0.02, 95% CI [0.97, 0.99]; p < .01, b = -0.38, 95% CI [0.52, 0.90]). Hours of group therapy was not found to significantly predict illicit opioid abstinence. CONCLUSIONS: Findings suggest that greater levels of individual therapy and 12-Step participation may be beneficial for individuals receiving medication treatment for OUD.

Racial and gender inequities in the implementation of a cannabis criminal justice diversion program in a large and diverse metropolitan county of the USA.

BACKGROUND: Diversion programs are considered alternatives to the arrest and incarceration of non-violent drug offenders, including those found in possession of smaller amounts of cannabis in states with prohibitive laws. Despite the progressive nature of such programs, the inability to complete diversion program requirements can often result in greater involvement with the criminal justice system than traditional case adjudication. Few studies have evaluated racial group differences in cannabis diversion program completion. METHODS: The current study examined a sample of 8323 adult participants in Harris County, Texas' Marijuana Misdemeanor Diversion Program (MMDP) between March 2017 and July 2019. Gender, age, and race/ethnicity were examined as predictors of program completion and time to completion using Chi square, Kruskal Wallis tests, and Cox proportional hazard regression models. RESULTS: Both males and African Americans were over-represented (80 % and 50 %, respectively) among participants of Harris County's MMDP. African American (HR = 0.782, 95 % CI [.735-.832], p < .001) and Latino American MMDP participants (HR = .822, 95 % CI [.720-.937], p = .003) had significantly lower odds of MMDP completion and a longer interval to program completion as compared to non-Latino White participants. CONCLUSIONS: The current study identified racial/ethnic and gender disparities in a large county's cannabis diversion program. These findings may be related to law enforcement disparities which disproportionately target males and people of color. Findings may serve to inform the continued reform of the criminal justice system, particularly laws relating to cannabis.