Enhancing emotion recognition in young autistic children with or without attention-deficit/hyperactivity disorder in Hong Kong using a Chinese App version of The Transporters.

TRIAL REGISTRATION: This study was registered with the German Clinical Trials Register - Deutschen Register Klinischer Studien (DRKS) on 23 December 2018. The Trial Registration Number (TRN) is DRKS00016506. LAY ABSTRACT: The Transporters App is an intervention programme with 15 animated episodes that teach emotion recognition skills to autistic children between 4 and 6 years of age. Each episode contains a story depicting social interactions between characters in the form of a vehicle, with human faces grafted on to each of them. Each episode teaches a specific emotion in a story context. Autistic children watched at least three episodes at home for about 15 min daily for a month, with parental guidance. Its automated, home-based format is cost-saving and readily accessible. This study translated The Transporters to a Cantonese-Chinese version. Results showed a significant improvement in emotion recognition following viewing The Transporters in a group of Hong Kong Chinese autistic children, between 4 and 6 years of age, with and without attention-deficit/hyperactivity disorder (n = 48) relative to a control group (n = 24). A non-autistic group (n = 23) showed that the autistic children scored lower in emotion recognition pre-intervention. Post-intervention, the autistic children had improved in emotion recognition to the level of the non-autistic children. The autistic children in the intervention groups also generalized their learning to novel situations/characters not taught within The Transporters. There was no dosage effect, with the standard recommended number of episodes viewed being sufficient to achieve significant improvement. This study confirms the effectiveness of The Transporters for Chinese autistic children and contributes to the literature/practice by expanding the range of applicability of The Transporters to autistic children with attention-deficit/hyperactivity disorder, which is important given the high rate of co-occurrence between autism and attention-deficit/hyperactivity disorder.

Digital citizenship of children and youth with autism: Developing guidelines and strategies for caregivers and clinicians to support healthy use of screens.

LAY ABSTRACT: Children and youth with autism use screens in their daily lives and in their rehabilitation programs. Although parents and clinicians experience specific challenges when supporting positive screen time use of children and youth with autism, no detailed information for this group exists. Therefore, this study aimed to develop clear guidelines that are agreed by expert clinicians and parents of children and youth with autism. Using a method called Delphi, 30 experts-20 clinicians and 10 caregivers, who have experience working with or caring for children and youth with autism were invited to complete a series of three surveys. In each round, the experts had to rate their agreement with statements regarding screen time management. The agreement level was set to 75%. The final themes to be included in the guidelines were accepted by more than 75% of the panel. The final guidelines included six main sections: (1) general principles, (2) considerations for timing and content of leisure screen time use, (3) strategies for caregivers and clinicians to monitor and regulate screen time use, (4) behaviors to monitor for screen time overuse, (5) additional guidelines for clinicians, and (6) resources. The new guidelines developed in this study can provide potential guidance on how to further the development of digital citizenship for children and youth with autism and provide strategies to families to help manage screen time use.

Zingiber zerumbet: A Scoping Review of its Medicinal Properties.

Zingiber zerumbet, a plant native to tropical and subtropical Asia, has a vast range of traditional uses and has been continuously studied for its medicinal properties. However, a systematic methodological approach in evidence synthesis on the plant's efficacy is lacking, and there is a need to elicit the current research status of this plant. This scoping review was conducted to systematically explore and collate the available scientific evidence on the efficacy of Z. zerumbet and its main phytoconstituents in various formulations, their biological mechanisms, and their safety. Results included 54 articles consisting of animal studies, while there were no published human studies. Only half of the included studies provided adequate reporting on the quality-related details of Z. zerumbet formulations. Identified pharmacological activities were analgesic, anti-inflammatory, anti-diabetic, anti-hyperlipidemic, anti-neoplastic, immunomodulatory, antioxidant, antipyretic, hepatoprotective, nephroprotective, gastroprotective, and locomotor-reducing activities. Notably, the ethanolic extract of Z. zerumbet was found to be well tolerated for up to 28 days. In conclusion, Z. zerumbet and zerumbone have various pharmacological effects, especially in analgesic and anti-inflammatory models. However, there is still a pressing need for comprehensive safety data to conduct clinical trials.

Resilience practices among a broad spectrum of individuals with physical disabilities during the COVID-19 pandemic: A qualitative photo elicitation study.

This community-based study explored resilience practices among people living with physical disabilities (i.e., stroke, spinal cord injury, and other physical disabilities) during the COVID-19 pandemic. In this photo elicitation study, during 1:1 interviews, participants shared and described photos that reflected their pandemic-related experiences. Data were analyzed thematically to identify resilience-related practices. Our analysis revealed three themes: (1) reflecting on the importance of family, friends, and community (e.g., recalling past memories and strengthening existing connections); (2) engaging in social and recreational activities (e.g., experiencing the outdoors and gardening); and (3) reframing personal contexts and social environment (e.g., adjusting to new social norms and overcoming physical barriers to navigating safely during the pandemic). The resilience that participants identified encompassed not only individual strategies but also family and community supports. Resilience can be fostered through community initiatives that support more equitable responses to health emergencies for people with disabilities.

Salutogenic-based interventions among community-dwelling older adults: a systematic review and meta-analysis.

Salutogenesis is a health-promoting orientation and sense of coherence (SOC) is a vital coping factor associated with quality of life (QOL) and self-efficacy. Although salutogenic-based interventions showed potential in improving health outcomes, the application of salutogenic concepts and effectiveness on SOC, QOL and self-efficacy among community-dwelling older adults remained unclear. This review aimed to consolidate evidence on salutogenic approaches and evaluate the effectiveness of salutogenic-based interventions on SOC, QOL and self-efficacy in community-dwelling older adults. Databases systematically searched include PubMed, CINAHL, Embase, Cochrane Central Register of Controlled Trials, Scopus, Medline, PsycINFO and ProQuest Dissertations & Theses Global electronic databases. Two reviewers screened study eligibility, assessed risk of bias and extracted data of included studies independently. Meta-analyses on SOC and QOL were performed using RevMan. Where meta-analysis was not possible, narrative synthesis was employed. Eight studies involving 1201 older adults were included in this review. Subgroup analysis on SOC showed significant effects favouring salutogenic-based interventions using the empowering self-management model or strengths/resource-based approaches. However, results were mixed for the reflection-based approach. No significant effect favouring salutogenic-based interventions on QOL outcomes were found. High heterogeneity was observed for the outcome on self-efficacy. Two SOC strengthening processes, empowerment and reflection, were found to potentially underlie salutogenic-based intervention mechanisms. Effectiveness of salutogenic-based interventions on SOC, QOL and self-efficacy among community-dwelling older adults remained inconclusive due to high heterogeneity. Future salutogenic-based interventions should employ longitudinal designs and standardization on intervention delivery, utilizing a dual pathway via empowerment and reflection.

Molecular landscapes of longitudinal NF2/22q and non-NF2/22q meningiomas show different life histories.

Recurrence is a major complication of some meningiomas. Although there were many studies on biomarkers associated with higher grades or increased aggressiveness, few studies specifically examined longitudinal samples of primary meningiomas and recurrences from the same patients for molecular life history. We studied 99 primary and recurrent meningiomas from 42 patients by FISH for 22q, 1q, 1p, 3p, 5q, 6q, 10p, 10q, 14q, 18q, CDKN2A/B homozygous deletion, ALT (Alternative Lengthening of Telomere), TERT re-arrangement, targeted sequencing and TERTp sequencing. Although NF2 mutation and 22q were well known to be aetiological events in meningiomas, we found that in these paired meningiomas, combining the two events resulted in an NF2/22q group (57 tumors from 25 patients) which were almost mutually exclusive with those cases without these two changes (42 tumors from 17 patients) for NF2/22q. No other molecular changes were totally unique to NF2/22q or non-NF2/22q tumors. For molecular evolution, NF2/22q meningiomas had higher cytogenetic abnormalities than non-NF2/22q meningiomas (p = 0.003). Most of the cytogenetic changes in NF2/22q meningiomas were present from the outset whereas for non-NF2/22q meningiomas, cytogenetic events were uncommon in the primary tumors and most were acquired in recurrences. For non-NF2/22q tumors, CDKN2A/B homozygous deletion, 1q gain, 18p loss, 3p loss, and ALT were preferentially found in recurrences. Mutations were largely conserved between primary and recurrent tumors. Phylogenetic trees showed 11/11 patients with multiple recurrent tumors had a conserved evolutionary pattern. We conclude that for molecular life history, NF2 and 22q should be regarded as a group. NF2/22q recurring meningiomas showed more cytogenetic abnormalities in the primary tumors, whereas non-NF2/22q meningiomas showed CDKN2A/B deletion and other cytogenetic abnormalities and ALT at recurrences. Although chromosome 1p loss is a known poor prognostic marker in meningiomas, it was also associated with a shorter TBR (time between resection) in this cohort (p = 0.002).

A Waitlist Randomized Implementation Trial of Classroom Pivotal Response Teaching for Students With Autism.

Classroom Pivotal Response Teaching (CPRT) is a community-partnered adaptation of a naturalistic developmental behavioral intervention identified as an evidence-based practice for autistic children. The current study evaluated student outcomes in a randomized, wait-list controlled implementation trial across classrooms. Participants included teachers (n = 126) and students with autism (n = 308). Teachers participated in 12 hours of didactic, interactive training and additional in-classroom coaching. Generalized Estimating Equations accounted for clustering. Adjusted models evaluated the relative effects of training group, CPRT fidelity, and classroom quality on student outcomes. Results indicate higher CPRT fidelity was associated with greater increases in student learning. Having received CPRT training predicted increased student engagement and greater decreases in reported approach/withdrawal problems. These differences may be linked to the theoretical foundations of CPRT of increasing student motivation and engagement and collaborative adaptation to increase feasibility in schools. Overall, results suggest CPRT may be a beneficial approach for supporting autistic students.

Molecular landscape of IDH-wild type, pTERT-wild type adult glioblastomas.

Telomerase reverse transcriptase (TERT) promoter (pTERT) mutation has often been described as a late event in gliomagenesis and it has been suggested as a prognostic biomarker in gliomas other than 1p19q codeleted tumors. However, the characteristics of isocitrate dehydrogenase (IDH) wild type (wt) (IDHwt), pTERTwt glioblastomas are not well known. We recruited 72 adult IDHwt, pTERTwt glioblastomas and performed methylation profiling, targeted sequencing, and fluorescence in situ hybridization (FISH) for TERT structural rearrangement and ALT (alternative lengthening of telomeres). There was no significant difference in overall survival (OS) between our cohort and a the Cancer Genome Atlas (TCGA) cohort of IDHwt, pTERT mutant (mut) glioblastomas, suggesting that pTERT mutation on its own is not a prognostic factor among IDHwt glioblastomas. Epigenetically, the tumors clustered into classic-like (11%), mesenchymal-like (32%), and LGm6-glioblastoma (GBM) (57%), the latter far exceeding the corresponding proportion seen in the TCGA cohort of IDHwt, pTERTmut glioblastomas. LGm6-GBM-clustered tumors were enriched for platelet derived growth factor receptor alpha (PDGFRA) amplification or mutation (p = 0.008), and contained far fewer epidermal growth factor receptor (EGFR) amplification (p < 0.01), 10p loss (p = 0.001) and 10q loss (p < 0.001) compared with cases not clustered to this group. LGm6-GBM cases predominantly showed ALT (p = 0.038). In the whole cohort, only 35% cases showed EGFR amplification and no case showed combined chromosome +7/-10. Since the cases were already pTERTwt, so the three molecular properties of EGFR amplification, +7/-10, and pTERT mutation may not cover all IDHwt glioblastomas. Instead, EGFR and PDGFRA amplifications covered 67% and together with their mutations covered 71% of cases of this cohort. Homozygous deletion of cyclin dependent kinase inhibitor 2A (CDKN2A)/B was associated with a worse OS (p = 0.031) and was an independent prognosticator in multivariate analysis (p = 0.032). In conclusion, adult IDHwt, pTERTwt glioblastomas show epigenetic clustering different from IDHwt, pTERTmut glioblastomas, and IDHwt glioblastomas which are pTERTwt may however not show EGFR amplification or +7/-10 in a significant proportion of cases. CDKN2A/B deletion is a poor prognostic biomarker in this group.

TOP2B Is Required to Maintain the Adrenergic Neural Phenotype and for ATRA-Induced Differentiation of SH-SY5Y Neuroblastoma Cells.

The neuroblastoma cell line SH-SY5Y is widely used to study retinoic acid (RA)-induced gene expression and differentiation and as a tool to study neurodegenerative disorders. SH-SY5Y cells predominantly exhibit adrenergic neuronal properties, but they can also exist in an epigenetically interconvertible alternative state with more mesenchymal characteristics; as a result, these cells can be used to study gene regulation circuitry controlling neuroblastoma phenotype. Using a combination of pharmacological inhibition and targeted gene inactivation, we have probed the requirement for DNA topoisomerase IIB (TOP2B) in RA-induced gene expression and differentiation and in the balance between adrenergic neuronal versus mesenchymal transcription programmes. We found that expression of many, but not all genes that are rapidly induced by ATRA in SH-SY5Y cells was significantly reduced in the TOP2B null cells; these genes include BCL2, CYP26A1, CRABP2, and NTRK2. Comparing gene expression profiles in wild-type versus TOP2B null cells, we found that long genes and genes expressed at a high level in WT SH-SY5Y cells were disproportionately dependent on TOP2B. Notably, TOP2B null SH-SY5Y cells upregulated mesenchymal markers vimentin (VIM) and fibronectin (FN1) and components of the NOTCH signalling pathway. Enrichment analysis and comparison with the transcription profiles of other neuroblastoma-derived cell lines supported the conclusion that TOP2B is required to fully maintain the adrenergic neural-like transcriptional signature of SH-SY5Y cells and to suppress the alternative mesenchymal epithelial-like epigenetic state.

'Make the Most of the Situation'. Older Adults' Experiences during COVID-19: A Longitudinal, Qualitative Study.

The COVID-19 pandemic restrictions have been associated with increased social isolation and reduced participation in older adults. This longitudinal qualitative study drew on life course theory to analyse data from a series of four sequential semi-structured interviews conducted between May 2020-February 2021 with adults aged 65+ (n = 12) to explore older adults' experiences adjusting to the COVID-19 pandemic. We identified three themes: (1) Struggling 'You realize how much you lost' describes how older adults lost freedoms, social connections and activities; (2) Adapting 'whatever happens, happens, I'll do my best', revealing how older adults tried to maintain well-being, participation and connection; and (3) Appreciating 'enjoy what you have', exploring how older adults found pleasure and contentment. Engagement in meaningful activities and high-quality social interactions supported well-being during the COVID-19 pandemic for older adults. This finding highlights the need for policies and services to promote engagement during longstanding global crises.

Common outcome, different pathways: Social information-processing deficits in autism spectrum disorder and attention-deficit/hyperactivity disorder.

Social functioning is a key domain of impairment in both autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). This review adopts the social information-processing model as the theoretical framework to compare and contrast the deficits of ASD and ADHD at each of the six steps of social information-processing. Both disorders show deficits at each step, but the nature and origins of the deficits are different. Thus, while both disorders exhibit a common outcome of social impairment, the exact pathways that each disorder traverses along the six steps of social information-processing are different. For ASD, there is a social knowledge/behaviour deficit arising from difficulties in social/emotional cue detection, encoding, and interpretation, leading to problems in joining and initiating social interaction. For ADHD, there is a performance deficit incurred by disruption arising from the ADHD symptoms of inattention and hyperactivity/impulsivity, while its acquisition capacity on social knowledge is relatively intact. The inattentive, intrusive, and impulsive behaviours of ADHD unsettle social interaction. Finally, this review proposes training targets for intervention along the six steps of the social information-processing model for ASD and ADHD, as well as areas for future research in further elucidating the social impairment of the two disorders.

Effectiveness of non-pharmacological interventions on individuals with anorexia nervosa: A systematic review and meta-analysis.

OBJECTIVE: This study aimed to synthesize the best available evidence regarding the effectiveness of non-pharmacological interventions on body mass index (BMI), body dissatisfaction, depression and anxiety among individuals with anorexia nervosa (AN). METHODS: Published studies in English were searched using seven databases (such as PubMed). Grey literature was searched using ProQuest and Scopus. Studies were screened, appraised and extracted by two independent reviewers. Meta-analysis was performed and standardized mean difference was used as an effect measure. Heterogeneity was determined by I2 statistics and Cochran χ2 test. Publication bias was appraised using funnel plots. Sensitivity and subgroup analyses were also conducted. RESULTS: Nineteen RCTs from eight different countries were included in this review. Behavioral family system therapy (BFST) was found to enhance BMI while conjoint family therapy (CFT) was more effective in ameliorating depression. Studies implementing combined family and individual therapy and those with longer therapeutic durations produced larger effect sizes. CONCLUSION: This review provided evidence to support BSFT, CFT and combined family and individual therapy for adolescents with AN. PRACTICAL IMPLICATIONS: Healthcare professionals may offer the two interventions to adolescents with AN in clinical settings. Future research may further investigate the effectiveness of BSFT and CFT on BMI and depression.

Patient pIgR-enriched extracellular vesicles drive cancer stemness, tumorigenesis and metastasis in hepatocellular carcinoma.

BACKGROUND & AIMS: Extracellular vesicles (EVs) play a pivotal role in connecting tumor cells with their local and distant microenvironments. Herein, we aimed to understand the role (on a molecular basis) patient-derived EVs play in modulating cancer stemness and tumorigenesis in the context of hepatocellular carcinoma (HCC). METHODS: EVs from patient sera were isolated, quantified and characterized. The EVs were vigorously tested, both in vitro and in vivo, through various functional assays. Proteomic analysis was performed to identify the functional components of EVs. The presence and level of polymeric immunoglobulin receptor (pIgR) in circulating EVs and tumor and non-tumorous tissues of patients with HCC were determined by ELISA, immunoblotting, immunohistochemistry and quantitative PCR. The functional role and underlying mechanism of EVs with enhanced pIgR expression were elucidated. Blockade of EV-pIgR with neutralizing antibody was performed in nude mice implanted with patient-derived tumor xenografts (PDTXs). RESULTS: Circulating EVs from patients with late-stage HCC (L-HCC) had significantly elevated pIgR expression compared to the EVs released by control individuals. The augmenting effect of L-HCC-EVs on cancer stemness and tumorigenesis was hindered by an anti-pIgR antibody. EVs enriched with pIgR consistently promoted cancer stemness and cancerous phenotypes in recipient cells. Mechanistically, EV-pIgR-induced cancer aggressiveness was abrogated by Akt and ß-catenin inhibitors, confirming that the role of EV-pIgR depends on the activation of the PDK1/Akt/GSK3ß/ß-catenin signaling axis. Furthermore, an anti-pIgR neutralizing antibody attenuated tumor growth in mice implanted with PDTXs. CONCLUSIONS: This study illustrates a previously unknown role of EV-pIgR in regulating cancer stemness and aggressiveness: EV-pIgR activates PDK1/Akt/GSK3ß/ß-catenin signaling cascades. The blockade of the intercellular communication mediated by EV-pIgR in the tumor microenvironment may provide a new therapeutic strategy for patients with cancer. LAY SUMMARY: The World Health Organization estimates that more than 1 million patients will die from liver cancer, mostly hepatocellular carcinoma (HCC), in 2030. Understanding the underlying mechanism by which HCC acquires aggressive attributes is crucial to improving the diagnosis and treatment of patients. Herein, we demonstrated that nanometer-sized extracellular vesicles released by tumors promote cancer stemness and tumorigenesis. Within these oncogenic vesicles, we identified a key component that functions as a potent modulator of cancer aggressiveness. By inhibiting this functional component of EVs using a neutralizing antibody, tumor growth was profoundly attenuated in mice. This hints at a potentially effective therapeutic alternative for patients with cancer.

The Impact of COVID-19-Related Restrictions on Social and Daily Activities of Parents, People With Disabilities, and Older Adults: Protocol for a Longitudinal, Mixed Methods Study.

BACKGROUND: The COVID-19 pandemic has led to wide-scale changes in societal organization. This has dramatically altered people's daily activities, especially among families with young children, those living with disabilities such as spinal cord injury (SCI), those who have experienced a stroke, and older adults. OBJECTIVE: We aim to (1) investigate how COVID-19 restrictions influence daily activities, (2) track the psychosocial effects of these restrictions over time, and (3) identify strategies to mitigate the potential negative effects of these restrictions. METHODS: This is a longitudinal, concurrent, mixed methods study being conducted in British Columbia (BC), Canada. Data collection occurred at four time points, between April 2020 and February 2021. The first three data collection time points occurred within phases 1 to 3 of the Province of BC's Restart Plan. The final data collection coincided with the initial distribution of the COVID-19 vaccines. At each time point, data regarding participants' sociodemographics, depressive and anxiety symptoms, resilience, boredom, social support, instrumental activities of daily living, and social media and technology use were collected in an online survey. These data supplemented qualitative videoconference interviews exploring participants' COVID-19-related experiences. Participants were also asked to upload photos representing their experience during the restriction period, which facilitated discussion during the final interview. Five groups of participants were recruited: (1) families with children under the age of 18 years, (2) adults with an SCI, (3) adults who experienced a stroke, (4) adults with other types of disabilities, and (5) older adults (>64 years of age) with no self-reported disability. The number of participants we could recruit from each group was limited, which may impact the validity of some subgroup analyses. RESULTS: This study was approved by the University of British Columbia Behavioural Research Ethics Board (Approval No. H20-01109) on April 17, 2020. A total of 81 participants were enrolled in this study and data are being analyzed. Data analyses are expected to be completed in fall 2021; submission of multiple papers for publication is expected by winter 2021. CONCLUSIONS: Findings from our study will inform the development and recommendations of a new resource guide for the post-COVID-19 period and for future public health emergencies. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/28337.

Effectiveness of psychosocial interventions among older adults with mild cognitive impairment: a systematic review and meta-analysis.

OBJECTIVES: This review aimed to examine available evidence concerning the effectiveness of psychosocial interventions in improving memory, executive function, depression and activities of daily living (ADL) in older adults with MCI. METHODS: Eight electronic databases were used to conduct a comprehensive literature search for published and unpublished studies. A primary outcome was cognitive function, including memory and executive function. Secondary outcomes were depression and ADL. Two researchers independently appraised quality of included studies and extracted data. Meta-analysis, heterogeneity test, subgroup analysis and sensitivity analyses were performed. RESULTS: Ten studies (out of 1,265 records) were included in this review. Psychosocial interventions contributed to a significant improvement in memory, not executive function, depression and ADL. Subgroup analyses suggested that interventions with a longer duration, more therapeutic sessions, and individual format had larger effect sizes. Strategies found to enhance memory entailed behavior modification and activation, memory training, visual imagery, storytelling, memory aids, journaling, and exercise. CONCLUSION: Healthcare providers may offer psychosocial interventions to client with MCI in clinical settings. Higher quality trials should be conducted to increase solid evidence in this domain.

The effectiveness of e-interventions on fall, neuromuscular functions and quality of life in community-dwelling older adults: A systematic review and meta-analysis.

BACKGROUND: Falls in older adults result in serious, life-limiting consequences. An increasing number of fall prevention interventions have used technology to reduce the number of falls in community-dwelling adults. Various types of e-interventions are being tested in clinical trials and in the community. These include telehealth, exergames, cognitive games, socialized training, smart home systems and non-conventional balance training. Currently, no systematic review and meta-analysis has assessed the overall effectiveness of e-interventions and compared the effectiveness of the different types. OBJECTIVES: The aim of this review was to synthesize best available evidence concerning the effectiveness of e-interventions on fall, neuromuscular functions and quality of life in community-dwelling older adults. METHODS: A rigorous three-step search was conducted in nine online databases for published and unpublished randomized controlled trials studying e-interventions. Studies were screened and assessed for individual and overall risk of bias by two independent reviewers. Six fall-related outcomes were evaluated in the meta-analysis: fall risk, balance, lower extremity strength, fall efficacy, cognitive function and health-related quality of life. Subgroup and sensitivity analysis were conducted during meta-analysis. RESULTS: Thirty-one studies fit the eligibility criteria and had an overall 74.7% low risk of bias. A total of 4,877 older adults from 17 countries were included in narrative synthesis and meta-analysis. Telehealth combined with exercise programmes and smart home systems were able to reduce fall risk significantly (risk ratio=0.79, 95% CI [0.72, 0.86]). E-interventions also significantly improved balance and fall efficacy (standardized mean difference=0.28, 95% CI [0.04, 0.53]). However, lower extremity strength, cognitive function and health-related quality of life did not show significant improvements. CONCLUSION: Telehealth combined with exercise and smart home systems demonstrated the best evidence of effectiveness in reduction of falls in community-dwelling older adults. Future research should focus on forecasting falls using smart home technology and Artificial Intelligence, and testing promising e-interventions on larger samples to improve the strength of evidence of fall prevention by e-interventions.

Fidelity Assessment in Community Programs: An Approach to Validating Simplified Methodology.

Fidelity to intervention protocol is linked to best outcomes for individuals with autism spectrum disorder (ASD; see Boyd & Corley [Autism 5(4):430-441, 2001]; Pellecchia et al. [J Autism Dev Disord 45(9):2917-2927, 2015]); however, fidelity measurement tools that are both accurate and feasible for community use are often not available. In this paper we explore methods for validated simplification of fidelity assessment procedures toward the goal of increased use in clinical practice. Video recordings (n = 36) of therapists working with children with ASD were coded using three variations of fidelity assessment methodology (trial-by-trial, 5-point Likert Scale, and 3-point Likert Scale), and the results were compared for exact agreement, mastery criterion agreement, and overall reliability. The results indicated overall a very high percentage of exact agreement (mean 99.44%, range 94.4-100%) and excellent reliability (mean Krippendorff's alpha [Kα] 1.0) between the trial-by-trial and 5-point Likert Scale across all components; however, the 3-point method may be viewed as being the more feasible strategy within community programs.

Evidence for activation of nitenpyram by a mitochondrial cytochrome P450 in Drosophila melanogaster.

BACKGROUND: Nitenpyram is a member of the economically important neonicotinoid class of insecticides. The in vivo metabolism of nitenpyram is not well characterised, but cytochrome P450 activity is the major mechanism of resistance to neonicotinoids identified in insect pests, and P450s metabolise other neonicotinoids including imidacloprid. RESULTS: Here, we used the GAL4-UAS targeted expression system to direct RNA interference (RNAi) against the cytochrome P450 redox partners to interrupt P450 functions in specific tissues in Drosophila melanogaster. RNAi of the mitochondrial redox partner defective in the avoidance of repellents (dare) in the digestive tissues reduced nitenpyram mortality, suggesting an activation step in the metabolism of nitenpyram carried out by a mitochondrial P450. RNAi of the mitochondrial cytochrome P450 Cyp12a5, which is expressed in the digestive tissues, resulted in the same phenotype, and transgenic overexpression of Cyp12a5 increased nitenpyram sensitivity. CONCLUSION: These results suggest that in vivo metabolism of nitenpyram by the mitochondrial P450 CYP12A5 results in the formation of a product with higher toxicity than the parent compound. © 2018 Society of Chemical Industry.

Family-based association study of DRD4 gene in methylphenidate-responded Attention Deficit/Hyperactivity Disorder.

The 48-basepair (48-bp) variable number tandem repeat (VNTR) polymorphism in exon 3 of the dopamine receptor D4 gene (DRD4) is implicated in the etiology of attention-deficit/ hyperactivity disorder (ADHD). In particular, ADHD in European-ancestry population is associated with an increased prevalence of the 7-repeat (7R) allele of the exon 3 VNTR. However, it is intriguing to note that the 7R allele has been found to be of very low prevalence in the Chinese general population. In a previous case-control study, our research team had found that the 7R allele was similarly absent in Chinese ADHD children in Hong Kong. Instead, there was an increased prevalence of the 2R allele in Chinese ADHD children. Interestingly, in Asian samples, the 2R allele had been found to be an evolutionary derivative of the 7R allele with equivalent biochemical functionality. So, the finding of an association between ADHD and 2R allele in Chinese population does not exactly contradict the original 7R allele finding in European-ancestry population. However, given the potential pitfall of population stratification in the previous case-control design, this current study tested the 2R allele and ADHD association using a methodologically more rigorous family-based approach on 33 Chinese ADHD probands who had favorable clinical responses to stimulant medication (methylphenidate). Haplotype Relative Risk (HRR) analysis and Transmission Disequilibrium Test (TDT) both showed a significant preferential transmission of the 2R allele from the biological parents to ADHD probands (pone-tailed = 0.038, OR = 2.04; pone-tailed = 0.048, OR = 2.29, respectively). A second hypothesis speculates that it is the deviation, including 7R and 2R alleles, from the conserved ancestral 4R allele which confers risk to ADHD. Thus, a preferential transmission of non-4R alleles, against the 4R allele, from biological parents to their ADHD probands is predicted. Both HRR analysis and TDT confirmed such prediction (pone-tailed = 0.029, OR = 2.07; pone-tailed = 0.032, OR = 2.43, respectively). This study re-confirmed the original finding of a previous study that in Chinese population, the 2R allele of the DRD4 exon 3 VNTR was related to ADHD. This endorses the general thesis that DRD4 exon 3 VNTR polymorphism is related to ADHD, despite that the exact length or number of repeats of the associated alleles varies across ethnicity. This in turn supports the dopamine dysregulation theory of ADHD.

Evolution, Expression, and Function of Nonneuronal Ligand-Gated Chloride Channels in Drosophila melanogaster.

Ligand-gated chloride channels have established roles in inhibitory neurotransmission in the nervous systems of vertebrates and invertebrates. Paradoxically, expression databases in Drosophila melanogaster have revealed that three uncharacterized ligand-gated chloride channel subunits, CG7589, CG6927, and CG11340, are highly expressed in nonneuronal tissues. Furthermore, subunit copy number varies between insects, with some orders containing one ortholog, whereas other lineages exhibit copy number increases. Here, we show that the Dipteran lineage has undergone two gene duplications followed by expression-based functional differentiation. We used promoter-GFP expression analysis, RNA-sequencing, and in situ hybridization to examine cell type and tissue-specific localization of the three D. melanogaster subunits. CG6927 is expressed in the nurse cells of the ovaries. CG7589 is expressed in multiple tissues including the salivary gland, ejaculatory duct, malpighian tubules, and early midgut. CG11340 is found in malpighian tubules and the copper cell region of the midgut. Overexpression of CG11340 increased sensitivity to dietary copper, and RNAi and ends-out knockout of CG11340 resulted in copper tolerance, providing evidence for a specific nonneuronal role for this subunit in D. melanogaster Ligand-gated chloride channels are important insecticide targets and here we highlight copy number and functional divergence in insect lineages, raising the potential that order-specific receptors could be isolated within an effective class of insecticide targets.