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.

High prevalence of exon-13 variants in USH2A-related retinal dystrophies in Taiwanese population.

BACKGROUND: Biallelic pathogenic variants in USH2A lead to Usher syndrome or non-syndromic retinitis pigmentosa, and shown to have geographical and ethnical distribution in previous studies. This study provided a deeper understanding of the detailed clinical features using multimodal imaging, genetic spectrum, and genotype-phenotype correlations of USH2A-related retinal dystrophies in Taiwan. RESULTS: In our cohort, the mean age at first visit was 47.66 ± 13.54 years, and the mean age at symptom onset, which was referred to the onset of nyctalopia and/or visual field constriction, was 31.21 ± 15.24 years. Among the variants identified, 23 (50%) were missense, 10 (22%) were splicing variants, 8 (17%) were nonsense, and 5 (11%) were frameshift mutations. The most predominant variant was c.2802T>G, which accounted for 21% of patients, and was located in exon 13. Patients with truncated alleles had significantly earlier symptom onset and seemly poorer disease progression regarding visual acuity, ellipsoid zone line length, and hypofluorescent lesions in the macula than those who had the complete gene. However, the clinical presentation revealed similar progression between patients with and without the c.2802T>G variant. During long-term follow-up, the patients had different ellipsoid zone line progression rates and were almost evenly distributed in the fast, moderate, and slow progression subgroups. Although a younger onset age and a smaller baseline intact macular area was observed in the fast progression subgroup, the results showed no significant difference. CONCLUSIONS: This is the first cohort study to provide detailed genetic and longitudinal clinical analyses of patients with USH2A-related retinal dystrophies in Taiwan. The mutated allele frequency in exon 13 was high in Taiwan due to the predominant c.2802T>G variant. Moreover, truncated variants greatly impacted disease progression and determined the length of therapeutic windows. These findings provide insight into the characteristics of candidates for future gene therapies.

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.

Corneal Endothelial Morphology and Ocular Biometric Indexes in Premature Children With and Without Retinopathy of Prematurity.

Purpose: The purpose of this study was to analyze human corneal endothelial cells (HCECs) morphology and ocular biometrics in premature (PM) children with or without retinopathy of prematurity (ROP). Methods: Retrospective data on patient demographics, HCECs status, and ocular biometrics with at least 2 visits between 2016 and 2021 were reviewed. The main outcomes were endothelial cell density (ECD), coefficient of variation (CV), hexagonal cell ratio (HEX), central corneal thickness (CCT), axial length, anterior chamber depth, keratometry, corneal diameter, pupil diameter, and refraction status. Generalized estimating equation was used to evaluate the differences between PM no-ROP and ROP groups. We also analyzed the trend of ECD, CV, HEX, and CCT change with age between groups. Results: The study included 173 PM patients without ROP and 139 patients with ROP. A total of 666 and 544 measurements were recorded in the PM no-ROP and ROP groups, respectively. The ROP group had higher spherical power, myopic spherical equivalent (SE), and steeper steep keratometry (K; P < 0.05). The ROP group had higher CV (P = 0.0144), lower HEX (P = 0.0012) and thicker CCT (P = 0.0035). In the HCECs parameters, the ROP group had slower ECD decrement (P < 0.0001), faster CV decrement (P = 0.0060), and faster HEX increment (P = 0.0001). A difference in corneal morphology changes between the ROP and PM no-ROP groups were prominent in patients with lower gestational age (GA) in the subgroup analysis. Conclusions: Worse HCECs morphology and higher myopic status were initially observed in patients with prior ROP but not in PM patients with no-ROP. ECD and HCECs morphology improved with age, especially in patients with low GA.

Effects of modafinil on nocturnal sleep patterns in patients with narcolepsy: A cohort study.

BACKGROUND: Patients with narcolepsy often experience disturbed nighttime sleep. Modafinil is commonly prescribed for hypersomnolence, but its impacts on nocturnal sleep remain unclear. This study uses actigraphy to examine the effect of modafinil on both hypersomnolence and nocturnal sleep patterns in patients with narcolepsy. METHODS: Prior to treatment, 87 patients with narcolepsy wore an actigraphy for 7-14 days to assess their nighttime sleep. After evaluation, they received a daily dose of 200-400 mg of modafinil in the morning and wore an actigraphy again six months after initiating treatment. Questionnaires, including the Epworth-Sleepiness-Scale (ESS), the Visual-Analogue-for-Hypersomnolence (VAS), and the Short-Form-36-Health-Survey (SF-36), were used to evaluate hypersomnolence and quality of life both before and after treatment. Paired t-tests and independent samples t-tests were used for pre- and post-treatment comparisons and subgroup analysis. We used the Pearson's correlation test to measure the correlations between the sleep parameters of the actigraphy and data of the questionnaires. RESULTS: Improvements in hypersomnolence were noted following modafinil treatment, and we observed no significant deterioration in nocturnal sleep parameters by the actigraphy. The total number of awakenings by actigraphy significantly decreased (p = 0.005), especially in females (p = 0.008), while sleep onset latency significantly increased in children/adolescents (p = 0.014). Correlations were found between the sleep parameters of the actigraphy and ESS, VAS, and SF-36 scores. CONCLUSION: Modafinil treatment may not worsen nighttime sleep in patients with narcolepsy. However, it should be administered with care in children and adolescents.

The application of machine learning on brain imaging features of different narcolepsy subtypes.

STUDY OBJECTIVES: Narcolepsy is a central hypersomnia disorder, and differential diagnoses between its subtypes can be difficult. Hence, we applied machine learning to analyze the positron emission tomography (PET) data of patients with type 1 or type 2 narcolepsy, and patients with type 1 narcolepsy and comorbid schizophrenia, to construct predictive models to facilitate the diagnosis. METHODS: This is a retrospective and prospective case-control study of adolescent and young adult patients with type 1 or type 2 narcolepsy, and type 1 narcolepsy and comorbid schizophrenia. All participants received 18-F-fluorodeoxy glucose PET, sleep studies, neurocognitive tests, sleep questionnaires, and human leukocyte antigen typing. The collected PET data were analyzed by feature selections and classification methods in machine learning to construct predictive models. RESULTS: A total of 314 participants with narcolepsy were enrolled; 204 had type 1 narcolepsy, 90 had type 2 narcolepsy, and 20 had type 1 narcolepsy and comorbid schizophrenia. We used three filter methods for feature selection followed by a comparative analysis of classification methods. To apply a small number of regions of interest (ROI) and high classification accuracy, the Naïve Bayes classifier with the Term Variance as feature selection achieved the goal with only three ROIs (left basal ganglia, left Heschl, and left striatum) and produced an accuracy of higher than 99%. CONCLUSIONS: The accuracy of our predictive model of PET data are promising and can aid clinicians in the diagnosis of narcolepsy subtypes. Future research with a larger sample size could further refine the predictive model of narcolepsy.

Tailoring the oral sensation and digestive behavior of konjac glucomannan-gelatin binary hydrogel based bigel: Effects of composition and ratio.

In the food industry, there is a growing demand for bigels that offer both adaptable oral sensations and versatile delivery properties. Herein, we developed bigels using a binary hydrogel of konjac glucomannan (KGM) and gelatin (G) combined with a stearic acid oleogel. We closely examined how the oleogel/hydrogel volume ratio (φ) and the KGM/G mass ratio (γ) influenced various characteristics of the bigels, including their microstructure, texture, rheological properties, thermal-sensitivity, oral tribology, digestive stability, and nutraceutical delivery efficiency. A noteworthy observation was the structural evolution of the bigels with increasing φ values: transitioning from oleogel-in-hydrogel to a bicontinuous structure, and eventually to hydrogel-in-oleogel. Lower γ values yielded a softer, thermally-responsive bigel, whereas higher γ values imparted enhanced viscosity, stickiness, and spreadability to the bigel. Oral tribology assessments demonstrated that φ primarily influenced the friction sensations at lower chewing intensities. In contrast, γ played a significant role in augmenting oral friction perceptions during more intense chewing. Additionally, φ dictated the controlled release and bioaccessibility of curcumin, while γ determined digestive stability. This study provides valuable insights, emphasizing that through meticulous selection and adjustment of the hydrogel matrix composition, bigels can be custom-fabricated to achieve specific oral sensations and regulated digestive behaviors.

Validity of Diagnostic Support Model for Attention Deficit Hyperactivity Disorder: A Machine Learning Approach.

An accurate and early diagnosis of attention deficit hyperactivity disorder can improve health outcomes and prevent unnecessary medical expenses. This study developed a diagnostic support model using a machine learning approach to effectively screen individuals for attention deficit hyperactivity disorder. Three models were developed: a logistic regression model, a classification and regression tree (CART), and a neural network. The models were assessed by using a receiver operating characteristic analysis. In total, 74 participants were enrolled into the disorder group, while 21 participants were enrolled in the control group. The sensitivity and specificity of each model, indicating the rate of true positive and true negative results, respectively, were assessed. The CART model demonstrated a superior performance compared to the other two models, with region values of receiver operating characteristic analyses in the following order: CART (0.848) > logistic regression model (0.826) > neural network (0.67). The sensitivity and specificity of the CART model were 78.8% and 50%, respectively. This model can be applied to other neuroscience research fields, including the diagnoses of autism spectrum disorder, Tourette syndrome, and dementia. This will enhance the effect and practical value of our research.

Flexible control of bigel microstructure for enhanced stability and flavor release during oral consumption.

Edible delivery systems such as emulsions and gels that possess flexible oral flavor sensation and comprehensive stability under freeze-thaw processing are highly demanded in the frozen food industry. Bigels were fabricated via emulsification of stearic acid based oleogel with konjac glucomannan (KGM)-gelatin (G) based binary hydrogel. By varing the KGM/G mass ratio (γ) and oleogel/hydrogel volume ratio (φ) of bigels, modulation over the micromorphology, tribology, flavor sensation and cheese stick imitating capacity were achieved. Notably, as φ increased from O4:W6 to O5:W5, the microstructural transformation from oleogel-in-hydrogel to bicontinuous morphology emerged as a remarkable feature. The influence of γ was evident in bicontinuous bigels, significantly enhancing water holding capacity (WHC) by 3.38-fold as γ transitioned from 1KGM:5G to 6KGM:5G during freeze-thaw cycles. φ and γ both played pivotal roles in altering the microstructure and rheological properties of the bigels, enabling customizable release of bioactive components and flavor perception. Oleogel-in-hydrogel bigels effectively prevented bioactive compound leakage during freeze-thaw conditions, while bicontinuous bigels demonstrated sustained flavor release during oral mastication. Release behaviors were dual-controlled by φ and γ, reducing oil-soluble flavor release with increased φ and lowering hydrophilic volatile release with elevated γ. Moreover, bigel-based cheese sticks showcased lower viscosity, higher creep recovery rates, and enhanced mouthfeel during minimal oral chewing, suggesting their potential in mimicking the properties of commercial counterparts. These findings extend insights into bigel design for tailored flavor release and bioactive preservation in food products.

Factors influencing engagement in online dual practice by public hospital doctors in three large cities: A mixed-methods study in China.

Background: In the digital age, a rising number of public sector doctors are providing private telemedicine and telehealth services on online health care platforms. This novel practice pattern - termed online dual practice - may profoundly impact health system performance in both developed and developing countries. This study aims to understand the factors influencing doctors' engagement in online dual practice. Methods: Using a mixed-methods design, this study concurrently collects quantitative demographic and practice data (n = 71 944) and semi-structured interview data (n = 32) on secondary and tertiary public hospital doctors in three large Chinese cities: Beijing, Shanghai and Guangzhou. We use the quantitative data to examine the prevalence of the online dual practice and its associated factors via the binary logit regression model. The qualitative data are used to further explore associated factors of online dual practice via thematic analysis. The findings about associated factors from the two parts were merged using the categories of personal, professional, and organisational characteristics. Results: Our quantitative analysis shows that at least 47.1% of public hospital doctors are involved in online dual practice. The shares in Beijing, Shanghai, and Guangzhou are 43.7%, 53.1%, and 44.8%, respectively. This practice is more prevalent among doctors who are male, senior, and non-managerial. Different specialties, hospital ownership, hospital levels, and locations are also significantly associated with this practice. The qualitative analysis further suggests that financial returns, perceived effectiveness of telemedicine, and hospital directors' attitude towards telemedicine may affect doctors' engagement with online dual practice. Conclusions: Online dual practice is prevalent among doctors at tertiary and secondary public hospitals in Beijing, Shanghai, and Guangzhou. Personal, professional, and organisational characteristics are all associated with doctors' choice to engage in online dual practice. The findings in this study provide implications for promoting telemedicine adoption and developing relevant regulatory policies in China and other countries.

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.

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.

Dietary profile of pediatric obstructive sleep apnea patients, effects of routine educational counseling, and predictors for outcomes.

Background: Dietary behavior is a main contributing yet modifiable factor to the body weight status of children and may be involved in the pathophysiology of childhood obstructive sleep apnea (OSA). This study aimed to investigate the dietary profile of pediatric OSA patients, effects of educational counseling after adenotonsillectomy, and predictor for disease resolution. Methods: This observational study included 50 pediatric OSA patients undergoing adenotonsillectomy with routine educational counseling (Group 1), 50 pediatric OSA patients undergoing adenotonsillectomy without formal educational counseling (Group 2), and 303 healthy children without OSA (Control). The three groups were matched by age. The consumption frequency of 25 food items/groups was assessed by the Short Food Frequency Questionnaire. Quality of life was evaluated by the OSA-18 questionnaire. Sleep architecture and OSA severity were measured by standard polysomnography. Between- and within-group comparisons were analyzed by non-parametric approaches and generalized estimating equations. Prediction of disease recovery was performed by multivariable logistic regression models. Results: Group 1 children consumed fruit drinks with sugar, vegetables, sweets, chocolate, rice, and noodles more frequently than Control Group children. At baseline, the distributions of sex, weight status, OSA-18 scores, and polysomnographic variables were comparable between Group 1 and Group 2. After a 12-month follow-up, Group 1 had better improvements in physical suffering, caregiver concerns, sleep architecture, and mean peripheral oxygen saturation compared to Group 2. Furthermore, Group 1 no longer had excessive consumption of fruit drinks with sugar, chocolate, and noodles; however, food consumption frequencies did not change significantly. Notably, younger age and reduced intake of butter/margarine on bread and noodles were independent predictors of cured OSA in Group 1. Conclusion: The present study preliminarily characterized an unhealthy dietary profile among pediatric OSA patients and suggested that routine educational counseling in addition to adenotonsillectomy yielded some clinical benefits. Certain items/groups of food frequencies may be associated with disease recovery and further investigations are warranted.

Understanding Impacts of Online Dual Practice on Health System Performance: A Qualitative Study in China.

The outbreak of the COVID-19 pandemic has boosted the global development of online healthcare platforms. An increasing number of public hospital doctors are providing online services on private third-party healthcare platforms, creating a new form of dual practice-online dual practice. To explore the impacts of online dual practice on health system performance as well as potential policy responses, we undertook a qualitative approach that uses in-depth interviews and thematic analysis. Following a purposive sampling, we interviewed 57 Chinese respondents involved in online dual practice. We asked respondents for their opinions on the effects of online dual practice on access, efficiency, quality of care, and advice on regulatory policy. The results suggest that online dual practice can generate mixed impacts on health system performance. The benefits include improved accessibility due to increased labor supply of public hospital doctors, better remote access to high-quality services, and lower privacy concerns. It can improve efficiency and quality by optimizing patient flows, reducing repetitive tasks, and improving the continuity of care. However, the potential distraction from designated work at public hospitals, inappropriate use of virtual care, and opportunistic physician behaviors may undermine overall accessibility, efficiency, and quality. Countries should mitigate these adverse consequences via regulations that are appropriate to their healthcare system context, policy priority, and governance capacity.

Seasonal associations between air pollutants and influenza in 10 cities of southern China.

Few studies have explored the associations between air pollutants and influenza across seasons, especially at large scales. This study aimed to evaluate seasons' modifying effects on associations between air pollutants and influenza from 10 cities of southern China. Through scientific evidence, it provides mitigation and adaptation strategies with practical guidelines to local health authorities and environmental protection agencies. Daily influenza incidence, meteorological, and air pollutants data from 2016 to 2019 were collected. Quasi-Poisson regression with a distributed lag nonlinear model was used to evaluate city-specific air pollutants and influenza associations. Meta-analysis was used to pool site-specific estimates. Attributable fractions (AFs) of influenza incidence due to pollutants were calculated. Stratified analyses were conducted by season, sex, and age. Overall, the cumulative relative risk (CRR) of influenza incidence for a 10-unit increase in PM2.5, PM10, SO2, NO2, and CO was 1.45 (95% CI: 1.25, 1.68), 1.53 (95% CI: 1.29, 1.81), 1.87 (95% CI: 1.40, 2.48), 1.74 (95% CI: 1.49, 2.03), and 1.19 (95% CI: 1.04, 1.36), respectively. Children aged 0-17 were more sensitive to air pollutants in spring and winter. PM10 had greater effect on influenza than PM2.5 in autumn, winter, and overall, lesser in spring. The overall AF due to PM2.5, PM10, SO2, NO2, and CO was 4.46% (95% eCI: 2.43%, 6.43%), 5.03% (95% eCI: 2.33%, 7.56%), 5.36% (95% eCI: 3.12%, 7.58%), 24.88% (95% eCI: 18.02%, 31.67%), and 23.22% (95% eCI: 17.56%, 28.61%), respectively. AF due to O3 was 10.00% (95% eCI: 4.76%, 14.95%) and 3.65% (95% eCI: 0.50%, 6.59%) in spring and summer, respectively. The seasonal variations in the associations between air pollutants and influenza in southern China would provide evidence to service providers for tailored intervention, especially for vulnerable populations.

Impact of Taiwan's 2021 COVID-19 lockdown on the symptom severity and quality of life of patients with narcolepsy.

COVID-19 lockdowns can influence the sleep quality and daytime condition of patients with narcolepsy. Using data from our cohort study, we investigated changes in the quality of life and the symptom severity of patients with narcolepsy during Taiwan's 2021 lockdown and investigated differences by narcolepsy subtype, sex, and age. Patients with type 1 and type 2 narcolepsy (NT1 and NT2, respectively) aged 6-40 years were retrospectively recruited from our narcolepsy cohort study. These patients were regularly evaluated using the Short Form 36 Health Survey questionnaire (SF-36), the Epworth Sleepiness Scale (ESS), the visual analog scale (VAS) for hypersomnolence, the VAS for cataplexy and sleep diary. We compared the differences between the lockdown and the prelockdown periods by narcolepsy subtype, sex, and age. We used a paired t test analysis to compare differences in the SF-36, ESS, VAS scores and data of sleep diary between the prelockdown and lockdown periods (p1), and an independent t test analysis was used to compare the changes in different subgroups between the prelockdown and lockdown periods (p2). A total of 120 patients with narcolepsy were recruited (mean age 24.22 ± 6.87 years; 58% male); 80 of the patients had NT1 (mean age 25.25 ± 6.79 years; 60% male) and 40 had NT2 (mean age 22.16 ± 6.64, 53% male). During the lockdown period, the ESS score of total patients was decreased (p = 0.039) and body mass index was increased (p = 0.02). The NT1 group decreased significantly (p1 = 0.017), especially in men (p1 = 0.016) and adults (p1 = 0.04); scores for the VT domain of the SF-36 increased significantly in male and adult patients with NT2 (p1 = 0.048 and 0.012). Additionally, male patients with NT2 exhibited significantly decreased scores in the physical and emotional role functioning domains (p1 = 0.028, 0.024). The children and adolescents with NT1 had significantly decreased scores in the general health domain of the SF-36, but no significant change was noted in that of adults (p1 = 0.027, p2 = 0.012). We observed both negative and positive impacts of Taiwan's 2021 lockdown on patients with narcolepsy. A more flexible but structured daily routine with adequate sleep time should be considered for this population during lockdown and nonlockdown periods.

Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy.

Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix®. Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 and DPB1*04:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB1*06:02 loci were found in 245 vaccination-related cases, who also shared polygenic risk. T cell receptor associations in NT1 modulated TRAJ*24, TRAJ*28 and TRBV*4-2 chain-usage. Partitioned heritability and immune cell enrichment analyses found genetic signals to be driven by dendritic and helper T cells. Lastly comorbidity analysis using data from FinnGen, suggests shared effects between NT1 and other autoimmune diseases. NT1 genetic variants shape autoimmunity and response to environmental triggers, including influenza A infection and immunization with Pandemrix®.

Oral sensation and gastrointestinal digestive profiles of bigels tuned by the mass ratio of konjac glucomannan to gelatin in the binary hydrogel matrix.

Bigels with tunable oral sensation and controlled gastrointestinal digestive profiles are highly demanded in the food industry. A binary hydrogel consisting of different mass ratio of konjac glucomannan to gelatin (φ) was designed to fabricate bigels with stearic acid oleogel. The impacts of φ on the structural, rheological, tribological, flavor release, and delivery properties of bigels were investigated. Structural transition of bigels from hydrogel-in-oleogel to bi-continuous, and then to oleogel-in-hydrogel type, as φ increased from 0.6 to 0.8, and then to 1.0-1.2. Enhanced storage modulus and yield stress were achieved along with the increased φ, while the structure-recovery properties of bigel decreased with increased φ. Under all the tested φ, the viscoelastic modulus and viscosity decreased significantly at oral temperatures but maintained the gel state, and the friction coefficient increased along with the increased φ under high chewing degree. Flexible control over the swelling, the lipid digestion and the release of lipophilic cargos were also observed, with the total release of free fatty acids and quercetin significantly reduced with the increased φ. This study presents a novel manipulation strategy to control oral sensation and gastrointestinal digestive profiles of bigels via tuning the fraction of konjac glucomannan in the binary hydrogel.

Effect of Preoperative Weight Status and Disease Presentation on Postoperative Elevated Blood Pressure After Childhood Adenotonsillectomy.

OBJECTIVE: To investigate the risk factors of postoperative elevated blood pressure (BP) in children with childhood obstructive sleep apnea syndrome (OSAS) after adenotonsillectomy (AT). STUDY DESIGN: Case series with planned data collection. SETTING: Tertiary referral center. METHODS: Two hundred forty-five consecutive children (180 boys and 65 girls, median age 6.6 years) with polysomnography-diagnosed OSAS who underwent AT between January 2010 and August 2019. Clinical, polysomnographic, and evening BP data were assessed preoperatively and postoperatively (≥3 months after AT). Changes in the variables before and after AT and between individuals with and without hypertension were compared. RESULTS: Postoperatively, the median (interquartile range) apnea-hypopnea index significantly decreased from 10.4 (5.3-22.6) to 2.2 (1.0-3.8) events/h. In addition, the mean (standard deviation) evening diastolic BP z-score significantly decreased from 0.7 (0.94) to 0.5 (0.81) in the overall cohort, and both systolic (2.1 [0.94]-1.0 [1.31]) and diastolic BP z-scores (1.6 [0.98]-0.7 [0.85]) significantly decreased in the preoperative elevated BP subgroup. Multivariate logistic regression analysis showed that preoperative obesity (adjusted odds ratio = 4.36, 95% confidence interval = 2.24-8.49) and mean peripheral oxygen saturation <95% during sleep (adjusted odds ratio = 2.73, 95% confidence interval = 1.29-5.79) were independently associated with postoperative elevated BP. CONCLUSION: Preoperative obesity and mean peripheral oxygen saturation <95% during sleep were significantly associated with postoperative elevated BP in the children with OSAS, further indicating the importance of careful BP monitoring in this subgroup despite AT treatment.

Adenotonsillectomy-related changes in systemic inflammation among children with obstructive sleep apnea.

BACKGROUND: Adenotonsillar hypertrophy is the most common cause of pediatric obstructive sleep apnea (OSA). Although adenotonsillectomy considerably reduces OSA and systemic inflammation, whether and how systemic inflammation influences the effects of adenotonsillectomy on OSA has yet to be determined. METHODS: This study investigated the associations between changes in anatomical variables, % changes in subjective OSA-18 questionnaire scores, % changes in 11 polysomnographic parameters, and % changes in 27 systemic inflammatory biomarkers in 74 children with OSA. RESULTS: Fifty-six (75.6%) boys and 18 (24.4%) girls with the mean age of 7.4 ± 2.2 years and apnea-hypopnea index (AHI) of 14.2 ± 15.9 events/h were included in the statistical analysis. The mean period between before and after adenotonsillectomy was 5.6 ± 2.6 months. After adenotonsillectomy, the OSA-18 score, eight of 11 polysomnographic parameters, and 20 of 27 inflammatory biomarkers significantly improved (all p < 0.005). Notably, there were significant associations between change in tonsil size and % change in AHI ( r = 0.23), change in tonsil size and % changes in interleukin-8 (IL-8) ( r = 0.34), change in tonsil size and % change in and IL-10 ( r = -0.36), % change in IL-8 and % change in C-C chemokine ligand 5 (CCL5) ( r = 0.30), and % change in CCL5 and % change in AHI ( r = 0.38) (all p < 0.005). Interestingly, % change in IL-8 and % change in CCL5 serially mediated the relationship between change in tonsil size and % change in AHI (total effect: ß = 16.672, standard error = 8.274, p = 0.048). CONCLUSION: These preliminary findings suggest that systemic inflammation is not only a complication of OSA but also that it mediates the surgical effects, which may open avenues for potential interventions to reduce tonsil size and OSA severity through the regulation of IL-8 and CCL5.