Association between heatwaves and risk and economic burden of injury related hospitalizations in China.

BACKGROUND: Public health is greatly affected by heatwaves, especially as a result of climate change. It is unclear whether heatwaves affect injury hospitalization, especially as developing countries facing the impact of climate change. OBJECTIVES: To assess the impact of heatwaves on injury-related hospitalization and the economic burden. METHODS: The daily hospitalizations and meteorological data from 2014 to 2019 were collected from 23 study sites in 11 meteorological geographic zones in China. We conducted a two-stage time series analysis based on a time-stratified case-crossover design, combined with DLNM to assess the association between heatwaves and daily injury hospitalization, and to further assess the regional and national economic losses resulting from hospitalization by calculating excess hospitalization costs (direct economic losses) and labor losses (indirect economic losses). To determine the vulnerable groups and areas, we also carried out stratified analyses by age, sex, and region. RESULTS: We found that 6.542% (95%CI: 3.939%, 9.008 %) of injury hospitalization were attributable to heatwaves during warm season (May to September) from 2014 to 2019. Approximately 361,447 injury hospitalizations were attributed to heatwaves each year in China, leading to an excess economic loss of 5.173 (95%CI: 3.104, 7.196) billion CNY, of which 3.114 (95%CI: 1.454, 4.720) billion CNY for males and 4.785 (95%CI: 3.203, 6.321) billion CNY for people aged 15-64 years. The attributable fraction (AF) of injury hospitalizations due to heatwaves was the highest in the plateau mountain climate zone, followed by the subtropical monsoon climate zone and the temperate monsoon climate zone. CONCLUSIONS: Heatwaves significantly increase the disease and economic burden of injury hospitalizations, and vary across populations and regions. Our findings implicate the necessity for targeted measures, including raising public awareness, improving healthcare infrastructure, and developing climate resilience policies, to reduce the threat of heatwaves to vulnerable populations and the associated disease and economic burden.

Administering Intravitreal Bevacizumab for Retinopathy of Prematurity: 8-Year Cognitive Outcomes in a Prospective Cohort.

PURPOSE: Determine whether intravitreal injection of bevacizumab (IVB) exerts long-term effects on neurodevelopmental outcomes in children with retinopathy of prematurity (ROP) when reaching the age of 8 years. METHODS: We enrolled 277 children. Patients were stratified into the groups full-term, preterm without ROP, ROP without treatment, or ROP with treatment, based on gestational age (GA) and ROP status. Children under GA of 37 weeks were considered premature. Patients' cognitive outcomes were evaluated using Full-Scale Intelligence Quotient (FIQ) (full score and percentile) generated by the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) every 1 to 2 years. RESULTS: At the mean age of 7.8 years, ROP without and with treatment groups demonstrated lower FIQ scores and percentiles, compared with full-term and premature groups (both p<0.05). FIQ scores and percentiles didn't significantly differ between patients who received different treatments for ROP (full score p=0.19; percentile p=0.37). After adjusting for GA, LogMAR best corrected visual acuity (BCVA) was negatively associated with FIQ scores (p=0.0008) and percentiles (p=0.0002). CONCLUSIONS: At the mean age of 8 years, patients with ROP undergoing IVB didn't exhibit worse cognitive outcomes than those who underwent laser photocoagulation or both treatments. GA and BCVA correlated with cognitive development in children.

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.

Weight Status, Autonomic Function, and Systemic Inflammation in Children with Obstructive Sleep Apnea.

Children with obstructive sleep apnea (OSA) frequently experience chronic low-grade systemic inflammation, with the inflammasome playing a central role in OSA. This cross-sectional study evaluated the relationship between weight status, autonomic function, and systemic inflammation in a cohort of 55 children with OSA, predominantly boys (78%) with an average age of 7.4 ± 2.2 years and an apnea-hypopnea index of 14.12 ± 17.05 events/hour. Measurements were taken of body mass index (BMI), sleep heart-rate variability, morning circulatory levels of interleukin-1ß, interleukin-1 receptor antagonist, and interleukin-6, and tumor necrosis factor-α, anthropometry, and polysomnography. Multiple linear regression modeling showed that an apnea-hypopnea index was significantly associated with BMI, the standard deviation of successive differences between normal-to-normal intervals during N3 sleep, and the proportion of normal-to-normal interval pairs differing by more than 50 ms during rapid-eye-movement sleep. A moderated mediation model revealed that interleukin-1 receptor antagonist levels mediated the association between BMI and interleukin-6 levels, with sympathovagal balance during N3 sleep and minimum blood oxygen saturation further moderating these relationships. This study highlights the complex relationships between BMI, polysomnographic parameters, sleep heart-rate-variability metrics, and inflammatory markers in children with OSA, underlining the importance of weight management in this context.

Interseason waning of vaccine-induced hemagglutination inhibition antibody titers and contributing factors to pre-existing humoral immunity against influenza in community-dwelling older adults 75 years and older.

BACKGROUND: Seasonal influenza causes significant morbidity and mortality with a disproportionately high disease burden in older adults. Strain-specific hemagglutination-inhibition (HAI) antibody titer is a well-established measure of humoral immunity against influenza and pre-vaccination HAI titer is a valuable indicator of pre-existing humoral immunity at the beginning of each influenza season in highly vaccinated older adults. While vaccine-induced HAI antibody titers are known to wane over time, accurate assessment of their interseason waning has been challenging. This is because pre-vaccination HAI titers are routinely measured using current season vaccine strain antigens instead of the prior season vaccines with which individuals were immunized; as such, they do not accurately represent residual antibody titers from prior season vaccination. This study took advantage of available pre-vaccination HAI titers measured using both current and prior season vaccine strain antigens in a longitudinal influenza immunization study with participants enrolled for multiple consecutive influenza seasons from 2014 through 2017. Influenza A virus (IAV) H3N2 and influenza B virus (IBV) strains in the vaccine formula changed in 2015 and again in 2016 season. IAV H1N1 vaccine strain remained the same from 2014 through 2016 seasons, but changed in 2017. We also investigated factors contributing to pre-existing humoral immunity. RESULTS: Interseason waning of HAI titers was evident, but rates of waning varied among vaccine strains and study seasons, from 18% (p = .43) to 61% (p < .01). Rates of waning were noticeably greater when pre-vaccination HAI titers were measured by the routine approach, i.e., using current season vaccine strain antigens, from 33% (p = .12) to 83% (p < .01), adjusting for age at prior study season, sex, race, and education. This was largely because the routinely measured pre-vaccination HAI titers underrepresented residual HAI titers from prior season vaccinations. Moreover, interseason antibody waning and prior season post-vaccination HAI titers had significant and independent associations with pre-vaccination HAI titers. CONCLUSIONS: The routinely measured pre-vaccination HAI titer overestimates interseason HAI antibody waning as it underestimates residual antibody titers from prior season vaccination when virus strains in the vaccine formula change. Moreover, interseason antibody waning and prior season post-vaccination HAI titers independently contribute to pre-existing humoral immunity in this highly vaccinated, community-dwelling older adult population.

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.

Association of Frailty, Age, and Biological Sex With Severe Acute Respiratory Syndrome Coronavirus 2 Messenger RNA Vaccine-Induced Immunity in Older Adults.

BACKGROUND: Male sex and old age are risk factors for severe coronavirus disease 2019, but the intersection of sex and aging on antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines has not been characterized. METHODS: Plasma samples were collected from older adults (aged 75-98 years) before and after 3 doses of SARS-CoV-2 mRNA vaccination, and from younger adults (aged 18-74 years) post-dose 2, for comparison. Antibody binding to SARS-CoV-2 antigens (spike protein [S], S receptor-binding domain, and nucleocapsid), functional activity against S, and live-virus neutralization were measured against the vaccine virus and the Alpha, Delta, and Omicron variants of concern (VOCs). RESULTS: Vaccination induced greater antibody titers in older females than in older males, with both age and frailty associated with reduced antibody responses in males but not females. Responses declined significantly in the 6 months after the second dose. The third dose restored functional antibody responses and eliminated disparities caused by sex, age, and frailty in older adults. Responses to the VOCs, particularly the Omicron variant, were significantly reduced relative to the vaccine virus, with older males having lower titers to the VOCs than older females. Older adults had lower responses to the vaccine and VOC viruses than younger adults, with greater disparities in males than in females. CONCLUSIONS: Older and frail males may be more vulnerable to breakthrough infections owing to low antibody responses before receipt of a third vaccine dose. Promoting third dose coverage in older adults, especially males, is crucial to protecting this vulnerable population.

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.

Rod-Shaped Micelles Based on PHF- g-(PCL-PEG) with pH-Triggered Doxorubicin Release and Enhanced Cellular Uptake.

A biodegradable brush-type copolymer PHF- g-(PCL-PEG) based on a cleavable polyacetal backbone and biodegradable side chain modified with polyethylene glycol (PEG) was synthesized in this paper. This particular structure was directional to facilitate the formation of spherical or rod-shaped micelles. Flow cytometry showed that rod-shaped micelles displayed enhanced cellular uptake compared to spherical micelles. Rod-shaped micelles were selected to investigate their drug delivery abilities in detail. In vitro experiments verified the pH-triggered drug release of DOX-loaded micelles, and the release rate of doxorubicin (DOX) was 77% at pH 5.0 and 26% at pH 7.4. In drug-release kinetic analysis, a double-exponential model achieved the best fit. The copolymer appeared to be almost nontoxic, while the DOX-loaded micelles showed equivalent cytotoxicity compared to DOX at high concentration. The endocytosis of DOX-loaded micelles was two times that of DOX. Our findings suggest that the pH-sensitive brush type copolymer could be a possible carrier in drug delivery.

Fabrication of Cellulose-Nanocrystal-Based Folate Targeted Nanomedicine via Layer-by-Layer Assembly with Lysosomal pH-Controlled Drug Release into the Nucleus.

To increase the cellular uptake and drug loading of cellulose nanocrystal (CNC)-based nanomedicines, folate/ cis-aconityl-doxorubicin@polyethylenimine@CNC (FA/CAD@PEI@CNC) nanomedicines were built up by the building blocks of folate (FA), cis-aconityl-doxorubicin (CAD), polyethylenimine (PEI), and CNCs via the robust layer-by-layer (LbL) assembly technique. The drug loading content (DLC) of FA/CAD@PEI@CNC hybrids was 11.3 wt %, which was almost 20-fold higher than that of the CNC-based nano-prodrug we reported previously. FA/CAD@PEI@CNC nanomedicines showed lysosomal pH-controlled drug release profiles over 24 h. In detail, the cumulative drug release was over 95% at pH 5.5, while the cumulative drug release was only 17% at pH 7.4. In vitro, FA/CAD@PEI@CNC hybrid nanomedicines had a higher (9.7-fold) mean fluorescent intensity (MFI) than that of DOX·HCl, with enhanced cytotoxicity and decreased IC50 against MCF-7. Thus, FA/CAD@PEI@CNC hybrid nanomedicines displayed efficient targetability and enhanced cellular uptake. In addition, FA/CAD@PEI@CNC nanomedicine could deliver more DOX to the nucleus than the control group, due to the ß-carboxylic acid catalyzed breakage of the pH-labile cis-aconityl amide linkages in CAD. These results indicated that FA/CAD@PEI@CNC nanomedicines achieved lysosomal pH-controlled drug release into the nucleus and showed great potential to be high-performance nanomedicines to improve the delivery efficiency and therapy efficacy. This study for CNC-based nanomedicines provided important insights into the bioapplication of CNCs modified by LbL assembly.

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.

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.