Predictive Validity of the K-CAT-SS in High-Risk Adolescents and Young Adults.

OBJECTIVE: Suicide is a leading cause of death in adolescents and young adults and has increased substantially in the past 15 years. Accurate suicide risk stratification based on rapid screening can help reverse these trends. To study the ability of the K-CAT-SS, a brief computerized adaptive test of suicidality, to predict suicide attempts (SA) in high-risk youth. METHOD: 652 participants aged 12-24, 78% of whom presented with suicidal ideation or behavior, were recruited within one month of mental health contact. The K-CAT-SS, scaled from 0-100, was administered at baseline, and participants were assessed at around 1-, 3-, and 6-months post-intake. Weekly incidence of SAs, assessed using the Adolescent Longitudinal Interval Follow-up Evaluation and Columbia-Suicide Severity Rating Scale. A secondary outcome was suicidal behavior (SB), including aborted, interrupted, and actual SA. RESULTS: The K-CAT-SS showed a 4.91-fold increase in SAs for every 25-point increase in the baseline score, (95% CI=2.83,8.52) and a 3.51-fold increase in SBs (95% CI=2.32,5.30) These relationships persisted following adjustment for prior attempts, and demographic variables including age, sex, gender identity, sexual orientation, race/ethnicity, and other measures of psychopathology. No moderating effects were identified. At 3 months, the Area Under the Receiver Operating Curve [AUROC]=0.83 (95% CI=0.72, 0.93) for 1 or more SA. CONCLUSION: The K-CAT-SS is an excellent tool for suicide risk stratification, particularly in higher-risk populations where other measures have shown lower predictive validity.

Weekly links among irritability and suicidal thoughts and behaviors in high-risk youth.

BACKGROUND: Previous studies demonstrate a link between irritability and suicidal thoughts and behaviors (STBs) in youth samples. However, they have mostly assessed irritability in community samples and as a largely dispositional (i.e. trait-like) construct. Thus, it remains unclear to what extent links between irritability and STBs reflect within-person processes of elevated risk in clinically meaningful time periods. METHODS: The present study used clinical data from 689 adolescents aged 12-19 years attending a total of 6,128 visits at a specialty Intensive Outpatient Program for depressed and suicidal youth to examine patterns in weekly assessments of irritability and STBs throughout treatment, including associations among trends and fluctuations departing from these trends via multilevel structural equation modeling. Youth completed self-report measures of irritability, depression, and STBs weekly as part of standard IOP clinical care. RESULTS: Overall, two-thirds of variance in weekly irritable mood was accounted for by between-person differences and the remaining portion by weekly fluctuations. After controlling for depression, during weeks when youth were more irritable they experienced increased STBs. Rates of change in irritability and STBs tended to track together at early stages of treatment, but these effects were generally accounted for by depression severity. CONCLUSIONS: Our results suggest that although changes in STBs are best accounted for by depression, irritability can be understood as a specific, proximal risk factor for youth STBs that exacerbates youth STBs in clinically informative timeframes above and beyond depression.

Impact of trauma exposure and depression comorbidity on response to transdiagnostic behavioral therapy for pediatric anxiety and depression.

By adolescence, two-thirds of youth report exposure to at least one traumatic event, yet the impact of trauma history is not routinely considered when evaluating the effect of psychotherapeutic interventions. Trauma may be a particularly important moderator of the effects of transdiagnostic therapies for emotional disorders, as trauma exposure is associated with risk for the development of comorbid depression and anxiety. The current study examined the history of trauma exposure and the presence of clinically significant depression as moderators of treatment outcomes in the Brief Behavioral Therapy (BBT) trial, the largest study of transdiagnostic psychotherapy for youth. Youths (age 8-16 years) were randomized to BBT (n = 89) based in pediatric primary care or assisted referral to outpatient community care (ARC; n = 86). Clinical response, functioning, anxiety symptoms, and depression symptoms were assessed at post-treatment (Week 16) and at follow-up (Week 32). A significant three-way interaction emerged between the treatment group, comorbid depression, and trauma exposure. BBT was broadly effective for 3/4 of the sample, but, for anxious-depressed youth with trauma exposure, BBT never significantly separated from ARC. Differences in outcome were not accounted for by other participant characteristics or by therapist-rated measures of alliance, youth engagement, or homework completion. Implications for models of learning and for intervention theory and development are discussed.

Ligand-Free Silver Nanoparticles: An Innovative Strategy against Viruses and Bacteria.

The spread of antibiotic-resistant bacteria and the rise of emerging and re-emerging viruses in recent years constitute significant public health problems. Therefore, it is necessary to develop new antimicrobial strategies to overcome these challenges. Herein, we describe an innovative method to synthesize ligand-free silver nanoparticles by Pulsed Laser Ablation in Liquid (PLAL-AgNPs). Thus produced, nanoparticles were characterized by total X-ray fluorescence, zeta potential analysis, transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to evaluate the nanoparticles' cytotoxicity. Their potential was evaluated against the enveloped herpes simplex virus type 1 (HSV-1) and the naked poliovirus type 1 (PV-1) by plaque reduction assays and confirmed by real-time PCR and fluorescence microscopy, showing that nanoparticles interfered with the early stage of infection. Their action was also examined against different bacteria. We observed that the PLAL-AgNPs exerted a strong effect against both methicillin-resistant Staphylococcus aureus (S. aureus MRSA) and Escherichia coli (E. coli) producing extended-spectrum ß-lactamase (ESBL). In detail, the PLAL-AgNPs exhibited a bacteriostatic action against S. aureus and a bactericidal activity against E. coli. Finally, we proved that the PLAL-AgNPs were able to inhibit/degrade the biofilm of S. aureus and E. coli.

PLASTAMINATION: Outcomes on the Central Nervous System and Reproduction.

BACKGROUND: Environmental exposures to non-biodegradable and biodegradable plastics are unavoidable. Microplastics (MPs) and nanoplastics (NPs) from the manufacturing of plastics (primary sources) and the degradation of plastic waste (secondary sources) can enter the food chain directly or indirectly and, passing biological barriers, could target both the brain and the gonads. Hence, the worldwide diffusion of environmental plastic contamination (PLASTAMINATION) in daily life may represent a possible and potentially serious risk to human health. OBJECTIVE: This review provides an overview of the effects of non-biodegradable and the more recently introduced biodegradable MPs and NPs on the brain and brain-dependent reproductive functions, summarizing the molecular mechanisms and outcomes on nervous and reproductive organs. Data from in vitro, ex vivo, non-mammalian and mammalian animal models and epidemiological studies have been reviewed and discussed. RESULTS: MPs and NPs from non-biodegradable plastics affect organs, tissues and cells from sensitive systems such as the brain and reproductive organs. Both MPs and NPs induce oxidative stress, chronic inflammation, energy metabolism disorders, mitochondrial dysfunction and cytotoxicity, which in turn are responsible for neuroinflammation, dysregulation of synaptic functions, metabolic dysbiosis, poor gamete quality, and neuronal and reproductive toxicity. In spite of this mechanistic knowledge gained from studies of non-biodegradable plastics, relatively little is known about the adverse effects or molecular mechanisms of MPs and NPs from biodegradable plastics. CONCLUSION: The neurological and reproductive health risks of MPs/NPs exposure warrant serious consideration, and further studies on biodegradable plastics are recommended.

Biomimetic proteolipid vesicles for reverting GPI deficiency in paroxysmal nocturnal hemoglobinuria.

Nano-vesicular carriers are promising tissue-specific drug delivery platforms. Here, biomimetic proteolipid vesicles (BPLVs) were used for delivery of glycosylphosphatidylinositol (GPI)-anchored proteins to GPI deficient paroxysmal nocturnal hemoglobinuria (PNH) cells. BPLVs were assembled as single unilamellar monodispersed (polydispersity index, 0.1) negatively charged (ζ-potential, -28.6 ± 5.6 mV) system using microfluidic technique equipped with Y-shaped chip. GPI-anchored and not-GPI proteins on BPLV surface were detected by flow cytometry. Peripheral blood mononuclear cells (PBMCs) from healthy and PNH subjects were treated with BPLVs (final concentration, 0.5 mg/mL), and cells displayed an excellent protein uptake, documented by flow cytometry immunophenotyping and confocal microscopy. BPLV-treated cells stressed with complement components showed an increased resistance to complement-mediated lysis, both healthy and PNH PBMCs. In conclusion, BPLVs could be effective nanocarriers for protein transfer to targeted cells to revert protein deficiency, like in PNH disease. However, further in vivo studies are required to validate our preclinical in vitro results.

Testing the interpersonal theory of suicide in adolescents: A multi-wave longitudinal study.

BACKGROUND: Suicide is a major public health crisis among youth. Several prominent theories, including the Interpersonal Theory of Suicide (IPTS), aim to characterize the factors leading from suicide ideation to action. These theories are largely based on findings in adults and require testing and elaboration in adolescents. METHODS: Data were examined from high-risk 13-18-year-old adolescents (N = 167) participating in a multi-wave, longitudinal study; 63% of the sample exhibited current suicidal thoughts or recent behaviors (n = 105). The study included a 6-month follow-up period with clinical interviews and self-report measures at each of the four assessments as well as weekly smartphone-based assessments of suicidal thoughts and behaviors. Regression and structural equation models were used to probe hypotheses related to the core tenets of the IPTS. RESULTS: Feelings of perceived burdensomeness were associated with more severe self-reported suicidal ideation (b = 0.58, t(158) = 7.64, p < .001). Similarly, burdensomeness was associated with more frequent ideation based on weekly smartphone ratings (b = 0.11, t(1460) = 3.41, p < .001). Contrary to IPTS hypotheses, neither feelings of thwarted belongingness, nor interactions between burdensomeness and thwarted belongingness were significantly associated with ideation (ps > .05). Only elevated depression severity was associated with greater odds of suicide events (i.e., suicide attempts, psychiatric hospitalizations, and/or emergency department visits for suicide concerns) during the follow-up period (OR = 1.83, t(158) = 2.44, p = .01). No effect of acquired capability was found. CONCLUSIONS: Perceptions of burdensomeness to others reflect a critical risk factor for suicidal ideation among high-risk adolescents. Null findings with other IPTS constructs may suggest a need to adopt more developmentally sensitive models or measures of interpersonal and acquired capability risk factors for youth. Refining methods and theoretical models of suicide risk may help improve the identification of high-risk cases and inform clinical intervention.

The Other Side of Plastics: Bioplastic-Based Nanoparticles for Drug Delivery Systems in the Brain.

Plastics have changed human lives, finding a broad range of applications from packaging to medical devices. However, plastics can degrade into microscopic forms known as micro- and nanoplastics, which have raised concerns about their accumulation in the environment but mainly about the potential risk to human health. Recently, biodegradable plastic materials have been introduced on the market. These polymers are biodegradable but also bioresorbable and, indeed, are fundamental tools for drug formulations, thanks to their transient ability to pass through biological barriers and concentrate in specific tissues. However, this "other side" of bioplastics raises concerns about their toxic potential, in the form of micro- and nanoparticles, due to easier and faster tissue accumulation, with unknown long-term biological effects. This review aims to provide an update on bioplastic-based particles by analyzing the advantages and drawbacks of their potential use as components of innovative formulations for brain diseases. However, a critical analysis of the literature indicates the need for further studies to assess the safety of bioplastic micro- and nanoparticles despite they appear as promising tools for several nanomedicine applications.

Endotenon-Derived Type II Tendon Stem Cells Have Enhanced Proliferative and Tenogenic Potential.

Tendon injuries caused by overuse or age-related deterioration are frequent. Incomplete knowledge of somatic tendon cell biology and their progenitors has hindered interventions for the effective repair of injured tendons. Here, we sought to compare and contrast distinct tendon-derived cell populations: type I and II tendon stem cells (TSCs) and tenocytes (TNCs). Porcine type I and II TSCs were isolated via the enzymatic digestion of distinct membranes (paratenon and endotenon, respectively), while tenocytes were isolated through an explant method. Resultant cell populations were characterized by morphology, differentiation, molecular, flow cytometry, and immunofluorescence analysis. Cells were isolated, cultured, and evaluated in two alternate oxygen concentrations (physiological (2%) and air (21%)) to determine the role of oxygen in cell biology determination within this relatively avascular tissue. The different cell populations demonstrated distinct proliferative potential, morphology, and transcript levels (both for tenogenic and stem cell markers). In contrast, all tendon-derived cell populations displayed multipotent differentiation potential and immunophenotypes (positive for CD90 and CD44). Type II TSCs emerged as the most promising tendon-derived cell population for expansion, given their enhanced proliferative potential, multipotency, and maintenance of a tenogenic profile at early and late passage. Moreover, in all cases, physoxia promoted the enhanced proliferation and maintenance of a tenogenic profile. These observations help shed light on the biological mechanisms of tendon cells, with the potential to aid in the development of novel therapeutic approaches for tendon disorders.

A chatbot-delivered intervention for optimizing social media use and reducing perceived isolation among rural-living LGBTQ+ youth: Development, acceptability, usability, satisfaction, and utility.

Background: Lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ+) youth are at higher risk of isolation and depression than their heterosexual peers. Having access to tailored mental health resources is a documented concern for rural living LGBTQ+ youth. Social media provides access to connections to a broader and like-minded community of peers, but it also is a vehicle for negative interactions. We developed REALbot, an automated, social media-based educational intervention to improve social media efficacy, reduce perceived isolation, and bolster connections for rural living LGBTQ+ youth. This report presents data on the acceptability, feasibility, and utility of REALbot among its target audience of rural living LGBTQ+ youth. Methods: We conducted a week-long exploratory study with a single non-comparison group of 20 rural-living LGBTQ+ youth aged 14-19 recruited from social media to test our Facebook- and Instagram-delivered chatbot. We assessed pre- and post-test scores of social media self-efficacy, social isolation (4-item Patient-Reported Outcomes Measurement System - PROMIS), and depressive symptoms (Patient Health Questionnaire, Adolescent Version - PHQ-A). At post-test, we assessed acceptability (User Experience Questionnaire - UEQ-S), usability (Chatbot Usability Questionnaire -CUQ and Post-Study Satisfaction and Usability Questionnaire -PSSUQ), and satisfaction with the chatbot (Client Satisfaction Questionnaire - CSQ), along with two open-ended questions on 'likes' and 'dislikes' about the intervention. We compared pre- and post-test scores with standard univariate statistics. Means and standard deviations were calculated for usability, acceptability, and satisfaction. To analyze the responses to post-test open-end questions, we used a content analysis approach. Results: Acceptability of REALbot was high with UEQ-S 5.3 out of 7 (SD = 1.1) and received high usability scores with CUQ and PSSUQ (mean score (M) = 78.0, SD = 14.5 and M = 86.9, SD = 25.2, respectively), as well as high user satisfaction with CSQ (M = 24.9, SD = 5.4). Themes related to user 'likes' and 'dislikes' were organized in two main categories: usability and content provided. Participants were engaged with the chatbot, sending an average of 49.3 messages (SD = 43.6, median = 30). Pre-/post- changes in scores of perceived isolation, depressive symptoms and social media self-efficacy were not significant (p's > 0.08). Conclusion: REALbot deployment was found to be feasible and acceptable, with good usability and user satisfaction scores. Participants reported changes from pre- to post-test in most outcomes of interest and effect sizes were small to medium. Additional development and a formal evaluation of feasibility and engagement with behavioral targets is warranted.

Tendon tissue engineering: An overview of biologics to promote tendon healing and repair.

Tendons are dense connective tissues with a hierarchical polarized structure that respond to and adapt to the transmission of muscle contraction forces to the skeleton, enabling motion and maintaining posture. Tendon injuries, also known as tendinopathies, are becoming more common as populations age and participation in sports/leisure activities increases. The tendon has a poor ability to self-heal and regenerate given its intrinsic, constrained vascular supply and exposure to frequent, severe loading. There is a lack of understanding of the underlying pathophysiology, and it is not surprising that disorder-targeted medicines have only been partially effective at best. Recent tissue engineering approaches have emerged as a potential tool to drive tendon regeneration and healing. In this review, we investigated the physiochemical factors involved in tendon ontogeny and discussed their potential application in vitro to reproduce functional and self-renewing tendon tissue. We sought to understand whether stem cells are capable of forming tendons, how they can be directed towards the tenogenic lineage, and how their growth is regulated and monitored during the entire differentiation path. Finally, we showed recent developments in tendon tissue engineering, specifically the use of mesenchymal stem cells (MSCs), which can differentiate into tendon cells, as well as the potential role of extracellular vesicles (EVs) in tendon regeneration and their potential for use in accelerating the healing response after injury.

Early indicators of response to transdiagnostic treatment of pediatric anxiety and depression.

BACKGROUND: Pediatric anxiety and depression are prevalent, impairing, and highly comorbid. Available evidence-based treatments have an average response rate of 60%. One path to increasing response may be to identify likely non-responders midway through treatment to adjust course prior to completing an episode of care. The aims of this study, thus, were to identify predictors of post-intervention response assessing (a) mid-treatment symptom severity, (b) session-by-session treatment process factors, and (c) a model optimizing the combination of these. METHOD: Data were drawn from the treatment arm (N = 95, ages 8-16) of a randomized transdiagnostic intervention trial (Msessions = 11.2). Mid-point measures of youth- and parent-reported anxiety and depression were collected, and therapists rated homework completion, youth and parent engagement, and youth therapeutic alliance at each session. Logistic regression was used to predict response on the Clinical Global Impression Improvement Scale (CGI-I ≤2) rated by independent evaluators masked to treatment condition. RESULTS: Mid-point symptom measures were significant predictors of treatment response, as were therapist-ratings of youth and parent engagement, therapeutic alliance, and homework completion. Therapist ratings were significant when tested as mean ratings summing across the first eight sessions of treatment (all ps < .004) and at individual session points (all ps <0.05). A combined prediction model included youth-reported anxiety, parent-reported depression, youth engagement at Session 2, and parent engagement at Session 8. This model correctly classified 76.5% of youth as non-responders and 91.3% as responders at post-treatment (Nagelkerke R2 = .59, χ2 (4, 80) = 46.54, p < .001). CONCLUSION: This study provides initial evidence that response to transdiagnostic intervention for pediatric anxiety and depression may be reliably predicted by mid-point. These data may serve as foundational evidence to develop adaptive treatment strategies to personalize intervention, correct treatment course, and optimize outcomes for youth with anxiety and depression.

Contribution of peripheral blood mononuclear cells isolated by advanced filtration system to myogenesis of human bone marrow mesenchymal stem cells co-cultured with myoblasts.

Background: Contribution of peripheral blood mononuclear cells (PBMCs) in myogenesis is still under debate, even though blood filtration systems are commonly used in clinical practice for successfully management of critic limb ischemia. Objectives: A commercial blood filter used for autologous human PBMC transplantation procedures is characterized and used to collect PBMCs, that are then added to well-established 2D in vitro myogenic models assembled with a co-culture of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) and skeletal myoblasts (hSkMs) whit the aim of investigating their potential contribution to stem cell myogenic commitment. Methods: A commercial blood filter was physically and chemically studied to understand its morphological characteristics and composition. PBMCs were concentrated using this system, further isolated by Ficoll-Paque density gradient centrifugation, and then added in an upper transwell chamber to a 2D co-culture of hBM-MSCs and hSkMs. Myogenic commitment was investigated by RT-PCR, immunofluorescence, and flow cytometry immunophenotyping. Cytokine levels were monitored by ELISA assay in culture media. Results: The blood filtration system was disassembled and appeared to be formed by twelve membranes of poly-butylene terephthalate fibers (diameters, 0.9-4.0 µm) with pore size distribution of 1-20 µm. Filter functional characterization was achieved by characterizing collected cells by flow cytometry. Subsequently, collected PBMCs fraction was added to an in-vitro model of hBM-MSC myogenic commitment. In the presence of PBMCs, stem cells significantly upregulated myogenic genes, such as Desmin and MYH2, as confirmed by qRT-PCR and expressed related proteins by immunofluorescence (IF) assay, while downregulated pro-inflammatory cytokines (IL12A at day 14) along the 21 days of culture. Novelty: Our work highlights chemical-physical properties of commercial blood filter and suggests that blood filtrated fraction of PBMC might modulate cytokine expression in response to muscle injury and promote myogenic events, supporting their clinical use in autologous transplantation.

Activity and Selectivity of Novel Chemical Metallic Complexes with Potential Anticancer Effects on Melanoma Cells.

Human malignant melanoma cells from lymph node metastatic site (MeWo) were selected for testing several synthesized and purified silver(I) and gold(I) complexes stabilized by unsymmetrically substituted N-heterocyclic carbene (NHC) ligands, called L20 (N-methyl, N'-[2-hydroxy ethylphenyl]imidazol-2-ylide) and M1 (4,5-dichloro, N-methyl, N'-[2-hydroxy ethylphenyl]imidazol-2-ylide), having halogenide (Cl- or I-) or aminoacyl (Gly=N-(tert-Butoxycarbonyl)glycinate or Phe=(S)-N-(tert-Butoxycarbonyl)phenylalaninate) counterion. For AgL20, AuL20, AgM1 and AuM1, the Half-Maximal Inhibitory Concentration (IC50) values were measured, and all complexes seemed to reduce cell viability more effectively than Cisplatin, selected as control. The complex named AuM1 was the most active just after 8 h of treatment at 5 µM, identified as effective growth inhibition concentration. AuM1 also showed a linear dose and time-dependent effect. Moreover, AuM1 and AgM1 modified the phosphorylation levels of proteins associated with DNA lesions (H2AX) and cell cycle progression (ERK). Further screening of complex aminoacyl derivatives indicated that the most powerful were those indicated with the acronyms: GlyAg, PheAg, AgL20Gly, AgM1Gly, AuM1Gly, AgL20Phe, AgM1Phe, AuM1Phe. Indeed, the presence of Boc-Glycine (Gly) and Boc-L-Phenylalanine (Phe) showed an improved efficacy of Ag main complexes, as well as that of AuM1 derivatives. Selectivity was further checked on a non-cancerous cell line, a spontaneously transformed aneuploid immortal keratinocyte from adult human skin (HaCaT). In such a case, AuM1 and PheAg complexes resulted as the most selective allowing HaCaT viability at 70 and 40%, respectively, after 48 h of treatment at 5 µM. The same complexes tested on 3D MeWo static culture induced partial spheroid disaggregation after 24 h of culture, with almost half of the cells dead.

Intensive Longitudinal Assessment of Adolescents to Predict Suicidal Thoughts and Behaviors.

OBJECTIVE: Suicide is a leading cause of death among adolescents. However, there are no clinical tools to detect proximal risk for suicide. METHOD: Participants included 13- to 18-year-old adolescents (N = 103) reporting a current depressive, anxiety, and/or substance use disorder who owned a smartphone; 62% reported current suicidal ideation, with 25% indicating a past-year attempt. At baseline, participants were administered clinical interviews to assess lifetime disorders and suicidal thoughts and behaviors (STBs). Self-reports assessing symptoms and suicide risk factors also were obtained. In addition, the Effortless Assessment of Risk States (EARS) app was installed on adolescent smartphones to acquire daily mood and weekly suicidal ideation severity during the 6-month follow-up period. Adolescents completed STB and psychiatric service use interviews at the 1-, 3-, and 6-month follow-up assessments. RESULTS: K-means clustering based on aggregates of weekly suicidal ideation scores resulted in a 3-group solution reflecting high-risk (n = 26), medium-risk (n = 47), and low-risk (n = 30) groups. Of the high-risk group, 58% reported suicidal events (ie, suicide attempts, psychiatric hospitalizations, emergency department visits, ideation severity requiring an intervention) during the 6-month follow-up period. For participants in the high-risk and medium-risk groups (n = 73), mood disturbances in the preceding 7 days predicted clinically significant ideation, with a 1-SD decrease in mood doubling participants' likelihood of reporting clinically significant ideation on a given week. CONCLUSION: Intensive longitudinal assessment through use of personal smartphones offers a feasible method to assess variability in adolescents' emotional experiences and suicide risk. Translating these tools into clinical practice may help to reduce the needless loss of life among adolescents.

Measurement-based care for suicidal youth: Outcomes and recommendations from the Services for Teens At Risk (STAR) Center.

Measurement-based care has demonstrable benefits, but significant implementation barriers slow dissemination in real-world clinical settings, especially youth behavioral health care. Here, we describe use of measurement-based care in a specialty clinic offering a continuum of outpatient care for suicidal youth. We characterize strategies used to facilitate measurement-based care in this population and ways in which challenges to implementation have been addressed. We examined adherence to measurement-based care procedures relative to treatment engagement data from electronic medical records, as well as data from clinicians regarding acceptability and utility of measurement-based care. Results suggest that measurement-based care is both feasible and acceptable for use with suicidal youth. Here we provide future directions in measurement-based care in this, and other, behavioral health settings.

Reduction in avoidance mediates effects of brief behavioral therapy for pediatric anxiety and depression.

Brief behavioral therapy (BBT) is an efficacious transdiagnostic intervention for pediatric anxiety and depression that targets behavioral avoidance as a key mechanism. It is unknown if change in avoidance mediates treatment effects, as theorized. Data on avoidance at baseline and Week 16 were available on 52 youth (ages 8-16 years) from a randomized controlled trial (Weersing, Jeffreys, et al., 2017) comparing BBT and assisted referral to community care (ARC). BBT had significant effects on youth-reported behavioral avoidance, and significant indirect effects on functioning and anxiety, statistically mediated through changes in youth-reported behavioral avoidance. Change in youth-reported avoidance was not a significant mediator of depression. Parent-report of avoidance was not impacted by treatment and was not a significant mediator. Overall, BBT appears to be an effective treatment for targeting behavioral avoidance, which in turn, may improve functioning and lessen anxiety. CLINICAL TRIAL REGISTRATION INFORMATION: https://clinicaltrials.gov; NCT01147614.

Bottom-Up Strategy to Forecast the Drug Location and Release Kinetics in Antitumoral Electrospun Drug Delivery Systems.

Electrospun systems are becoming promising devices usable for topical treatments. They are eligible to deliver different therapies, from anti-inflammatory to antitumoral. In the current research, polycaprolactone electrospun membranes loaded with synthetic and commercial antitumoral active substances were produced, underlining how the matrix-filler affinity is a crucial parameter for designing drug delivery devices. Nanofibrous membranes loaded with different percentages of Dacarbazine (the drug of choice for melanoma) and a synthetic derivative of Dacarbazine were produced and compared to membranes loaded with AuM1, a highly active Au-complex with low affinity to the matrix. AFM morphologies showed that the surface profile of nanofibers loaded with affine substances is similar to one of the unloaded systems, thanks to the nature of the matrix-filler interaction. FTIR analyses proved the efficacy of the interaction between the amidic group of the Dacarbazine and the polycaprolactone. In AuM1-loaded membranes, because of the weak matrix-filler interaction, the complex is mainly aggregated in nanometric domains on the nanofiber surface, which manifests a nanometric roughness. Consequently, the release profiles follow a Fickian behavior for the Dacarbazine-based systems, whereas a two-step with a highly prominent burst effect was observed for AuM1 systems. The performed antitumoral tests evidence the high-cytotoxic activity of the electrospun systems against melanoma cell lines, proving that the synthetic substances are more active than the commercial dacarbazine.

Brief Behavioral Therapy for Anxiety and Depression in Pediatric Primary Care: Breadth of Intervention Impact.

OBJECTIVE: To report on broad-based outcomes of the Brief Behavioral Therapy (BBT) trial for pediatric anxiety and depression. Secondary data analyses expand on previous reports by assessing diagnostic remission and independent functioning, impact on targeted psychopathology, and spillover effects on non-targeted outcomes. METHOD: Youth (N = 185; 8-16.9 years; 58% female; 78% White; 21% Hispanic) with anxiety and/or depression were eligible for this multi-site trial. Enrolled youth were randomly assigned to receive 8 to 12 sessions of BBT in primary care or assisted referral to outpatient care (ARC). Assessments were conducted 16 and 32 weeks post randomization. RESULTS: BBT was superior to ARC on remission of all targeted diagnoses (week 16: 56.8% vs 28.2%, p < .001; week 32: 62.5% vs 38.9%, p = .004), clinician-rated independent functioning (week 16: 75.0% vs 45.7%, p < .001; week 32: 81.2% vs 55.7%, p < .001), and on measures of anxiety, depression, suicide items, total comorbid behavioral and emotional problems, and hyperactivity (d = 0.21-0.49). Moderation analyses revealed superior outcomes for Hispanic youth in BBT vs ARC for diagnostic remission, anxiety, emotional problems, and parent-child conflict. Youth depression at baseline moderated effects on peer problems and parent-child conflict, with effects favoring BBT. Significant main and moderated effects of BBT on change in non-targeted outcomes were largely mediated by change in anxiety (24.2%-49.3% of total effects mediated). CONCLUSION: BBT has positive effects on youth, mediated by the strong impact of the intervention on anxiety. Analyses continue to support positive outcomes for Hispanic youth, suggesting that BBT is a broadly effective transdiagnostic treatment option for diverse populations. CLINICAL TRIAL REGISTRATION INFORMATION: Brief Cognitive Behavioral Therapy (CBT) for Pediatric Anxiety and Depression in Primary Care; https://clinicaltrials.gov; NCT01147614.

c-Kit M541L variant is related to ineffective hemopoiesis predisposing to clonal evolution in 3D in vitro biomimetic co-culture model of bone marrow niche.

Hematopoietic stem cell (HSC) maintenance in vitro is challenging because stem cell survival relies on cell-to-cell contacts and paracrine signals from bone marrow (BM) microenvironment. Indeed, HSCs easily differentiate in conventional culture systems, and in vitro study of stem cell biology, leukemogenesis, and evolutionary trajectories is limited. 3D-culture systems can mimic tissue architecture and microenvironment thus preserving HSC phenotype. In this study, we developed a calcium alginate hydrogel-based 3D co-culture system of BM mononuclear cells (BMMCs) and BM-derived mesenchymal stem cells (BM-MSCs) to study hemopoiesis in health and disease, such as biological roles of c-Kit M541L somatic mutation of unknown significance. BMMCs and peripheral blood stem cells were obtained from an acute myeloid leukemia patient who experienced graft failure and his haploidentical donor, and from a healthy donor. Cells embedded in alginate scaffolds were cultured for up to 21 days, and flow cytometry immunophenotyping was performed at baseline and every seven days. Our results showed suitability of our 3D culture system in preserving HSC vitality and phenotype throughout the culture period, and also in maintaining composition and vitality of total BMMCs. Moreover, 3D in vitro culture results suggested that M541L c-Kit somatic mutation could be a loss-of-function alteration by reducing HSC maintenance ability thus quickly promoting differentiation, as documented by in vivo graft failure and in vitro absence of long-term culture stability. In conclusions, our 3D BM-like biomimetic culture system allowed long-term stemness maintenance, making it a valid and effective tool for in vitro study of physiological and pathological hemopoiesis.