Exchange Broadening Underlies the Enhancement of IDE-Dependent Degradation of Insulin by Anionic Membranes.

Insulin-degrading enzyme (IDE) is an evolutionarily conserved ubiquitous zinc metalloprotease implicated in the efficient degradation of insulin monomer. However, IDE also degrades monomers of amyloidogenic peptides associated with disease, complicating the development of IDE inhibitors. In this work, we investigated the effects of the lipid composition of membranes on the IDE-dependent degradation of insulin. Kinetic analysis based on chromatography and insulin's helical circular dichroic signal showed that the presence of anionic lipids in membranes enhances IDE's activity toward insulin. Using NMR spectroscopy, we discovered that exchange broadening underlies the enhancement of IDE's activity. These findings, together with the adverse effects of anionic membranes in the self-assembly of IDE's amyloidogenic substrates, suggest that the lipid composition of membranes is a key determinant of IDE's ability to balance the levels of its physiologically and pathologically relevant substrates and achieve proteostasis.

Differential Effects of Polyphenols on Insulin Proteolysis by the Insulin-Degrading Enzyme.

The insulin-degrading enzyme (IDE) possesses a strong ability to degrade insulin and Aß42 that has been linked to the neurodegeneration in Alzheimer's disease (AD). Given this, an attractive IDE-centric strategy for the development of therapeutics for AD is to boost IDE's activity for the clearance of Aß42 without offsetting insulin proteostasis. Recently, we showed that resveratrol enhances IDE's activity toward Aß42. In this work, we used a combination of chromatographic and spectroscopic techniques to investigate the effects of resveratrol on IDE's activity toward insulin. For comparison, we also studied epigallocatechin-3-gallate (EGCG). Our results show that the two polyphenols affect the IDE-dependent degradation of insulin in different ways: EGCG inhibits IDE while resveratrol has no effect. These findings suggest that polyphenols provide a path for developing therapeutic strategies that can selectively target IDE substrate specificity.

Preparing Master of Social Work Students for Interprofessional Practice.

PURPOSE: This study aims to measure growth in interprofessional knowledge, skills, and values in MSW students from three universities who participated in a Behavioral Health Workforce Education and Training program focused on serving children, adolescents, and transition-age youth. METHODS: Students participated in an interprofessional field placement and specialized educational sessions that addressed interprofessional team-based care, engaging at-risk youth and families, and working with vulnerable populations. The Interprofessional Socialization and Valuing Scale (ISVS) was administered pre- and post-experience. RESULTS: Paired t-tests of the ISVS total score and each subscale showed statistically significant increases over time. Multiple regression models indicated only the pretest score was a significant predictor of the posttest score for the total or subscale of the ISVS. CONCLUSION: Social work programs that create interprofessional education and training opportunities can achieve positive outcomes in student attitudes toward interprofessional practice.

The effect of California's paid family leave policy on parent health: A quasi-experimental study.

The U.S. is the only high-income country without a national paid family leave (PFL) policy. While a handful of U.S. states have implemented PFL policies in recent years, there are few studies that examine the effects of these policies on health. In this study, we tested the hypothesis that California's PFL policy-implemented in 2004-improved parent health outcomes. Data were drawn from the 1993-2017 waves of the Panel Study of Income Dynamics, a large diverse national cohort study of U.S. families (N = 6,690). We used detailed longitudinal sociodemographic information about study participants and a quasi-experimental difference-in-differences analytic technique to examine the effects of California's PFL policy on families who were likely eligible for the paid leave, while accounting for underlying trends in these outcomes among states that did not implement PFL policies in this period. Outcomes included self-rated health, psychological distress, overweight and obesity, and alcohol use. We found improvements in self-rated health and psychological distress, as well as decreased likelihood of being overweight and reduced alcohol consumption. Improvements in health status and psychological distress were greater for mothers, and reductions in alcohol use were greater for fathers. Results were robust to alternative specifications. These findings suggest that California's PFL policy had positive impacts on several health outcomes, providing timely evidence to inform ongoing policy discussions at the federal and state levels. Future studies should examine the effects of more recently implemented state and local PFL policies to determine whether variation in policy implementation and generosity affects outcomes.

Does short-term memory develop?

Such is the consistency by which performance on measures of short-term memory (STM) increase with age that developmental increases in STM capacity are largely accepted as fact. However, our analysis of a robust but almost ignored finding - that span for digit sequences (the traditional measure of STM) increases at a far greater rate than span for other verbal material - fundamentally undermines the assumption that increased performance in STM tasks is underpinned by developmental increases in capacity. We show that this digit superiority with age effect is explained by the relatively greater linguistic exposure to random sequences of digits versus other stimuli such as words. A simple associative learning process that learns incrementally from exposure to language accounts for the effect, without any need to invoke an STM mechanism, much less one that increases in capacity with age. By extension, using corpus data directed at 2-3 year old children, 4-6 year old children, and adults, we show that age-related performance increases with other types of verbal material are equally driven by the same basic associative learning process operating on the expanding exposure to language experienced by the child. Our results question the idea that tests such as digit span are measuring a dedicated system for the temporary maintenance and manipulation of verbal material, and as such have implications for our understanding of those aspects of typical and atypical development that are usually accounted for with respect to the operation of such a system.

2'-O-ribose methylation of transfer RNA promotes recovery from oxidative stress in Saccharomyces cerevisiae.

Chemical modifications that regulate protein expression at the translational level are emerging as vital components of the cellular stress response. Transfer RNAs (tRNAs) are significant targets for methyl-based modifications, which are catalyzed by tRNA methyltransferases (Trms). Here, Saccharomyces cerevisiae served as a model eukaryote system to investigate the role of 2'-O-ribose tRNA methylation in the cell's response to oxidative stress. Using 2'-O-ribose deletion mutants for trms 3, 7, 13, and 44, in acute and chronic exposure settings, we demonstrate a broad cell sensitivity to oxidative stress-inducing toxicants (i.e., hydrogen peroxide, rotenone, and acetic acid). A global analysis of hydrogen peroxide-induced tRNA modifications shows a complex profile of decreased, or undetectable, 2'-O-ribose modification events in 2'-O-ribose trm mutant strains, providing a critical link between this type of modification event and Trm status post-exposure. Based on the pronounced oxidative stress sensitivity observed for trm7 mutants, we used a bioinformatic tool to identify transcripts as candidates for regulation by Trm7-catalyzed modifications (i.e., enriched in UUC codons decoded by tRNAPheGmAA). This screen identified transcripts linked to diverse biological processes that promote cellular recovery after oxidative stress exposure, including DNA repair, chromatin remodeling, and nutrient acquisition (i.e., CRT10, HIR3, HXT2, and GNP1); moreover, these mutants were also oxidative stress-sensitive. Together, these results solidify a role for TRM3, 7, 13, and 44, in the cellular response to oxidative stress, and implicate 2'-O-ribose tRNA modification as an epitranscriptomic strategy for oxidative stress recovery.

Inhibition of the Self-Assembly of Aß and of Tau by Polyphenols: Mechanistic Studies.

The amyloid-ß (Aß) peptide and tau protein are thought to play key neuropathogenic roles in Alzheimer's disease (AD). Both Aß and tau self-assemble to form the two major pathological hallmarks of AD: amyloid plaques and neurofibrillary tangles, respectively. In this review, we show that naturally occurring polyphenols abundant in fruits, vegetables, red wine, and tea possess the ability to target pathways associated with the formation of assemblies of Aß and tau. Polyphenols modulate the enzymatic processing of the amyloid-ß precursor protein and inhibit toxic Aß oligomerization by enhancing the clearance of Aß42 monomer, modulating monomer-monomer interactions and remodeling oligomers to non-toxic forms. Additionally, polyphenols modulate tau hyperphosphorylation and inhibit tau ß-sheet formation. The anti-Aß-self-assembly and anti-tau-self-assembly effects of polyphenols increase their potential as preventive or therapeutic agents against AD, a complex disease that involves many pathological mechanisms.

Psychological Well-Being, Risk, and Resilience of Youth in Out-Of-Home Care and Former Foster Youth.

This study assesses psychological well-being, risk, and resilience of youth currently in-care and former foster youth and how preparation for independent living affects these factors. Findings suggest significant psychosocial distress for former foster youth. Youth currently in-care fared better but demonstrated high scores on measures suggesting risk and potential for future mental health challenges. For former foster youth, independent living preparation positively impacted well-being. The more preparation for independence a youth received, the lower the psychological challenges. Findings suggest the need for mental health support for transitioning youth as well as preparation for independent living as a way to improve the well-being of former foster youth.

Impact of a Care Management Entity on Use of Psychiatric Services Among Youths With Severe Mental or Behavioral Disorders.

OBJECTIVE: Care management entity models have a positive impact on functioning and symptom control among youths with serious emotional and behavioral disorders. However, little is known about whether treatment benefits are sustained after discharge. The study objective was to examine the association between enrollment in a care management entity and mental health outcomes during the year after discharge. METHODS: Data from care management entity administrative claims were linked with Medicaid claims for youths enrolled in a care management entity anytime from December 2009 through December 2013. Inverse probability treatment weighting was used to balance baseline characteristics between the youths enrolled in the care management entity and a comparison group. Study outcomes were psychiatry-related hospitalizations and emergency department (ED) visits during the year after discharge. Two models were used to compare the two groups, one modeling the probability of using any psychiatric service and one modeling the number of visits for each outcome among users of either service. RESULTS: After adjustment with inverse probability treatment weighting, 2,381 youths (care management, N=488; comparison, N=1,893) were identified. Care management was associated with a significantly lower likelihood of any psychiatry-related ED visit (odds ratio [OR]=.65, p=.017) and any psychiatric hospitalization (OR=.60, p=.011). No significant differences in outcomes were observed when the comparison was limited to users of services. CONCLUSIONS: Reduced use of psychiatric inpatient and ED services among youths enrolled in a care management entity was sustainable after discharge. Multiagency collaboration is needed to enrich the ability to assess outcomes across broader domains.

Psychotropic Polypharmacy Among Youths With Serious Emotional and Behavioral Disorders Receiving Coordinated Care Services.

OBJECTIVE: The study examined differences in psychotropic polypharmacy among youths with serious emotional and behavioral disorders who received coordinated care services (CCS) that used a wraparound model and a matched sample of youths who received traditional services. METHODS: A quasi-experimental design compared psychotropic polypharmacy one year before and one year after discharge from CCS. The cohort was youths with serious emotional and behavioral disorders who were enrolled in CCS from December 2009 through May 2014. The comparison group was youths with serious emotional and behavioral disorders who received outpatient mental health services during the same time. Administrative data from Medicaid, child welfare, and juvenile justice services were used. A difference-in-difference analysis with propensity score matching evaluated the CCS intervention by time effect on psychotropic polypharmacy. RESULTS: In both groups, most youths were male, black, and 10-18 years old, with attention-deficit hyperactivity disorder (54%-55%), mood disorder (39%-42%), depression (26%-27%), and bipolar disorder (25%-26%). About half of each group was taking an antipsychotic. The percentage reduction in polypharmacy from one year before CCS enrollment to one year after discharge was 28% for the CCS group and 29% for the non-CCS group, a nonsignificant difference. CCS youths excluded from the analysis had more complex mental health needs and a greater change in polypharmacy than the CCS youths who were included in the analytic sample. CONCLUSIONS: Mental health care coordination had limited impact in reducing psychotropic polypharmacy for youths with less complex mental health needs. Further research is needed to evaluate the effect on psychotropic polypharmacy among youths with the greatest mental health needs.

Impact of Coordinated Behavioral Health Management on Quality Measures of Antipsychotic Use.

A state Care Management Entity (CME) using the wraparound practice model provided intensive care coordination for youth with severe mental illness, those most likely to receive antipsychotics. The model has led to improved clinical/functional outcomes, but little is known about the impact on antipsychotic prescribing and safety monitoring. A pre-post study was conducted to evaluate antipsychotic dosing, concomitant antipsychotic use, and metabolic monitoring among CME-enrolled and non-CME-enrolled comparison groups. CME-enrolled youth had greater decrease in concomitant antipsychotic use than non-CME-enrolled youth, but no difference in dosing or metabolic monitoring. More education of prescribing antipsychotics and team-based engagement in care coordination are needed.

The common elements of engagement in children's mental health services: which elements for which outcomes?

Using the distillation component of the Distillation and Matching Model framework (Chorpita, Daleiden, & Weisz, 2005 ), we examined which engagement practices were associated with three domains of treatment engagement: attendance, adherence, and cognitive preparation (e.g., understanding of, readiness for treatment). Eighty-nine engagement interventions from 40 randomized controlled trials in children' s mental health services were coded according to their engagement practices and outcomes. Analyses examined whether the practices used in successful interventions differed according to engagement domain. Practice patterns differed somewhat depending on whether attendance, adherence, or cognitive preparation was the outcome of interest. For example, assessment of barriers to treatment frequently occurred in successful interventions targeting attendance, whereas homework assignment frequently occurred in successful interventions when adherence was the target outcome. Modeling and expectation setting were frequently used in successful interventions targeting cognitive preparation for treatment. Distillation provides a method for examining the practice patterns associated with different engagement outcomes. An example of the application of these findings to clinical practice includes using certain practices (e.g., assessment, psychoeducation about services, and accessibility promotion) with all youth and families to promote attendance, adherence, and cognitive preparation. Then, other practices (e.g., modeling, homework assignment) can be added on an as-needed basis to boost engagement or to address interference in a particular engagement domain. The use of a distillation framework promotes a common language around engagement and highlights practices that lend themselves well to training, thereby promoting the dissemination of engagement interventions.

Program and practice elements for placement prevention: a review of interventions and their effectiveness in promoting home-based care.

Preventing unnecessary out-of-home placement for youth with behavioral and emotional needs is a goal of several public child-serving services, including child welfare, juvenile justice, and child mental health. Although a small number of manualized interventions have been created to promote family driven and community-based services and have empirical support, other less established programs have been initiated by local jurisdictions to prevent out-of-home placement. To synthesize what is known about efforts to prevent placement, this article describes the common program and practice elements of interventions described in 37 studies (published in 51 articles) that measured placement prevention outcomes for youth at risk for out-of-home care because of behavioral or mental health needs. The most common program elements across published interventions were program monitoring, case management, and accessibility promotion. The most common clinical practice elements for working with youth were assessment and individual therapy; for caregivers, problem solving skills were most frequently included; and family therapy was most common for the family unit. Effect size estimates for placement-related outcomes (decreased out-of-home placement, decreased hospitalization, decreased incarceration, and decreased costs) were calculated to estimate the treatment effectiveness of the interventions in which the program components and clinical practices are embedded.

Identifying the common elements of treatment engagement interventions in children's mental health services.

Difficulty engaging families in mental health treatment is seen as an underlying reason for the disparity between child mental health need and service use. Interpretation of the literature on how best to engage families is complicated by a diversity of operational definitions of engagement outcomes and related interventions. Thus, we sought to review studies of engagement interventions using a structured methodology allowing for an aggregate summary of the most common practices associated with effective engagement interventions. We identified 344 articles through a combination of database search methods and recommendations from engagement research experts; 38 articles describing 40 studies met our inclusion criteria. Following coding methods described by Chorpita and Daleiden (J Consul Clin Psychol 77(3):566-579, 2009, doi: 10.1037/a0014565 ), we identified 22 engagement practice elements from 89 study groups that examined or implemented family engagement strategies. Most frequently identified engagement practice elements included assessment, accessibility promotion, psychoeducation about services, homework assignment, and appointment reminders. Assessment and accessibility promotion were two practice elements present in at least 50 % of treatment groups that outperformed a control group in a randomized controlled trial. With the exception of appointment reminders, these frequently identified engagement practice elements had a high likelihood of being associated with winning treatments when they were used. This approach offers a novel way of summarizing the engagement literature and provides the foundation for enhancing clinical decision-making around treatment engagement.

Translating the common elements approach: social work's experiences in education, practice, and research.

The expansion of the use of evidence-based practices (EBPs) in mental health services is well under way and social work seeks to further its appropriate implementation in both specialty and nonspecialty mental health settings. The common elements approach is now recognized as demonstrating promise for use in a range of settings. This article discusses the attractiveness of the common elements approach and describes several efforts to integrate its content into social work education and to disseminate this approach into the field. Then the article presents research initiatives regarding two areas of nonspecialty mental health practice with children and families: (a) engaging clients in mental health services and (b) preventing the need for out-of-home placement for youth. Finally, we consider the challenges of the common elements framework for social work education and practice and future directions for research.

Identifying and predicting problem behavior trajectories among pre-school children investigated for child abuse and neglect.

OBJECTIVE: Young children involved with child welfare services are at high risk for behavior problems. This study aims to identify externalizing behavior paths that preschoolers in this high-risk population follow over a 6 year period, and the predictors of membership in normative and problematic pathways. METHODS: Using data from the National Study of Child and Adolescent Well-being (NSCAW), the sample included 246 4-year-olds who remained home after investigation. Latent class growth analysis (LCGA) was used to estimate the number, size, and shape of subgroups of preschoolers following distinct behavioral pathways. Early predictors of membership in the resulting groups were then examined. RESULTS: Four groups of preschool children following distinct behavior trajectories over 6 years were identified. Weighted results show that more than half (61%) of the children followed a low/normal problem behavior trajectory while just over one tenth (12%) were on a persistent high trajectory, remaining in the clinical range throughout the study. Improving (23%) and worsening (4%) problem behavior groups were also identified. Internalizing problems, attention problems, child ethnicity, and maltreatment type reported at age 4 predicted membership in the trajectory groups. CONCLUSIONS: Internalizing behavior problems and maltreatment type may distinguish preschool children who are more likely to experience worsening or persistent problematic externalizing behaviors from those likely to follow a normal behavior trajectory. PRACTICE IMPLICATIONS: Identifying early indicators of externalizing behavior problems and addressing them with evidence-based interventions to reduce negative behaviors may avert long-term negative outcomes.

Comparing three years of well-being outcomes for youth in group care and nonkinship foster care.

Using three waves of data from the National Survey of Child and Adolescent Well-Being, this study examines differences in cognitive, academic, and affective well-being of youth first placed in nonkinship foster care (N = 259) and youth first placed in group care (N = 89). To compare nonrandomized groups, propensity score matching was used. Results from hierarchical linear modeling suggest that both groups of youth show improved behavior and below-average academics over time.

Examining externalizing behavior trajectories of youth in group homes: is there evidence for peer contagion?

Although concerns about peer contagion are often cited in critiques of group treatments for troubled youths, few studies have examined the effects of exposure to deviant peers in residential group care settings. This study used administrative data of youth served at Boys Town, a nationally-known group care provider. Using latent class growth analysis, this study identified the externalizing behavior trajectories of youth in group care as well as the behavior trajectory of the peers with whom they lived, assessed the relationship between youth trajectory classes and individual and peer group characteristics as well as the relationship between an individual youth's behavior pattern and the behavior pattern of proximal peers. Several results suggested the presence of peer contagion in group care: a trajectory class of gradually increasing externalizing behavior problems, the strength of deviant peer density in predicting an individual youth's externalizing behavior trajectories and significant associations between behavior patterns of youth and proximal peers. While there is some evidence that suggests an increase in problem behavior during care, results from this study indicated that over 90% of the youth did not have an increase in problem behaviors and that positive peer influences may also be protective and inhibit problem behaviors.

Outcomes for youth residential treatment programs using administrative data from the child welfare system: a risk-adjustment application.

This study assessed whether administrative data from the public child welfare system could be used to develop risk-adjusted performance reports for residential mental health programs for adolescents. Regression methods were used with 3,759 residential treatment spells for 2,784 children and youth to determine which outcomes could be adequately risk adjusted for case mix. Expected outcomes were created for each residential program given its case mix; then, expected and achieved outcomes were compared. For most programs, achieved results did not differ significantly from expected results for individual outcomes. Overall, outcomes achieved were not impressive. Only one quarter of spells resulted in a youth being maintained in a single less restrictive setting in the year following discharge. Methodological implications of this study suggest further refinements are needed for child welfare administrative data in order to develop risk-adjusted report cards of program performance.