Sluggish Cognitive Tempo in Autism Spectrum Disorder, ADHD, and Their Comorbidity: Implications for Impairment.

Objective: Sluggish Cognitive Tempo (SCT), characterized by lethargy and daydreaming, has most commonly been studied in community samples and in youth with Attention-Deficit/Hyperactivity Disorder (ADHD). Despite shared neurodevelopmental symptoms with ADHD, few studies have investigated SCT in Autism Spectrum Disorders (ASD). The current study investigated SCT symptoms in youth with ASD, ADHD, and comorbid ASD+ADHD to explore the relations between SCT and global and social impairment.Method: Caregivers of children and adolescents (n = 98; ages 6-17) diagnosed with ADHD (n = 46), ASD (n = 28), or ASD+ADHD (n = 24) completed measures of social impairment, SCT, and demographic variables.Results: All three clinical groups demonstrated comparable levels of SCT. Diagnosis and SCT independently contributed to parent-rated social impairment, while SCT and IQ, but not diagnosis, contributed to clinician-rated global functioning. Specifically, having comorbid ASD+ADHD, but not an ASD or ADHD diagnosis alone, significantly predicted greater social impairment.Conclusion: These results extend previous literature investigating SCT in ASD and provide evidence to suggest that SCT is associated with social and global impairment above and beyond the impairment associated with ADHD and/or ASD. These results may have implications for clinical assessment and treatment of ASD and ADHD.

Pivotal response treatment for autism: A brief report on training for rural communities.

Many providers from rural communities feel ill-prepared to treat children with autism spectrum disorder (ASD). Cost-effective training in Pivotal Response Treatment (PRT), an evidence-based ASD treatment, can address unmet needs for rural communities. The current study examined a 1-day general PRT workshop for parents and professionals followed by a 3-day small, intensive training for professionals. Fifty-two parents and providers completed surveys before and after Day 1, indicating improvements in perceived stress and confidence. Three providers were trained during Days 2-4, and submitted four 10-min videos (i.e., baseline, 1-week, 1-month, and 2-months post-training) working with a target child discussed in the training and another child. Videos were coded for correct PRT implementation and analyzed using a single-subject A-B design with generalization and maintenance probes. All providers learned to apply PRT techniques with the target child and generalized skills to another child within 1-week post-training, with partial maintenance. Implications for rural mental health training in evidence-based practices are discussed.

An Initial Pilot Study Examining Child Social Skills, Caregiver Styles, and Family Functioning in the PEERS® for Preschoolers Program for Young Autistic Children and their Caregivers.

BACKGROUND: Social impairments characteristic of autism spectrum disorder (ASD) are evident in early childhood and worsen as the child matures. Though many interventions for young children exist, few specifically target social skills and involve caregivers. AIMS: This pilot study examined PEERS® for Preschoolers, focusing on temporal change in child social skills, caregiver style, and family functioning in the context of a caregiver-assisted social skills intervention. This extension of the PEERS® program builds on the success of the intervention for older children, presenting skills in a developmentally appropriate manner to young autistic children and their caregivers. METHODS AND PROCEDURES: The present pilot study used a non-concurrent multiple baseline design to examine the above variables with 15 autistic children (Mage = 4.87, SD = 1.25; 11 boys). Children and caregivers participated in PEERS® for Preschoolers groups, with each group randomly assigned three different baseline periods (1.5, 2, or 2.5 weeks) before beginning. OUTCOMES AND RESULTS: Simulation Modeling Analysis (SMA) revealed concurrent improvements in social and caregiving skills, with subsequent changes in family functioning occurring over the course of this 16-session intervention. CONCLUSIONS AND IMPLICATIONS: Future research will need to examine mechanisms of change in PEERS® for Preschoolers for children and caregivers. WHAT THIS PAPER ADDS: There is a dearth of research that specifically examines social skills interventions for young autistic children that incorporates caregivers and examines family functioning as well. This paper is one of the first to evaluate the PEERS® for Preschoolers (P4P) intervention by: 1) exploring changes in child social skills, caregiver efficacy, and family functioning, and 2) analyzing the sequence of improvements in the aforementioned variables to measure systematic change. This pilot study presents results using appropriate methodology for a small sample size of children and caregivers. Results suggested concurrent improvements in social and caregiving skills and subsequent changes in family functioning. These can be built upon for further research on the PEERS® for Preschoolers intervention. This study supports PEERS® for Preschoolers as a feasible intervention that likely contributes to improvements for the child, caregiver in their relationship with their child and parenting styles in general, as well as functioning of the entire family. In sum, this work is essential to furthering the provision of a much needed service of social skills interventions for young autistic children.

A systematic review of technological approaches for autism spectrum disorder assessment in children: Implications for the COVID-19 pandemic.

BACKGROUND: Screening and diagnostic assessments tools for autism spectrum disorder (ASD) are important to administer during childhood to facilitate timely entry into intervention services that can promote developmental outcomes across the lifespan. However, assessment services are not always readily available to families, as they require significant time and resources. Currently, in-person screening and diagnostic assessments for ASD are limited due to the COVID-19 pandemic and will continue to be a concern for situations that limit in-person contact. Thus, it is important to expand the modalities in which child assessments are provided, including the use of technology. AIMS: This systematic review aims to identify technologies that screen or assess for ASD in 0-12 year-old children, summarizing the current state of the field and suggesting future directions. METHODS: An electronic database search was conducted to gather relevant articles to synthesize for this review. OUTCOMES AND RESULTS: 16 studies reported use of novel technology to assess children suspected of ASD. CONCLUSIONS AND IMPLICATIONS: Results strongly supported live-video evaluations, video observations, and online or phone methods, but there is a need for research targeting the feasibility of these methods as it applies to the stay-at-home orders required by the pandemic, and other situations that limit clients from seeing providers in-person.

Integrating Measurement-Based Care into Treatment for Autism Spectrum Disorder: Insights from a Community Clinic.

Measurement-based care (MBC), an evidence-based approach that has demonstrated efficacy for improving treatment outcomes, has yet to be investigated in clients with Autism Spectrum Disorder. The current paper investigates the use of MBC in autistic (n = 20) and non-autistic (n = 20) clients matched on age, sex, and presenting problem. Results of change score analysis indicated that utilizing routine symptom monitoring can enhance treatment evaluation. Autistic clients participated in significantly more sessions, made significantly less progress, and were less compliant with MBC than non-autistic clients. Though hierarchical linear modeling demonstrated no significant differences in treatment slope, results indicated moderate effect size. These results inform the use of MBC in community clinics, highlighting policy implications and need for targeted measurement.

Access to Autism Spectrum Disorder Services for Rural Appalachian Citizens.

Background: Low-resource rural communities face significant challenges regarding availability and adequacy of evidence-based services. Purposes: With respect to accessing evidence-based services for Autism Spectrum Disorder (ASD), this brief report summarizes needs of rural citizens in the South-Central Appalachian region, an area notable for persistent health disparities. Methods: A mixed-methods approach was used to collect quantitative and qualitative data during focus groups with 33 service providers and 15 caregivers of children with ASD in rural southwest Virginia. Results: Results supported the barriers of availability and affordability of ASD services in this region, especially relating to the need for more ASD-trained providers, better coordination and navigation of services, and addition of programs to assist with family financial and emotional stressors. Results also suggested cultural attitudes related to autonomy and trust towards outside professionals that may prevent families from engaging in treatment. Implications: Relevant policy recommendations are discussed related to provider incentives, insurance coverage, and telehealth. Integration of autism services into already existing systems and multicultural sensitivity of providers are also implicated.

BTG3 tumor suppressor gene promoter demethylation, histone modification and cell cycle arrest by genistein in renal cancer.

BTG3/ANA/APRO4 has been reported to be a tumor suppressor gene in some malignancies. It constitutes important negative regulatory mechanism for Src-mediated signaling, a negative regulator of the cell cycle and inhibits transcription factor E2F1. We report that BTG3 is downregulated in renal cancer and that the mechanism of inactivation is through promoter hypermethylation. Quantitative real-time polymerase chain reaction (PCR) showed that BTG3 was downregulated in cancer tissues and cells. Genistein and 5-aza-2'-deoxycytidine (5Aza-C) induced BTG3 messenger RNA (mRNA) expression in A498, ACHN and HEK-293 renal cell carcinoma (RCC) cell lines. Bisulfite-modified PCR and DNA sequencing results showed complete methylation of BTG3 promoter in tumor samples and cancer cell lines. Genistein and 5Aza-C treatment significantly decreased promoter methylation, reactivating BTG3 expression. Chromatin immunoprecipitation assay revealed that genistein and 5Aza-C increased levels of acetylated histones 3, 4, 2H3K4, 3H3K4 and RNA polymerase II at the BTG3 promoter indicative of active histone modifications. Enzymatic assays showed genistein and 5Aza-C decreased DNA Methyltransferase, methyl-CpG-binding domain 2 activity and increased HAT activity. Cell cycle and 3-(4,5-dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide cell proliferation assays showed that genistein has antiproliferative effect on cancer cell growth through induction of cell cycle arrest. This is the first report to show that BTG3 is epigenetically silenced in RCC and can be reactivated by genistein-induced promoter demethylation and active histone modification. Genistein had similar effects to that of 5Aza-C, which is a potent demethylating agent with high toxicity and instability. Genistein being a natural, non-toxic, dietary isoflavone is effective in retarding the growth of RCC cells, making it a promising candidate for epigenetic therapy in renal carcinoma.

Polymorphisms of MLH1 in benign prostatic hyperplasia and sporadic prostate cancer.

Mismatch repair is one of several DNA repair pathways of which defects may lead to cancer. We hypothesize that polymorphisms of the MLH1 gene can be a risk factor for benign prostatic hyperplasia (BPH) and prostate cancer. The genetic distribution of MLH1 polymorphisms that lead to amino acid changes at codons 132, 219, 384, and 723 were analyzed in BPH and sporadic prostate cancer patients, and compared to healthy controls from an Asian population. These experiments demonstrate a protective role for the codon 384 variant allele against prostate cancer (P=0.031) but not BPH when compared to normal controls and furthermore, an inverse association was observed with stage (P=0.074) and grade (P=0.056) of cancer. This is the first report that demonstrates a protective effect for the race-related MLH1 polymorphism at codon 384 against prostate cancer and these results are important in understanding their role in this disease.

CXCL12 G801A polymorphism is a risk factor for sporadic prostate cancer susceptibility.

PURPOSE: The chemokine CXCL12 and its receptor CXCR4 have been found to be associated with cancer metastasis. A single nucleotide polymorphism of CXCL12 G801A has been described and is regarded as a target for cis-acting factor that has the ability to up-regulate CXCL12 expression. Currently, there are no reports investigating the role of CXCL12 G801A polymorphism in prostate cancer (PC). EXPERIMENTAL DESIGN: We genotyped CXCL12 G801A and p53Arg72Pro in 167 PC patients and 167 age-matched healthy subjects. Genotyping was done with PCR-RFLP and confirmed by direct DNA sequencing. To investigate the effect of the CXCL12 G801A polymorphism on CXCL12 and CXCR4 expression, immunohistochemistry was done in genotyped PC tissues. RESULTS: A significant increase in the GA + AA genotype of the CXCL12 G801A polymorphism was observed in PC patients compared with healthy controls. The frequency of CXCL12 AA genotype was significantly higher in a group of patients with lymph node metastasis (23%) compared with those without metastasis (7%). The frequency of CXCL12 expression in AA + GA genotype carriers was significantly higher than that in GG genotype carriers. Among the carriers with CXCL12 GA + AA genotypes, CXCR4 expression was also significantly higher compared with those with the GG genotype. Moreover, among the groups with both CXCL12- and CXCR4-positive staining, the frequency of the CXCL12 GA + AA genotype was high. Although we did not find a significant relationship between the frequency of the Arg/Pro + Pro/Pro genotype of p53 Arg72Pro and susceptibility in PC, there was a combined effect of CXCL12 GA + AA genotype and the p53 72Arg/Pro + Pro/Pro genotype on the frequency of PC. These results indicate that the p53 codon 72 polymorphism may interact with CXCL12 G801A. CONCLUSIONS: This is the first report showing that CXCL12 G801A polymorphism may be a risk factor for PC. Moreover, this study suggests that this polymorphism can be an important marker for detecting microinvasion and PC metastasis.

Genistein reverses hypermethylation and induces active histone modifications in tumor suppressor gene B-Cell translocation gene 3 in prostate cancer.

BACKGROUND: : B-cell translocation gene 3 (BTG3/ANA/APRO4) is a candidate tumor suppressor gene in some malignancies. We report here that B-cell translocation gene 3 (BTG3) is transcriptionally down-regulated in prostate cancer and the mechanism of inactivation is through promoter hypermethylation. METHODS: : Prostate cancer and normal cell lines were treated with different doses of genistein and 5-aza-2'-deoxycytidine (5Aza-C). BTG3 messenger ribonucleic acid (mRNA) expression was determined by quantitative real-time polymerase chain reaction in tissues and cell lines. Bisulfate-modified polymerase chain reaction, cloning and sequencing were used to examine promoter methylation in tumor samples and cell lines. Enzyme activity/inhibition assays were done to check the effect of genistein and 5Aza-C on DNA methyltransferases. ChIP assay was performed to analyze chromatin modifications caused by genistein treatment. RESULTS: : BTG3 mRNA expression was down-regulated in cancer tissues and cells. Genistein and 5Aza-C induced BTG3 mRNA expression in all PC cell lines. Complete methylation of BTG3 promoter in tumor samples and cancer cell lines was observed. Genistein and 5Aza-C treatment significantly decreased promoter methylation, reactivating BTG3 expression. Genistein and 5Aza-C increased levels of acetylated histones 3, 4, histone 3 dimethylated at lysine 4, histone 3 trimethylated at lysine 4, and RNA polymerase II, decreased DNA methyl transferase and methyl-binding domain protein 2 activity, and increased histone acetyl transferase (HAT) activity. CONCLUSIONS: : This is the first report to show that BTG3 is silenced in prostate cancer and can be reactivated by genistein-induced promoter demethylation and active histone modification. Genistein showed similar effects to that of 5Aza-C, which is currently undergoing phase 2 clinical trials as a treatment for prostate cancer. Because genistein is a natural, nontoxic, and dietary isoflavone, these results indicate that genistein is a novel, advantageous therapeutic agent for treating prostate cancer.