The Impact of Sex on Antiplatelet and Anticoagulant Thromboprophylaxis in Patients with Peripheral Artery Disease Post-revascularization.

OBJECTIVE: The aim of this prospective study was to 1) objectively quantify the impact of sex on platelet function in patients with PAD taking antiplatelet and anticoagulant medications and 2) to develop and test a personalized, iterative algorithm which personalizes thromboprophylaxis that incorporates platelet function testing. SUMMARY BACKGROUND DATA: Women with Peripheral Artery Disease (PAD) have worse outcomes as compared to their male counterparts in spite of having lower risk factors. This health disparity may be mitigated by personalizing thromboprophylaxis regimens. METHODS: Patients undergoing revascularization were enrolled. Serial thromboelastography (TEG) and TEG with Platelet Mapping (TEG-PM) was performed up to 6-months post-operatively to determine objective coagulation profiles. In a subset of patients, the Antiplatelet Coagulation Exactness (ACE) algorithm was implemented where patients were iteratively evaluated with TEG and given antiplatelet medications to maintain platelet inhibition at >29%. Statistical analysis was performed using unpaired t-test, ANOVA and Fisher's exact test. RESULTS: One hundred and eighty-one patients met study criteria. 58(32%) patients were females and 123(68%) were males. In the Aspirin cohort, females showed significantly greater clot strength as Maximum Amplitude - Arachidonic Acid (MAAA) and significantly lower platelet inhibition than males: [37.26 vs.32.38, P<0.01] and [52.95% vs.61.65%, P<0.05], respectively. In the Clopidogrel cohort, females showed higher Maximum Amplitude - Adenosine Diphosphate (MAADP) [42.58 vs.40.35, P=NS] compared to males. Females on dual antiplatelet therapy had higher MAADP [39.74 vs.35.07, P=NS] and lower platelet inhibition [45.25% vs.54.99%, P=NS] than males. The incidence of thrombosis of the revascularized segment, defined as thrombotic event, was objectively identified on an arterial duplex. Women showed significantly higher thrombotic events than men [22.95% vs.10.57%, P<0.05] on the same medication. In our pilot study, implementation of the ACE algorithm led to a significant decrease in the thrombosis rate (3%), including non-thrombotic events for females, vs. the historic thrombotic rate (22%) from our institution. CONCLUSIONS: Women with PAD exhibited higher platelet reactivity, clot strength, and reduced platelet inhibition in response to antiplatelet therapy. The use of the ACE algorithm to tailor antiplatelet medication in patients with PAD post-revascularization, resulted in a significant decrease in thrombotic event rates. This may serve as an opportune way to mitigate outcome sex-specific disparities caused by inadequate thromboprophylaxis in women.

Exploring the Nature of Arhopalus ferus (Coleoptera: Cerambycidae: Spondylidinae) Pheromone Attraction.

Cerambycid species of the Spondylidinae subfamily are distributed worldwide and are known for being prolific invaders that infest conifers. In New Zealand, Arhopalus ferus (Mulsant), the burnt pine longhorn beetle, is well-established and requires monitoring at high-risk sites such as ports, airports, and sawmills as part of the requirements to meet pine log export standards set by the New Zealand Ministry of Primary Industries (MPI). Currently, its surveillance relies on traps baited with host volatiles (i.e., ethanol and α-pinene). We used volatile collections from adult beetles, electroantennograms, and field trapping bioassays to identify the pheromones emitted by the burnt pine longhorn beetle A. ferus and their effects on its behaviour. We show that A. ferus males emit mainly (E)-fuscumol and geranylacetone, as well as the minor components, α-terpinene and p-mentha-1,3,8-triene, and that all four compounds elicit a dose-dependent response in antennae of both sexes. Traps baited with the binary combination of geranylacetone plus fuscumol captured significantly more female A. ferus than did unbaited traps in two of three field experiments. α-Terpinene did not affect A. ferus trap catches and effects of p-mentha-1,3,8-triene on trap catch were not determined. Our findings provide further evidence of the use of fuscumol and geranylacetone as aggregation-sex pheromones by longhorn beetles in the Spondylidinae subfamily, and suggest that their deployment in survey traps may improve the efficacy of A. ferus monitoring in New Zealand and elsewhere.

Characterization of the Effect of N-(2-Methoxyphenyl)-1-methyl-1H-benzimidazol-2-amine, Compound 8, against Leishmania mexicana and Its In Vivo Leishmanicidal Activity.

Chemotherapy currently available for leishmaniasis treatment has many adverse side effects and drug resistance. Therefore, the identification of new targets and the development of new drugs are urgently needed. Previously, we reported the synthesis of a N-(2-methoxyphenyl)-1-methyl-1H-benzimidazol-2-amine, named compound 8, with an IC50 value in the micromolar range against L. mexicana, it also inhibited 68.27% the activity of recombinant L. mexicana arginase. Herein, we report studies carried out to characterize the mechanism of action of compound 8, as well as its in vivo leishmanicidal activity. It was shown in our ultrastructural studies that compound 8 induces several changes, such as membrane blebbing, the presence of autophagosomes, membrane detachment and mitochondrial and kinetoplast disorganization, among others. Compound 8 triggers the production of ROS and parasite apoptosis. It reduced 71% of the parasite load of L. mexicana in an experimental model of cutaneous leishmaniasis in comparison with a control. Altogether, the data obtained suggest the potential use of compound 8 in the treatment of cutaneous leishmaniasis.

TATA-Binding Protein-Based Virtual Screening of FDA Drugs Identified New Anti-Giardiasis Agents.

Parasitic diseases, predominantly prevalent in developing countries, are increasingly spreading to high-income nations due to shifting migration patterns. The World Health Organization (WHO) estimates approximately 300 million annual cases of giardiasis. The emergence of drug resistance and associated side effects necessitates urgent research to address this growing health concern. In this study, we evaluated over eleven thousand pharmacological compounds sourced from the FDA database to assess their impact on the TATA-binding protein (TBP) of the early diverging protist Giardia lamblia, which holds medical significance. We identified a selection of potential pharmacological compounds for combating this parasitic disease through in silico analysis, employing molecular modeling techniques such as homology modeling, molecular docking, and molecular dynamics simulations. Notably, our findings highlight compounds DB07352 and DB08399 as promising candidates for inhibiting the TBP of Giardia lamblia. Also, these compounds and DB15584 demonstrated high efficacy against trophozoites in vitro. In summary, this study identifies compounds with the potential to combat giardiasis, offering the prospect of specific therapies and providing a robust foundation for future research.

Impact of Acute High Glucose on Mitochondrial Function in a Model of Endothelial Cells: Role of PDGF-C.

An increase in plasma high glucose promotes endothelial dysfunction mainly through increasing mitochondrial ROS production. High glucose ROS-induced has been implicated in the fragmentation of the mitochondrial network, mainly by an unbalance expression of mitochondrial fusion and fission proteins. Mitochondrial dynamics alterations affect cellular bioenergetics. Here, we assessed the effect of PDGF-C on mitochondrial dynamics and glycolytic and mitochondrial metabolism in a model of endothelial dysfunction induced by high glucose. High glucose induced a fragmented mitochondrial phenotype associated with the reduced expression of OPA1 protein, high DRP1pSer616 levels and reduced basal respiration, maximal respiration, spare respiratory capacity, non-mitochondrial oxygen consumption and ATP production, regarding normal glucose. In these conditions, PDGF-C significantly increased the expression of OPA1 fusion protein, diminished DRP1pSer616 levels and restored the mitochondrial network. On mitochondrial function, PDGF-C increased the non-mitochondrial oxygen consumption diminished by high glucose conditions. These results suggest that PDGF-C modulates the damage induced by HG on the mitochondrial network and morphology of human aortic endothelial cells; additionally, it compensates for the alteration in the energetic phenotype induced by HG.

Tibolone Pre-Treatment Ameliorates the Dysregulation of Protein Translation and Transport Generated by Palmitic Acid-Induced Lipotoxicity in Human Astrocytes: A Label-Free MS-Based Proteomics and Network Analysis.

Excessive accumulation and release of fatty acids (FAs) in adipose and non-adipose tissue are characteristic of obesity and are associated with the leading causes of death worldwide. Chronic exposure to high concentrations of FAs such as palmitic acid (pal) is a risk factor for developing different neurodegenerative diseases (NDs) through several mechanisms. In the brain, astrocytic dysregulation plays an essential role in detrimental processes like metabolic inflammatory state, oxidative stress, endoplasmic reticulum stress, and autophagy impairment. Evidence shows that tibolone, a synthetic steroid, induces neuroprotective effects, but its molecular mechanisms upon exposure to pal remain largely unknown. Due to the capacity of identifying changes in the whole data-set of proteins and their interaction allowing a deeper understanding, we used a proteomic approach on normal human astrocytes under supraphysiological levels of pal as a model to induce cytotoxicity, finding changes of expression in proteins related to translation, transport, autophagy, and apoptosis. Additionally, tibolone pre-treatment showed protective effects by restoring those same pal-altered processes and increasing the expression of proteins from cell survival processes. Interestingly, ARF3 and IPO7 were identified as relevant proteins, presenting a high weight in the protein-protein interaction network and significant differences in expression levels. These proteins are related to transport and translation processes, and their expression was restored by tibolone. This work suggests that the damage caused by pal in astrocytes simultaneously involves different mechanisms that the tibolone can partially revert, making tibolone interesting for further research to understand how to modulate these damages.

Smartphone applications for physical activity promotion from physical education.

Smartphone applications (apps) are thought to be an adequate instructional strategy not only to improve the quality of the teaching in physical education (PE), but also to effectively promote leisure-time physical activity (PA) of adolescent students in this context. Although the use of smartphone apps has been generalized in PE, little is known about the curricular approach of smartphone apps to be implemented by teacher to teach specific curricular contents in PE lessons. Therefore, the aim of this research was threefold: a) to conduct a systematic search for smartphone apps focused on PA and sport; b) to assess the features, content and quality of every included smartphone app; and c) to analyze the relationships between every selected app and the secondary PE curriculum. Systematic searches were completed on Google Play Store from January 2021 to March 2021. Apps were included when they met: main goal focused on PA and sport; permitted use by underage; they are free; user scores of at least 4. The app selection process was carried out by several reviewers and concordance measures were estimated. Additionally, an app quality assessment was independently conducted by three reviewers. A total of 18 apps focused on PA were included. Particularly, eight apps were suitable for fitness, health and quality of life curricular content; two for sports content; four for body expression content; and four apps for outdoor PA content. The mean quality score was 4.00. Apps could be helpful for teachers to implement the secondary PE curriculum and effectively promote PA among adolescent students.

In vitro, ex vivo and in vivo short-term screening of DHEA nitrate derivatives activity over Trypanosoma cruzi Ninoa and TH strains from Oaxaca State, México.

Chagas disease is a health problem that affects millions of persons, currently Nifurtimox (Nfx) and Benznidazole (Bz) are the unique drugs to treat it. However, these drugs produce adverse effects and high toxicity, which has motivated the search for new candidate drugs. Based on reports about the extensive biological activity of steroidal nitrate esters, in this study three nitrate esters steroids (1b, 2b and 4b) were synthetized and characterized from Dehydroepiandrosterone (DHEA, 1a), 19-hydroxy-DHEA (2a), and Androst-5-en-3ß,17ß-diol (4a), respectively. In addition, compounds 3a and 3b were obtained by introducing an α-ethynyl and a ß-hydroxyl groups at position 17 of 2b and further nitration of the hydroxyl group. The trypanocidal activity of these steroids was evaluated in vitro against the epimastigote stage of two T. cruzi strains, Ninoa and TH, and their cytotoxicity over J774.2 macrophage cell line was assayed. Compounds 3a, 3b, and 4a shown higher trypanocidal activity than Bz and Nfx against epimastigotes of Ninoa strain, whereas DHEA (1a) and its nitrate derivative 1b showed higher activity than the reference drugs against the TH strain epimastigote. None of the compounds showed activity in the ex vivo assays against the blood trypomastigote of both strains. Interestingly, the selectivity index of Androst-5-en-3ß,17ß-diol 4a was almost twice the value of Nfx and 50 times more than Bz, against Ninoa and TH strains, respectively. Therefore, compound 4a could represent a valuable starting point toward the optimization of steroid derivatives as trypanocidal agents.

Community providers' experiences with evidence-based practices: The role of therapist race/ethnicity.

OBJECTIVES: Examining therapists' experiences implementing evidence-based practices (EBPs) is fundamental to understanding how these interventions are perceived, adapted, and delivered in community settings. However, little is known about racial/ethnic variation in the experiences of therapists serving racial/ethnic minority youth and their families. Through an innovative QUAN → qual → QUAN mixed-methods approach, we examined differences in therapists' perceptions, adaptations performed, and client-engagement challenges in the largest county-operated department of mental health in the United States. METHOD: Surveys were completed by 743 therapists (Latinx [44%], White [34%], other ethnic minority [22%]), most of whom were female (88%), master's level (85%), and unlicensed (58%). A subset of therapists (n = 60) completed semistructured interviews. RESULTS: Latinx therapists reported more positive experiences implementing EBPs, making more adaptations to EBPs, and encountering fewer client-engagement challenges than therapists from other racial/ethnic groups. Qualitative analyses expanded on these results, revealing that Latinx therapists commonly described adapting EBPs in terms of language and culture to improve fit and promote client engagement. Informed by these qualitative themes, a refined statistical model revealed that the ability to deliver EBPs in languages other than English might have accounted for differences in therapist-reported EBP adaptations and client-engagement challenges. CONCLUSIONS: The findings suggest that racial/ethnic minority therapists have positive experiences in implementing EBPs in community settings. In the case of Latinx therapists, bilingual/bicultural competence may facilitate adapting EBPs in ways that reduce perceptions of engagement challenges with racially/ethnically diverse clients. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

A Mixed-Method Analysis on the Impacts of a System-Driven Implementation of Multiple Child Evidence-Based Practices on Community Mental Health Providers.

Initiatives to scale up evidence-based practices (EBPs) in routine care are likely to have myriad impacts on community providers, but these impacts have not yet been examined in depth. This is especially true within the context of simultaneous implementation of multiple evidence-based practices. The aim of this study was to characterize the multifaceted impacts on community mental health therapists within a system-driven implementation of multiple EBPs for youth and families. Semistructured interview and survey data were gathered from 60 therapists at 11 agencies contracted with the Los Angeles County Department of Mental Health to deliver EBPs within the Prevention and Early Intervention initiative. Therapists' accounts of impacts varied, and were either predominately negative, predominantly positive, or mixed-valence. Mixed-methods analyses using Kruskal-Wallis tests showed therapist valence groups varied on mean levels of self-reported burnout on surveys. Themes from qualitative data revealed several favorable (e.g., increased EBP knowledge, structure) and unfavorable (e.g., distress, feeling constrained by EBPs) impacts of county-contracted EBP implementation. These findings inform the development and implementation of future system-driven EBP initiatives that consider therapist perspective to optimize positive impacts and minimize negative impacts on therapists.

Interpersonal Psychotherapy-Adolescent Skills Training With Youth From Asian American and Immigrant Families: Cultural Considerations and Intervention Process.

Although research has identified effective evidence-based depression prevention interventions for diverse youth, little is known about how the intervention process unfolds with immigrant family youth. This study utilized a qualitative approach to explore cultural and clinical differences in the implementation of Interpersonal Psychotherapy-Adolescent Skills Training (IPT-AST) in two schools, one serving youth from primarily immigrant, Asian American families and the second, youth from mostly nonimmigrant, non-Hispanic White families. A total of 131 IPT-AST sessions were audio recorded, transcribed, and coded for presence and patterns of cultural and clinical constructs. Results revealed that sessions with immigrant family youth were more likely to contain discussions of interpersonal problems characterized by estrangement, goals of spending time together with important others, mentions of emotion suppression and academic achievement expectations, conversations about acculturation, differences in value orientation, and discomfort with implementing new intervention skills. Dialogue from interventionist and youth exchanges is presented to illustrate how these themes emerged and were addressed by interventionists in a culturally responsive manner. The study highlights how IPT-AST with immigrant family and Asian American youth may unfold differently compared to youth from nonimmigrant families. Implications of findings for providers are discussed.

Heating Intravenous Fluid Tubing in an Experimental Setting for Prehospital Hypothermia.

OBJECTIVE: Hypothermia secondary to environmental exposure is a serious condition. Active external warming measures to treat it may prove challenging in the prehospital setting. We conducted an experimental study to measure the ability of commercially available heating elements to warm intravenous (IV) fluids during infusion. METHODS: 250-milliliter bags of dextrose 10% solution were suspended inside a refrigerator. IV tubing was coiled, and the tubing output was placed inside a thermally insulated cup. The tubing was heated directly with a hand warmer, a meals ready-to-eat heater, or a heating blanket. Fluids were run through the IV line. The temperature of the fluid at the tubing output was measured. The initial and final infusion temperatures for the methods were compared. RESULTS: The use of hand warmers, meals ready-to-eat heaters, and heating blankets to warm IV tubing did increase the temperature of the fluids but was ineffective at achieving the desired mean infusion temperature of 35°C to 42°C. CONCLUSION: Although the mean temperature increase did not meet the established experimental threshold, further research is needed to determine whether the fluid warming effect of these commercial heating elements used in the prehospital environment is significant enough to limit heat loss while repleting the dextrose of a hypothermic, hypoglycemic patient.

Novel thiosemicarbazones induce high toxicity in estrogen-receptor-positive breast cancer cells (MCF7) and exacerbate cisplatin effectiveness in triple-negative breast (MDA-MB231) and lung adenocarcinoma (A549) cells.

Cis-diamminedichloroplatinum(II) (CDDP), known as cisplatin, has been extensively used against breast cancer, which is the most frequent cancer among women, and lung cancer, the leading cancer that causes death worldwide. Novel compounds such as thiazole derivatives have exhibited antiproliferative activity, suggesting they could be useful against cancer treatment. Herein, we synthesized two novel thiosemicarbazones and an aldehyde to combine with CDDP to enhance efficacy against ER-positive breast MCF7 cancer cells, triple-negative/basal-B mammary carcinoma cells (MDA-MB231) and lung adenocarcinoma (A549) human cells. We synthesized 2,3,5,6-tetrafluoro-4-(2-mercaptoetanothiolyl)benzaldehyde (ALD), 5-[(2,3,5,6-tetrafluoro-4-(trifluoromethyl)phenyl)thio]-2-furaldehyde thiosemicarbazone (TSC1) and 5-[(4-(trifluoromethyl)phenyl)thio]-2-furaldehyde thiosemicarbazone (TSC2) and used them alone or in combination with subtoxic CDDP concentrations to evaluate cytotoxicity, cytoskeleton integrity and mitochondrial function. We found that none of the synthesized compounds improved CDDP activity against MCF7 cell cultures; however, TSC2 was effective in enhancing the cytotoxicity of CDDP against MDA-MB231 and A549 cancer cell cultures. We demonstrated that the cytotoxic effect is related to the TSC2 capacity to induce disruption in the cytoskeleton network and to decrease mitochondrial function.

Epigenetic Priming of Human Pluripotent Stem Cell-Derived Cardiac Progenitor Cells Accelerates Cardiomyocyte Maturation.

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) exhibit a fetal phenotype that limits in vitro and therapeutic applications. Strategies to promote cardiomyocyte maturation have focused interventions on differentiated hPSC-CMs, but this study tests priming of early cardiac progenitor cells (CPCs) with polyinosinic-polycytidylic acid (pIC) to accelerate cardiomyocyte maturation. CPCs were differentiated from hPSCs using a monolayer differentiation protocol with defined small molecule Wnt temporal modulation, and pIC was added during the formation of early CPCs. pIC priming did not alter the expression of cell surface markers for CPCs (>80% KDR+/PDGFRα+), expression of common cardiac transcription factors, or final purity of differentiated hPSC-CMs (∼90%). However, CPC differentiation in basal medium revealed that pIC priming resulted in hPSC-CMs with enhanced maturity manifested by increased cell size, greater contractility, faster electrical upstrokes, increased oxidative metabolism, and more mature sarcomeric structure and composition. To investigate the mechanisms of CPC priming, RNAseq revealed that cardiac progenitor-stage pIC modulated early Notch signaling and cardiomyogenic transcriptional programs. Chromatin immunoprecipitation of CPCs showed that pIC treatment increased deposition of the H3K9ac activating epigenetic mark at core promoters of cardiac myofilament genes and the Notch ligand, JAG1. Inhibition of Notch signaling blocked the effects of pIC on differentiation and cardiomyocyte maturation. Furthermore, primed CPCs showed more robust formation of hPSC-CMs grafts when transplanted to the NSGW mouse kidney capsule. Overall, epigenetic modulation of CPCs with pIC accelerates cardiomyocyte maturation enabling basic research applications and potential therapeutic uses. Stem Cells 2019;37:910-923.

Metabolic syndrome in indigenous communities in Mexico: a descriptive and cross-sectional study.

BACKGROUND: An Amerindian genetic background could play an important role in susceptibility to metabolic diseases, which have alarmingly increased in recent decades. Mexico has one of the highest prevalences of metabolic disease worldwide. The purpose of this study was to determine the prevalence of metabolic syndrome and its components in a population with high Amerindian ancestry. METHODS: We performed a descriptive, quantitative, and analytical cross-sectional study of 2596 adult indigenous volunteers from 60 different ethnic groups. Metabolic syndrome and its components were evaluated using the American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement criteria. RESULTS: The overall prevalence of metabolic syndrome in the indigenous Mexican population was 50.3%. Although females had a higher prevalence than males (55.6% vs. 38.2%), the males presented with combinations of metabolic syndrome components that confer a higher risk of cardiovascular disease. The most frequent metabolic syndrome component in both genders was low HDL-cholesterol levels (75.8%). Central obesity was the second most frequent component in females (61%), though it had a low prevalence in males (16.5%). The overall prevalence of elevated blood pressure was 42.7% and was higher in males than females (48.8 vs. 40%). We found no gender differences in the overall prevalence of elevated triglycerides (56.7%) or fasting glucose (27.9%). CONCLUSIONS: We documented that individuals with Amerindian ancestry have a high prevalence of metabolic syndrome. Health policies are needed to control the development of metabolic disorders in a population with high genetic risk.

Repositioned Drugs for Chagas Disease Unveiled via Structure-Based Drug Repositioning.

Chagas disease, caused by the parasite Trypanosoma cruzi, affects millions of people in South America. The current treatments are limited, have severe side effects, and are only partially effective. Drug repositioning, defined as finding new indications for already approved drugs, has the potential to provide new therapeutic options for Chagas. In this work, we conducted a structure-based drug repositioning approach with over 130,000 3D protein structures to identify drugs that bind therapeutic Chagas targets and thus represent potential new Chagas treatments. The screening yielded over 500 molecules as hits, out of which 38 drugs were prioritized following a rigorous filtering process. About half of the latter were already known to have trypanocidal activity, while the others are novel to Chagas disease. Three of the new drug candidates-ciprofloxacin, naproxen, and folic acid-showed a growth inhibitory activity in the micromolar range when tested ex vivo on T. cruzi trypomastigotes, validating the prediction. We show that our drug repositioning approach is able to pinpoint relevant drug candidates at a fraction of the time and cost of a conventional screening. Furthermore, our results demonstrate the power and potential of structure-based drug repositioning in the context of neglected tropical diseases where the pharmaceutical industry has little financial interest in the development of new drugs.

Research Community Collaboration in Observational Implementation Research: Complementary Motivations and Concerns in Engaging in the Study of Implementation as Usual.

Implementation research is dominated by studies of investigator-driven implementation of evidence-based practices (EBPs) in community settings. However, systems of care have increasingly driven the scale-up of EBPs through policy and fiscal interventions. Research community partnerships (RCPs) are essential to generating knowledge from these efforts. Interviews were conducted with community stakeholders (system leaders, program managers, therapists) involved in a study of a system-driven implementation of multiple EBPs in children's mental health services. Findings suggest novel considerations in initial engagement phases of an RCP, given the unique set of potentially competing and complementary interests of different stakeholder groups in implementation as usual.

When Do Therapists Stop Using Evidence-Based Practices? Findings from a Mixed Method Study on System-Driven Implementation of Multiple EBPs for Children.

Therapist discontinuation of delivering an evidence-based practice (EBP) is a critical outcome in the community implementation of EBPs. This mixed methods study examined factors associated with therapist discontinuation within a large reimbursement-driven implementation of multiple EBPs in public children's mental health services. The study integrated quantitative survey data from 748 therapists across 65 agencies, and qualitative interviews from a subset of 79 therapists across 14 agencies. Therapists adopted, on average, 2.41 EBPs (SD = 1.05, range = 1-5), and nearly half (n = 355, 47.5%) reported discontinuing at least one EBP. Multi-level models were used to predict the binary outcome of discontinuation, and qualitative analyses were used to expand upon quantitative findings. Quantitative models revealed that therapist factors, including fewer direct service hours per week, a greater number of EBPs adopted, higher emotional exhaustion, and more negative attitudes toward EBPs in general were associated with discontinuation. In addition, EBP-specific factors including more negative perceptions of the particular EBP and lower self-efficacy for delivering the specific EBP predicted discontinuation. Themes from interview responses highlighted the importance of fit of the EBP with the agency's client base, as well as therapist perceptions of adequate EBP training supports, and the alignment of an EBP with therapists' professional goals. Together, the findings suggest the need for strategic sustainment planning interventions that target EBP fit (i.e., fit between adopted EBPs and agency target population, fit between EBP and therapist preferences and career goals) and support therapist self-efficacy in delivering EBPs.

Qualitative Reports of How and When Therapists Adapt Children's Evidence-Based Practices during Community Implementation.

This study analyzed qualitative therapist reports of adaptations to the delivery of multiple evidence-based practices (EBPs) within the context of a system-driven reform of children's community mental health services to understand how therapists adapt EBPs as well as contexts of these adaptations to identify when these adaptations are made. The study sought to complement and expand upon previous quantitative survey findings of two categories of Augmenting and Reducing/Reordering adaptations to EBPs. Data included interviews from 60 therapists (88.3% female, 61.7% Latina/o, 80.0% unlicensed) across 20 program sites in 11 mental health agencies that served racial/ethnically diverse children. Interviews were coded to identify themes surrounding the types of adaptations made and the contexts for these adaptations. The majority of therapists' qualitative descriptions of adaptations converged with the 2 broad categories in the Augmenting and Reducing/Reordering Framework, with therapists describing augmenting (e.g., modifying presentation, lengthening or extending pacing) most often, and reducing/reordering adaptations were discussed less frequently. Child and family characteristics were most frequently cited as indications prompting adaptations; however, the specific characteristics motivating adaptations differed by type. Therapists reporting using augmenting adaptations in the context of a wide range of client characteristics, whereas reducing/reordering adaptations occurred more specifically as a function of clinical presentation, family and caregiver functioning, and emergent life events. Therapists described making adaptations to improve the fit of multiple EBPs for the clients they served. Findings could have implications for implementation efforts with diverse clients served in community settings.

Visceral endoderm and the primitive streak interact to build the fetal-placental interface of the mouse gastrula.

Hypoblast/visceral endoderm assists in amniote nutrition, axial positioning and formation of the gut. Here, we provide evidence, currently limited to humans and non-human primates, that hypoblast is a purveyor of extraembryonic mesoderm in the mouse gastrula. Fate mapping a unique segment of axial extraembryonic visceral endoderm associated with the allantoic component of the primitive streak, and referred to as the "AX", revealed that visceral endoderm supplies the placentae with extraembryonic mesoderm. Exfoliation of the AX was dependent upon contact with the primitive streak, which modulated Hedgehog signaling. Resolution of the AX's epithelial-to-mesenchymal transition (EMT) by Hedgehog shaped the allantois into its characteristic projectile and individualized placental arterial vessels. A unique border cell separated the delaminating AX from the yolk sac blood islands which, situated beyond the limit of the streak, were not formed by an EMT. Over time, the AX became the hindgut lip, which contributed extensively to the posterior interface, including both embryonic and extraembryonic tissues. The AX, in turn, imparted antero-posterior (A-P) polarity on the primitive streak and promoted its elongation and differentiation into definitive endoderm. Results of heterotopic grafting supported mutually interactive functions of the AX and primitive streak, showing that together, they self-organized into a complete version of the fetal-placental interface, forming an elongated structure that exhibited A-P polarity and was composed of the allantois, an AX-derived rod-like axial extension reminiscent of the embryonic notochord, the placental arterial vasculature and visceral endoderm/hindgut.