Sleep problems in children with autism spectrum disorder in Hong Kong: a cross-sectional study

BackgroundAutism spectrum disorder (ASD) is a neurodevelopmental disorder with a growing prevalence of sleep problems associated with significant behavioral problems and more severe autism clinical presentation. Little is known about the relationships between autism traits and sleep problems in Hong Kong. Therefore, this study aimed to examine whether children with autism have increased sleep problems than non-autistic children in Hong Kong. The secondary objective was to examine the factors associated with sleep problems in an autism clinical sample.MethodsThis cross-sectional study recruited 135 children with autism and 102 with the same age range of non-autistic children, aged between 6 and 12 years. Both groups were screened and compared on their sleep behaviors using the Children's Sleep Habits Questionnaire (CSHQ).ResultsChildren with autism had significantly more sleep problems than non-autistic children [t(226.73) = 6.20, p < 0.001]. Bed -sharing [beta = 0.25, t(165) = 2.75, p = 0.07] and maternal age at birth [beta = 0.15, t(165) = 2.05, p = 0.043] were significant factors associated with CSHQ score on the top of autism traits. Stepwise linear regression modeling identified that only separation anxiety disorder (beta = 4.83, t = 2.40, p = 0.019) best-predicted CSHQ.ConclusionIn summary, autistic children suffered from significantly more sleep problems and co-occurring separation anxiety disorder brings greater sleep problems as compared to non-autistic children. Clinicians should be more aware of sleep problems to provide more effective treatments to children with autism

Prevalence and correlates of subjective cognitive impairment in Chinese psychiatric patients during the fifth wave of COVID-19 in Hong Kong

IntroductionThe extent of cognitive impairment and its association with psychological distress among people with pre-existing mental illness during COVID-19 is understudied. This study aimed to investigate prevalence and correlates of subjective cognitive impairment (SCI) in Chinese psychiatric patients during fifth-wave of COVID-19 in Hong Kong (HK).MethodsFour-hundred-eight psychiatric outpatients aged 18–64 years were assessed with questionnaires between 28 March and 8 April 2022, encompassing illness profile, psychopathological symptoms, coping-styles, resilience, and COVID-19 related factors. Participants were categorized into moderate-to-severe and intact/mild cognitive impairment (CI+ vs. CI-) groups based on severity of self-reported cognitive complaints. Univariate and multivariate regression analyses were conducted to determine variables associated with CI+ status.ResultsOne-hundred-ninety-nine participants (48.8%) experienced CI+. A multivariate model on psychopathological symptoms found that depressive and post-traumatic-stress-disorder (PTSD)-like symptoms were related to CI+, while a multivariate model on coping, resilience and COVID-19 related factors revealed that avoidant coping, low resilience and more stressors were associated with CI+. Final combined model demonstrated the best model performance and showed that more severe depressive and PTSD-like symptoms, and adoption of avoidant coping were significantly associated with CI+.ConclusionAlmost half of the sample of psychiatric patients reported cognitive complaints during fifth-wave of COVID-19 in HK. Greater depressive and PTSD-like symptom severity, and maladaptive (avoidant) coping were found as correlates of SCI. COVID-19 related factors were not independently associated with SCI in psychiatric patients. Early detection with targeted psychological interventions may therefore reduce psychological distress, and hence self-perceived cognitive difficulties in this vulnerable population

Meta-analysis Followed by Replication Identifies Loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as Associated with Systemic Lupus Erythematosus in Asians

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic involvement and ethnic differences. Susceptibility genes identified so far only explain a small portion of the genetic heritability of SLE, suggesting that many more loci are yet to be uncovered for this disease. In this study, we performed a meta-analysis of genome-wide association studies on SLE in Chinese Han populations and followed up the findings by replication in four additional Asian cohorts with a total of 5,365 cases and 10,054 corresponding controls. We identified genetic variants in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with the disease. These findings point to potential roles of cell-cycle regulation, autophagy, and DNA demethylation in SLE pathogenesis. For the region involving TET3 and that involving CDKN1B, multiple independent SNPs were identified, highlighting a phenomenon that might partially explain the missing heritability of complex diseases

Rhinovirus-Induced Major Airway Mucin Production Involves a Novel TLR3-EGFR–Dependent Pathway

Mucociliary clearance is a critical innate defense system responsible for clearing up invading pathogens including bacteria and virus. Although the right amount of mucus is good, excessive mucus causes airway obstruction and tends to precipitate disease symptoms. Rhinovirus (RV) is a common cold virus that causes asthma and chronic obstructive pulmonary disease exacerbation. Mucus overproduction has been linked to the pathogenesis of RV-induced diseases and disease exacerbations. However, the molecular mechanism is not clear. In this study, using one of the major airway mucin-MUC5AC as marker, we found that both major and minor groups of RV induced mucin production in primary human epithelial cells and cell line. RV1A (a minor group of RV) could induce mucous cell metaplasia in vivo. Viral replication was needed for RV-induced mucin expression, and this induction was also dependent on TLR3, suggesting the involvement of double-stranded (ds) RNA signaling. Indeed, dsRNA alone could also induce mucin expression. TLR3-mediated mucin induction was negatively regulated by MyD88, and only partially dependent on TRIF, which suggests a departure from well-documented TLR3 signaling paradigm that mediates inflammatory and other innate defense gene inductions. In addition, TLR3 signaling activated epidermal growth factor receptor (EGFR) through inductions of the expression of EGFR ligands (transforming growth factor-α and amphiregulin), which in turn activated EGFR-ERK signaling and mucin expression through an autocrine/paracrine loop. This novel coupling of antiviral defense machinery (i.e., TLR3) and major epithelial proliferation/repair pathway (i.e., EGFR) might play an important role in viral-induced airway remodeling and airway disease exacerbation

Vanadium pentoxide (V2O5) induced mucin production by airway epithelium

Exposure to environmental pollutants has been linked to various airway diseases and disease exacerbations. Almost all chronic airway diseases such as chronic obstructive pulmonary disease and asthma are caused by complicated interactions between gene and environment. One of the major hallmarks of those diseases is airway mucus overproduction (MO). Excessive mucus causes airway obstruction and significantly increases morbidity and mortality. Metals are major components of environmental particulate matters (PM). Among them, vanadium has been suggested to play an important role in PM-induced mucin production. Vanadium pentoxide (V2O5) is the most common commercial source of vanadium, and it has been associated with occupational chronic bronchitis and asthma, both of which are MO diseases. However, the underlying mechanism is not entirely clear. In this study, we used both in vitro and in vivo models to demonstrate the robust inductions of mucin production by V2O5. Furthermore, the follow-up mechanistic study revealed a novel v-raf-1 murine leukemia viral oncogene homolog 1-IKK-NF-κB pathway that mediated V2O5-induced mucin production. Most interestingly, the reactive oxygen species and the classical mucin-inducing epidermal growth factor receptor (EGFR)-MAPK pathway appeared not to be involved in this process. Thus the V2O5-induced mucin production may represent a novel EGFR-MAPK-independent and environmental toxicant-associated MO model. Complete elucidation of the signaling pathway in this model will not only facilitate the development of the treatment for V2O5-associated occupational diseases but also advance our understanding on the EGFR-independent mucin production in other chronic airway diseases

Rhinovirus Induces Airway Epithelial Gene Expression through Double-Stranded RNA and IFN-Dependent Pathways

Rhinovirus (RV) infection is the major cause of common colds and of asthma exacerbations. Because the epithelial cell layer is the primary target of RV infection, we hypothesize that RV-induced airway disease is associated with the perturbation of airway epithelial gene expression. In this study, well differentiated primary human airway epithelial cells were infected with either RV16 (major group) or RV1B (minor group). Transcriptional gene profiles from RV-infected and mock-infected control cells were analyzed by Affymetrix Genechip, and changes of the gene expression were confirmed by real-time RT-PCR analysis. At 24 h after infection, 48 genes induced by both viruses were identified. Most of these genes are related to the IFN pathway, and have been documented to have antiviral functions. Indeed, a significant stimulation of IFN-β secretion was detected after RV16 infection. Neutralizing antibody specific to IFN-β and a specific inhibitor of the Janus kinase pathway both significantly blocked the induction of RV-inducible genes. Further studies demonstrated that 2-aminopurine, a specific inhibitor double-stranded RNA–dependent protein kinase, could block both IFN-β production and RV-induced gene expression. Thus, IFN-β–dependent pathway is a part of the double-stranded RNA–initiated pathway that is responsible for RV-induced gene expression. Consistent with its indispensable role in the induction of antiviral genes, deactivation of this signaling pathway significantly enhanced viral production. Because increase of viral yield is associated with the severity of RV-induced airway illness, the discovery of an epithelial antiviral signaling pathway in this study will contribute to our understanding of the pathogenesis of RV-induced colds and asthma exacerbations

Involvement of adenosine in depression of synaptic transmission during hypercapnia in isolated spinal cord of neonatal rats

Adenosine is one of the most important neuromodulators in the CNS, both under physiological and pathological conditions. In the isolated spinal cord of the neonatal rat in vitro, acute hypercapnic acidosis (20% CO(2), pH 6.7) reversibly depressed electrically evoked spinal reflex potentials. This depression was partially reversed by 8-cyclopentlyl-1,3-dimethylxanthine (CPT), a selective A(1) adenosine receptor antagonist. Isohydric hypercapnia (20% CO(2), pH 7.3), but not isocapnic acidosis (5% CO(2), pH 6.7), depressed the reflex potentials, which were also reversed by CPT. An ecto-5′-nucleotidase inhibitor did not affect the hypercapnic acidosis-evoked depression. An inhibitor of adenosine kinase, but not deaminase, mimicked the inhibitory effect of hypercapnic acidosis on the spinal reflex potentials. Accumulation of extracellular adenosine and inhibition of adenosine kinase activity were caused by hypercapnic acidosis and isohydric hypercapnia, but not isohydric acidosis. These results indicate that the activation of adenosine A(1) receptors is involved in the hypercapnia-evoked depression of reflex potentials in the isolated spinal cord of the neonatal rat. The inhibition of adenosine kinase activity is suggested to cause the accumulation of extracellular adenosine during hypercapnia

Table_1_Relationships between psychopathological symptoms, pandemic-related stress, perceived social support, and COVID-19 infection history: a network analysis in Chinese college students.docx

IntroductionPrevious coronavirus, 2019 (COVID-19) research has applied network analysis to examine relationships between psychopathological symptoms but rarely extended to potential risk and protective factors or the influence of COVID-19 infection history. This study examined complex inter-relationships between psychopathological symptoms, COVID-19–related stressors, perceived social support, and COVID-19 infection history among Chinese university/college students during the peak of fifth pandemic wave using a network analysis approach.MethodsA Least Absolute Shrinkage and Selection Operator–regularized partial correlation network using Gaussian graphical model was constructed in 1,395 Chinese university/college students in Hong Kong who completed a survey between 15 March and 3 April, 2022. Depressive, anxiety, and acute/traumatic stress symptoms were measured by Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and Impact of Event Scale-6, respectively. COVID-19–related stressors and perceived social support were measured. Network differences by COVID-19 infection history (COVID-network vs. no_COVID-network) and network communities were examined.ResultsOur results showed that the most influential nodes were depressed mood, uncontrollable worries, and uncontrollable thoughts about COVID-19. The main bridging symptoms were concentration problems and psychomotor problems. The COVID-network, comprising participants with a history of COVID-19 infection only, was significantly stronger than the no_COVID-network. Perceived social support and stress from conflicts with family/friends formed a unique community with negative cognition and suicidal idea in the COVID-network only.ConclusionOur findings indicate that specific interventions targeting interpersonal conflicts and concentration problems as well as facilitating stress buffering effects of social support may represent effective strategies to reduce psychological distress in university/college students during COVID-19 and should be considered for future pandemic preparedness.</p