Prevalence of autism in first-episode psychosis in two Hong Kong teaching hospitals.

LAY ABSTRACT: Autistic features are commonly observed in children and adolescents with first-episode psychosis, but they are sometimes overlooked by clinicians and caregivers. By comprehensively examining the clinical profiles of 103 children and adolescents (below 18 years old) with first-episode psychosis and conducting the Autism Diagnostic Interview-Revised (the 'gold standard' autism diagnostic tool) with their primary caregivers, we showed that around 28% of patients with first-episode psychosis had a comorbid autism diagnosis, and boys were 3.57 times more likely to have first-episode psychosis-autism spectrum disorder comorbidity than girls. After administering the Autism Diagnostic Interview-Revised, we also observed that an additional 30% of patients with first-episode psychosis met the autism spectrum disorder diagnostic cut-off; their autism spectrum disorder symptoms were probably overshadowed by prodromal psychotic symptoms and left undetected before this study. The co-occurrence of autism and first-episode psychosis might be more common than we previously thought. Careful autism screening and assessment is highly recommended for clinicians working with patients with psychosis.

Effects of multisession cathodal transcranial direct current stimulation with cognitive training on sociocognitive functioning and brain dynamics in autism: A double-blind, sham-controlled, randomized EEG study.

BACKGROUND: Few treatment options are available for targeting core symptoms of autism spectrum disorder (ASD). The development of treatments that target common neural circuit dysfunctions caused by known genetic defects, namely, disruption of the excitation/inhibition (E/I) balance, is promising. Transcranial direct current stimulation (tDCS) is capable of modulating the E/I balance in healthy individuals, yet its clinical and neurobiological effects in ASD remain elusive. OBJECTIVE: This double-blind, randomized, sham-controlled trial investigated the effects of multisession cathodal prefrontal tDCS coupled with online cognitive remediation on social functioning, information processing efficiency and the E/I balance in ASD patients aged 14-21 years. METHODS: Sixty individuals were randomly assigned to receive either active or sham tDCS (10 sessions in total, 20 min/session, stimulation intensity: 1.5 mA, cathode: F3, anode: Fp2, size of electrodes: 25 cm2) combined with 20 min of online cognitive remediation. Social functioning, information processing efficiency during cognitive tasks, and theta- and gamma-band E/I balance were measured one day before and after the treatment. RESULTS: Compared to sham tDCS, active cathodal tDCS was effective in enhancing overall social functioning [F(1, 58) = 6.79, p = .012, ηp2 = 0.105, 90% CI: (0.013, 0.234)] and information processing efficiency during cognitive tasks [F(1, 58) = 10.07, p = .002, ηp2 = 0.148, 90% CI: (0.034, 0.284)] in these individuals. Electroencephalography data showed that this cathodal tDCS protocol was effective in reducing the theta-band E/I ratio of the cortical midline structures [F(1, 58) = 4.65, p = .035, ηp2 = 0.074, 90% CI: (0.010, 0.150)] and that this reduction significantly predicted information processing efficiency enhancement (b = -2.546, 95% BCa CI: [-4.979, -0.113], p = .041). CONCLUSION: Our results support the use of multisession cathodal tDCS over the left dorsolateral prefrontal cortex combined with online cognitive remediation for reducing the elevated theta-band E/I ratio in sociocognitive information processing circuits in ASD patients, resulting in more adaptive regulation of global brain dynamics that is associated with enhanced information processing efficiency after the intervention.

Effects of prefrontal transcranial direct current stimulation on social functioning in autism spectrum disorder: A randomized clinical trial.

LAY ABSTRACT: Currently available pharmacological and behavioral interventions for adolescents and young adults with autism spectrum disorder (ASD) yield only modest effect in alleviating their core behavioral and cognitive symptoms, and some of these treatment options are associated with undesirable side effects. Hence, developing effective treatment protocols is urgently needed. Given emerging evidence shows that the abnormal connections of the frontal brain regions contribute to the manifestations of ASD behavioral and cognitive impairments, noninvasive treatment modalities that are capable in modulating brain connections, such as transcranial direct current stimulation (tDCS), have been postulated to be potentially promising for alleviating core symptoms in ASD. However, whether tDCS can reduce behavioral symptoms and enhance cognitive performance in ASD remains unclear. This randomized controlled trial involving 105 adolescents and young adults with ASD showed that multiple sessions of a tDCS protocol, which was paired up with computerized cognitive training, was effective in improving social functioning in adolescents and young adults with ASD. No prolonged and serious side effects were observed. With more future studies conducted in different clinical settings that recruit participants from a wider age range, this tDCS protocol may be potentially beneficial to a broad spectrum of individuals with autism.

Disentangling the relationship of gut microbiota, functional gastrointestinal disorders and autism: a case-control study on prepubertal Chinese boys.

Emerging evidence of an altered gut microbiome in autism spectrum disorder (ASD) suggests a pathomechanism through the gut-brain axis despite the inconsistent microbiome profile reported across studies. One of the knowledge gaps in the existing ASD microbiota studies is the lack of systematic exploration of the role of comorbid functional gastrointestinal disorder (FGID) in the association of ASD and altered gut microbiome. Consequently, 92 ASD and 112 age-matched typically developing (TD) boys were profiled on general psychopathology, FGID status by Rome IV classification, and gut microbiota using 16S ribosomal RNA amplicon sequencing at the V4 hypervariable region. Compared to TD, a significant decrease in the within-sample abundance of taxa was observed in ASD, regardless of FGID status. The microbiota of ASD FGID+ and ASD FGID- clustered apart from the TD groups. The microbiota of ASD FGID+ also showed qualitative differences from that of ASD FGID- and had the highest-level Firmicutes: Bacteroidetes ratio, which was paralleled by elevated levels of anxiety and overall psychopathology. The altered gastrointestinal microbiota composition in ASD appeared to be independent of comorbid FGID. Further studies should address how FGID may mediate neuropsychiatric symptoms in ASD through inflammation along the microbiota-gut-brain axis.

Posterior Rectus Sheath Defect with Interparietal Hernia Causing a Small Bowel Obstruction.

Posterior rectus sheath hernias are exceptionally rare, with around twelve reported cases to date. This case report examines a 38-year-old female who demonstrated symptoms of intermittent small bowel obstruction five days following an abdominal hysterectomy. The patient was diagnosed via CT to have a small bowel obstruction within the rectus abdominis. Exploratory laparotomy determined the etiology to be an interparietal hernia through a posterior rectus wall defect, which was repaired with primary closure. Postoperatively, the patient was again unable to tolerate food. Repeat CT showed concern for repeat SBO, though symptoms subsided without intervention. The patient had no complaints during her follow up at one month. This report was aimed at building upon the few reported cases as well as enumerating potential risk factors that may allow for the consideration of this diagnosis in the future.

Investigating group-based classes ('weaning workshops') to support complementary infant feeding in Irish primary care settings: a cross-sectional survey.

OBJECTIVE: This study aims to (1) investigate current practice regarding 'weaning workshops' to support complementary infant feeding delivered within Irish primary care, (2) explore the experiences and opinions of community dietitians regarding optimal content and modes of delivery of weaning workshops and (3) identify the key factors to be considered in the development and implementation of weaning workshops delivered within primary care. DESIGN: Cross-sectional survey. SETTING: Irish primary care. PARTICIPANTS: Forty-seven community-based dietitians. RESULTS: Sixteen dietitians reported that workshops were run in their area with variable frequency, with ten reporting that workshops were never run in their area. Participants reported that mostly mothers of medium socio-economic status (SES) attended weaning workshops when infants were aged between 4 and 7 months, and that feedback from workshop attendees was predominantly positive. Dietitians identified that key factors to be considered in future development and delivery of weaning workshops are (1) workshop characteristics such as content, timing and venue, (2) organisational characteristics such as availability of resources and multidisciplinary involvement and (3) attendee characteristics such as SES. CONCLUSIONS: This study highlights substantial variability regarding provision of weaning workshops in Ireland, and a lack of standardisation regarding the provider, content and frequency of workshops where workshops are being delivered. The study also provides unique insights into the experiences and opinions of primary care community dietitians regarding the development and delivery of weaning workshops in terms of optimal content and delivery options. These perspectives will make a valuable contribution given the dearth of evidence in this area internationally.

Neurophysiological and behavioral effects of multisession prefrontal tDCS and concurrent cognitive remediation training in patients with autism spectrum disorder (ASD): A double-blind, randomized controlled fNIRS study.

BACKGROUND: The clinical effects and neurophysiological mechanisms of prefrontal tDCS and concurrent cognitive remediation training in individuals with autism spectrum disorder (ASD) remain unclear. OBJECTIVE: This two-armed, double-blind, randomized, sham-controlled trial aimed to investigate the beneficial effects of tDCS combined with concurrent cognitive remediation training on adolescents and young adults with ASD. METHODS: Participants were randomly assigned to either active or sham tDCS groups and received 1.5 mA prefrontal tDCS with left dorsolateral prefrontal cortex (dlPFC) cathode placement and right supraorbital region anode placement for 20 minutes over two consecutive weeks. tDCS was delivered concurrently with a computerized cognitive remediation training program. Social functioning and its underlying cognitive processes, as well as prefrontal resting-state functional connectivity (rsFC), were measured. RESULTS: The results from 41 participants indicated that multisession prefrontal tDCS, compared to sham tDCS, significantly enhanced the social functioning of ASD individuals [F(1,39) = 4.75, p = .035, ηp2 = 0.11]. This improvement was associated with enhanced emotion recognition [F(1,39) = 8.34, p = .006, ηp2 = 0.18] and cognitive flexibility [F(1,39) = 4.91, p = .033, ηp2 = 0.11]. Specifically, this tDCS protocol optimized information processing efficiency [F(1,39) = 4.43, p = .042, ηp2 = 0.10], and the optimization showed a trend to be associated with enhanced rsFC in the right medial prefrontal cortex (ρ = 0.339, pFDR = .083). CONCLUSION: Multisession tDCS with left dlPFC cathode placement and right supraorbital region anode placement paired with concurrent cognitive remediation training promoted social functioning in individuals with ASD. This appeared to be associated with the enhancement of the functional connectivity of the right medial PFC, a major hub for flexible social information processing, allowing these individuals to process information more efficiently in response to different social situations. TRIAL REGISTRATION: ClinicalTrials.gov (ID: NCT03814083).

Genetic Overlap Between Attention Deficit/Hyperactivity Disorder and Autism Spectrum Disorder in SHANK2 Gene.

Background: Recent findings indicated a high comorbidity between attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), as well as shared genetic influences on them. The latter might contribute at least partly to the former clinical scenario. This study aimed at investigating whether SHANK genes were potential pleiotropic genes to the two said disorders, underlying their genetic overlap. Methods: This study recruited 298 boys with ADHD (including 256 family trios of 1 ADHD boy and his 2 biological parents), 134 boys with ASD, 109 boys with both ADHD and ASD, and 232 typically developing boys as community controls. They were aged between 6 and 11 years old. Results: There was no significant difference in allele frequency of a number of single nucleotide polymorphisms (SNPs) in SHANK2/SHANK3 between the three clinical groups (ADHD, ASD, and ADHD + ASD) and between the two control groups (community controls and pseudo-controls), respectively. The three clinical groups and the two control groups were thus, respectively, combined. A comparison between the two aggregated samples identified significant evidence of disease association for three SHANK2 SNPs with both ADHD and ASD, even after multiple testing correction: rs11236616 (OR = 0.762, permuted p = 0.0376), rs7106631 (OR = 0.720, permuted p = 0.0034), and rs9888288 (OR = 0.770, permuted p = 0.0407). Comparisons among individual groups pointed to a similar trend of findings. Conclusion: SHANK2 could be considered a potential pleiotropic gene underlying the genetic overlap between ADHD and ASD. This might contribute partly to their high comorbidity in the afflicted children.

Gastrointestinal Problems in Chinese Children with Autism Spectrum Disorder.

PURPOSE: Gastrointestinal symptoms in individuals with autism spectrum disorder may constitute a subgroup with complex gut-brain interactions underlying the pathogenesis. This study examined the prevalence of gastrointestinal symptoms in a sample of Chinese children with autism spectrum disorder, as well as the factors related to them. PARTICIPANTS AND METHODS: The participants included a clinic sample of 107 children with autism spectrum disorder and 249 gender- and age-matched typically developing community children. RESULTS: Results found children with autism spectrum disorder to be twice as likely to suffer from gastrointestinal symptoms, reporting increased rates of constipation, abdominal migraine and aerophagia. Autism spectrum disorder diagnosis remained a significant predictor of gastrointestinal symptoms after taking into account the potential confounders that included comorbid psychopathologies, diets, and parental anxiety and depression. CONCLUSION: Our results suggest that autism spectrum disorder with gastrointestinal symptoms may constitute a subgroup within the autism spectrum disorder population that warrants further investigation.

Prevalence of Anxiety Disorders in Hong Kong Chinese Children With ADHD.

OBJECTIVE: This study examined the prevalence and correlates of anxiety disorders in Chinese children with ADHD. METHOD: Overall, 120 children with ADHD aged 6 to 12 years were recruited, and the parent version of computerized Diagnostic Interview Schedule for Children-Version 4 was administrated to their primary caretakers. RESULTS: The prevalence rate of anxiety disorders was 27.5%, which is consistent with the reports of previous Asian and Western studies. Among the children with ADHD and anxiety disorders, more than 50% of them also had comorbid oppositional defiant disorder or conduct disorder (ODD/CD), which yielded an adjusted odds ratio of 3.0 in multivariable analysis for anxiety disorder, with comorbid ODD/CD. In addition, anxiety disorders were positively associated with inattention symptoms in children with both disorders. CONCLUSION: Clinicians should perform screening and careful assessment for anxiety symptoms in children with ADHD, particularly those suffering from comorbid ODD/CD.

Ambient and Dosed Exposure to Quaternary Ammonium Disinfectants Causes Neural Tube Defects in Rodents.

BACKGROUND: Quaternary ammonium compounds are a large class of chemicals used for their antimicrobial and antistatic properties. Two common quaternary ammonium compounds, alkyldimethylbenzyl ammonium chloride (ADBAC) and didecyldimethyl ammonium chloride (DDAC), are combined in common cleaners and disinfectants. Introduction of a cleaner containing ADBAC+DDAC in the vivarium caused neural tube defects (NTDs) in mice and rats. METHODS: To further evaluate this finding, male and female mice were dosed in the feed at 60 or 120 mg/kg/day, or by oral gavage at 7.5, 15, or 30 mg/kg ADBAC+DDAC. Mice also received ambient exposure to ADBAC+DDAC from the disinfectant used in the mouse room. Embryos were evaluated on gestational day 10 for NTDs, and fetuses were evaluated on gestational day 18 for gross and skeletal malformations. RESULTS: We found increased NTDs with exposure to ADBAC+DDAC in both rats and mice. The NTDs persisted for two generations after cessation of exposure. Notably, male exposure alone was sufficient to cause NTDs. Equally significant, ambient exposure from disinfectant use in the vivarium, influenced the levels of NTDs to a greater extent than oral dosing. No gross or significant axial skeletal malformations were observed in late gestation fetuses. Placental abnormalities and late gestation fetal deaths were increased at 120 mg/kg/day, which might explain the lack of malformations observed in late gestation fetuses. CONCLUSION: These results demonstrate that ADBAC+DDAC in combination are teratogenic to rodents. Given the increased use of these disinfectants, further evaluation of their safety in humans and their contribution to health and disease is essential. Birth Defects Research 109:1166-1178, 2017. © 2017 The Authors. Birth Defects Research Published by Wiley Periodicals, Inc.

Prevalence of motor problems in children with attention deficit hyperactivity disorder in Hong Kong.

INTRODUCTION: Local data on the occurrence of motor problems in children with attention deficit hyperactivity disorder are not available but an understanding of this important issue may enable better planning of medical services. We aimed to determine the prevalence of motor problems in children with attention deficit hyperactivity disorder in a local population. METHODS: In this descriptive cross-sectional study, children aged 6 to 9 years diagnosed with attention deficit hyperactivity disorder over a period of 6 months from 1 July to 31 December 2011 were recruited from the Joint Paediatric and Child Psychiatric ADHD Program in New Territories East Cluster in Hong Kong. Movement Assessment Battery for Children and Developmental Coordination Disorder Questionnaire-Chinese version were used to determine the presence of motor problems. RESULTS: Data from 95 participants were included in the final analysis. The number of children who had no, borderline, or definite motor problems was 63, 15, and 17, respectively. It is estimated that up to one third of local children with attention deficit hyperactivity disorder might have developmental coordination disorder. CONCLUSIONS: Motor problems are common in local children with attention deficit hyperactivity disorder and figures are comparable with those from other parts of the world. Despite the various limitations of this study, the magnitude of the problem should not be overlooked.

Quaternary ammonium disinfectants cause subfertility in mice by targeting both male and female reproductive processes.

Alkyl dimethyl benzyl ammonium chloride (ADBAC) and didecyl dimethyl ammonium chloride (DDAC) are common ingredients in household bathroom and kitchen cleaning sprays. ADBAC+DDAC cause reproductive toxicity in mice. The aim of the present study was to investigate gender-specific reproductive effects from ADBAC+DDAC. Female reproduction was assessed through ovulation, oocyte implantation, and estrus cycling. Male reproductive function was assessed by sperm concentration, motility, and viability. Numbers of corpora lutea were not different after 2 weeks, but decreased after 8 weeks of ADBAC+DDAC exposure. Dams exposed for 5 weeks to ADBAC+DDAC spent significantly less time in estrus. ADBAC+DDAC exposed males exhibited declines in both sperm concentration and motility, but not sperm viability. Subfertility in mice from ADBAC+DDAC exposure is, therefore, mediated through reproductive disturbances in both females and males. While the effect of ADBAC+DDAC exposure on human health is unclear, widespread exposure necessitates further consideration of their potential reproductive toxicity.

Validation of the Developmental, Dimensional and Diagnostic Interview (3Di) Among Chinese Children in a Child Psychiatry Clinic in Hong Kong.

Autism spectrum disorder (ASD) is a disorder with high levels of co-morbidities. The Developmental, Dimensional and Diagnostic Interview (3 Di) is a relatively new instrument designed to provide dimensional as well as categorical assessment of autistic behaviours among children with normal intelligence. Its sound psychometric properties and relatively short administration time make it a versatile instrument. The 3 Di was translated into Chinese (Cantonese) and its applicability among 194 clinic children was examined. Results found excellent reliability and validity, and achieved a sensitivity of 95% and specificity of 77%. It was able to capture the diagnosis of ASD among children presenting with attention deficit hyperactivity disorder. However, although the disorder of ASD is considered universal, the use of a western instrument in a Chinese context should also take note of cultural influences that may impact on the manifestation of its symptoms.

In vitro demonstration of the heavy-atom effect for photodynamic therapy.

Photodynamic therapy (PDT) is an emerging treatment modality for a range of disease classes, both cancerous and noncancerous. This has brought about an active pursuit of new PDT agents that can be optimized for the unique set of photophysical characteristics that are required for a successful clinical agent. We now describe a totally new class of PDT agent, the BF2-chelated 3,5-diaryl-1H-pyrrol-2-yl-3,5-diarylpyrrol-2-ylideneamines (tetraarylazadipyrromethenes). Optimized synthetic procedures have been developed to facilitate the generation of an array of specifically substituted derivatives to demonstrate how control of key therapeutic parameters such as wavelength of maximum absorbance and singlet-oxygen generation can be achieved. Photosensitizer absorption maxima can be varied within the body's therapeutic window between 650 and 700 nm, with high extinction coefficients ranging from 75,000 to 85,000 M(-1) cm(-1). Photosensitizer singlet-oxygen generation level was modulated by the exploitation of the heavy-atom effect. An array of photosensitizers with and without bromine atom substituents gave rise to a series of compounds with varying singlet-oxygen generation profiles. X-ray structural evidence indicates that the substitution of the bromine atoms has not caused a planarity distortion of the photosensitizer. Comparative singlet-oxygen production levels of each photosensitizer versus two standards demonstrated a modulating effect on singlet-oxygen generation depending upon substituent patterns about the photosensitizer. Confocal laser scanning microscopy imaging of 18a in HeLa cervical carcinoma cells proved that the photosensitizer was exclusively localized to the cellular cytoplasm. In vitro light-induced toxicity assays in HeLa cervical carcinoma and MRC5-SV40 transformed fibroblast cancer cell lines confirmed that the heavy-atom effect is viable in a live cellular system and that it can be exploited to modulate assay efficacy. Direct comparison of the efficacy of the photosensitizers 18b and 19b, which only differ in molecular structure by the presence of two bromine atoms, illustrated an increase in efficacy of more than a 1000-fold in both cell lines. All photosensitizers have very low to nondeterminable dark toxicity in our assay system.

An unusual cause of neonatal respiratory distress.

Nasal cysts representing cystic extension of the nasolacrimal duct are a rare cause of nasal obstruction and respiratory distress in neonates. A medial canthal mass, epiphora, dacryocystitis or preseptal/orbital cellulitis are the usual presenting symptoms; however, this case shows that patients may present with eye findings so minimal as to be overlooked.

Expression of ADAM-9 mRNA and protein in human breast cancer.

The ADAMs (a disintegrin and metalloprotease) are membrane proteins containing both protease and adhesion domains and thus may be potentially important in cancer invasion and metastasis. The aim of our study was to investigate the distribution and potential clinical significance of ADAM-9 in breast cancer. ADAM-9 expression was measured using both reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. ADAM-9 mRNA was expressed more frequently in both breast carcinomas (72/110, 66%) and fibroadenomas (21/38, 55%) compared to normal breast tissue (6/25, 24%) (p = 0.0004, p = 0.028, respectively). Multiple forms of ADAM-9 protein were detected by Western blotting, i.e., at 124, 84 and 48 kDa under reducing conditions and at 115, 76, 55, 52 and 46 kDa under nonreducing conditions. The 84 and 55 kDa forms were detected more frequently in the primary cancers compared to normal breast tissue (p < 0.0001, p = 0.0002, respectively). In addition, relative levels of the 84 kDa mature form were significantly higher in the primary cancers than in the fibroadenomas (p = 0.003), while the reverse was found for the 124 kDa precursor form (p = 0.026). In the carcinomas, the 84 kDa form of ADAM-9 protein was expressed at higher levels in node-positive than node-negative cancers (p = 0.05) and correlated positively with HER-2/neu protein levels (r = 0.313, p = 0.016). This is the first report to describe expression of any ADAM in a large number of human carcinomas.

The ADAMs family of proteins: from basic studies to potential clinical applications.

The ADAMs are a family of membrane proteins possessing a disintegrin and metalloprotease domain. Currently, 34 members are known to exist. Approximately 50% of the ADAMs contain a metalloprotease-like domain and some of these have been shown to possess protease activity. Most of the protein substrates identified to date for ADAMs are either integral membrane or extracellular matrix (ECM) proteins. In addition to hydrolysing proteins, a number of ADAMs bind to integrins. The attachment to integrins occurs via the disintegrin domain. Since the ADAMs can play a role in both proteolysis and adhesion, they have been implicated in a variety of biological processes such as sperm-egg fusion, somatic cell-cell adhesion, ectodomain shedding, myoblast fusion and development. Altered expression of certain ADAMs has been associated with a number of diseases including asthma, arthritis, Alzheimer's disease, atherosclerosis and cancer.