Initial updosing phase of oral immunotherapy improves quality of life and psychological burden in parents of children with food allergy.

Background: Oral immunotherapy (OIT) can impose psychological burdens on patients and their parents due to the necessary preparations and repeated adverse reactions. Objective: To investigate changes in quality of life (QoL) and psychological burden in parents of children receiving OIT for food allergy (FA). Methods: Children aged 3-13 years with FA were enrolled. Parents were asked to fill out the Korean versions of the Food Allergy Quality of Life-Parental Burden (FAQL-PB), the Korean versions of the Food Allergy Quality of Life-Parental Form (K-FAQLQ-PF), the Korean versions of the Beck Anxiety Inventory (K-BAI), and the Korean version of the Patient Health Questionnaire-9 (PHQ-9) for depression before OIT (T1), after 2 months of updosing (T2), and after the end of the updosing phase (T3). Results: A total of 111 parents were enrolled. The total FAQL-PB scores were decreased at T2 and T3 compared with those at T1 (all p < 0.001). Greater improvement in the total FAQL-PB score at T2 was noted in parents with a higher parental burden (FAQL-PB score ≥ 74 points) at baseline than in those with a lower parental burden (p = 0.001). Among the K-FAQLQ-PF domains, "food anxiety" scores were decreased at T2 and T3 compared with those at T1 (p = 0.049 and p = 0.030, respectively), whereas there was no change in "social and dietary limitation" and "emotional impact" scores between T1 and T2 and between T1 and T3. However, no differences were observed in K-BAI and PHQ-9 scores between T1 and T2 and between T1 and T3. Conclusion: Our results suggest that OIT improves parental burden and QoL in parents of children with FA.

Effects of functional polymorphisms of opioid receptor mu 1 and catechol-O-methyltransferase on the neural processing of pain.

AIM: Pain is reconstructed by brain activities and its subjectivity comes from an interplay of multiple factors. The current study aims to understand the contribution of genetic factors to the neural processing of pain. Focusing on the single-nucleotide polymorphism (SNP) of opioid receptor mu 1 (OPRM1) A118G (rs1799971) and catechol-O-methyltransferase (COMT) val158met (rs4680), we investigated how the two pain genes affect pain processing. METHOD: We integrated a genetic approach with functional neuroimaging. We extracted genomic DNA information from saliva samples to genotype the SNP of OPRM1 and COMT. We used a percept-related model, in which two different levels of perceived pain intensities ("low pain: mildly painful" vs "high pain: severely painful") were employed as experimental stimuli. RESULTS: Low pain involves a broader network relative to high pain. The distinct effects of pain genes were observed depending on the perceived pain intensity. The effects of low pain were found in supramarginal gyrus, angular gyrus, and anterior cingulate cortex (ACC) for OPRM1 and in middle temporal gyrus for COMT. For high pain, OPRM1 affected the insula and cerebellum, while COMT affected the middle occipital gyrus and ACC. CONCLUSION: OPRM1 primarily affects sensory and cognitive components of pain processing, while COMT mainly influences emotional aspects of pain processing. The interaction of the two pain genes was associated with neural patterns coding for high pain and neural activation in the ACC in response to pain. The proteins encoded by the OPRM1 and COMT may contribute to the firing of pain-related neurons in the human ACC, a critical center for subjective pain experience.

Neural representations of the perception of handwritten digits and visual objects from a convolutional neural network compared to humans.

We investigated neural representations for visual perception of 10 handwritten digits and six visual objects from a convolutional neural network (CNN) and humans using functional magnetic resonance imaging (fMRI). Once our CNN model was fine-tuned using a pre-trained VGG16 model to recognize the visual stimuli from the digit and object categories, representational similarity analysis (RSA) was conducted using neural activations from fMRI and feature representations from the CNN model across all 16 classes. The encoded neural representation of the CNN model exhibited the hierarchical topography mapping of the human visual system. The feature representations in the lower convolutional (Conv) layers showed greater similarity with the neural representations in the early visual areas and parietal cortices, including the posterior cingulate cortex. The feature representations in the higher Conv layers were encoded in the higher-order visual areas, including the ventral/medial/dorsal stream and middle temporal complex. The neural representations in the classification layers were observed mainly in the ventral stream visual cortex (including the inferior temporal cortex), superior parietal cortex, and prefrontal cortex. There was a surprising similarity between the neural representations from the CNN model and the neural representations for human visual perception in the context of the perception of digits versus objects, particularly in the primary visual and associated areas. This study also illustrates the uniqueness of human visual perception. Unlike the CNN model, the neural representation of digits and objects for humans is more widely distributed across the whole brain, including the frontal and temporal areas.

The effects of epigenetic age and its acceleration on surface area, cortical thickness, and volume in young adults.

DNA methylation age has been used in recent studies as an epigenetic marker of accelerated cellular aging, whose contribution to the brain structural changes was lately acknowledged. We aimed to characterize the association of epigenetic age (i.e. estimated DNA methylation age) and its acceleration with surface area, cortical thickness, and volume in healthy young adults. Using the multi-tissue method (Horvath S. DNA methylation age of human tissues and cell types. 2013. Genome Biol 14), epigenetic age was computed with saliva sample. Epigenetic age acceleration was derived from residuals after adjusting epigenetic age for chronological age. Multiple regression models were computed for 148 brain regions for surface area, cortical thickness, and volume using epigenetic age or accelerated epigenetic age as a predictor and controlling for sex. Epigenetic age was associated with surface area reduction of the left insula. It was also associated with cortical thinning and volume reduction in multiple regions, with prominent changes of cortical thickness in the left temporal regions and of volume in the bilateral orbital gyri. Finally, accelerated epigenetic age was negatively associated with right cuneus gyrus volume. Our findings suggest that understanding the mechanisms of epigenetic age acceleration in young individuals may yield valuable insights into the relationship between epigenetic aging and the cortical change and on the early development of neurocognitive pathology among young adults.

Psychological Distress and Perceived Burden in Parents of Korean Children With IgE-Mediated Food Allergy.

BACKGROUND: Food allergy (FA) can have a profound effect on quality of life (QoL), stress, and anxiety in the family. We aimed to validate the Korean version of the Food Allergy Quality of Life-Parental Burden (FAQL-PB) and identify factors related to the parental psychosocial burden of caring for children with FAs. METHODS: Parents of children aged between 6 months and 17 years with immunoglobulin E (IgE)-mediated FAs from the Pediatric Allergy Department of five university hospitals in Korea were enrolled in the study. Parents were asked to complete the FAQL-PB, Food Allergy Independent Measure-Parent Form (FAIM-PF), Child Health Questionnaire-Parents Form 28 (CHQ-PF28), Beck's Anxiety Inventory, Connor-Davidson Resilience Scale, and Patient Health Questionnaire-9 for depression. Statistical analyses included internal consistency, test-retest reliability, concurrent validity, discriminative validity, and logistic regression analyses. RESULTS: A total of 190 parents were enrolled. Social activity limitation was the item with the highest FAQL-PB scores. The Cronbach's α for each item was higher than 0.8. The test-retest reliability was good (intra-class correlation coefficient, 0.716; 95% confidence interval [CI], 0.100-0.935). An increase in the FAQL-PB was significantly associated with an increase in the FAIM-PF (ß = 0.765, P < 0.001) (concurrent validity). There was a positive correlation between parental burden, anxiety, and depression, while resilience was inversely correlated with parental burden (all P < 0.001). The total FAQL-PB score in parents of children who had experienced anaphylaxis was significantly higher than that in parents of children who did not experience it (P = 0.008). When adjusting for age, sex, and underlying diseases, anaphylaxis (ß = 9.32; 95% CI, 2.97 to 15.68), cow's milk (CM) allergy (ß = 8.24; 95% CI, 2.04 to 14.44), soybean allergy (ß = 13.91; 95% CI, 1.62 to 26.20), higher anxiety (ß = 1.05; 95% CI, 0.07 to 1.41), higher depression (ß = 2.15; 95% CI, 1.61 to 2.69), and lower resilience (ß = -0.42; 95% CI, -0.61 to -0.2) were significantly associated with greater parental burden in children with IgE-mediated FAs. CONCLUSION: FAQL-PB is a reliable and valid tool for use in Korea. Anaphylaxis, CM or soybean allergies, more anxiety and depression symptoms, and lower resilience are associated with poorer QoL in parents of children with FAs.

Extracellular vesicles from IFN-γ-primed mesenchymal stem cells repress atopic dermatitis in mice.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by immune dysregulation, pruritus, and abnormal epidermal barrier function. Compared with conventional mesenchymal stem cell (MSC), induced pluripotent stem cell (iPSC)-derived mesenchymal stem cell (iMSC) is recognized as a unique source for producing extracellular vesicles (EVs) because it can be obtained in a scalable manner with an enhanced homogeneity. Stimulation of iMSCs with inflammatory cytokines can improve the immune-regulatory, anti-inflammatory, and tissue-repairing potential of iMSC-derived EVs. RESULTS: Proteome analysis showed that IFN-γ-iMSC-EVs are enriched with protein sets that are involved in regulating interferon responses and inflammatory pathways. In AD mice, expression of interleukin receptors for Th2 cytokines (IL-4Rα/13Rα1/31Rα) and activation of their corresponding intracellular signaling molecules was reduced. IFN-γ-iMSC-EVs decreased itching, which was supported by reduced inflammatory cell infiltration and mast cells in AD mouse skin; reduced IgE receptor expression and thymic stromal lymphopoietin and NF-kB activation; and recovered impaired skin barrier, as evidenced by upregulation of key genes of epidermal differentiation and lipid synthesis. CONCLUSIONS: IFN-γ-iMSC-EVs inhibit Th2-induced immune responses, suppress inflammation, and facilitate skin barrier restoration, contributing to AD improvement.

Clinical Characteristics of Atopic Dermatitis in Korean School-Aged Children and Adolescents According to Onset Age and Severity.

BACKGROUND: Atopic dermatitis (AD) is a heterogeneous disease with different age of onset, disease course, clinical symptoms, severity, and risk of comorbidity. The characteristics of children with AD also vary by age or country. However, little is known about the clinical characteristics of AD in Korean school-aged children and adolescents. Furthermore, there are few studies on phenotypic differences according to onset age. This study aimed to explore the clinical characteristics and phenotypes according to onset age and severity of AD in children and adolescents in Korea. METHODS: AD patients aged 6-18 years who presented to 18 hospitals nationwide were surveyed. The patients were examined for disease severity by pediatric allergy specialists, and data on history of other allergic diseases, familial allergy history, onset age, trigger factors, lesion sites, treatment history and quality of life were collected. The results of the patient's allergy test were also analyzed. The patients were classified into infancy-onset (< 2 years of age), preschool-onset (2-5 years of age), and childhood-onset (≥ 6 years of age) groups. Study population was analyzed for clinical features according to onset-age groups and severity groups. RESULTS: A total of 258 patients with a mean age of 10.62 ± 3.18 years were included in the study. Infancy-onset group accounted for about 60% of all patients and presented significantly more other allergic diseases, such as allergic rhinitis and asthma (P = 0.002 and P = 0.001, respectively). Food allergy symptoms and diagnoses were highly relevant to both earlier onset and more severe group. Inhalant allergen sensitization was significantly associated with both infancy-onset group and severe group (P = 0.012 and P = 0.024, respectively). A family history of food allergies was significantly associated with infancy-onset group (P = 0.036). Severe group was significantly associated with a family history of AD, especially a paternal history of AD (P = 0.048 and P = 0.004, respectively). Facial (periorbital, ear, and cheek) lesions, periauricular fissures, hand/foot eczema, and xerosis were associated with infancy-onset group. The earlier the onset of AD, the poorer the quality of life (P = 0.038). Systemic immunosuppressants were used in only 9.6% of the patients in the severe group. CONCLUSION: This study analyzed the clinical features of AD in Korean children and adolescents through a multicenter nationwide study and demonstrated the phenotypic differences according to onset age and severity. Considering the findings that the early-onset group is more severe and accompanied by more systemic allergic diseases, early management should be emphasized in young children and infants.

Natural Course and Prognostic Factors of Immediate-Type Peanut Allergy in Children.

BACKGROUND: Predicting food allergy resolution is essential to minimize the number of restricted foods in children. However, there have been no studies on the natural history of peanut allergy (PA) in Korea. OBJECTIVE: This study aimed to evaluate the natural course and prognostic factors of immediate-type PA in children till the age of 10 years. METHODS: We retrospectively collected data of 122 children who developed PA before 60 months of age from 3 tertiary hospitals in Korea. Diagnosis and resolution of PA was defined as an oral food challenge test or a convincing history of symptoms within 2 h after peanut ingestion. The prognostic factors for resolution of PA were identified using the Cox proportional hazard model. RESULTS: The median (interquartile range) age at diagnosis was 2.0 (1.3-3.0) years. Among the 122 children, PA resolved in 18 (14.8%) children. The level of peanut-specific IgE (sIgE) at diagnosis in the persistence group was significantly higher than that in the resolution group (p = 0.026). The probabilities of resolution of PA were 10.3% and 32.8% at the ages of 6 and 10 years, respectively. A peanut-sIgE level ≥1 kU/L at diagnosis was significantly associated with persistent PA (hazard ratio, 5.99; 95% confidence interval, 1.89-18.87). CONCLUSIONS: Only 10.3% of our patients had a probability of developing spontaneous resolution of PA by 6 years of age. Peanut-sIgE levels ≥1 kU/L at diagnosis were associated with the persistence of PA.

Thalamic Volume Is Related to Increased Anterior Thalamic Radiations in Children with Reactive Attachment Disorder.

Reactive attachment disorder (RAD) is associated with childhood maltreatment and affects approximately 1% of the general population. Recent data suggest that childhood maltreatment is associated with brain alterations in white and gray matter. However, the neural mechanisms of RAD-related brain alterations remain unknown. Herein, we evaluated the white matter pathways and gray matter volumes in 31 and 41 age-matched children with RAD and typical development (TD), respectively, by analyzing T1- and diffusion-weighted images. An increased fractional anisotropy (FA) and axial diffusivity in the anterior thalamic radiations (ATR) and an increased volume in the bilateral pallidum and right thalamus were observed in children with RAD compared with those with TD. Moreover, the volume of the thalamus was associated with increased ATR FA in children with RAD. Our study confirmed the existence of atypical neurodevelopment processes in the thalamus, pallidum, and ATR in children with RAD and highlighted an interdependent relationship between the alterations in the thalamus and ATR. These findings may help to improve our understanding of the comprehensive neural mechanisms of RAD.

Effect of prenatal phthalate exposure on childhood atopic dermatitis: A systematic review and meta-analysis.

Background: The association between prenatal exposure to phthalate and childhood atopic dermatitis (AD) has previously been investigated; however, the results are inconsistent. Objective: We aimed to perform a systematic review and meta-analysis of birth cohort studies to investigate whether prenatal exposure to phthalate increases the risk of developing AD in children. Methods: We performed an electronic search of medical literature data bases. Studies were critically appraised, and a meta-analysis was performed. Results: Among 129 articles identified, 11 studies met the eligibility criteria. Included studies originated from Europe (n = 5), the United States (n = 4), and Asia (n = 2). The study sample size ranged from 147 to 1024 mother-child pairs. Quality assessment by using the Newcastle-Ottawa scale of all the studies had scores of ≥6. A meta-analysis of data from eight selected studies suggested that monobenzyl phthalate (MBzP) exposure was significantly associated with the risk of AD development (odds ratio 1.16 [95% confidence interval, 1.04-1.31]; I² = 17.36%). However, AD development was not associated with other phthalate metabolites, such as mono-(2-ethylhexyl) phthalate, monoethyl phthalate, mono-isobutyl phthalate, mono-n-butyl phthalate, and the sum of di-[2-ethylhexyl] phthalate on the development of AD (all p values were > 0.05). Conclusion: Our meta-analysis suggested that prenatal exposure to phthalates may be associated with the development of childhood AD. However, further research is needed because only MBzP showed statistical significance and the number of articles in the literature is still insufficient.

Association between Parental Cotinine-verified Smoking Status and Childhood Asthma: a Population-based Nationally Representative Analysis.

BACKGROUND: Environmental tobacco smoke exposure due to parents is a modifiable risk factor for childhood asthma, but many studies have evaluated parental smoking using self-reported data. Therefore, we aimed to analyze the relationship between parental cotinine-verified smoking status and asthma in their children. METHODS: This population-based cross-sectional study used data from the Korean National Health and Nutrition Examination Survey from 2014 to 2017. Participants aged 0 to 18 years with complete self-reported physician-diagnosed childhood asthma and measurement of their parental urinary cotinine levels were included. Parental urinary cotinine-verified smoking status was defined using both urinary cotinine levels and self-report, as active, passive, and non-smoker. Sample weights were applied to all statistical analyses because of a complex, multistage and clustered survey design. Logistic regression model was used to analyze the relationship between childhood asthma and parental smoking. RESULTS: A total of 5,264 subjects aged < 19 years were included. The prevalence of asthma was 3.4%. The proportions of paternal and maternal urinary cotinine-verified active smokers during the study period were 50.4% and 16.9%, respectively. When parental urinary cotinine level increased, the proportion of parental low household income was increased (P < 0.001). There was no significant association between the parental urinary cotinine-verified smoking group and childhood asthma group. However, the adjusted odds ratios of childhood asthma in the middle and highest tertile of paternal urinary cotinine levels compared with those in lowest tertile were 1.95 (95% confidence interval [CI], 0.98-3.89) and 2.34 (95% CI, 1.21-4.54), respectively. CONCLUSION: There seems to be a dose-related association between paternal urinary cotinine levels and the risk of childhood asthma. Because of the high rate of paternal smoking, further studies are needed to develop a targeted strategy to reduce parental smoking for childhood asthma.

fMRI volume classification using a 3D convolutional neural network robust to shifted and scaled neuronal activations.

Deep-learning methods based on deep neural networks (DNNs) have recently been successfully utilized in the analysis of neuroimaging data. A convolutional neural network (CNN) is a type of DNN that employs a convolution kernel that covers a local area of the input sample and moves across the sample to provide a feature map for the subsequent layers. In our study, we hypothesized that a 3D-CNN model with down-sampling operations such as pooling and/or stride would have the ability to extract robust feature maps from the shifted and scaled neuronal activations in a single functional MRI (fMRI) volume for the classification of task information associated with that volume. Thus, the 3D-CNN model would be able to ameliorate the potential misalignment of neuronal activations and over-/under-activation in local brain regions caused by imperfections in spatial alignment algorithms, confounded by variability in blood-oxygenation-level-dependent (BOLD) responses across sessions and/or subjects. To this end, the fMRI volumes acquired from four sensorimotor tasks (left-hand clenching, right-hand clenching, auditory attention, and visual stimulation) were used as input for our 3D-CNN model to classify task information using a single fMRI volume. The classification performance of the 3D-CNN was systematically evaluated using fMRI volumes obtained from various minimal preprocessing scenarios applied to raw fMRI volumes that excluded spatial normalization to a template and those obtained from full preprocessing that included spatial normalization. Alternative classifier models such as the 1D fully connected DNN (1D-fcDNN) and support vector machine (SVM) were also used for comparison. The classification performance was also assessed for several k-fold cross-validation (CV) schemes, including leave-one-subject-out CV (LOOCV). Overall, the classification results of the 3D-CNN model were superior to that of the 1D-fcDNN and SVM models. When using the fully-processed fMRI volumes with LOOCV, the mean error rates (± the standard error of the mean) for the 3D-CNN, 1D-fcDNN, and SVM models were 2.1% (± 0.9), 3.1% (± 1.2), and 4.1% (± 1.5), respectively (p = 0.041 from a one-way ANOVA). The error rates for 3-fold CV were higher (2.4% ± 1.0, 4.2% ± 1.3, and 10.1% ± 2.0; p < 0.0003 from a one-way ANOVA). The mean error rates also increased considerably using the raw fMRI 3D volume data without preprocessing (26.2% for the 3D-CNN, 75.0% for the 1D-fcDNN, and 75.0% for the SVM). Furthermore, the ability of the pre-trained 3D-CNN model to handle shifted and scaled neuronal activations was demonstrated in an online scenario for five-class classification (i.e., four sensorimotor tasks and the resting state) using the real-time fMRI of three participants. The resulting classification accuracy was 78.5% (± 1.4), 26.7% (± 5.9), and 21.5% (± 3.1) for the 3D-CNN, 1D-fcDNN, and SVM models, respectively. The superior performance of the 3D-CNN compared to the 1D-fcDNN was verified by analyzing the resulting feature maps and convolution filters that handled the shifted and scaled neuronal activations and by utilizing an independent public dataset from the Human Connectome Project.

The Effects of COMT Polymorphism on Cortical Thickness and Surface Area Abnormalities in Children with ADHD.

The catechol-O-methyltransferase (COMT) gene is associated with frontal cortex development and the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). However, how the COMT gene impacts brain structure and behavior in ADHD remains unknown. In the present study, we identify the effect of COMT on cortical thickness and surface area in children with ADHD and children with typically developing (TD) using a machine learning approach. In a sample of 39 children with ADHD and 34 age- and IQ-matched TD children, we found that cortical thickness and surface area differences were predominantly observed in the frontal cortex. Furthermore, a path analysis revealed that a COMT genotype affected abnormal development of the frontal cortex in terms of both cortical thickness and surface area and was associated with working memory changes in children with ADHD. Our study confirms that the role of COMT in ADHD is not restricted to the development of behavior but may also affect the cortical thickness and surface area. Thus, our findings may help to improve the understanding of the neuroanatomic basis for the relationship between the COMT genotype and ADHD pathogenesis.

Beneficial effect of nasal saline irrigation in children with allergic rhinitis and asthma: A randomized clinical trial.

BACKGROUND: Asthma and allergic rhinitis (AR) are chronic inflammatory diseases of airway and affect the disease severity each other. OBJECTIVE: We performed this study to examine whether nasal saline irrigation (NSI) improves bronchial hyperresponsiveness and clinical parameters in children with asthma and allergic rhinitis (AR). METHODS: We enrolled 20 children with AR and asthma aged between 6-18 years. Patients were randomized into two groups: irrigation group (8 boys and 2 girls) and control group (8 boys and 2 girls). The irrigation group performed daily NSI. All patients received 12-week treatment with montelukast, levocetirizine, and inhaled glucocorticoids. Provocative concentrations of methacholine causing a 20% decrease in FEV1 (PC20), Asthma Control Test (ACT), the Questionnaire for Quality-of-Life Specific to Allergic Rhinitis in Korean Children (QQOL-ARK) and exhaled nitric oxide (FENO) were compared before and after the study. RESULTS: The PC20 at week 12 was higher than baseline measurements in the irrigation group (P = 0.017), while there was no difference in PC20 before and after treatment in the control group (P = 0.333). ACT score increased after 12 weeks of NSI (P = 0.007), while QQOL-ARK score decreased compared to baseline scores (P = 0.028) in the irrigation group. No differences in ACT and QQOL-ARK were found between weeks 0 and 12 in the control group. No differences were found in the median value of changes in PC20, ACT, QQOL-ARK and FENO between the irrigation and control groups. CONCLUSIONS: Our results suggest that NSI is beneficial for treatment of asthma and AR in children.

Exposure to cold airflow alters skin pH and epidermal filaggrin degradation products in children with atopic dermatitis.

BACKGROUND: We aimed to evaluate the influence of cold airflow from the air conditioner on skin barrier function and filaggrin degradation products (FDPs) in children with atopic deramtitis (AD). METHODS: In a case-control study, 28 children with AD and 12 normal children without AD were exposed to one of two air conditioner modes (conventional or wind-free) for 2 h. Skin temperature, transepidermal water loss (TEWL), and skin pH were measured on right cheek and forearm at pre- and post-exposure time points. We also measured filaggrin and FDPs from the volar surface of the forearm. RESULTS: In AD patients, skin temperature on the forearm decreased after exposure to the conventional and wind-free modes (P < 0.001 and P = 0.026), and TEWL on the cheek and the forearm decreased in the wind-free mode (P = 0.037 and 0.002). Skin pH on the cheek increased only after exposure to the conventional mode in AD group (P = 0.002). However, no changes in TEWL and skin pH were found after exposure to either the conventional or the wind-free mode in the control group. In AD children, the levels of pyrrolidone carboxylic acid (PCA) and cis-urocanic acid (UCA) were reduced only after exposure to the conventional mode (all P = 0.033). The percent changes of PCA and cis-UCA were higher in the AD group than those in the control group after exposure to conventional mode (P = 0.029 and 0.046). CONCLUSIONS: Skin barrier function in children with AD may be altered by the exposure to cold airflow from a conventional air conditioner.

Decreased structural connectivity and resting-state brain activity in the lateral occipital cortex is associated with social communication deficits in boys with autism spectrum disorder.

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder characterized by atypical social communication and repetitive behaviors. In this study, we applied a multimodal approach to investigate brain structural connectivity, resting state activity, and surface area, as well as their associations with the core symptoms of ASD. Data from forty boys with ASD (mean age, 11.5 years; age range, 5.5-19.5) and forty boys with typical development (TD) (mean age, 12.3; age range, 5.8-19.7) were extracted from the Autism Brain Imaging Data Exchange II (ABIDE II) for data analysis. We found significantly decreased structural connectivity, resting state brain activity, and surface area at the occipital cortex in boys with ASD compared to boys with TD. In addition, we found that resting state brain activity and surface area in the lateral occipital cortex was negatively correlated with communication scores in boys with ASD. Our results suggest that decreased structural connectivity and resting-state brain activity in the occipital cortex may impair the integration of verbal and non-verbal communication cues in boys with ASD, thereby impacting their social development.

Surface-based shared and distinct resting functional connectivity in attention-deficit hyperactivity disorder and autism spectrum disorder.

BACKGROUND: Both attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are neurodevelopmental disorders with a high prevalence. They are often comorbid and both exhibit abnormalities in sustained attention, yet common and distinct neural patterns of ASD and ADHD remain unidentified.AimsTo investigate shared and distinct functional connectivity patterns in a relatively large sample of boys (7- to 15-year-olds) with ADHD, ASD and typical development matched by age, gender and IQ. METHOD: We applied machine learning techniques to investigate patterns of surface-based brain resting-state connectivity in 86 boys with ASD, 83 boys with ADHD and 125 boys with typical development. RESULTS: We observed increased functional connectivity within the limbic and somatomotor networks in boys with ASD compared with boys with typical development. We also observed increased functional connectivity within the limbic, visual, default mode, somatomotor, dorsal attention, frontoparietal and ventral attention networks in boys with ADHD compared with boys with ASD. In addition, using a machine learning approach, we were able to discriminate typical development from ASD, typical development from ADHD and ASD from ADHD with accuracy rates of 76.3%, 84.1%, and 79.3%, respectively. CONCLUSIONS: Our results may shed new light on the underlying mechanisms of ASD and ADHD and facilitate the development of new diagnostic methods for these disorders.Declaration of interestJ.K. holds equity in a startup company, MNT.

Identifying brain regions associated with the neuropathology of chronic low back pain: a resting-state amplitude of low-frequency fluctuation study.

BACKGROUND: Previous studies have found widespread pain processing alterations in the brain in chronic low back pain (cLBP) patients. We aimed to (1) identify brain regions showing altered amplitude of low-frequency fluctuations (ALFF) using MRI and use these regions to discriminate cLBP patients from healthy controls (HCs) and (2) identify brain regions that are sensitive to cLBP pain intensity changes. METHODS: We compared ALFF differences by MRI between cLBP subjects (90) and HCs (74), conducted a discriminative analysis to validate the results, and explored structural changes in key brain regions of cLBP. We also compared ALFF changes in cLBP patients after pain-exacerbating manoeuvres. RESULTS: ALFF was increased in the post-/precentral gyrus (PoG/PrG), paracentral lobule (PCL)/supplementary motor area (SMA), and anterior cingulate cortex (ACC), and grey matter volume was increased in the left ACC in cLBP patients. PCL/SMA ALFF reliably discriminated cLBP patients from HCs in an independent cohort. cLBP patients showed increased ALFF in the insula, amygdala, hippocampal/parahippocampal gyrus, and thalamus and decreased ALFF in the default mode network (DMN) when their spontaneous low back pain intensity increased after the pain-exacerbating manoeuvre. CONCLUSIONS: Brain low-frequency oscillations in the PCL, SMA, PoG, PrG, and ACC may be associated with the neuropathology of cLBP. Low-frequency oscillations in the insula, amygdala, hippocampal/parahippocampal gyrus, thalamus, and DMN are sensitive to manoeuvre-induced spontaneous back pain intensity changes.

Age-Specific Distribution of Diagnosis and Outcomes of Children Admitted to ICUs: A Population-Based Cohort Study.

OBJECTIVES: Although several studies have reported outcome data on critically ill children, detailed reports by age are not available. We aimed to evaluate the age-specific estimates of trends in causes of diagnosis, procedures, and outcomes of pediatric admissions to ICUs in a national representative sample. DESIGN: A population-based retrospective cohort study. SETTING: Three hundred forty-four hospitals in South Korea. PATIENTS: All pediatric admissions to ICUs in Korea from August 1, 2009, to September 30, 2014, were covered by the Korean National Health Insurance Corporation, with virtually complete coverage of the pediatric population in Korea. Patients less than 18 years with at least one ICUs admission between August 1, 2009, and September 30, 2014. We excluded neonatal admissions (< 28 days), neonatal ICUs, and admissions for health status other than a disease or injury. The final sample size was 38,684 admissions from 32,443 pediatric patients. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The overall age-standardized admission rate for pediatric patients was 75.9 admissions per 100,000 person-years. The most common primary diagnosis of admissions was congenital malformation (10,897 admissions, 28.2%), with marked differences by age at admission (5,712 admissions [54.8%] in infants, 3,994 admissions [24.6%] in children, and 1,191 admissions [9.9%] in adolescents). Injury was the most common primary diagnosis in adolescents (3,248 admissions, 27.1%). The overall in-hospital mortality was 2,234 (5.8%) with relatively minor variations across age. Neoplasms and circulatory and neurologic diseases had both high frequency of admissions and high in-hospital mortality. CONCLUSIONS: Admission patterns, diagnosis, management, and outcomes of pediatric patients admitted to ICUs varied by age groups. Strategies to improve critical care qualities of pediatric patients need to be based on the differences of age and may need to be targeted at specific age groups.

Natural course and prognostic factors of chronic urticaria in Korean children: A single center experience.

BACKGROUND: Chronic urticaria (CU) has an adverse effect on academic achievement and psychosocial development in children. OBJECTIVE: We aimed to investigate the natural course of CU and to identify relevant factors associated with a poor CU prognosis in Korean children. METHODS: We retrospectively analyzed 253 children with episodes of wheals or angioedema at least 3 times a week that persisted for at least 6 weeks. Clinical data and laboratory results were obtained from medical records and parental telephone interviews. Kaplan-Meier survival analysis and log rank tests were performed to assess the median time to remission of CU and prognostic factors. RESULTS: Median age at onset was 5.0 years (interquartile range, 2.5-9.1) and median follow-up period was 7.6 months (interquartile range, 3.9-19.7). Of 253 patients, 68.8% had chronic inducible urticaria and 31.2% had chronic spontaneous urticaria. Physical urticaria was the only cause of chronic inducible urticaria, and the most common physical urticaria was dermographism. Median duration to remission of CU was 10.2 months (95% confidence intervals, 8.0-12.5 months). Kaplan-Meier analysis revealed that 33.4%, 53.0%, and 71.2% of children were in remission at 6, 12, and 24 months, respectively, after the onset of CU. The presence of allergic sensitization was significantly associated with a poor CU prognosis in univariable and multivariable analyses (P=0.010 and P=0.014, respectively). CONCLUSION: Half of children with CU were in remission 10.2 months after onset. Allergic sensitization was a risk factor associated with longer duration CU.