Intestinal Enteroid Monolayers Model the Human Intestinal Environment for Escherichia coli Infection.

Enterohemorrhagic Escherichia coli O157:H7 is an enteric pathogen responsible for bloody diarrhea, hemolytic uremic syndrome, and in severe cases, even death. The study of O157:H7 is difficult due to the high specificity of the bacteria for the human intestine, along with our lack of sufficiently complex human cell culture models. The recent development of human intestinal enteroids derived from intestinal crypt multipotent stem cells has allowed us to construct two-dimensional differentiated epithelial monolayers grown in transwells that mimic the human intestine. Unlike previous studies, saline was added to the apical surface, while maintaining culture media in the basolateral well. The monolayers continued to grow and differentiate with apical saline. Apical infection with O157:H7 or commensal E. coli resulted in robust bacterial growth from 105 to over 108 over 24 h. Despite this robust bacterial growth, commensal E. coli neither adhered to nor damaged the epithelial barrier over 30 h. However, O157:H7 was almost fully adhered (>90%) by 18 h with epithelial damage observed by 30 h. O157:H7 contains the locus of enterocyte effacement (LEE) pathogenicity island responsible for attachment and damage to the intestinal epithelium. Previous studies report the ability of nutrients such as biotin, d-serine, and L-fucose to downregulate LEE gene expression. O157:H7 treated with biotin or L-fucose, but not d-serine displayed both decreased attachment and reduced epithelial damage over 36 h. These data illustrate enteroid monolayers can serve as a suitable model for the study of O157:H7 pathogenesis, and identification of potential therapeutics. IMPORTANCE O157:H7 is difficult to study due to its high specificity for the human intestine and the lack of sufficiently complex human cell culture models. The recent development of human intestinal enteroids derived from intestinal crypt multipotent stem cells has allowed us to construct two-dimensional differentiated epithelial monolayers grown in transwells that mimic the human intestine. Our data illustrates enteroid monolayers can serve as a suitable model for the study of O157:H7 pathogenesis, and allow for identification of potential therapeutics.

Fidelity of Motivational Interviewing in School-Based Intervention and Research.

Educational researchers and school-based practitioners are increasingly infusing motivational interviewing (MI) into new and existing intervention protocols to provide support to students, parents, teachers, and school administrators. To date, however, the majority of the research in this area has focused on feasibility of implementation rather than fidelity of implementation. In this manuscript, we will present MI fidelity data from 245 audio-recorded conversations with 113 unique caregivers and 20 coaches, who implemented a school-based, positive parenting intervention. The aggregate fidelity scores across coaches, parents, and sessions provide evidence the training and support procedures were effective in assisting school-based personnel to implement MI with reasonable levels of fidelity in practice settings. Further, results suggest that MI fidelity varied between sessions and coaches and that within-coach variation (e.g., session-level variation in the quality of MI delivered) greatly exceeded between-coach variation. Implications for practice and future research are discussed.

Mechanisms of Motivational Interviewing: a Conceptual Framework to Guide Practice and Research.

Reviews of the motivational interviewing (MI) training literature demonstrate MI is a nuanced skill set that takes carefully planned didactic training, application of skills in context-specific practice settings, and ongoing support to promote reflective practice and sustained proficiency. Despite the robust knowledge base related to training and how MI works to achieve favorable outcomes, these two literature bases are not well integrated. In an effort to inform and guide future research, we propose the mechanisms of motivational interviewing (MMI) conceptual framework, which expands upon previous work. Specifically, the framework adds training as an ongoing process consistent with Bennett-Levy's (Behav Cogn Psychother 34:57-78, 2006) model of skill development and acquisition to the existing two-path framework that helps us to understand how MI works to achieve its desired effects (Magill et al., J Consult Clin Psychol 82:973-983, 2014). Herein, we describe measures used to evaluate the mechanisms within the four MMI framework links: initial training to competency, competency to proficiency, proficiency to talk about change, and talk about change to behavior change. Next, we synthesize the literature associated with each of the mechanisms of the MMI. We conclude by discussing implications for practice and research. This framework offers a more complete path structure to understand the mechanisms of change associated with MI that could improve our understanding of inconsistent effect sizes observed across prior trials evaluating MI effectiveness.

Comprehensive Cost Analysis of First Step Next for Preschoolers with Disruptive Behavior Disorder: Using Real-World Intervention Data to Estimate Costs at Scale.

While the long-term societal costs for youth with disruptive behavior disorders are well documented, there is a dearth of information about the comprehensive costs of implementing even the most well-regarded early intervention programs, and the costs of scaling effective interventions are even less well understood. This study estimated the costs of delivering and disseminating First Step Next (FSN), an established tier two school-based early intervention, in preschool and kindergarten settings, including the training and ongoing technical assistance that support sustained, high-quality implementation. Using the Ingredients Method, we estimated (a) the per student costs of implementation, (b) the incremental cost of offering FSN to an additional student, and (c) the cost to disseminate FSN to 40 preschool and kindergarten students, including a sensitivity analysis to examine potential areas of cost savings. The per child cost to implement the FSN intervention with 29 triads in two cohorts was $4330. The incremental cost per additional student was only $2970, highlighting efficiencies gained once intervention infrastructure had been established. The cost of disseminating the intervention to a single cohort of 40 students was $170,106, or $4253 per student. The range in sensitivity analysis was $3141-$7829 per student, with variability in personnel wages having the greatest impact on cost estimates. This research expands on existing literature by providing a more comprehensive understanding of the cost of effective disruptive behavior interventions based on real-world implementation data, using these data to estimate dissemination costs, and showing how dissemination costs are particularly sensitive to personnel wages.

Comparative use of the Ages and Stages Questionnaires in low- and middle-income countries.

AIM: To map the breadth of use of the Ages and Stages Questionnaires (ASQ) in low- and middle-income countries (LMICs) across world regions, and examine procedures for ASQ translation, adaptation, psychometric evaluation, and administration. METHOD: We conducted a review of all original, peer-reviewed studies written in English referencing use of the ASQ in LMICs. We used a consensus rating procedure to classify each article into one of four categories: feasibility study, psychometric study, prevalence study, or research study. RESULTS: We analysed 53 peer-reviewed articles written in English detailing use of the ASQ in LMICs. We found evidence of ASQ use in 23 LMICs distributed across all world regions. The ASQ was translated into 16 languages. Just over half of the studies reported parent completion of the ASQ (50.9%). We identified eight feasibility studies, 12 psychometric studies, and nine prevalence studies. Study type varied by economy and region. INTERPRETATION: Findings suggest broad global use of the ASQ in a range of countries and cultural and linguistic contexts. There is need for further validation studies across all cited regions and countries and in countries ready to begin to design systems for providing universal developmental screening services. WHAT THIS PAPER ADDS: The Ages and Stages Questionnaires (ASQ) has been used in at least 23 low- and middle-income countries (LMICs). The ASQ has been translated into at least 16 languages in LMICs. Over half the identified studies reported parent completion of the ASQ.

Effects of the First Step to Success Intervention on Preschoolers with Disruptive Behavior and Comorbid Anxiety Problems.

Preschoolers with elevated anxiety symptoms are at high risk not only for developing more severe mental health disorders in later life but are also apt to respond more poorly to intervention if they present with comorbid disruptive behavior. Because early signs of anxiety disorders may not be recognized as such in preschool settings, many children selected for Tier 2 interventions that target externalizing problem behaviors may also have co-occurring anxiety symptoms and disorders. The First Step to Success intervention has recently been adapted for preschoolers with externalizing behaviors and was found to be efficacious in a randomized controlled trial. The current report examines effects of the First Step intervention on a subsample of 38 preschoolers with comorbid anxiety symptoms. Compared to usual-care controls, preschoolers who were assigned to the First Step intervention demonstrated medium to large effects in reducing externalizing behavior and improving social functioning outcomes, but had small effects for reductions in internalizing behaviors. Implications for intervening with preschoolers at risk for comorbid disruptive and anxiety behaviors are discussed.

Early Intervention for Preschoolers at Risk for Attention-Deficit/Hyperactivity Disorder: Preschool First Step to Success.

This study evaluated the efficacy of the Preschool First Step (PFS) to Success early intervention for children at risk for attention deficit hyperactivity disorder (ADHD). PFS is a targeted intervention for children 3-5 years old with externalizing behavior problems and addresses secondary prevention goals and objectives. As part of a larger multisite, randomized controlled trial, the efficacy of the PFS program was evaluated on a subsample of 45 children who also had elevated comorbid ADHD symptoms as rated by parents and teachers. The PFS program was found to produce significantly higher social skills, and significantly fewer behavior problems across a variety of teacher-and parent-reported measures at postintervention. Effect sizes for teacher-reported effects were large across a variety of social competency indicators, including those specific to ADHD. Effect sizes for parent-reported social skills and problem behaviors were medium. Although not specifically designed for preschoolers at risk for comorbid ADHD, this generic behavioral intervention appeared to be successful for this population. Implications and limitations of the study are discussed.

First Step to Success: Applications to Preschoolers at Risk of Developing Autism Spectrum Disorders.

Preschool children with Autism Spectrum Disorder (ASD) may not always be recognized as such during their early years, but some of their behavioral problems may nonetheless prompt a referral for behavioral intervention. Whether such an intervention brings any benefit has not been well studied. We identified a subsample of 34 preschool children at risk for autism spectrum disorder from a large randomized controlled trial (N = 126) of the First Step to Success program. Children at risk of developing ASD demonstrated significant improvements on seven of 11 outcome measures and on a responder analyses based on symptom severity. Process and fidelity measures also suggested that First Step was both feasible and socially acceptable. Implications for early intervention for children at risk of developing ASD are discussed.

The Efficacy of a Home-School Intervention for Preschoolers With Challenging Behaviors: A Randomized Controlled Trial of Preschool First Step to Success.

The field of early intervention is currently faced with the challenge of reducing the prevalence of antisocial behavior in children. Longitudinal outcomes research indicates that increased antisocial behavior and impairments in social competence skills during the preschool years often serve as harbingers of future adjustment problems in a number of domains including mental health, interpersonal relations, and academic achievement. This article reports the results of a cross-site randomized controlled trial, in which 128 preschool children with challenging behaviors were assigned to either a Preschool First Step to Success (PFS) intervention (i.e., experimental) or a usual-care (i.e., control) group. Regression analyses indicated that children assigned to the Preschool First Step intervention had significantly higher social skills, and significantly fewer behavior problems, across a variety of teacher- and parent-reported measures at postintervention. Effect sizes for teacher-reported effects ranged from medium to large across a variety of social competency indicators; effect sizes for parent-reported social skills and problem behaviors were small to medium, respectively. These results suggest that the preschool adaptation of the First Step intervention program provides early intervention participants, staff, and professionals with a viable intervention option to address emerging antisocial behavior and externalizing behavior disorders prior to school entry.

The Feasibility of First Step to Success with Preschoolers.

The primary purpose of this study was to examine feasibility of the preschool version of the First Step to Success (FSS) intervention. Toward this end, the following four research questions were addressed: (1) To what extent was the intervention implemented with integrity? (2) To what extent do teachers and parents perceive the intervention to be socially valid? (3) To what extent were teachers and parents satisfied with the intervention? and (4) To what extent was the intervention effective in reducing problem behavior and improving social skills? Twelve students participated in the study. Treatment integrity, social validity, and satisfaction results were analyzed at the aggregate level, and a reliable change index was calculated at the case level for primary outcome measures to assess the potential efficacy of the intervention. Fidelity data suggest the preschool version of the intervention can be implemented with acceptable integrity by coaches and teachers in preschool settings. Social validity outcomes suggest parents' perceptions of the program's goals, procedures, and outcomes were extremely favorable, and social validity from the teacher perspective was acceptable. The results provide initial evidence that participating in the preschool version of the FSS intervention improves children's social skills and decreases problem behavior.

Subthreshold conditions as precursors for full syndrome disorders: a 15-year longitudinal study of multiple diagnostic classes.

BACKGROUND: There has been increasing interest in the distinction between subthreshold and full syndrome disorders and specifically whether subthreshold conditions escalate or predict the onset of full syndrome disorders over time. Most of these studies, however, examined whether a single subthreshold condition escalates into the full syndrome form of that disorder. Equally important, though, is whether subthreshold conditions are likely to develop other full syndrome disorders and whether these associations are maintained after adjusting for comorbidity. METHODS: A 15-year longitudinal study of subthreshold psychiatric conditions was conducted with 1,505 community-drawn young adults. We examined whether 1) subthreshold major depression, bipolar, anxiety disorders, alcohol use, substance use, conduct disorder and/or ADHD were precursors for the corresponding (homotypic) full syndrome disorder; 2) subthreshold conditions were precursors for other (heterotypic) full syndrome disorders; and 3) these homotypic and heterotypic precursors persisted after adjusting for comorbidity. RESULTS: Subthreshold major depression, anxiety, alcohol use, substance use, and conduct all escalated into their corresponding full syndrome and nearly all homotypic developments were maintained after adjusting for comorbid subthreshold and full syndrome conditions. Many heterotypic associations were also observed and most remained after controlling for comorbidity, particularly among externalizing disorders (e.g., alcohol, substance, conduct/antisocial personality disorder). CONCLUSIONS: Many subthreshold conditions have predictive validity as they may represent precursors for full syndrome disorders. Alternatively, dimensional conceptualizations of psychopathology which include these more minor conditions may yield greater validity. Subthreshold conditions may represent good targets for preventive interventions.

Separation anxiety disorder in childhood as a risk factor for future mental illness.

OBJECTIVE: To ascertain the extent to which childhood separation anxiety disorder (SAD) confers risk for the development of psychopathology during young adulthood (ages 19-30). METHOD: A subset of the participants of the Oregon Adolescent Depression Project (n = 816) was used. Subjects provided retrospective reports of lifetime mental illness (including SAD) and concurrent reports of current mental illness at age 16 and were then followed prospectively until age 30. Diagnostic assessments were conducted twice during adolescence and again at ages 24 and 30. Based on diagnosis during childhood/adolescence, the subjects were partitioned into four orthogonal groups: SAD (n = 42), other anxiety disorders (n = 88), a heterogeneous psychiatric disorders control group (n = 389), and a not mentally ill control group (n = 297). Adjusting for demographic variables that were significantly associated with group status and for comorbid disorders prior to age 19, the results were analyzed with hierarchical multiple logistic regression. RESULTS: SAD was a strong (78.6%) risk factor for the development of mental disorders during young adulthood. The major vulnerabilities were for panic disorder and depression. CONCLUSIONS: Because SAD creates a major vulnerability for mental disorders during young adulthood, clinicians should be sensitive to the presence of SAD, and children and adolescents with SAD should be treated. Future research should evaluate whether successful treatment of SAD and/or the provision of a preventive intervention during childhood/adolescence reduce the risk for future psychopathology.

Specificity of social anxiety disorder as a risk factor for alcohol and cannabis dependence.

Social anxiety disorder (SAD) is highly comorbid with alcohol use disorders (AUDs) and cannabis dependence. However, the temporal sequencing of these disorders has not been extensively studied to determine whether SAD serves as a specific risk factor for problematic substance use. The present study examined these relationships after controlling for theoretically-relevant variables (e.g., gender, other Axis I pathology) in a longitudinal cohort over approximately 14 years. The sample was drawn from participants in the Oregon Adolescent Depression Project. After excluding those with substance use disorders at baseline, SAD at study entry was associated with 6.5 greater odds of cannabis dependence (but not abuse) and 4.5 greater odds of alcohol dependence (but not abuse) at follow-up after controlling for relevant variables (e.g., gender, depression, conduct disorder). The relationship between SAD and alcohol and cannabis dependence remained even after controlling for other anxiety disorders. Other anxiety disorders and mood disorders were not associated with subsequent cannabis or alcohol use disorder after controlling for relevant variables. Among the internalizing disorders, SAD appears to serve as a unique risk factor for the subsequent onset of cannabis and alcohol dependence.

Psychosocial functioning of adults who experienced substance use disorders as adolescents.

The authors examined whether substance use disorder (SUD) before age 19 was associated with functioning at age 30. Participants (N = 773) were assessed twice during adolescence and at ages 24 and 30. Eight of 14 adult measures were associated with adolescent SUD: education, unemployment, income, risky sexual behavior, suicide attempt, coping, stressful life events, and global adjustment. After adolescent comorbidity and functioning and adult SUD were controlled for, education and unemployment remained associated, and three variables emerged as significant: being a parent (significant only for participants without adult SUD), being currently married, and having decreased life satisfaction (significant only for participants with adult SUD). Adolescent SUD is associated with numerous functioning difficulties at age 30, some of which appear to be related to recurrent SUD, comorbid adolescent disorders, or functioning problems already evident in adolescence.