PRACTICE makes progress, a self-care course for mental health professionals in the child trauma field: A preliminary investigation.

OBJECTIVE: Mental health professionals who work with clients exposed to trauma commonly experience secondary traumatic stress (STS) and burnout, which have a well-documented negative impact on clinicians as well as clients. As self-care has been identified as a protective factor against STS and burnout, the current study aimed to examine the effects of a self-care course for mental health professionals working with trauma-exposed clients. METHOD: This pretest-posttest pilot study examined the impact of a six-session virtual self-care course on the well-being of 43 mental health professionals previously trained in Trauma-focused Cognitive Behavioral Therapy(TF-CBT), a well-established, evidence-based treatment for childhood trauma. The components of TF-CBT comprise the acronym PRACTICE, and we are referring to this self-care course as PRACTICE Makes Progress (PMP), as participants receive weekly assignments that encourage the use of many of the same PRACTICE skills clients are taught in the context of TF-CBT. RESULTS: Results comparing pre- and postcourse survey responses indicated significant increases in the use of PRACTICE skills (p = .006, d = .44) as well as the utilization of humor as a coping skill (p < .001, d = .53), and significant decreases in STS symptoms (p < .001, d = .63) and burnout (p = .004, d = .47). CONCLUSIONS: These results provide preliminary evidence that mental health professionals working with clients exposed to trauma may benefit from participation in an evidence-informed, standalone virtual self-care course. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

TF-CBT Training Augmented with a Self-Care Focus: Understanding Facilitators and Barriers to Treatment Implementation.

Clinicians working with youth exposed to trauma may be at increased risk for experiencing elevated levels of stress and symptoms of secondary traumatic stress, which can negatively impact clinician wellbeing and ultimately contribute to reduced access to quality care for clients. An innovative Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) training incorporating self-care practices (i.e., Practice What You Preach; PWYP) was developed to help facilitate the implementation of TF-CBT and to enhance clinicians' coping and decrease stress. The primary purpose of this study was to determine whether the PWYP-augmented training met three Objectives: (1) increase clinicians' feelings of TF-CBT competency; (2) improve clinicians' coping abilities/reduce clinicians' stress; and (3) increase clinicians' insight into the benefits and/or challenges clients may experience in treatment. An exploratory aim was also developed to identify additional facilitators and barriers of TF-CBT implementation. The written reflections of 86 community-based clinicians who participated in the PWYP-augmented TF-CBT training were examined using qualitative methods. The majority of clinicians indicated increased feelings of competency and improved coping abilities and/or stress levels; almost half mentioned increased insight into clients' experiences. The most frequently mentioned additional facilitators were related to elements of the TF-CBT treatment model. Anxiety/self-doubt was the barrier most frequently mentioned, though all clinicians who mentioned this barrier indicated it lessened or resolved over the course of the training. Incorporating self-care strategies into trainings may serve as a facilitator for TF-CBT implementation by enhancing the competency and well-being of clinicians. The additional insights into barriers and facilitators can be used to further improve the PWYP initiative and future training and implementation efforts.

Effectiveness of physical and mental health interventions for young people with heart conditions: protocol for a systematic review and meta-analysis.

INTRODUCTION: Cardiovascular disease is among the most common of non-communicable diseases, affecting 13.9 million children and young people (CYP) globally. Survival rates for CYP with heart conditions are rising, however, support for adjusting to life with a heart condition is lacking, as such it is unsurprising that one in three suffer from anxiety, depression or adjustment disorder. The proposed review aims to identify and assess the effectiveness of physical and mental health interventions across physical and mental health outcomes in young people with cardiac conditions using narrative synthesis and meta-analysis if appropriate. METHODS AND ANALYSIS: Embase, Medline, PubMed, PsycINFO, Cochrane Databases, Web of Science and reference lists of relevant publications will be searched from 1980 to June 2022 for articles published in English or Italian. Screening, data extraction, intervention coding and risk of bias will be performed by two independent reviewers using an extraction checklist. Intervention content and features will be identified and reported using the Template for Intervention Description and Replication checklist. A narrative review of the included studies will be conducted. If possible and appropriate, a random-effects model meta-analysis will be conducted to calculate the pooled within-group and between-group effect sizes for the primary outcome measures. If sufficient data are available, a subgroup meta-analysis will investigate whether specific intervention types are associated with different levels of intervention effectiveness. ETHICS AND DISSEMINATION: This systematic review does not directly involve the use of human beings, therefore, there is no requirement for ethical approval. Findings will be disseminated through peer-reviewed publication and in various media, such as conferences, congresses or symposia. PROSPERO REGISTRATION NUMBER: CRD42022330582.

Youth Metacognitive Therapy (YoMeta): protocol for a single-blind randomised feasibility trial of a transdiagnostic intervention versus treatment as usual in 11-16-year-olds with common mental health problems.

BACKGROUND: Mental health disorders in children and young people (CYP) are increasing but the provision of current evidence-based treatment for common mental health problems is limited. Treatment effects vary widely with no clear superiority of a single treatment approach. Further evaluation of contemporary and effective treatments in CYP is needed. Metacognitive therapy (MCT) has shown enhanced efficacy over 'gold standard' approaches in adult mental health, but so far has not been evaluated in a randomised trial of CYP. As such, we aim to assess the acceptability and feasibility of group-MCT for CYP with common mental health problems in comparison to usual treatment within Child and Adolescent Mental Health Services (CAMHS). METHOD: YoMeta is a multicentre, two-arm, single-blind randomised feasibility trial comparing group-MCT to usual care in CYP with common mental health problems in CAMHS. CYP (target sample n = 100) with a common mental health problem will be recruited across at least three CAMHS services in the UK. Participants in the intervention arm will receive up to eight sessions of group-MCT delivered by a CAMHS mental health practitioner. The control arm will receive usual care in CAMHS which includes individual or group-based therapy. Feasibility will be assessed by the success of recruitment, retention, and data quality. Acceptability of the intervention will be assessed by the number of sessions attended and through qualitative interviews aimed at exploring CYP acceptability and understanding of the intervention. Symptoms of psychological distress will be assessed using the Revised Children Anxiety and Depression Scale (RCADS) at 20 weeks. We will also assess psychological well-being, symptoms of depression, metacognitive beliefs, quality of life, and measures to support economic evaluation (health status and health and social care use). Qualitative interviews will be conducted to understand practitioner's views on training and delivery of group-MCT. DISCUSSION: The trial is designed to evaluate the acceptability and feasibility of group-MCT for CYP with common mental health problems. Group-MCT may aid in improving access to treatment, reduce waiting times, and improve outcomes for CYP with common mental health disorders. The study will provide important information and data to evaluate future research potential and confirm sample size estimation for a definitive large-scale RCT to test the effectiveness and cost-effectiveness of group-MCT in CYP. TRIAL REGISTRATION: NCT05260060; ISCTRN18335255.

Caregiver Satisfaction and Perceptions of Trauma-Focused Cognitive Behavioral Therapy.

Although caregivers have been found to be critical to children's healing, little has been documented about caregivers' experiences in Trauma-Focused Cognitive Behavioral Therapy (TF-CBT). The current study describes caregivers' satisfaction with and perceptions of TF-CBT. Caregivers (n = 431) of children/adolescents (n = 496) who completed TF-CBT filled out pre-treatment questionnaires on demographics and perceived aloneness in facing their child's trauma, and posttreatment questionnaires on treatment satisfaction and perceptions of TF-CBT. Caregivers rated treatment satisfaction an average of 30.59 (SD = 3.15) out of a maximum score of 32 on the Client Satisfaction Questionnaire-8. The majority of caregivers endorsed that talking about their child's trauma was more helpful than discussing other current problems, they spoke frequently with their child's therapist about their child's trauma, they reported information/skill building in therapy were more helpful than support received, they felt understood by their therapist, treatment helped them more effectively parent, and treatment helped improve their relationship with their child. Perceptions were associated with overall treatment satisfaction. There was a significant reduction in caregivers' feelings of aloneness in facing their child's trauma from pre- to posttreatment, which was also related to overall treatment satisfaction. Caregivers reported high satisfaction with TF-CBT, and identified talking about their child's trauma as more helpful than talking about problems not related to the trauma. Caregivers endorsed benefits of participating in TF-CBT, including feeling less alone in facing their child's trauma, improved relationship with their child, and more effective parenting skills. These results have important treatment implications.

Disseminating Trauma-Focused Cognitive Behavioral Therapy with a Systematic Self-care Approach to Addressing Secondary Traumatic Stress: PRACTICE What You Preach.

This pilot study evaluated the effectiveness of Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) training programs augmented with a systematic "PRACTICE What You Preach" (PWYP) self-care focus, which has trainees personally utilize the coping skills they teach their clients. Participants were 115 clinicians/supervisors who completed a PWYP TF-CBT training program. Pre- to post-training analyses documented significant increases in participants' competency and fidelity in implementing TF-CBT (ps < .001), significantly more frequent use of coping skills including instrumental social support (p < .01), active coping (p < .001), humor (p < .01), and restraint (p < .01), and significant decreases in secondary traumatic stress (STS; p < .001). Children's symptoms of PTSD (ps < .001) and behavior problems (p < .05) also decreased significantly. This preliminary evidence suggests that training augmented with PWYP may enhance clinicians'/supervisors' personal coping and reduce their levels of STS without compromising treatment implementation efforts and client outcomes.

Children who engaged in interpersonal problematic sexual behaviors.

BACKGROUND: Over one-third of inappropriate sexual contact experienced by children is initiated by other children. Many studies examined child initiators (CIs) of interpersonal problematic sexual behaviors (IPSBs). This study uniquely links CI information with types of sexual contact as described by children they engaged in IPSBs. OBJECTIVE: Describe CIs' characteristics and types of sexual acts they initiated. PARTICIPANTS/SETTING: Medical charts of CIs and children they engaged in IPSBs. Examinations occurred between 2002 and 2013. METHODS: Retrospective chart review. RESULTS: Most CIs were male (83%) and related to the child they engaged in IPSBs (75%); mean age was 10 years (range 4-17); 58% reported viewing sexually explicit media; 47% experienced sexual abuse. Most CIs (68%) engaged in multiple types of IPSBs. Children who experienced IPSBs initiated by males reported engagement in greater numbers of invasive acts (t(216) = 2.03, p = .043). Older CIs were more likely than younger CIs to report viewing sexually explicit media (χ2(1) = 7.81, p = .007) and those who did were more likely to initiate more invasive acts (t(169) = 2.52, p = .013) compared to CIs who did not. CONCLUSIONS: In this study, most CIs were young and experienced multiple adverse events; the most common types of IPSBs were invasive; and over half the CIs had been exposed to sexually explicit media, which was associated with initiating invasive sexual acts. These findings suggest aiming prevention efforts at young children to help them manage exposure to sexually explicit media and redress victimization experiences.

Photopatternable Biodegradable Aliphatic Polyester with Pendent Benzophenone Groups.

Highly efficient photo-cross-linking reactions enable numerous applications in biomaterials. Here, a photopatternable biodegradable aliphatic polyester with benzophenone pendent groups was synthesized by copper-catalyzed alkyne-azide cycloaddition, affording polyesters that undergo UV-induced cross-linking to yield photopatterned films. Using this material, a self-folding multilayer structure containing polyester/hydrogel bilayer hinges was fabricated. Upon swelling of the hydrogel layer, the construct folds into a triangular tube, which subsequently unfolds due to lipase-catalyzed degradation of the polyester layer. The ability to precisely design such degradation-induced structural changes offers potential for biomaterials and medical applications, such as evolving and responsive 2D and 3D tissue engineering scaffolds.

Polyester-graft-phosphorylcholine prepared by ring-opening polymerization and click chemistry.

Phosphorylcholine (PC)-substitution on aliphatic polyesters is accomplished by click chemistry with PC-substituted azides.

Trifluoromethylpyrimidine-based inhibitors of proline-rich tyrosine kinase 2 (PYK2): structure-activity relationships and strategies for the elimination of reactive metabolite formation.

The synthesis and SAR for a series of diaminopyrimidines as PYK2 inhibitors are described. Using a combination of library and traditional medicinal chemistry techniques, a FAK-selective chemical series was transformed into compounds possessing good PYK2 potency and 10- to 20-fold selectivity against FAK. Subsequent studies found that the majority of the compounds were positive in a reactive metabolite assay, an indicator for potential toxicological liabilities. Based on the proposed mechanism for bioactivation, as well as a combination of structure-based drug design and traditional medicinal chemistry techniques, a follow-up series of PYK2 inhibitors was identified that maintained PYK2 potency, FAK selectivity and HLM stability, yet were negative in the RM assay.

End-functionalized phosphorylcholine methacrylates and their use in protein conjugation.

Polymer-protein conjugation was performed using N-hydroxysuccinimide and aldehyde-terminated zwitterionic polymers, and the resulting polymer-protein conjugates were characterized by gel electrophoresis and fast protein liquid chromatography. Methacryloyloxyethyl phosphorylcholine (MPC) polymers were prepared by atom transfer radical polymerization in which the requisite functional end-groups for protein conjugation were embedded within the polymerization initiators. These phosphorylcholine polymers were conjugated to lysozyme as a model protein, as well as two therapeutic proteins, granulocyte colony stimulating factor (G-CSF) and erythropoietin (EPO). These MPC polymer-protein conjugates represent alternatives to PEGylated proteins, with the potential to provide improved efficacy in a therapeutic treatment relative to the protein itself.

Antitumor activity and pharmacology of a selective focal adhesion kinase inhibitor, PF-562,271.

Cancer cells are characterized by the ability to grow in an anchorage-independent manner. The activity of the nonreceptor tyrosine kinase, focal adhesion kinase (FAK), is thought to contribute to this phenotype. FAK localizes in focal adhesion plaques and has a role as a scaffolding and signaling protein for other adhesion molecules. Recent studies show a strong correlation between increased FAK expression and phosphorylation status and the invasive phenotype of aggressive human tumors. PF-562,271 is a potent, ATP-competitive, reversible inhibitor of FAK and Pyk2 catalytic activity with a IC(50) of 1.5 and 14 nmol/L, respectively. Additionally, PF-562,271 displayed robust inhibition in an inducible cell-based assay measuring phospho-FAK with an IC(50) of 5 nmol/L. PF-562,271 was evaluated against multiple kinases and displays >100x selectivity against a long list of nontarget kinases. PF-562,271 inhibits FAK phosphorylation in vivo in a dose-dependent fashion (calculated EC(50) of 93 ng/mL, total) after p.o. administration to tumor-bearing mice. In vivo inhibition of FAK phosphorylation (>50%) was sustained for >4 hours with a single p.o. dose of 33 mg/kg. Antitumor efficacy and regressions were observed in multiple human s.c. xenograft models. No weight loss, morbidity, or mortality were observed in any in vivo experiment. Tumor growth inhibition was dose and drug exposure dependent. Taken together, these data show that kinase inhibition with an ATP-competitive small molecule inhibitor of FAK decreases the phospho-status in vivo, resulting in robust antitumor activity.

Phthalate induction of CYP3A4 is dependent on glucocorticoid regulation of PXR expression.

Cytochrome P450 3A4 (CYP3A4) is responsible for oxidative metabolism of more than 60% of all pharmaceuticals. CYP3A4 is inducible by xenobiotics that activate pregnane X receptor (PXR), and enhanced CYP3A4 activity has been implicated in adverse drug interactions. Recent evidence suggest that the widely used plasticizer, di-2-ethylhexyl phthalate (DEHP), and its primary metabolite mono-2-ethylhexyl phthalate (MEHP) may act as agonists for PXR. Hospital patients are uniquely exposed to high levels of DEHP as well as being administered glucocorticoids. Glucocorticoids positively regulate PXR expression in a glucocorticoid receptor (GR)-mediated mechanism. We suggest that the magnitude of CYP3A4 induction by phthalates is dependent on the expression of PXR and may be significantly higher in the presence of glucocorticoids. DEHP and MEHP induced PXR-mediated transcription of the CYP3A4 promoter in a dose-dependent fashion. Coexposure to phthalates and dexamethasone (Dex) resulted in enhanced CYP3A4 promoter activity; furthermore, this induction was abrogated by both the GR antagonist RU486 and GR small interfering ribonucleic acid. Dex induced PXR protein expression in human hepatocytes and a liver-derived rat cell line. CYP3A4 protein was highly induced by Dex and DEHP coadministration in human hepatocyte cultures. Finally, enhanced 6beta-hydroxytestosterone formation in Dex and phthalate cotreated human hepatocytes confirmed CYP3A4 enzyme induction. Concomitant exposure to glucocorticoids and phthalates resulting in enhanced metabolic activity of CYP3A4 may play a role in altered efficacy of pharmaceutical agents. Understanding the role of glucocorticoid regulation of PXR as a key determinant in the magnitude of CYP3A4 induction by xenobiotics may provide insight into adverse drug effects in a sensitive population.

Cellular characterization of a novel focal adhesion kinase inhibitor.

Focal adhesion kinase (FAK) is a member of a family of non-receptor protein-tyrosine kinases that regulates integrin and growth factor signaling pathways involved in cell migration, proliferation, and survival. FAK expression is increased in many cancers, including breast and prostate cancer. Here we describe perturbation of adhesion-mediated signaling with a FAK inhibitor, PF-573,228. In vitro, this compound inhibited purified recombinant catalytic fragment of FAK with an IC(50) of 4 nM. In cultured cells, PF-573,228 inhibited FAK phosphorylation on Tyr(397) with an IC(50) of 30-100 nM. Treatment of cells with concentrations of PF-573,228 that significantly decreased FAK Tyr(397) phosphorylation failed to inhibit cell growth or induce apoptosis. In contrast, treatment with PF-573,228 inhibited both chemotactic and haptotactic migration concomitant with the inhibition of focal adhesion turnover. These studies show that PF-573,228 serves as a useful tool to dissect the functions of FAK in integrin-dependent signaling pathways in normal and cancer cells and forms the basis for the generation of compounds amenable for preclinical and patient trials.

Antiangiogenic and antitumor activity of a selective PDGFR tyrosine kinase inhibitor, CP-673,451.

CP-673,451 is a potent inhibitor of platelet-derived growth factor beta-receptor (PDGFR-beta) kinase- and PDGF-BB-stimulated autophosphorylation of PDGFR-beta in cells (IC(50) = 1 nmol/L) being more than 450-fold selective for PDGFR-beta versus other angiogenic receptors (e.g., vascular endothelial growth factor receptor 2, TIE-2, and fibroblast growth factor receptor 2). Multiple models have been used to evaluate in vivo activity of CP-673,451 and to understand the pharmacology of PDGFR-beta inhibition and the effect on tumor growth. These models include an ex vivo measure of PDGFR-beta phosphorylation in glioblastoma tumors, a sponge model to measure inhibition of angiogenesis, and multiple models of tumor growth inhibition. Inhibition of PDGFR-beta phosphorylation in tumors correlates with plasma and tumor levels of CP-673,451. A dose of 33 mg/kg was adequate to provide >50% inhibition of receptor for 4 hours corresponding to an EC(50) of 120 ng/mL in plasma at C(max). In a sponge angiogenesis model, CP-673,451 inhibited 70% of PDGF-BB-stimulated angiogenesis at a dose of 3 mg/kg (q.d. x 5, p.o., corresponding to 5.5 ng/mL at C(max)). The compound did not inhibit vascular endothelial growth factor- or basic fibroblast growth factor-induced angiogenesis at concentrations which inhibited tumor growth. The antitumor efficacy of CP-673,451 was evaluated in a number of human tumor xenografts grown s.c. in athymic mice, including H460 human lung carcinoma, Colo205 and LS174T human colon carcinomas, and U87MG human glioblastoma multiforme. Once-daily p.o. x 10 days dosing routinely inhibited tumor growth (ED(50) < or = 33 mg/kg). These data show that CP-673,451 is a pharmacologically selective PDGFR inhibitor, inhibits tumor PDGFR-beta phosphorylation, selectively inhibits PDGF-BB-stimulated angiogenesis in vivo, and causes significant tumor growth inhibition in multiple human xenograft models.

Surfactant layering on mixed monolayer-protected gold clusters.

Positively-charged monolayer protected gold clusters (MMPCs) were mixed with sodium dodecyl sulfate (SDS). At lower SDS concentration, the initially water-soluble particles became organic-soluble while remaining discrete. Upon further addition of SDS, the particles aggregate and become water-soluble. NaCN decomposition, TEM, and DLS characterization reveal the morphology and properties of these encapsulated assemblies.

Design and SAR of thienopyrimidine and thienopyridine inhibitors of VEGFR-2 kinase activity.

Novel classes of thienopyrimidines and thienopyridines have been identified as potent inhibitors of VEGFR-2 kinase. The synthesis and SAR of these compounds is presented, along with successful efforts to diminish EGFR activity present in the lead series.