Comparing the Implementation Context for Early Intervention Services Before and During the COVID-19 Pandemic.

The COVID-19 pandemic not only led to drastic changes in the implementation context for early intervention and early childhood special education services in 2020, but has had an enduring effect on the organizations, educators, families, and children with developmental delays and disorders. Through secondary data analysis, characteristics of toddlers with autism being served in a publicly funded center-based early intervention program as well as the characteristics of their educators are examined, comparing those who were enrolled in (a) two randomized trials conducted prior to the pandemic and (b) one ongoing randomized trial that launched in return to in-person educational services after the pandemic shutdown. Significant demographic differences are found for toddlers, where the current study includes more girls (p = 0.002), who are younger (p < .001) than the prior studies. Further, toddlers enrolled in the current trial are entering with significantly younger receptive (p < .001) and expressive language age-equivalent scores (p < .001) than toddlers from the prior studies. In addition, significant differences are also found for teaching assistants (TAs), who are younger (p < .001), less experienced supporting children with autism (p < .001), have spent less time in this position (p < .001), and who are still working toward college degrees (p < .001) than TAs in the prior studies. Implications of these changes for both intervention strategies to support the strengths and needs of the toddlers (e.g., reduce frequency of TA-child pairing changes to build rapport, increase time in adult-child JASPER before adding peers) as well as implementation strategies (e.g., increase foundational content, TA teaming) to support the training and retention of the TAs are discussed. Clinical Trials Registry number: NCT04283045.

Anti-adipogenic activities of pheophorbide a and pyropheophorbide a isolated from wild bitter gourd (Momordica charantia L. var. abbreviata Seringe) in vitro.

BACKGROUND: The wild bitter gourd (WBG) is a commonly consumed vegetable in Asia that has antioxidant and hypoglycemic properties. The present study aimed to investigate the anti-adipogenic activities of isolated compounds from WBG on 8-day differentiated cultures of 3 T3-L1 adipocytes that were then stained with Oil Red O (ORO) or diamidino-2-phenylindole (DAPI). RESULTS: ORO stains of the methanol extracts of de-seeded HM86 cultivar of WBG (WBG-M) and the ethyl acetate fractions (WBG-M-EA) showed anti-adipogenic activities against differentiated adipocytes. Two chlorophyll-degraded compounds, pheophorbide a (1) and pyropheophorbide a (2), were isolated from WBG-M-EA. Treatments with 1 (5, 10, and 20 µmol L-1 ) and 2 (2.5, 5, and 10 µmol L-1 ) showed dose-dependent reductions in lipid accumulations and reduced nuclear DAPI stains in differentiated 3 T3-L1 adipocytes. The concentrations for 50% inhibition against lipid accumulations of 1 and 2, respectively, were 16.05 and 7.04 µmol L-1 . Treatments with 1 and 2 showed enhanced lactate dehydrogenase release in the first 4-day cell mitotic clonal expansions during the differentiating cultural processes, although the effect was less on the non-differentiating cultural processes. Thus, 1 and 2 were more toxic to differentiating adipocytes than to non-differentiated pre-adipocytes, which partly resulted in anti-adipogenic activities with lowered lipid accumulations. CONCLUSION: Both 1 and 2 showed anti-adipogenic activities in cell models. These chlorophyll-degraded compounds commonly exist in several vegetables during storage or edible seaweeds, which will provide resources for further investigations aiming to test anti-obesity in animal studies. © 2022 Society of Chemical Industry.

Joint engagement is a potential mechanism leading to increased initiations of joint attention and downstream effects on language: JASPER early intervention for children with ASD.

BACKGROUND: Social communication interventions benefit children with ASD in early childhood. However, the mechanisms behind such interventions have not been rigorously explored. This study examines the mechanism underlying a naturalistic developmental behavioral intervention, JASPER (Joint Attention, Symbolic Play, Engagement, and Regulation), delivered by educators in the community. Specifically, the analyses focus on the mediating effect of joint engagement on children's initiations of joint attention (IJA) skills and whether IJA postintervention are associated with later gains in children's receptive and expressive language. METHODS: One hundred seventy-nine children, age 2-5 years, were randomized to immediate JASPER treatment or waitlist (treatment as usual) control. Independent assessors blinded to time and treatment coded children's time jointly engaged and IJA during a 10-min teacher-child interaction at baseline, exit, and follow-up. Age-equivalent receptive and expressive language scores from the Mullen Scales of Early Learning were collected at baseline and follow-up. Mediation analyses with linear mixed models were used to explore the potential mediating effect of joint engagement on IJA. RESULTS: Joint engagement significantly mediated 69% of the intervention effect on young children's IJA and IJA predicted improvements in standardized language scores. CONCLUSIONS: Small but sustained changes in child-initiated joint engagement improved IJA, a core challenge in children with ASD, which in turn led to improvements in language.

Hybrid implementation model of community-partnered early intervention for toddlers with autism: a randomized trial.

BACKGROUND: Interventions found to be effective in research settings are often not as effective when implemented in community settings. Considering children with autism, studies have rarely examined the efficacy of laboratory-tested interventions on child outcomes in community settings using randomized controlled designs. METHODS: One hundred and thirteen children with autism enrolled in public early intervention classrooms in low resource neighborhoods were randomized to Joint Attention, Symbolic Play, Engagement, and Regulation (JASPER) intervention or treatment as usual waitlist for 10 weeks with 1-month follow-up. RESULTS: Teaching assistants delivered JASPER at adequate fidelity. Children randomized to JASPER demonstrated significant gains over treatment as usual in core developmental outcomes of joint engagement, joint attention, and play skills that were maintained at follow-up. CONCLUSIONS: Supervised teaching assistants delivered JASPER intervention with a range of toddlers with autism leading to significant gains in developmental outcomes.

pks63787, a Polyketide Synthase Gene Responsible for the Biosynthesis of Benzenoids in the Medicinal Mushroom Antrodia cinnamomea.

Antrodia cinnamomea, a unique resupinate basidiomycete endemic to Taiwan, has potent medicinal activities. The reddish basidiocarps and mycelia generally exhibit abundant metabolites and higher biological activity. To investigate the pigments of A. cinnamomea, polyketide synthase (PKS) genes were characterized based on its partially deciphered genome and the construction of a fosmid library. Furthermore, a gene disruption platform was established via protoplast transformation and homologous recombination. Of four putative polyketide synthase genes, pks63787 was selected and disrupted in the monokaryotic wild-type (wt) strain f101. Transformant Δpks63787 was deficient in the synthesis of several aromatic metabolites, including five benzenoids and two benzoquinone derivatives. Based on these results, a biosynthetic pathway for benzenoid derivatives was proposed. The pks63787 deletion mutant not only displayed a reduced red phenotype compared to the wt strain but also displayed less 1,1-biphenyl-2-picrylhydrazyl free radical scavenging activity. This finding suggests that PKS63787 is responsible for the biosynthesis of pigments and metabolites related to the antioxidant activity of A. cinnamomea. The present study focuses on the functional characterization of the PKS gene, the fluctuations of its profile of secondary metabolites, and interpretation of the biosynthesis of benzenoids.

Longitudinal Effects of Adaptive Interventions With a Speech-Generating Device in Minimally Verbal Children With ASD.

There are limited data on the effects of adaptive social communication interventions with a speech-generating device in autism. This study is the first to compare growth in communications outcomes among three adaptive interventions in school-age children with autism spectrum disorder (ASD) who are minimally verbal. Sixty-one children, ages 5-8 years, participated in a sequential, multiple-assignment randomized trial (SMART). All children received a developmental behavioral communication intervention: joint attention, symbolic play, engagement and regulation (JASP) with enhanced milieu teaching (EMT). The SMART included three 2-stage, 24-week adaptive interventions with different provisions of a speech-generating device (SGD) in the context of JASP+EMT. The first adaptive intervention, with no SGD, initially assigned JASP+EMT alone, then intensified JASP+EMT for slow responders. In the second adaptive intervention, slow responders to JASP+EMT were assigned JASP+EMT+SGD. The third adaptive intervention initially assigned JASP+EMT+SGD; then intensified JASP+EMT+SGD for slow responders. Analyses examined between-group differences in change in outcomes from baseline to Week 36. Verbal outcomes included spontaneous communicative utterances and novel words. Nonlinguistic communication outcomes included initiating joint attention and behavior regulation, and play. The adaptive intervention beginning with JASP+EMT+SGD was estimated as superior. There were significant (p < .05) between-group differences in change in spontaneous communicative utterances and initiating joint attention. School-age children with ASD who are minimally verbal make significant gains in communication outcomes with an adaptive intervention beginning with JASP+EMT+SGD. Future research should explore mediators and moderators of the adaptive intervention effects and second-stage intervention options that further capitalize on early gains in treatment.

Diterpene glycosides and polyketides from Xylotumulus gibbisporus.

Four new tetracyclic diterpene glycosides, namely, sordarins C-F (1-4), and three new γ-lactone polyketides, namely, xylogiblactones A-C (5-7), along with sordarin were isolated from the ethyl acetate extracts of the fermented broths of Xylotumulus gibbisporus YMJ863. The structures of 1-7 were elucidated on the basis of spectroscopic data analyses. The configurations of 1-4 were deduced by NOESY, molecular modeling, and comparison with the literature. The relative configurations of 5-7 were deduced by X-ray crystallographic analysis of 5. Compounds 1-5 and sordarin were evaluated in an antifungal assay using Candida albicans ATCC 18804, C. albicans ATCC MYA-2876, and Saccharomyces cerevisiae ATCC 2345, and only sordarin exhibited significant antifungal activities against these fungal strains, with MIC values of 64.0, 32.0, and 32.0 µg/mL, respectively. The effect of compounds 1-7 and sordarin on the inhibition of NO production in lipopolysaccharide-activated murine macrophages was also evaluated. Compounds 2 and sordarin inhibited NO production with IC50 values of 327.2±46.6 and 157.1±24.1 µM, respectively.

Enzymatic synthesis of lipid II and analogues.

The emergence of antibiotic resistance has prompted active research in the development of antibiotics with new modes of action. Among all essential bacterial proteins, transglycosylase polymerizes lipid II into peptidoglycan and is one of the most favorable targets because of its vital role in peptidoglycan synthesis. Described in this study is a practical enzymatic method for the synthesis of lipid II, coupled with cofactor regeneration, to give the product in a 50-70% yield. This development depends on two key steps: the overexpression of MraY for the synthesis of lipid I and the use of undecaprenol kinase for the preparation of polyprenol phosphates. This method was further applied to the synthesis of lipid II analogues. It was found that MraY and undecaprenol kinase can accept a wide range of lipids containing various lengths and configurations. The activity of lipid II analogues for bacterial transglycolase was also evaluated.

Polyketides from the littoral plant associated fungus Pseudallescheria boydii.

Four previously unreported chemical entities, boydone A (1), boydone B (2), botryorhodine F (3), and botryorhodine G (4), along with five known compounds, fusidilactone A (5), (R)-(-)-mevalonolactone (6), (R)-(-)-lactic acid (7), ovalicin (8), and botryorhodine C (9), were isolated from the ethyl acetate extracts of the fermented broths of the fungal strain Pseudallescheria boydii NTOU2362. The structures of 1-9 were characterized on the basis of their spectroscopic data analyses. The absolute configurations of 1 and 2 were established by comparison with the literature and the modified Mosher's method. The growth inhibitory activities of 1-9 against the A549 non-small-cell lung cancer cell line were evaluated, and 2 and 8 exhibited moderate to potent bioactivities with GI50 values of 41.3 and 4.1 µM, respectively, in comparison with fluorouracil (GI50 = 3.6 µM).

Developmental Play Skills as Outcomes of Early Intervention.

Play is critical in the development of cognitive and language skills in young children with autism; however, few studies have examined the impact of the intervention on the development of play skills. The current study aims to address the change in developmental skills, including play after participation in the JASPER intervention, and to examine the initiation of joint attention as a moderator of the effect of treatment on changes in play skills. The study included 109 preschool-age children who participated in the JASPER intervention and examined changes in developmental skills, including play skills. Children who received JASPER improved significantly in both play diversity (F(1,99) = 4.89, p = 0.029, ES = 0.22) and complexity (F(1,98) = 5.21, p = 0.025; ES = 0.23) compared to children in control conditions. These gains in play skills were associated with concurrent improvements in cognition and communication skills. Additionally, children with more initiations of joint attention skills at entry made greater progress in play diversity (F(1,97) = 15.85, p < 0.001 ES = 0.40) and complexity (p = 0.096). Play and joint attention skills are critical intervention targets and outcomes for children with autism.

Social engagement and loneliness in school-age autistic girls and boys.

OBJECTIVES: This study examines the relationship between social engagement and loneliness in female and male autistic children and adolescents in school-based social settings. Secondary aims sought to explore the emergence of loneliness across different age groups and differences in social engagement and loneliness between genders. METHODS: This study conducted an analysis of previously collected data from two multi-site randomized control trials. This study included 58 autistic students (29 females, 29 males) between the ages 6 through 18 years. Female and male participants were matched on age and intelligence quotient. Concurrent mixed methods were used to examine participants' social engagement and loneliness. RESULTS: Findings revealed a significant relationship between joint engagement and loneliness, such that autistic students reported more loneliness when they were mutually engaged with social groups than when they were isolated or alone. Positive correlations between joint engage and loneliness were identified in elementary-age girls and secondary-age boys, suggesting that being mutually engaged with peers leads to increased loneliness. Negative correlations between parallel and loneliness identified in secondary-age boys suggested that boys in close proximity to peers felt less lonely than boys who were mutually engaged with peers. Qualitative analysis of social behaviors indicated that elementary girls and secondary boys were more likely to be mutually engaged or in close proximity to activities, but they had difficulty sustaining this engagement throughout the entire social period. Secondary girls and elementary boys, on the other hand, were more likely to be solitary and less likely to engage with peer groups. CONCLUSION: Study findings highlight the relationship between social engagement and loneliness in school-based autistic populations, and that more engagement itself can lead to more loneliness for younger girls and older boys. The influence of age and gender on engagement and loneliness highlights a need to tailor social interventions to leverage existing social strengths.

Evaluation of Immune Modulation by ß-1,3; 1,6 D-Glucan Derived from Ganoderma lucidum in Healthy Adult Volunteers, A Randomized Controlled Trial.

Fungi-derived ß-glucan, a type of glucopolysaccharide, has been shown to possess immune-modulatory properties in clinical settings. Studies have indicated that ß-glucan derived from Ganoderma lucidum (commonly known as Reishi) holds particular promise in this regard, both in laboratory and in vivo settings. To further investigate the efficacy and safety of Reishi ß-glucan in human subjects, a randomized, double-blinded, placebo-controlled clinical trial was conducted among healthy adult volunteers aged 18 to 55. Participants were instructed to self-administer the interventions or placebos on a daily basis for 84 days, with bloodwork assessments conducted at the beginning and end of the study. The results of the trial showed that subjects in the intervention group, who received Reishi ß-glucan, exhibited a significant enhancement in various immune cell populations, including CD3+, CD4+, CD8+ T-lymphocytes, as well as an improvement in the CD4/CD8 ratio and natural killer cell counts when compared to the placebo group. Additionally, a statistically significant difference was observed in serum immunoglobulin A levels and natural killer cell cytotoxicity between the intervention and placebo groups. Notably, the intervention was found to be safe and well tolerated, with no statistically significant changes observed in markers of kidney or liver function in either group. Overall, the study provides evidence for the ability of Reishi ß-glucan to modulate immune responses in healthy adults, thereby potentially bolstering their defense against opportunistic infections.

Brief Report: An Exploratory Study of Young Dual Language Learners with Autism in a School-Based Intervention.

Due to core challenges in social communication experienced by many young children with autism, children on the spectrum who are also dual language learners (DLLs) may benefit from developmentally-appropriate language supports in school settings. The current study examined whether home language status moderated the effect of a play-based intervention, JASPER, delivered in the classroom, in children with autism. Fifty-nine preschool children with autism received JASPER over eight weeks. Children who received JASPER improved significantly more in their language skills from entry to exit than children in preschool as usual. Home language status moderated the effect of treatment on receptive language where children of diverse linguistic backgrounds made greater gains in receptive language.

Promotion and implementation effectiveness of World Health Organization's Caregiver Skills Training program in Taiwan.

The World Health Organization (WHO) developed the Caregiver Skills Training for Families of Children with Developmental Delays and Disabilities (CST) with support from Autism Speaks to address the resource gaps and worldwide needs for interventions for children with developmental disorders or delays, especially those with autism spectrum disorder (ASD), and their families. Evidence has indicated that parent-mediated interventions benefit both caregivers and children by strengthening caregivers' knowledge and confidence and children's social communication skills and behavioral regulation. The CST-Taiwan team began the prepilot field trial in 2017 and developed the project to serve families in various locations. This study (1) delineated the adaptations and promotion of CST-Taiwan; (2) determined the program's effectiveness in the promotional stage, in terms of caregiver and child outcomes, and (3) examined the maintenance of its effects. The materials, delivery, and facilitator training procedure of the original CST were adapted to Taiwan. The quantitative data indicated that CST-Taiwan is a promising program, it positively affected caregiver knowledge and confidence and reduced the severity of the children's autistic symptoms. The 3-month follow-up results suggested that the effects persisted. Thus, CST-Taiwan, and its promotional strategies are feasible and effective.

Mothers' reports of play dates and observation of school playground behavior of children having high-functioning autism spectrum disorders.

BACKGROUND: Children with high-functioning autism spectrum disorders (ASD) are generally included with typically developing peers at school. They have difficulties interacting with peers on the school playground. Previous literature suggests that having play dates in the home may be related to better peer acceptance at school. METHODS: This study examines the relationship between mother-reported play date frequency and amount of conflict, and peer interaction observed on the school playground for a sample of 27 boys and 4 girls meeting structured interview and observation criteria for ASD. Measures of intellectual functioning, adaptive behavior, and social skills were included in a stepwise regression analysis to account for their impact on relationships between maternal play date reports, general peer acceptance at school (as rated by the child's teacher) and observations of school playground behavior. RESULTS: Results revealed that children with autism spectrum disorders who had more play dates in their home tended to spend a greater amount of time engaged in behaviors such as mutual offering of objects, conversing and other turn-taking activities with peers on the school playground. They also received more positive responses to their overtures from peers. These relationships remained highly significant even after accounting for other demographic, general social, and cognitive variables. CONCLUSIONS: The present results suggest that play date frequency is strongly related to school playground behavior. Owing to the design of this study, future research must assess whether play dates in the home promote better peer relationships on the playground or the reverse. In either case, the assessment of play dates, as well as observation of spontaneous unsupervised social interactions, are important outcome measures to consider in social skills interventions for children with high-functioning ASD.

Sesquiterpene glycosides from Cosmospora joca.

Five novel sesquiterpene glycosides, namely, cosmosporasides A-E (1-5), were isolated from the ethyl acetate extract of the fermented broth of Cosmospora joca. The structures of 1-5 were elucidated on the basis of spectroscopic data analyses, monosaccharide composition analyses, and monosaccharide chirality analyses. The relative configuration of the sesquiterpene moiety of 3-5 was determined by J-based configuration analyses and supported by NOESY assignments. The inhibitory effects of 1-5 on the nitric oxide (NO) production in lipopolysaccharide (LPS)-activated murine macrophage RAW264.7 cells were evaluated; all except 3 inhibited NO production at 100 µM. 4 was the most potent, with an average maximum inhibition and a median inhibitory concentration value of 71.70 ± 1.23% and 65.98 ± 0.53 µM, respectively.

A systematic review of school-based social skills interventions and observed social outcomes for students with autism spectrum disorder in inclusive settings.

LAY ABSTRACT: Most social skills interventions for students with autism spectrum disorder have been conducted in clinic-based settings. While students with autism spectrum disorder are able to acquire new skills, the generalization of these skills to authentic social environments, like school, is more difficult. To address this issue, there is an increase in research examining the implementation of social skills interventions for students with autism spectrum disorder who are educated in inclusive school settings. This review included 18 research studies that focused on school-based social interventions for students with autism spectrum disorder who were educated in inclusive school settings. Typically developing peers also participated in the interventions to varying degrees. Secondary aims explored naturalistic observation instruments and subsequent social outcomes used to record the social behaviors of students with autism spectrum disorder at school. Social intervention components varied across studies, but all studies reported improvement in the targeted social behaviors of students with autism spectrum disorder. There were many similarities in the ways in which researchers measured and defined social outcomes. Observation protocols were able to measure change in the social behaviors of students with autism spectrum disorder across a wide age range. The recognition of evidence-based practices used in school-based social skills interventions, as well as the identification of observation protocols and salient social outcomes, provides a starting point for school practitioners to consider as they move to implement social skills interventions for students with autism spectrum disorder into inclusive school settings.

Sustained Community Implementation of JASPER Intervention with Toddlers with Autism.

Intervention research is increasingly conducted in community settings, however it is not clear how well practices are sustained locally or how children progress once external research support is removed. Two school-year cohorts of toddlers with autism (year 1: n = 55, year 2: n = 63) received Joint Attention, Symbolic Play, Engagement, and Regulation (JASPER) intervention from teaching assistants (TAs) with external support in year 1 and local, internal support in year 2. TAs sustained intervention strategies with more modest maintenance of high-level skills. Children in both years 1 and 2 made similar gains in initiations of joint attention during independent assessment. Year 1 children made significantly greater play gains. JASPER sustained into year 2, however advancing play may require additional supports.

Phthalides from Pittosporum illicioides var. illicioides with inhibitory activity on superoxide generation and elastase release by neutrophils.

Six new phthalides, (S)-3-ethyl-7-hydroxy-6-methoxyphthalide (1), (S)-3-ethyl-7-hydroxy-5,6-dimethoxyphthalide (2), (S)-3-ethyl-5,6,7-trimethoxyphthalide (3), (R)-3-ethyl-7-hydroxy-6-methoxyphthalide (4), (Z)-3-ethylidene-7-hydroxy-6-methoxyphthalide (5), and (Z)-3-ethylidene-6,7-dimethoxyphthalide (6), have been isolated from the root of Pittosporum illicioides var. illicioides, together with seven known compounds. The structures of these new compounds were determined through spectroscopic and MS analyses. Compounds 1-4 exhibited inhibition (IC50

Symbolic Play in School-Aged Minimally Verbal Children with Autism Spectrum Disorder.

Few interventions exist for school-aged minimally verbal children with autism spectrum disorder (ASD). Even though play skills are associated with children's production of language, few studies have focused on play for minimally verbal children. Fifty-eight minimally verbal children with ASD received a naturalistic developmental behavioral intervention. Children were randomized to receive a speech generating device in the context of the intervention or not. Children in both conditions improved in play skills at exit. Children demonstrated an increase in play skills in proximal (sessions) and distal (during blind assessment) contexts. Minimally verbal children with ASD can improve their play skills within a targeted intervention. Increases in symbolic play were associated with increases in expressive language skills.