Caregiver Participation Engagement in Child Mental Health Prevention Programs: a Systematic Review

Prevention programs are a key method to reduce the prevalence and impact of mental health disorders in childhood and adolescence. Caregiver participation engagement (CPE), which includes caregiver participation in sessions as well as follow-through with homework plans, is theorized to be an important component in the effectiveness of these programs. This systematic review aims to (1) describe the terms used to operationalize CPE and the measurement of CPE in prevention programs, (2) identify factors associated with CPE, (3) examine associations between CPE and outcomes, and (4) explore the effects of strategies used to enhance CPE. Thirty-nine articles representing 27 unique projects were reviewed. Articles were included if they examined CPE in a program that focused to some extent on preventing child mental health disorders. There was heterogeneity in both the terms used to describe CPE and the measurement of CPE. The majority of projects focused on assessment of caregiver home practice. There were no clear findings regarding determinants of CPE. With regard to the impact of CPE on program outcomes, higher levels of CPE predicted greater improvements in child and caregiver outcomes, as well as caregiver-child relationship quality. Finally, a small number of studies found that motivational and behavioral strategies (e.g., reinforcement, appointment reminders) were successful in promoting CPE. This review highlights the importance of considering CPE when developing, testing, and implementing prevention programs for child mental health disorders. Increased uniformity is needed in the measurement of CPE to facilitate a better understanding of determinants of CPE. In addition, the field would benefit from further evaluating strategies to increase CPE as a method of increasing the potency of prevention programs

Redox proteomics of the inflammatory secretome identifies a common set of redoxins and other glutathionylated proteins released in inflammation, influenza virus infection and oxidative stress

Protein cysteines can form transient disulfides with glutathione (GSH), resulting in the production of glutathionylated proteins, and this process is regarded as a mechanism by which the redox state of the cell can regulate protein function. Most studies on redox regulation of immunity have focused on intracellular proteins. In this study we have used redox proteomics to identify those proteins released in glutathionylated form by macrophages stimulated with lipopolysaccharide (LPS) after pre-loading the cells with biotinylated GSH. Of the several proteins identified in the redox secretome, we have selected a number for validation. Proteomic analysis indicated that LPS stimulated the release of peroxiredoxin (PRDX) 1, PRDX2, vimentin (VIM), profilin1 (PFN1) and thioredoxin 1 (TXN1). For PRDX1 and TXN1, we were able to confirm that the released protein is glutathionylated. PRDX1, PRDX2 and TXN1 were also released by the human pulmonary epithelial cell line, A549, infected with influenza virus. The release of the proteins identified was inhibited by the anti-inflammatory glucocorticoid, dexamethasone (DEX), which also inhibited tumor necrosis factor (TNF)-α release, and by thiol antioxidants (N-butanoyl GSH derivative, GSH-C4, and N-acetylcysteine (NAC), which did not affect TNF-α production. The proteins identified could be useful as biomarkers of oxidative stress associated with inflammation, and further studies will be required to investigate if the extracellular forms of these proteins has immunoregulatory functions

Outer-context determinants in the sustainment phase of a reimbursement-driven implementation of evidence-based practices in children’s mental health services

Although there is increasing investment to implement evidence-based practices (EBPs) in public systems across the USA, continued or sustained use of EBPs after initial implementation remains a challenge. The low integration of EBPs in routine practice severely limits their public health impact, highlighting the need to understand factors that affect the return on costly investments in EBP implementation. This study aims to (1) characterize trajectories of EBP delivery volume through a reimbursement-driven implementation and (2) examine impacts of system-level policy regulatory activity and state-level mental health services funding on the implementation reimbursement strategy. This study involved secondary data analyses. Psychotherapy administrative claims and regulatory site visit data from the Los Angeles County Department of Mental Health and California state mental health expenditures were extracted from 2010 to 2017. Multilevel regression examined EBP claims volume over time with state expenditures and regulatory compliance as predictors. EBP claims volume trajectories demonstrated a rapid initial increase, followed by a period of decrease, and a small increase in the final year. State mental health expenditures increased across time reflecting increased funding availability. State mental health expenditures and system regulatory compliance were inversely related to EBP claims volume. The impact of reimbursement-driven EBP implementation strategy is sensitive to multiple outer-context determinants. At the system level, commitment to fidelity of implementation regulations resulted in reduced use of the reimbursement strategy. Alternative reimbursement streams not tied to EBPs coupled with an expanded array of reimbursable services also impacted the use of the reimbursement strategy to implement EBPs.https://doi.org/10.1186/s13012-021-01149-

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

Genome-Wide Association Study of the Modified Stumvoll Insulin Sensitivity Index Identifies BCL2 and FAM19A2 as Novel Insulin Sensitivity Loci

Genome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed a GWAS of the modified Stumvoll Insulin Sensitivity Index (ISI) within the Meta-Analyses of Glucose and Insulin-Related Traits Consortium. Discovery for genetic association was performed in 16,753 individuals, and replication was attempted for the 23 most significant novel loci in 13,354 independent individuals. Association with ISI was tested in models adjusted for age, sex, and BMI and in a model analyzing the combined influence of the genotype effect adjusted for BMI and the interaction effect between the genotype and BMI on ISI (model 3). In model 3, three variants reached genome-wide significance: Rs13422522 (NYAP2; P = 8.87 × 10-11), rs12454712 (BCL2; P = 2.7 × 10-8), and rs10506418 (FAM19A2; P = 1.9 × 10-8). The association at NYAP2 was eliminated by conditioning on the known IRS1 insulin sensitivity locus; the BCL2 and FAM19A2 associations were independent of known cardiometabolic loci. In conclusion, we identified two novel loci and replicated known variants associated with insulin sensitivity. Further studies are needed to clarify the causal variant and function at the BCL2 and FAM19A2 loci