Nanoscale sorting of extracellular vesicles via optically-induced dielectrophoresis on an integrated microfluidic system.

We reported a microfluidic system for sorting of extracellular vesicles (EVs), which can house DNAs, RNAs, lipids, proteins, and metabolites that are important in intercellular communication. Their presence within bodily fluids has demonstrated potential in both clinical diagnostic and therapeutic applications. Furthermore, EVs exhibit distinct subtypes categorized by their sizes, each endowed with unique biophysical properties. Despite several existing techniques for EV isolation and purification, diminished purity and prolonged processing times still hamper clinical utility; comprehensive capture of EVs remains an ongoing pursuit. To address these challenges, we devised an innovative method for automated sorting of nano-scale EVs employing optically-induced dielectrophoresis on an integrated microfluidic chip. With this approach, EVs of three distinct size categories (small: 100-150 nm, medium-sized: 150-225 nm, and large: 225-350 nm) could be isolated at a purity of 86%. This new method has substantial potential in expediting EV research and diagnostics.

Reasons for non-attendance in youth mental health clinics: Insights from mobile messaging communications.

AIM: Non-attendance at appointments in youth mental health services is a common problem which contributes to reduced service effectiveness and unmet needs. Reasons cited by young people for non-attendance are poorly understood. Information derived from short-message-service (SMS) conversations about appointments between patients and clinicians can uncover new insights about the circumstances leading to 'did not attend' events. METHODS: Text messages between young people and clinicians were examined in a retrospective audit of medical records in two youth mental health services in Perth, Australia. Frequently non-attending young people aged 16-24 (n = 40) engaged in 302 SMS message chains about appointments. Mixed methods included quantitative data and qualitative thematic analysis of textual data. RESULTS: Medical reasons (32/190, 16.8%) and forgetfulness (20/190, 10.5%) were the most frequent reasons for non-attendance. Major issues included non-avoidable events while others were potentially preventable and could be addressed by the service. CONCLUSIONS: The analysis of mobile communications in clinical practice can be used for service evaluation and to reveal barriers that impede attendance to ongoing care.

Effectiveness, durability, and clinical correlates of the PEERS social skills intervention in young adults with autism spectrum disorder: the first evidence outside North America.

BACKGROUND: Despite the fact that social deficits among individuals with autism spectrum disorder (ASD) are lifelong and impact many aspects of personal functioning, evidence-based programs for social skills training were not available until recently. The Program for the Education and Enrichment of Relational Skills (PEERS®) has been shown to effectively improve social skills for adolescents on the spectrum across different social cultures. However, the effectiveness for young adults beyond North America has yet to be examined. This study aimed to investigate the effectiveness of the PEERS intervention in Taiwanese young adults with ASD, and examine its durability and clinical correlates. METHODS: We recruited 82 cognitively-able young adults with ASD, randomized to the PEERS treatment or treatment-as-usual. RESULTS: Following treatment, significant improvement was found in aspects of social deficits, autism severity, social interaction anxiety, empathy, and social skills knowledge either by self-report or coach-report. Additionally, communicative behaviors rated by observers improved throughout the sessions, showing a trend toward more appropriate eye contact, gestures, facial expression during conversation, and appropriate maintenance of conversation and reciprocity. Most effects maintained at 3-month and 6-month follow-ups. The improvement of social deficits was positively correlated with baseline severity, while gains in social skills knowledge were positively correlated with IQ. The improvement of social deficits, autism severity, and empathy were positively correlated with each other. CONCLUSION: Overall, the PEERS intervention appears to effectively improve social functioning in Taiwanese young adults with ASD. Improvement of social response and knowledge may be predicted by baseline severity and intelligence respectively.

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.

Homelessness youth and mental health service utilization: A long-term follow-up study.

BACKGROUND: There is currently an incomplete picture of the long-term impact of homelessness on youth with mental health issues. There are also questions regarding homelessness as a predictor of mental health re-admissions. AIMS: To examine the mental health service presentation profile of young people affected by homelessness and mental health issues. METHODS: A retrospective analysis was conducted of the medical records of homeless (n = 29) and non-homeless (n = 32) youth who attended the YouthLink specialist mental health service in 2010. We tracked their pattern of mental health service admissions at five time points during a total period of 10 years, including 2 years prior to, and up to 8 years following the YouthLink presentation. A regression analysis was used to examine factors hypothesized to contribute to mental health re-admissions. RESULTS: Homeless youth had significantly more frequent presentations to inpatient and outpatient mental health services, and emergency departments for mental health reasons. They were 11 times more likely to be re-admitted to a mental health inpatient ward than non-homeless youth. Prior hospital admission was an independent predictor, increasing by a factor of 2.2 for every inpatient admission. CONCLUSION: The impact of homelessness on mental health issues is enduring, and is a long-term predictor of hospital re-admission.

Providing culturally informed mental health services to Aboriginal youth: The YouthLink model in Western Australia.

AIM: Aboriginal young people are more likely to experience mental health issues and to access mental health services than other young Australians, yet there are few culturally informed mental health programs and services available. This study describes and documents the effectiveness of the culturally sensitive model within YouthLink, a state-wide mental health service program in Western Australia for young people aged 13 to 24 years of age. METHODS: A mixed-method design including a descriptive approach reporting on the YouthLink framework and an empirical research design where 40 Aboriginal clients completed client feedback monitoring measures between 2014 and 2016. RESULTS: The YouthLink culturally informed conceptual framework adheres to best practice principles relevant to work with Indigenous people, family and communities. Aboriginal young people indicated improvement across the treatment period as shown by within-group differences between the first and last session scores on feedback measures. Therapeutic alliance (together with lower baseline acuity and female gender) also contributed significantly to positive treatment outcomes. CONCLUSIONS: Through a strong role of Aboriginal practitioners, relationships with Aboriginal communities, and greater service flexibility that embraces cultural meaning and knowledge, YouthLink has sought to enhance its response to the needs of Aboriginal youth.

Factors associated with treatment mode and termination among preschoolers with ADHD in Taiwan.

OBJECTIVES: This study examined the extent to which characteristics of family and health care providers predict treatment initiation, treatment mode, and treatment termination among preschool children with newly diagnosed ADHD. METHODS: A cohort of 3,583 preschoolers with ADHD was identified from the National Health Insurance Research Database of Taiwan. Individual characteristics and health care records, including medication and nonmedication treatment, were documented. Logistic regression and time-dependent survival analyses were used to evaluate association estimates. RESULTS: Over 80% of the children with newly diagnosed ADHD received initial treatment within a month of diagnosis, with 41% starting with combined treatment. Only one-quarter remained in treatment by the end of 12 months. In the first year, the termination rate was lowest for those who received rehabilitation treatment only (log-rank test, p<.001). Predictors of termination varied by treatment mode. For combined treatment, factors that marginally increased the likelihood of treatment termination were coming from a family in poverty (adjusted hazard ratio [AHR]=1.72) or from a rural region (AHR=1.40). Receiving initial treatment from a psychiatrist was associated with an increased likelihood of treatment termination for children receiving psychosocial treatment (AHR=1.80, 95% confidence interval [CI]=1.46-2.22) and combined treatment (AHR=1.38, CI=1.20-1.60). CONCLUSIONS: Family and service provider characteristics appeared to have differential effects on initial receipt and mode of treatment and on one-year treatment termination among preschoolers with ADHD in Taiwan's universal health insurance program. Future efforts should aim at reducing access barriers to comprehensive and continuous health care for very young children with mental or developmental disorders.

Development of T-STAT for early autism screening.

This study's purpose was to modify the Screening Tool for Autism in Two-Year-Olds (STAT) into a Taiwanese version called T-STAT. Study 1 included 15 children with Autism and 15 children with Developmental Delay (DD) or language impairment (LI) aged between 24 and 35 months. Study 2 had 77 young children with Autism, PDD-NOS, or DD/LI as a clinical-based validation sample. In Study 1, the signal detection procedure found that a cutoff score of 2 would yield high sensitivity and specificity in T-STAT. In Study 2, using a score of 2 as a cutoff, the agreement between T-STAT risk and ADOS classification was highly acceptable. Results were promising as a Level 2 screening tool for Autism for ages two to three.

Toddler autism screening questionnaire: development and potential clinical validity.

No feasible screening instrument is available for early detection of children with autism in Taiwan. The existing instruments may not be appropriate for use in Taiwan due to different health care systems and child-rearing cultures. The purpose of this study was to develop and test a screening questionnaire for generic autism. The initial 18-item screening questionnaire was developed by a child psychiatrist using face-to-face interviews with 10 families of children with autism and then tested on a sample of families of 18 children with autism and of 59 typically developing children. Of these 18 items, 15 had fair or better item discrimination (kappa >0.20) and were selected for the revised screening questionnaire. In the revised questionnaire, cutoff scores of 5 and 6 offered 100% sensitivity and 96.5% specificity, with the area under the receiver operating characteristic curve of 0.983. The revised screening instrument has high sensitivity and specificity, making it potentially useful for screening Taiwanese children at risk for autism. This instrument should be further tested in a population-based study.

The loss of asymmetry and reduced interhemispheric connectivity in adolescents with autism: a study using diffusion spectrum imaging tractography.

Evidence from neuroimaging and neurobiological studies suggests that abnormalities in cortical-cortical connectivity involving both local and long-distance scales may be related to autism. The present study analyzed the microstructural integrity of the long-range connectivity related to social cognition and language processing with diffusion tractography among adolescents with autism compared with neurotypical adolescents. Tract-specific analyses were used to study the long-range connectivity responsible for integrating social cognition and language processing. Specifically, three pairs of association fibers and three portions of callosal fiber tracts were analyzed. Generalized fractional anisotropy (GFA) values were measured along individual targeted fiber tracts to investigate alterations in microstructure integrity. The asymmetry patterns were also assessed in three pairs of association fibers. In neurotypical participants, we found a consistent leftward asymmetry in three pairs of association fibers. However, adolescents with autism did not demonstrate such asymmetry. Moreover, adolescents with autism had significantly lower mean GFA in three callosal fiber tracts than neurotypical participants. The loss of leftward asymmetry and reduction of interhemispheric connection in adolescents with autism suggest alterations of the long-range connectivity involved in social cognition and language processing. Our results warrant further investigation by combining developmental and neurocognitive data.

Association between symptoms and subtypes of attention-deficit hyperactivity disorder and sleep problems/disorders.

This study aimed to investigate the association between attention-deficit hyperactivity disorder (ADHD) symptoms and subtypes, and sleep schedules, daytime inadvertent napping, and sleep problems/disorders in children and adolescents with and without ADHD. The sample included 325 patients with ADHD, aged 10-17 years [male: 81.5%; combined type (ADHD-C): 174; predominantly inattentive type (ADHD-I): 130; predominantly hyperactive-impulsive type (ADHD-HI): 21], and 257 children and adolescents without lifetime ADHD (non-ADHD). We conducted psychiatric interviews with the participants and their mothers before making the diagnoses of ADHD, other psychiatric disorders, and sleep problems or disorders. We also collected the medication treatment data and parent and teacher reports of ADHD symptoms. Multi-level models were used for data analyses controlling for sex, age, psychiatric comorbidities, and treatment with methylphenidate. The ADHD-C and ADHD-I groups had more daytime inadvertent napping. In general, the three subtypes were associated with increased rates of sleep problems/disorders. Specifically, ADHD-C rather than ADHD-I was associated with circadian rhythm problems, sleep-talking, nightmares (also ADHD-HI), and ADHD-I was associated with hypersomnia. The most-related sleep schedules and problems for inattention and hyperactivity-impulsivity were earlier bedtime, later rise time, longer nocturnal sleep, more frequent daytime napping, insomnia, sleep terrors, sleep-talking, snoring, and bruxism across informants. The findings imply that in addition to the dichotomous approach of ADHD and considering the psychiatric comorbid conditions, ADHD subtypes and symptom dimensions need to be considered in clinical practice and in the research regarding the association between ADHD and sleep problems/disorders.

Psychopathology and symptom remission at adolescence among children with attention-deficit-hyperactivity disorder.

OBJECTIVE: The aim of the present study was to examine changes of attention-deficit-hyperactivity disorder (ADHD) symptoms and psychiatric comorbidities at adolescence, and mother-child agreement on reports of ADHD symptoms among children with ADHD as compared to unaffected controls. METHODS: The participants included 93 patients (male, 82.8%) aged 11-16, who were clinically diagnosed with ADHD at the mean age of 7.3 +/- 2.8 years, and 93 age-, sex-, and parental education-matched school controls. The participants and their mothers were first interviewed separately for baseline psychopathology at childhood, followed by current psychopathology using the Chinese Kiddie Epidemiologic version of the Schedule for Affective Disorders and Schizophrenia. RESULTS: At adolescence, 46 patients (49.5%) met full DSM-IV ADHD criteria, 31 (33.3%) had subthreshold ADHD, and 16 (17.2%) had recovered from ADHD. We found a significant progressive decline in the three ADHD core symptoms for the ADHD group: hyperactivity had the greatest effect size, followed by inattention, and then impulsivity. Children with ADHD tended to report less severe ADHD symptoms at childhood and adolescence than their mothers. They were more likely than the controls to have oppositional defiant disorder (odds ratio (OR)=18.0; 95% confidence interval (CI)=8.3-38.9), conduct disorder (OR=23.1, 95%CI =5.3-100.2), mood disorders (OR=3.8, 95%CI = 1.5-9.4), bipolar disorders (Fisher's exact p < 0.001), and sleep disorders (OR=3.1, 95%CI = 1.6-6.0) at adolescence. CONCLUSIONS: The present findings are similar to those of Western studies, regarding the patterns of comorbidity, stability of core symptoms, and mother-child differences on symptom reports.

Psychiatric comorbidity among children and adolescents with and without persistent attention-deficit hyperactivity disorder.

OBJECTIVES: The aims of the present study were to examine the current psychiatric comorbidity among children and adolescents with and without persistent attention-deficit hyperactivity disorder (ADHD) as compared to school controls, and to determine the factors predicting psychiatric comorbidity. METHOD: The sample included 296 patients (male, 85.5%), aged 11-17, who were diagnosed with DSM-IV ADHD at the mean age of 6.7 +/- 2.7 years and 185 school controls. The ADHD and other psychiatric diagnoses were made based on clinical assessments and confirmed by psychiatric interviews. The ADHD group was categorized into 186 patients (62.8%) with persistent ADHD and 110 (37.2%) without persistent ADHD. RESULTS: Compared to the controls, the two ADHD groups were more likely to have oppositional defiant disorder (ODD), conduct disorder (CD), tics, mood disorders, past and regular use of substances, substance use disorders and sleep disorders (odds ratios (ORs) = 1.8-25.3). Patients with persistent ADHD had higher risks for anxiety disorders, particularly specific phobia than the controls. Moreover, patients with persistent ADHD were more likely to have ODD than their partially remitted counterparts. Advanced analyses indicated that more severe baseline ADHD symptoms predicted ODD/CD at adolescence; longer methylphenidate treatment duration was associated with an increased risk for tics and ODD/CD at adolescence; and older age predicted higher risks for mood disorders and substance use disorders. CONCLUSION: Reduced ADHD symptoms at adolescence may not lead to decreased risks for psychiatric comorbidity, and identification of severe ADHD symptoms at childhood and age-specific comorbid patterns throughout the developmental stage is important to offset the long-term adverse psychiatric outcomes of ADHD.

Emotional/behavioral problems and functional impairment in clinic- and community-based children with attention-deficit/hyperactivity disorder in Taiwan.

Using a sample of 268 patients and 137 community-based children with DSM-IV ADHD, and 268 school controls, aged 6-15, this study aimed to compare the emotional/behavioral problems and functional impairment between clinic- and community-based children with ADHD. Children's ADHD-related symptoms, a wide range of emotional/behavioral problems, and functional impairments were assessed by the psychiatric interviews and self-, parent- and teacher-reported questionnaires. Both ADHD groups scored higher in parent- and teacher-reported ADHD-related symptoms, wide-ranging emotional/behavioral problems, and impairments in the school, peer, family, and leisure time domains than school controls. However, clinic-based children with ADHD had more physical/developmental problems, more severe functional impairments and teacher-reported hyperactivity/impulsivity symptoms, and higher family burdens than their community counterparts. Our findings suggest that a higher maternal educational level, parent's perceived child functional impairment, teacher's perceived impaired peer relationship and hyperactivity-impulsivity, and child physical and developmental problems may be related to the psychiatric referrals of children with ADHD.

Behavioral problems and parenting style among Taiwanese children with autism and their siblings.

AIMS: The purpose of the present study was to investigate the behavioral problems and parenting style among children with autism and their siblings in an ethnic Chinese population. METHODS: A total of 151 children with DSM-IV autistic disorder, aged 3-12, 134 siblings without autism, and 113 normally developing controls were recruited. Both parents reported their parenting styles and psychological status and mothers also reported children's behavioral problems. RESULTS: Children with autism had significantly more severe behavioral problems and obtained less affection and more overprotection and authoritarian controlling from their parents than the other two groups. Compared to the controls, unaffected siblings showed some behavioral problems, and obtained less maternal care. Withdrawal and attention, social, and thought problems were the most associated behavioral syndromes to distinguish children with autism from those without. CONCLUSIONS: In addition to children with autism, who have a wide range of behavioral problems and impaired parent-child interactions, their siblings may be at risk for such problems.

Association study of the SLC25A12 gene and autism in Han Chinese in Taiwan.

PURPOSE: Autism is a childhood-onset neurodevelopmental disorder with a strong genetic component in its etiology. Several studies reported that the solute carrier family 25 member A12 (SLC25A12) gene was associated with autism. This study aimed to replicate this finding in a Han Chinese sample from Taiwan using a population-based case-control approach. METHODS: We genotyped two single nucleotide polymorphisms (SNPs, rs2056202 and rs2292813) of the SLC25A12 gene that were previously reported to be associated with autism in 465 patients (402 males and 63 females) and 450 control subjects (227 males and 223 females) from Taiwan. Differences in the genotype, allele, and haplotype frequencies between the two groups were compared. RESULTS: We found no differences in the allele, genotype, or haplotype frequencies of these two SNPs between patients and controls. CONCLUSIONS: Our data do not support that the SLC25A12 gene is associated with autism in our population. The discrepant results of other studies may come from the clinical heterogeneity of patients recruited for studies, or the genetic heterogeneity of autism in different populations.

Executive function in adolescence among children with attention-deficit/hyperactivity disorder in Taiwan.

OBJECTIVE: Little is known about executive function among adolescents with a childhood diagnosis of attention-deficit/hyperactivity disorder (ADHD), and there is a lack of such information in an ethnic Chinese population. This study investigated nonverbal executive functions in adolescence among Taiwanese children with ADHD. METHODS: The sample included fifty-three 11- to 16-year-old adolescents (male, 75.5%) with a childhood diagnosis of ADHD according to the DSM-IV criteria, and 53 age-, sex-, IQ-, and parental education-matched comparison adolescents. They were assessed using psychiatric interviews (mothers included), the Weschler Intelligence Scale for Children-3rd edition, and the tasks involving the executive functions of the Cambridge neuropsychological test automated battery: the spatial span, spatial working memory, intradimensional/extradimensional shifts, and stocking of Cambridge. A linear multilevel model was used for data analysis for the matched case-control study design and repeated measures within the same participants. RESULTS: Forty-three adolescents (81.1%) had persistent DSM-IV ADHD diagnosis. The ADHD group made more errors in the spatial span and spatial working memory, had more complete stage trials in the intradimensional/extradimensional shifts, and had fewer problems solved and shorter initial and subsequent thinking time in the stockings of Cambridge than the controls. The magnitudes of group differences increased with increased task difficulties. Persistent ADHD and methylphenidate did not make significant difference in executive functions. CONCLUSIONS: The findings of the authors suggest that adolescents with childhood ADHD need extra assistance when they are assigned complex tasks regardless of persistence of ADHD at adolescence.

Demographic and perinatal factors for behavioral problems among children aged 4-9 in Taiwan.

AIM: To investigate the effects of age, gender, prenatal/perinatal factors, and maternal psychological distress on childhood emotional/behavioral problems, and the gender difference in the patterns of comorbid emotional/behavioral problems. METHODS: The sample included 1391 children aged 4-9 in Taipei using a multi-stage sampling method. Their mothers completed questionnaires including demographics, prenatal/perinatal variables, the Child Behavior Checklist, and the Chinese Health Questionnaire. The linear and non-linear mixed model was used for data analysis. RESULTS: Boys scored higher on externalizing problems, and girls scored higher on internalizing problems. Gender also modified the comorbid patterns of emotional/behavioral problems. Aggressive behaviors decreased, but attention and thought problems increased with age. Prenatal/perinatal exposure to alcohol and coffee, vaginal bleeding, and gestational diabetes, low birthweight, and postnatal incubation and resuscitation, and maternal psychological distress predicted the risk for several childhood emotional/behavioral problems. CONCLUSION: Prenatal/perinatal and maternal care, and gender-specific measures are important for prevention of childhood emotional/behavioral problems.

Parental characteristics, parenting style, and behavioral problems among chinese children with Down syndrome, their siblings and controls in Taiwan.

BACKGROUND/PURPOSE: The literature has documented maternal distress and behavioral problems among children with Down syndrome (DS), however, little is known about paternal adjustment and behavioural problems among the siblings of children with DS. Here, we examined parental psychopathology, parenting style and emotional/behavioral problems among children with DS, their siblings, and controls in Taiwan. METHODS: We recruited 45 families of children with DS (age, 2-4 years) and 50 families of normally developing children (age, 3-5 years). If there were more than two children in the case family, the sibling whose age was closest to the child with DS was recruited (age, 3-8 years). Both parents completed self-administered measures of their personality characteristics, psychopathology, family functioning, parenting styles, and child behavioral problems, using the Chinese versions of the Maudsley Personality Inventory, Brief Symptom Rating Scale, Family Adaptability and Cohesion Evaluation Scale, Parental Bonding Instrument, and Child Behavioral Checklist, respectively. RESULTS: Children with DS demonstrated significantly more severe symptoms than normal children of a wide range of behavioral problems such as attention problems, delinquency, social problems, somatic complaints, thought problems, and withdrawal compared with the other two groups, and obtained similar parental treatment, except for paternal overprotection. Their parents suffered from more psychopathology and their mothers were less often employed than their counterparts. The siblings of children with DS obtained less overprotection from their mothers than children with DS and less maternal care and control than normal children. There was no difference in emotional/behavioral problems between the siblings and normal controls. CONCLUSION: Our findings suggest that in addition to the physical, educational and psychological needs of children with DS, the psychological care of their mothers, fathers and siblings also needs to be evaluated. Moreover, parenting counseling should focus not only on children with DS, but their siblings as well.

Risk factors for suicide in Taiwanese college students.

OBJECTIVE: The authors investigated the personality characteristics, psychopathology, parenting style, and family function among Taiwanese college students with high, moderate, and low suicidal risks. PARTICIPANTS: The sample included 2,919 first-year college students (1,414 men, 1,505 women) from a university in Taipei, Taiwan. METHODS: A self-administered questionnaire assessed domains covering demographics, personality, psychopathology, frequency of substance use, parenting style, family functioning, and suicidal behaviors. The authors used mixed models for data analysis. RESULTS: The authors observed a positive linear trend between increased suicidal tendency and levels of neuroticism, harm avoidance, novelty seeking, psychopathology, and parenting styles of low affection, overprotection, and authoritarian controlling. Use of tobacco and alcohol and impaired family adaptation and cohesion were associated with high and moderate suicidal risks. CONCLUSIONS: Personality, psychopathology, substance use, and familial factors are important correlates of suicidal risks among college students in Taiwan. Optimal suicide prevention strategies in the college setting should incorporate the multiple facets of suicidal risks.