Kleine-Levin syndrome is associated with birth difficulties and genetic variants in the TRANK1 gene loci.

Kleine-Levin syndrome (KLS) is a rare disorder characterized by severe episodic hypersomnia, with cognitive impairment accompanied by apathy or disinhibition. Pathophysiology is unknown, although imaging studies indicate decreased activity in hypothalamic/thalamic areas during episodes. Familial occurrence is increased, and risk is associated with reports of a difficult birth. We conducted a worldwide case-control genome-wide association study in 673 KLS cases collected over 14 y, and ethnically matched 15,341 control individuals. We found a strong genome-wide significant association (rs71947865, Odds Ratio [OR] = 1.48, P = 8.6 × 10-9) within the 3'region of TRANK1 gene locus, previously associated with bipolar disorder and schizophrenia. Strikingly, KLS cases with rs71947865 variant had significantly increased reports of a difficult birth. As perinatal outcomes have dramatically improved over the last 40 y, we further stratified our sample by birth years and found that recent cases had a significantly reduced rs71947865 association. While the rs71947865 association did not replicate in the entire follow-up sample of 171 KLS cases, rs71947865 was significantly associated with KLS in the subset follow-up sample of 59 KLS cases who reported birth difficulties (OR = 1.54, P = 0.01). Genetic liability of KLS as explained by polygenic risk scores was increased (pseudo R2 = 0.15; P < 2.0 × 10-22 at P = 0.5 threshold) in the follow-up sample. Pathway analysis of genetic associations identified enrichment of circadian regulation pathway genes in KLS cases. Our results suggest links between KLS, circadian regulation, and bipolar disorder, and indicate that the TRANK1 polymorphisms in conjunction with reported birth difficulties may predispose to KLS.

Whole Genome Sequencing Revealed Inherited Rare Oligogenic Variants Contributing to Schizophrenia and Major Depressive Disorder in Two Families.

Schizophrenia and affective disorder are two major complex mental disorders with high heritability. Evidence shows that rare variants with significant clinical impacts contribute to the genetic liability of these two disorders. Also, rare variants associated with schizophrenia and affective disorders are highly personalized; each patient may carry different variants. We used whole genome sequencing analysis to study the genetic basis of two families with schizophrenia and major depressive disorder. We did not detect de novo, autosomal dominant, or recessive pathogenic or likely pathogenic variants associated with psychiatric disorders in these two families. Nevertheless, we identified multiple rare inherited variants with unknown significance in the probands. In family 1, with singleton schizophrenia, we detected four rare variants in genes implicated in schizophrenia, including p.Arg1627Trp of LAMA2, p.Pro1338Ser of CSMD1, p.Arg691Gly of TLR4, and Arg182X of AGTR2. The p.Arg691Gly of TLR4 was inherited from the father, while the other three were inherited from the mother. In family 2, with two affected sisters diagnosed with major depressive disorder, we detected three rare variants shared by the two sisters in three genes implicated in affective disorders, including p.Ala4551Gly of FAT1, p.Val231Leu of HOMER3, and p.Ile185Met of GPM6B. These three rare variants were assumed to be inherited from their parents. Prompted by these findings, we suggest that these rare inherited variants may interact with each other and lead to psychiatric conditions in these two families. Our observations support the conclusion that inherited rare variants may contribute to the heritability of psychiatric disorders.

Artificial Intelligence-Assisted Early Detection of Retinitis Pigmentosa - the Most Common Inherited Retinal Degeneration.

The purpose of this study was to detect the presence of retinitis pigmentosa (RP) based on color fundus photographs using a deep learning model. A total of 1670 color fundus photographs from the Taiwan inherited retinal degeneration project and National Taiwan University Hospital were acquired and preprocessed. The fundus photographs were labeled RP or normal and divided into training and validation datasets (n = 1284) and a test dataset (n = 386). Three transfer learning models based on pre-trained Inception V3, Inception Resnet V2, and Xception deep learning architectures, respectively, were developed to classify the presence of RP on fundus images. The model sensitivity, specificity, and area under the receiver operating characteristic (AUROC) curve were compared. The results from the best transfer learning model were compared with the reading results of two general ophthalmologists, one retinal specialist, and one specialist in retina and inherited retinal degenerations. A total of 935 RP and 324 normal images were used to train the models. The test dataset consisted of 193 RP and 193 normal images. Among the three transfer learning models evaluated, the Xception model had the best performance, achieving an AUROC of 96.74%. Gradient-weighted class activation mapping indicated that the contrast between the periphery and the macula on fundus photographs was an important feature in detecting RP. False-positive results were mostly obtained in cases of high myopia with highly tessellated retina, and false-negative results were mostly obtained in cases of unclear media, such as cataract, that led to a decrease in the contrast between the peripheral retina and the macula. Our model demonstrated the highest accuracy of 96.00%, which was comparable with the average results of 81.50%, of the other four ophthalmologists. Moreover, the accuracy was obtained at the same level of sensitivity (95.71%), as compared to an inherited retinal disease specialist. RP is an important disease, but its early and precise diagnosis is challenging. We developed and evaluated a transfer-learning-based model to detect RP from color fundus photographs. The results of this study validate the utility of deep learning in automating the identification of RP from fundus photographs.

Involvement of Rare Mutations of SCN9A, DPP4, ABCA13, and SYT14 in Schizophrenia and Bipolar Disorder.

Rare mutations associated with schizophrenia (SZ) and bipolar disorder (BD) usually have high clinical penetrance; however, they are highly heterogeneous and personalized. Identifying rare mutations is instrumental in making the molecular diagnosis, understanding the pathogenesis, and providing genetic counseling for the affected individuals and families. We conducted whole-genome sequencing analysis in two multiplex families with the dominant inheritance of SZ and BD. We detected a G327E mutation of SCN9A and an A654V mutation of DPP4 cosegregating with SZ and BD in one three-generation multiplex family. We also identified three mutations cosegregating with SZ and BD in another two-generation multiplex family, including L711S of SCN9A, M4554I of ABCA13, and P159L of SYT14. These five missense mutations were rare and deleterious. Mutations of SCN9A have initially been reported to cause congenital insensitivity to pain and neuropathic pain syndromes. Further studies showed that rare mutations of SCN9A were associated with seizure and autism spectrum disorders. Our findings suggest that SZ and BD might also be part of the clinical phenotype spectra of SCN9A mutations. Our study also indicates the oligogenic involvement in SZ and BD and supports the multiple-hit model of SZ and BD.

Translational Study of Copy Number Variations in Schizophrenia.

Rare copy number variations (CNVs) are part of the genetics of schizophrenia; they are highly heterogeneous and personalized. The CNV Analysis Group of the Psychiatric Genomic Consortium (PGC) conducted a large-scale analysis and discovered that recurrent CNVs at eight genetic loci were pathogenic to schizophrenia, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.23, 15q13.3, distal 16p11.2, proximal 16p11.2, and 22q11.2. We adopted a two-stage strategy to translate this knowledge into clinical psychiatric practice. As a screening test, we first developed a real-time quantitative PCR (RT-qPCR) panel that simultaneously detected these pathogenic CNVs. Then, we tested the utility of this screening panel by investigating a sample of 557 patients with schizophrenia. Chromosomal microarray analysis (CMA) was used to confirm positive cases from the screening test. We detected and confirmed thirteen patients who carried CNVs at these hot loci, including two patients at 1q21.1, one patient at 7q11.2, three patients at 15q13.3, two patients at 16p11.2, and five patients at 22q11.2. The detection rate in this sample was 2.3%, and the concordance rate between the RT-qPCR test panel and CMA was 100%. Our results suggest that a two-stage approach is cost-effective and reliable in achieving etiological diagnosis for some patients with schizophrenia and improving the understanding of schizophrenia genetics.

Neurodevelopmental Outcomes after Intravitreal Bevacizumab Therapy for Retinopathy of Prematurity: A Prospective Case-Control Study.

PURPOSE: To evaluate the neurodevelopmental and ocular developmental outcomes in premature children who have undergone intravitreal bevacizumab injection (IVB) for treatment of type 1 retinopathy of prematurity (ROP). DESIGN: Prospective case-control study. PARTICIPANTS: We enrolled 3 groups of premature patients: premature children who had no history of ROP (group 0), premature children with history of ROP without treatment (group 1), and premature children with ROP who had received a single IVB (0.625 mg; group 2). METHODS: Ocular developmental assessment, including cycloplegic refractometry, axial length, Cardiff acuity, and neurodevelopmental assessment via the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley III), were performed at 1 to 3 years of age and were compared between groups. MAIN OUTCOME MEASURES: Ocular developmental outcomes and Bayley III scores. RESULTS: A total of 148 patients (85 boys and 63 girls) were included. The mean age at assessment was 1.49±0.59 years. Group 0 patients demonstrated significantly higher gestational age (GA), birth weight, and Apgar scores compared with group 1 and 2 patients. There were no significant differences between groups 1 and 2 in demographics or systemic risk factors except for lower GA in group 2. The cylindrical power was significantly larger in groups 1 and 2 compared with group 0. The spherical equivalent was significantly more myopic and the Cardiff acuity was significantly poorer in group 2 than in group 0. There were no significant differences between groups 1 and 2 in refractive status, axial length, or Cardiff acuity. Neurodevelopmental assessment using Bayley III showed no significant difference among the 3 groups in any aspect after adjusting for GA and other systemic risk factors. The risks for poor neurodevelopmental outcomes also were not significantly different. CONCLUSIONS: At the mean age of 1.5 years, children with prior history of IVB (group 2) showed similar refractive and visual outcomes and similar neurodevelopmental outcomes compared with premature patients with ROP without requirement of treatment (group 1), although there is a possibility that a small but clinically significant difference may not have been detected in the current study.

Controllable Eu2+-Doped Orthophosphate Blue-/Red-Emitting Phosphors: Charge Compensation and Lattice-Strain Control.

Cation-substitution-induced controllable luminescence tuning could efficiently optimize and improve the luminescence performances of novel phosphor materials for realizing high-quality lighting. As important members of the orthophosphate family, ABPO4 (A = alkali metal Li, Na, K, Rb, Cs; B = alkali earth metal Mg, Ca, Sr, Ba) offers an abundant cation lattice environment for rare earth ions. Herein, we successfully prepared a broad-band red-emitting CsMgPO4:Eu2+ phosphor with an emission peak at 628 nm (fwhm = 118 nm). A series of cation-substitution strategies are designed to adjust and enhance its luminescence performances. The corresponding mechanisms are also investigated and proposed reasonably. A charge-compensation strategy of [Eu2+-Si4+] → [Cs+-P5+] could dramatically enhance the quenching concentration from 0.04 to 0.30, which is attributed to the decrease of Eu3+. Two cation-substitution strategies of larger Ba2+ (Sr2+) ions for Mg2+ ions could achieve superior emission adjustment of Eu2+ ions from the red to blue (yellow) region due to local lattice distortion. Interestingly, a consecutive emission adjustment from the red to blue region by simply changing the annealed temperature is reported for the first time, and the possible emission tuning mechanism is revealed based on a local lattice-strain control. This study could serve as a guide in developing Eu2+-activated ABPO4 phosphors with improving luminescence performance and controllable luminescence adjustment based on charge compensation and lattice-strain control through various cation substitutions.

Changes in craniofacial and airway morphology as well as quality of life after passive myofunctional therapy in children with obstructive sleep apnea: a comparative cohort study.

PURPOSE: To examine the craniofacial and airway morphology as well as the quality of life before and after passive myofunctional therapy (PMFT) for 1 year in children with obstructive sleep apnea (OSA). METHODS: Forty children with OSA wearing an oral device nightly (treatment group) and seventeen without the device (control group) were followed up for 1 year. Lateral cephalometric radiography, polysomnography (without participants wearing the oral device), and quality of life survey (OSA-18) were performed before and after the study period. RESULTS: The apnea-hypopnea index (AHI) during sleep, REM AHI, hypopnea count, and desaturation count in the treatment group dropped significantly, compared with the control group. The craniofacial linear measurements increased significantly in both groups, while the length of mandible (Co-Gn) and anterior facial height (N-Me) became significantly larger in the treatment group. For the airway morphology, the intergroup comparison showed that OPha-Ophp (distance between anterior and posterior sides of oropharynx) increased significantly in the treatment group. For quality of life, the intergroup comparison found statistically significant improvements in the following in the treatment group, based on the OSA-18 survey: loud snoring, dysphagia, mood swings, discipline problems, difficulty awakening, total score for the emotional distress portion, and total survey score. CONCLUSIONS: Preliminary evidence is substantiated for the benefits of 1-year PMFT using an oral device with a built-in tongue bead, including improvements in nasal breathing during sleep, mandible linear growth (Co-Gn and N-Me), airway morphology (OPha-Ophp), and patients' quality of life.

Snoring sound energy as a potential biomarker for disease severity and surgical response in childhood obstructive sleep apnoea: A pilot study.

OBJECTIVE: To investigate the relationship between baseline snoring sound energy (SSE) and disease severity, changes in SSE after adenotonsillectomy, and the predictors of surgical success in children with obstructive sleep apnoea (OSA). DESIGN: Prospective cohort study. SETTING: Tertiary referral medical centre. PARTICIPANTS: Thirty-two children with OSA whose apnoea-hypopnoea index ≥5 or apnoea-hypopnoea index ≥1.5 with OSA comorbidities were recruited. Patients with complicated OSA were excluded. All participants underwent snoring sound analysis, polysomnography, and adenotonsillectomy. MAIN OUTCOME MEASURES: Snoring sound energy and apnoea-hypopnoea index were assessed at baseline and 6 months after adenotonsillectomy. Surgical success was defined as a postoperative apnoea-hypopnoea index <1.5. RESULTS: The median age, body mass index, and apnoea-hypopnoea index was 9 years, 19.0 kg/m2 , and 13.2 events/h, respectively. Multivariate logistic regression showed that a baseline tonsil size of IV (odds ratio 15.7 [95% CI: 1.5-166.3]) and SSE of 801-1000 Hz > 21.9 dB (odds ratio 32.3 [95% CI: 2.6-396.6]) were significantly related to severe OSA. Following adenotonsillectomy, apnoea-hypopnoea index decreased significantly (P < 0.001). SSE of 41-200 Hz, 201-400 Hz and 801-1000 Hz also decreased significantly (P = 0.04, 0.01 and 0.006, respectively). Baseline SSE of 801-1000 Hz < 8.5 dB significantly predicted surgical success (odds ratio 11.0 [95% CI: 1.4-85.2]). CONCLUSIONS: Our findings suggest the potential utility of SSE of 801-1000 Hz to screen for severe OSA, predict surgical success and assess therapeutic outcomes. Specific baseline SSE may represent a potential biomarker for childhood OSA.

HLA-DPB1 and HLA class I confer risk of and protection from narcolepsy.

Type 1 narcolepsy, a disorder caused by a lack of hypocretin (orexin), is so strongly associated with human leukocyte antigen (HLA) class II HLA-DQA1(∗)01:02-DQB1(∗)06:02 (DQ0602) that very few non-DQ0602 cases have been reported. A known triggering factor for narcolepsy is pandemic 2009 influenza H1N1, suggesting autoimmunity triggered by upper-airway infections. Additional effects of other HLA-DQ alleles have been reported consistently across multiple ethnic groups. Using over 3,000 case and 10,000 control individuals of European and Chinese background, we examined the effects of other HLA loci. After careful matching of HLA-DR and HLA-DQ in case and control individuals, we found strong protective effects of HLA-DPA1(∗)01:03-DPB1(∗)04:02 (DP0402; odds ratio [OR] = 0.51 [0.38-0.67], p = 1.01 × 10(-6)) and HLA-DPA1(∗)01:03-DPB1(∗)04:01 (DP0401; OR = 0.61 [0.47-0.80], p = 2.07 × 10(-4)) and predisposing effects of HLA-DPB1(∗)05:01 in Asians (OR = 1.76 [1.34-2.31], p = 4.71 × 10(-05)). Similar effects were found by conditional analysis controlling for HLA-DR and HLA-DQ with DP0402 (OR = 0.45 [0.38-0.55] p = 8.99 × 10(-17)) and DP0501 (OR = 1.38 [1.18-1.61], p = 7.11 × 10(-5)). HLA-class-II-independent associations with HLA-A(∗)11:01 (OR = 1.32 [1.13-1.54], p = 4.92 × 10(-4)), HLA-B(∗)35:03 (OR = 1.96 [1.41-2.70], p = 5.14 × 10(-5)), and HLA-B(∗)51:01 (OR = 1.49 [1.25-1.78], p = 1.09 × 10(-5)) were also seen across ethnic groups in the HLA class I region. These effects might reflect modulation of autoimmunity or indirect effects of HLA class I and HLA-DP alleles on response to viral infections such as that of influenza.

Multiple sleep latency test in narcolepsy type 1 and narcolepsy type 2: A 5-year follow-up study.

Excessively sleepy teenagers and young adults without sleep-disordered breathing are diagnosed with either narcolepsy type 1 or narcolepsy type 2, or hypersomnia, based on the presence/absence of cataplexy and the results of a multiple sleep latency test. However, there is controversy surrounding this nomenclature. We will try to find the differences between different diagnoses of hypersomnia from the results of the long-term follow-up evaluation of a sleep study. We diagnosed teenagers who had developed excessive daytime sleepiness based on the criteria of the International Classification of Sleep Disorders, 3rd edition. Each individual received the same clinical neurophysiologic testing every year for 5 years after the initial diagnosis of narcolepsy type 1 (n = 111) or type 2 (n = 46). The follow-up evaluation demonstrated that narcolepsy type 1 (narcolepsy-cataplexy) is a well-defined clinical entity, with very reproducible clinical neurophysiologic findings over time, whereas patients with narcolepsy type 2 presented clear clinical and test variability. By the fifth year of the follow-up evaluation, 17.6% of subjects did not meet the diagnostic criteria of narcolepsy type 2, and 23.9% didn't show any two sleep-onset rapid eye movement periods in multiple sleep latency during the 5-year follow-up. Therefore narcolepsy type 1 (narcolepsy-cataplexy) is a well-defined syndrome, with the presentation clearly related to the known consequences of destruction of hypocretin/orexin neurons. Narcolepsy type 2 covers patients with clinical and test variability over time, thus bringing into question the usage of the term "narcolepsy" to label these patients.

Nocturnal Oximetry-based Evaluation of Habitually Snoring Children.

RATIONALE: The vast majority of children around the world undergoing adenotonsillectomy for obstructive sleep apnea-hypopnea syndrome (OSA) are not objectively diagnosed by nocturnal polysomnography because of access availability and cost issues. Automated analysis of nocturnal oximetry (nSpO2), which is readily and globally available, could potentially provide a reliable and convenient diagnostic approach for pediatric OSA. METHODS: Deidentified nSpO2 recordings from a total of 4,191 children originating from 13 pediatric sleep laboratories around the world were prospectively evaluated after developing and validating an automated neural network algorithm using an initial set of single-channel nSpO2 recordings from 589 patients referred for suspected OSA. MEASUREMENTS AND MAIN RESULTS: The automatically estimated apnea-hypopnea index (AHI) showed high agreement with AHI from conventional polysomnography (intraclass correlation coefficient, 0.785) when tested in 3,602 additional subjects. Further assessment on the widely used AHI cutoff points of 1, 5, and 10 events/h revealed an incremental diagnostic ability (75.2, 81.7, and 90.2% accuracy; 0.788, 0.854, and 0.913 area under the receiver operating characteristic curve, respectively). CONCLUSIONS: Neural network-based automated analyses of nSpO2 recordings provide accurate identification of OSA severity among habitually snoring children with a high pretest probability of OSA. Thus, nocturnal oximetry may enable a simple and effective diagnostic alternative to nocturnal polysomnography, leading to more timely interventions and potentially improved outcomes.

HCBP6 Is Involved in the Development of Hepatic Steatosis Induced by High-Fat Diet and CCL4 in Rats.

INTRODUCTION AND AIM: Hepatitis C virus core-binding protein 6 (HCBP6) was previously found to be an hepatitis C virus corebinding protein, its biological function remains unclear. Our research aims to investigate the role of HCBP6 in the development of hepatic steatosis induced by high-fat diet and carbon tetrachloride (CCL4) in rats. MATERIAL AND METHODS: Eighteen Wistar rats were randomly allocated into 3 groups: control group, model group 1, and model group 2. The control group was treated with a standard diet for 5 weeks. Model groups were treated with high-fat diet and CCL4 injection twice a week for 3 weeks in Group 1 and 5 weeks in Group 2, respectively. After the intervention, hepatic steatosis was observed by histological staining with hematoxylin and eosin (H&E) and Oil Red O staining. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total colesterol (TC), and triglycerides (TGs) were measured. The TG content in liver homogenates was evaluated. Expressions of HCBP6 and SREBP-1c were determined by immunofluorescence, quantitative real-time PCR, and Western blot analysis. RESULTS: Hepatic steatosis was successfully induced in model groups. ALT, AST, TC, and TGs elevated in model groups compared with those in control group (P < 0.05). Hepatic steatosis induced by high-fat diet and CCL4 resulted in low expression of HCBP6 and high expression of SREBP-1c in the liver of rats (P < 0.05). CONCLUSION: HCBP6 is involved in the development of high-fat diet- and CCL4-induced hepatic steatosis and related negatively with SREBP-1c.

Passive myofunctional therapy applied on children with obstructive sleep apnea: A 6-month follow-up.

BACKGROUND/PURPOSE: Myofunctional therapy is one of the recommended treatments for obstructive sleep apnea, but the level of compliance has often been low in children. This study aims to investigate the therapeutic effect of passive myofunctional therapy using an oral appliance during sleep in children suffering from obstructive sleep apnea. METHODS: Twenty-nine children who suffered from obstructive sleep apnea were divided into two groups: premature children and full-term children. All children wore an oral device to induce their tongue muscle activity during sleep for 6 months. Polysomnography during sleep was performed before and 1 week after the end of 6-month treatment. RESULTS: Both groups showed positive polysomnographic changes. Full-term children had a significant decrease in the apnea-hypopnea index, hypopnea index, and percentage of arousals. Prematurely born children had a significant decrease in the apnea-hypopnea index during rapid eye movement sleep and in the mean heart rate during sleep. CONCLUSION: Using a specialized oral device to perform myofunctional therapy during sleep may improve the breathing during sleep of children with obstructive sleep apnea.

Sleep Problems in Children with Attention Deficit/Hyperactivity Disorder: Current Status of Knowledge and Appropriate Management.

Attention deficit hyperactivity disorder (ADHD) affects approximately 5 % of children and adolescents, and sleep problems are common in these patients. There is growing evidence informing the significant importance of sleep problems in youth with ADHD. The sleep problems in children with ADHD include specific sleep disorders and sleep disturbances due to comorbid psychiatric disorders or ADHD medications. The specific sleep disorders of ADHD children include behaviorally based insomnia, sleep-disordered breathing, and restless legs syndrome/periodic limb movement disorder. Current practices on the management of sleep problems for ADHD children are based mostly on expert consensus, whereas more evidence-based literature can be found only recently. Assessment of the sleep conditions in ADHD children before initiation of pharmacotherapy is the currently recommended guideline, and good sleep hygiene can be considered as the first-line treatment option. In addition to modifying the dose regimens, formulation, or alternative stimulants when sleep problems are encountered in ADHD children, atomoxetine, once daily guanfacine extended release, and melatonin are potential choices for ADHD children with more severe sleep problems. In this review, we aimed to provide the most updated information, preferably based on meta-analyses, systemic review, and randomized controlled trials published in the latest 3 years, in order to be clinically useful for practitioners and clinicians.

Genome wide analysis of narcolepsy in China implicates novel immune loci and reveals changes in association prior to versus after the 2009 H1N1 influenza pandemic.

Previous studies in narcolepsy, an autoimmune disorder affecting hypocretin (orexin) neurons and recently associated with H1N1 influenza, have demonstrated significant associations with five loci. Using a well-characterized Chinese cohort, we refined known associations in TRA@ and P2RY11-DNMT1 and identified new associations in the TCR beta (TRB@; rs9648789 max P = 3.7 × 10(-9) OR 0.77), ZNF365 (rs10995245 max P = 1.2 × 10(-11) OR 1.23), and IL10RB-IFNAR1 loci (rs2252931 max P = 2.2 × 10(-9) OR 0.75). Variants in the Human Leukocyte Antigen (HLA)- DQ region were associated with age of onset (rs7744020 P = 7.9×10(-9) beta -1.9 years) and varied significantly among cases with onset after the 2009 H1N1 influenza pandemic compared to previous years (rs9271117 P = 7.8 × 10(-10) OR 0.57). These reflected an association of DQB1*03:01 with earlier onset and decreased DQB1*06:02 homozygosity following 2009. Our results illustrate how genetic association can change in the presence of new environmental challenges and suggest that the monitoring of genetic architecture over time may help reveal the appearance of novel triggers for autoimmune diseases.

Clinical manifestations of pediatric obstructive sleep apnea syndrome: Clinical utility of the Chinese-version Obstructive Sleep Apnea Questionaire-18.

AIMS: Childhood obstructive sleep apnea syndrome (OSA) affects not only the children's physical health, but also their mental development, behavioral problems and learning difficulties. Therefore, an early diagnosis is important. However, the assessment tools of polysomnography are demanding. The Obstructive Sleep Apnea Questionnaire-18 (OSA-18) is designed to screen OSA and has good reliability and validity. The goal of this study was to validate the Chinese version of the OSA-18, to analyze the frequency of symptoms and find the most common symptoms of OSA in Taiwanese children. METHODS: We validated the OSA-18 in an ethnic Chinese group and compared the treatment outcomes to show the sensitivity of the questionnaire. The caregivers completed the questionnaire twice at an interval of 4 weeks to test reliability. In the validation study, we included 88 OSA children. The OSA-18 and follow-up polysomnography were performed before and 6 months after adenotonsillectomy. RESULTS: Results showed the excellent test-retest reliability (r = 0.84**) of the OSA-18. There was a statistically significant correlation between the OSA-18 and, respectively, the Apnea-Hypopnea Index (r = 0.29*), and the Hypopnea Index (r = 0.29*). Quality of life showed a significant correlation with the Apnea Index (r = 0.43**), central apnea count (r = 0.50***), and mixed apnea count (r = 0.36*). The cut-off point of the OSA-18 total scores for detecting pediatric OSA in children aged 6-12 years was 66. The common symptoms of pediatric OSA were poor attention span, loud snoring, caregiver worried about child's health, difficulty awakening, and mouth breathing. CONCLUSIONS: Our results show that the Chinese version of the OSA-18 is a reliable and valid instrument. The questionnaire also showed improvement in the quality of life of OSA children post-adenotonsillectomy.

Sleep and breathing in premature infants at 6 months post-natal age.

BACKGROUND: Poor sleep contributes to the developmental problems seen in preterm infants. We evaluated sleep problems in preterm infants 6 months of post-gestational age using the subjective Brief Infant Sleep Questionnaire (BISQ) and objective sleep tests. We also compared the sleep of premature infants with that of full-term infants. METHODS: The study included 68 6-month-old full-term healthy infants and 191 premature infants born at <37 weeks gestation. All parents completed the BISQ-Chinese version and sleep diaries. At the same time, all premature infants were submitted to one night of polysomnography (PSG) in the sleep laboratory and also were set up with an actigraph kept for 7 days. Statistical analyses were performed using correlation coefficients and the t-test with SPSS version 18 to compare questionnaire responses with other subjective and objective measures of sleep. RESULTS: The sleep problems indicated in the subjective questionnaire for the premature infants, particularly: "the nocturnal sleep duration, number of night awakenings, daytime sleep duration, duration of time with mouth breathing, and loud-noisy breathing" had significant correlations with sleep diaries, actigraphy and PSG results. The BISQ showed that duration of infant's sleeping on one side, nocturnal sleep duration, being held to fall asleep, number of nighttime awakenings, daytime sleep duration, subjective consideration of sleep problems, loud-noisy breathing, and duration spent crying during the night were significantly different between the premature infants and the term infants. PSG confirmed the presence of a very high percentage (80.6%) of premature infants with AHI > 1 event/hour as indicated by the questionnaire. CONCLUSION: Premature infants have more sleep problems than full-term infants, including the known risk of abnormal breathing during sleep, which has been well demonstrated already with the BISQ-Chinese (CBISQ).

Neurocognitive effects of aripiprazole in adolescents and young adults with schizophrenia.

BACKGROUND: The use of aripiprazole has been associated with a positive influence on mood and improved cognitive skills and social interactions; however, studies of its effects on young schizophrenic patients have been limited to active symptoms. AIMS: This prospective, open-label study investigated the neurocognitive effects of aripiprazole in adolescents and young adults with first and repeated episodes of schizophrenia. METHODS: Twenty-three of 42 schizophrenic outpatients aged 12-26 completed a trial of aripiprazole, and its efficacy was determined using the Brief Psychiatric Rating Scale (BPRS), Clinical Global Impressions Severity (CGI-S) and WHO Quality of Life (WHOQOL) scales. Cognitive function was measured with the Cognitive Performance Test (CPT) and Wisconsin Card Sorting Test (WCST) at 4, 12 and 24 weeks of treatment. RESULTS: Results showed statistically significant improvements in BPRS, CGI-S and WHOQOL scores in certain (but not all) subcategories of cognitive measures including CPT detectability and total errors and perseverative errors on the WCST. There were few adverse side-effects. CONCLUSIONS: Psychotic symptoms and cognitive skills improved during treatment with aripiprazole in adolescents and young adults with schizophrenia. Patients with first psychotic episodes did better than did those with repeat episodes.

Long-term follow-up of symptom and quality of life changes in patients with narcolepsy during and after the COVID-19 pandemic.

The COVID-19 pandemic may have a significant impact on patients with narcolepsy, yet a long-term follow-up study is currently lacking. This study aims to investigate changes in symptom severity and the quality of life of patients with narcolepsy during and after the pandemic. Patients with type 1 or type 2 narcolepsy (NT1, NT2) were retrospectively recruited and prospectively followed from 2020 to 2023. They received evaluations including the Epworth Sleepiness Scale (ESS), the visual analog scale (VAS) for hypersomnolence, the VAS for cataplexy, the Short-form 36 Health Survey questionnaire (SF-36), and a sleep diary. We compared the differences between the pre-lockdown, the lockdown, the post-lockdown, and the post-pandemic periods by repeated measures ANOVA or the Friedman test, with the Bonferroni test for post hoc analysis. A total of 100 patients completed the 4-year study (mean age, 24.06 ± 7.00 years; 55% male). We observed significant differences in the ESS (p = 0.037), total nighttime sleep (p = 0.03), total sleep time (p = 0.035), and sleep efficiency (p = 0.035) during the study period. There was also significantly worse physical role functioning in the post-pandemic period (p = 0.014). In particular, the NT1 group had significantly decreased VAS-C scores (p < 0.001) but experienced worse physical role functioning in the post-pandemic period (p = 0.009). Patients with narcolepsy continue to face challenges after the pandemic. A more flexible lifestyle with an adequate sleep time may be beneficial, and medication adherence should be emphasized.