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We examined COVID-19 symptoms and infection rates, disruptions to functioning, and moderators of pandemic response for 620 youth with ADHD and 614 individually matched controls (70% male; M age = 12.4) participating in the Adolescent Brain and Cognitive Development study. There were no group differences in COVID-19 infection rate; however, youth with ADHD were more likely to exhibit COVID-19 symptoms (d = 0.25), greater sleep problems (d = −0.52), fear and negative emotions to infection risk (d = −0.56), trouble with remote learning (d = −0.54), rule-breaking behavior related to COVID-19 restrictions (d = −0.23), family conflict (d = −0.13), and were less prepared for the next school year (d = 0.38). Youth with ADHD were less responsive to protective environmental variables (e.g., parental monitoring, school engagement) during the pandemic and may need more specialized support with return to in-person schooling and daily activities. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) is a leading cause of respiratory tract infections in infants. Macroautophagy/autophagy is a catalytic metabolic process required for cellular homeostasis. Although intracellular metabolism is important for immune responses in dendritic cells, the link between autophagy and immunometabolism remains unknown. Here, we show that the autophagy-related protein ATG5 regulates immunometabolism. Atg5-deficient mouse dendritic cells showed increased CD8A+ T-cell response and increased secretion of proinflammatory cytokines upon RSV infection. Transcriptome analysis showed that Atg5 deficiency alters the expression of metabolism-related genes. Atg5-deficient dendritic cells also showed increased activation of glycolysis and the AKT-MTOR-RPS6KB1 pathway and decreased mitochondrial activity, all of which are cellular signatures for metabolic activation. These cells also showed elevated CD8A+ T-cell priming and surface major histocompatibility complex (MHC) class I expression. Our results suggested that ATG5 regulated host immune responses by modulating dendritic cell metabolism. These findings may help develop potential antiviral therapies that alter host immunity by regulating autophagy and immunometabolism. Abbreviations : 2-DG: 2-deoxyglucose; AAK1: AP2 associated kinase 1; AKT: AKT serine/threonine kinase; AM: alveolar macrophage; ATG: autophagy; ATP: adenosine triphosphate; BAL: bronchoalveolar lavage; BMDC: bone marrow dendritic cell; CSF2/GM-CSF: colony-stimulating factor 2 (granulocyte-macrophage); CTL: cytotoxic T lymphocyte; ELISA: enzyme-linked immunosorbent assay; GFP: green fluorescent protein; GSEA: gene-set enrichment analysis; H-2Db: H-2 class I histocompatibility antigen, D-B alpha chain; H-2Kb: MHC class I H2-K-b; HIF1A: hypoxia-inducible factor 1 alpha; IFNG: interferon-gamma; IL: interleukin; ITGAX: integrin alpha X; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MHC: major histocompatibility complex; MTORC1: mammalian target of rapamycin kinase complex 1; PBS: phosphate-buffered saline; PFU: plaque-forming unit; RLR: retinoic acid-inducible-I-like receptor; ROS: reactive oxygen species; RPMI: Roswell Park Memorial Institute; RPS6KB1/S6K: ribosomal protein S6 kinase, polypeptide 1; RSV: respiratory syncytial virus; Th: T helper; TLR: toll-like receptor; Treg: regulatory T cells; UMAP: uniform manifold approximation and projection. [ABSTRACT FROM AUTHOR]

We aimed to examine the difference in rest-activity rhythm (RAR) and light exposure rhythm (LER) between patients with mild cognitive impairment (MCI) and normal controls (NC), and to verify their relationships with cognitive functions. The neuropsychological battery was administered to participants above 50 years old. The MCI diagnosis was made according to Petersen’s criteria. Ten patients with MCI (77.90 ± 6.95 years) and eight NC (74.75 ± 5.06 years) were studied. Actigraphy (Actiwatch 2; Philips Respironics) was recorded at home for 5 days. RAR and LER variables, including interdaily stability (IS), intradaily variability (IV) and relative amplitude, were calculated using nonparametric analyses. The associations between cognitive performance and RAR and LER variables were explored using generalized linear models. There were no significant differences in RAR or LER variables between MCI and NC. There was a significant main effect of RAR-IS on the Stroop Color and Word Test (SCWT), indicating a positive relationship between RAR stability and SCWT performance. There was a significant group by RAR-IS interaction on Trail Making Test-A, indicating a negative relationship in MCI compared to NC. There was a significant group by LER-IV interaction on the Boston Naming Test, indicating a positive relationship in MCI compared to NC. There was no disruption in RAR and LER in patients with MCI. Our study showed that circadian rhythm abnormality was associated with a decline in executive function. However, circadian rhythm abnormality was not associated with declines in processing speed and language function in patients with MCI, implying an altered pathophysiology compared to NC.

Bile acids (BAs) control metabolism and inflammation by interacting with several receptors. Here, we report that intravenous infusion of taurodeoxycholate (TDCA) decreases serum pro-inflammatory cytokines, normalizes hypotension, protects against renal injury, and prolongs mouse survival during sepsis. TDCA increases the number of granulocytic myeloid-derived suppressor cells (MDSCLT) distinctive from MDSCs obtained without TDCA treatment (MDSCL) in the spleen of septic mice. FACS-sorted MDSCLT cells suppress T-cell proliferation and confer protection against sepsis when adoptively transferred better than MDSCL. Proteogenomic analysis indicated that TDCA controls chromatin silencing, alternative splicing, and translation of the immune proteome of MDSCLT, which increases the expression of anti-inflammatory molecules such as oncostatin, lactoferrin and CD244. TDCA also decreases the expression of pro-inflammatory molecules such as neutrophil elastase. These findings suggest that TDCA globally edits the proteome to increase the number of MDSCLT cells and affect their immune-regulatory functions to resolve systemic inflammation during sepsis. [ABSTRACT FROM AUTHOR]

Background and Objective Sleep disturbance in patients with Alzheimer’s disease (AD) could increase institutionalization due to caregiver burden. The objective of this study was to examine the relationship of subjective and objective sleep quality with caregiver burden in AD patients with insomnia symptoms. Methods AD patients of mild to moderate degree were recruited. They were assessed with the Pittsburgh Sleep Quality Index (PSQI), Korean version of the Epworth Sleepiness Scale, and Mini-Mental Status Examination in the Korean version of Consortium to Establish a Registry for Alzheimer’s Disease Assessment Packet. Caregiver burden was evaluated with Korean version of the Neuropsychiatric Inventory Questionnaire (KNPI-Q) and Korean version of the Zarit Burden Interview (ZBI-K). Actigraphy recording (Actiwatch 2; Philips Respironics) was conducted for five days at home. Thirty-four patients (age 78.44 ± 6.14, M:F = 9:25) were analyzed. These patients were divided into two groups by the median of KNPI-Q for caregiver distress [KNPI-Q(d)] and ZBI-K scores. Sleep parameters were compared between the two groups. Results Among seven components of PSQI, sleep latency was correlated with KNPI-Q(d) score. The patients with higher KNPI-Q(d) scores had lower sleep efficiency (SE) (p = 0.002), greater wake after sleep onset (p = 0.037), and higher fragmentation index (p = 0.040) than those with lower KNPI-Q(d) scores. Those with higher ZBI-K scores had lower SE (p = 0.026) than those with lower ZBI-K scores. Stepwise multiple regression revealed that SE predicted 16% of KNPI-Q(d) scores (p = 0.012). Conclusions Difficulty in sleep initiation according to subjective reports was associated with caregiver burden in our AD patients. In objective sleep quality, a significant difference in difficulty of sleep maintenance was found between higher and lower caregiver burden groups. This suggests that sleep maintenance is essential for reducing caregiver burden.

Abstract Conflicting results have been reported regarding the effectiveness of light treatment (LT) in patients with Alzheimer’s disease (AD). We investigated the effectiveness of blue-enriched white LT on sleep, cognition, mood and behavior in patients with mild and moderate AD. The treatment group (n = 14) sat about 60 cm away from a small (136 × 73 × 16 mm) LED light box for 1 h each morning for 2 weeks. The control group (n = 11) wore dark, blue-attenuating sunglasses during the 1 h exposures. The morning light started 9–10 h after each individual’s dim light melatonin onset (DLMO). Assessments were done at baseline (T0), immediate post-treatment (T1), and 4 weeks after the end of the 2 weeks of LT (T2). Sleep was measured by actigraphy. Blue-enriched LT had a significantly better effect on the Pittsburgh Sleep Quality Index at T2 compared to blue-attenuated LT, and a trend of better effectiveness on total sleep time at T2. There was a significant increase in Mini-Mental State Examination score at T2 after blue-enriched LT than that at T0. Our findings suggest that morning blue-enriched LT has a benefit in improving sleep and cognitive function in AD patients.

Selecting participants who constitute a representative sample while protecting them from potential adverse outcomes is a concern for clinical researchers. Our research group conducts deep phenotyping studies of the circadian timing system and sleep–wake regulation in long (up to 3 months) laboratory experiments, similar in many ways to “exceptional environment” conditions. Here, we describe the psychological screening process we have used for more than 30 years. We outline our “Select In” and “Select Out” measures within three major categories: psychological, psychophysiological, and psychosocial factors. We describe the screening process, inclusion–exclusion criteria on standard questionnaires, and clinical interview questions. We also describe how we manage the exclusion process during screening, ensure continued psychological health during the laboratory study, and manage study terminations. We present data from one recent study, outlining the number of individuals excluded at each stage of the process and present subjective mood data from the included individuals, showing the trajectory of mood across the five-week laboratory study and the end-of-study debriefing, during which the participants rated their comfort with various aspects of the study and their willingness to return for a future study. While designed for our inpatient research studies, elements of these procedures may also be useful for selecting individuals for other exceptional environments.

Background and Objective We aimed to compare the differences in the subjective and objective sleep quality, and quality of life (QOL) according to the duration and timing of exercise in community-dwelling adults, and to compare these between the exercise group (EG) and non-exercise group (non-EG) in insomnia patients. Methods We recruited 223 volunteers (EG: n = 119, age: 60.8 ± 12.8 years; non-EG: n = 104, age 61.6 ± 13.3 years), who visited to 3 Public Health Centers in a rural area of South Korea. The Pittsburgh Sleep Quality Index (PSQI), Korean version of Epworth Sleepiness Scale (KESS), and Short Form-12 Health Survey Questionnaire (SF-12) were administered for each subject. Actigraphy (Actiwatch-2, Philips Respironics Co.) recording was done for 7 days at home, and we included the data of 183 subjects in our analysis. We compared the scores of questionnaires and objective sleep parameters according to the duration and timing of exercise, and compared these between the EG and non-EG in insomnia patients. Results Physical component summary (PCS) scores in SF-12 were higher in the EG for more than 60 minutes per day. In the subjects with outdoor exercise, the afternoon EG had lower PSQI scores and higher KESS scores. In insomnia patients, PCS scores in the EG was higher than those of the non-EG. Conclusions Community-dwelling adults who exercised for more than one hour showed higher physical QOL compared to those for less than one hour. Insomnia patients who exercised also showed higher physical QOL. In outdoor exercise, afternoon exercise would be beneficial for subjective sleep quality than morning exercise.

Background and Objective Individuals have a unique circadian preference, which is based on differences in endogenous rhythm and environmental factors. There has been no study on the relationship between the morningness-eveningness (ME) preference and the polymorphisms of PER2 and CRY1 genes, which may play an essential role in the modulation of circadian rhythm. Our present study aims to examine the difference in the polymorphisms of PER2-2221A/G and CRY1-2790T/G, which are related to a greater cancer risk, according to the ME preference. Methods The Korean version of the Morningness-Eveningness Questionnaire was administered and buccal DNA samples were obtained from 425 Korean adults aged 18 years or older. We excluded subjects who were being treated for sleep disorders or those with shift work. 47 morning type (MT) (age: 44.57 ± 12.33, M:F = 14:33) subjects, 59 neither type (NT) (age: 35.20 ± 9.53, M:F = 20:39) subjects and 51 evening type (ET) (age: 28.80 ± 8.03, M:F = 14:37) subjects were finally included in the present study. The above candidate single nucleotide polymorphisms were analyzed by DNA sequencing or a SNaPshot assay. Results For the PER2-2221A/G and CRY1-2790T/G, there were no significant differences in the genotype distribution, allele frequency, or proportion of G allele positive subjects between the MT and ET groups. There was no significant difference in the mean scores of the MEQ-K, KESS, or PSQI between G allele positive and negative subjects for either PER2-A2221A/G or CRY1-2790T/G. Conclusions Our study did not support the association of the ME preference with the PER2-2221 A/G and CRY1-2790T/G in Korean adults.

Influenza viruses cause infectious respiratory disease characterized by fever, myalgia, and congestion, ranging in severity from mild to life-threating. Although enormous efforts have aimed to prevent and treat influenza infections, seasonal and pandemic influenza outbreaks remain a major public health concern. This is largely because influenza viruses rapidly undergo genetic mutations that restrict the long-lasting efficacy of vaccine-induced immune responses and therapeutic regimens. In this review, we discuss the virological features of influenza A viruses and provide an overview of current knowledge of the innate sensing of invading influenza viruses and the protective immune responses in the host. [ABSTRACT FROM AUTHOR]

Background and Objective Previous studies in adults have focused on differences in sleep timing with respect to morning and evening (ME) types, or gender difference in the distribution of ME types. We aimed to examine sleep habits and behaviors (daytime sleepiness and caffeine consumption) of adult ME types, and to examine whether the factors associated with ME type differed between men and women. Methods Among 1,086 subjects to whom we administered the Korean version of Horne-Ostberg Morningness-Eveningness Questionnaire (MEQ-K), the Korean version of the Epworth Sleepiness Scale (KESS), the Pittsburgh Sleep Quality Index (PSQI) and asked questions about their sleep-wake timing and caffeine use, the data from 911 subjects (age: 38.4 ± 10.9 years, range: 18–88; F : M = 565 : 346) were analyzed. Standard scores of the MEQ were used to categorize the subjects as morning type (MT), evening type (ET) and neither type (NT). Results In the overall group, results from the PSQI indicated a significantly shorter sleep duration and greater caffeine consumption in ET when compared to those of MT or NT (p < 0.05). This was also found in the subgroup of women (p < 0.01), but not in the subgroup of men. Daytime sleepiness as reported on the KESS was significantly greater in the ET than the NT or MT overall (p < 0.05) and among the women (p < 0.01), but did not reach significance among men. Conclusions Our study found that ET subjects perceived their sleep quality as poorer than that of MT or NT subjects regardless of gender. We also found that ET women had significantly shorter sleep duration, greater daytime sleepiness, and larger caffeine consumption than MT or NT women, but we did not find the same findings in the men.

Background and Objective Sleep disturbances resulting from a mismatch between the sleep-wake schedule and an individual’s chronotype can influence work or school performance and numerous health outcomes. Individual chronotype can be determined by genetic factors, and is influenced by environmental factors which could change throughout life. We aimed to examine self-reported changes in chronotype during three different periods of life (childhood, teenage years, and adulthood). Methods Three hundred forty-three (age: 37.8 ± 11.6 years, range: 18–82; F: M = 214: 129) adult visitors to a National Museum in Korea were recruited for this study. The Korean version of the Horne-Östberg Morningness-Eveningness Questionnaire (MEQ-K) was administered and standard MEQ-K scores were used to categorize subjects as morning type (MT), evening type (ET), or neither type (NT). Binary logistic regression analyses were applied to examine the relationships of gender, current age, and childhood/teenager ME type with change in chronotype between childhood, teenage years, and adulthood. Results The ages, gender distribution, and years of education were different between the chronotype groups (p < 0.01). Individuals who reported childhood MT or ET had a lower probability of changing their chronotype between childhood and their teenage years compared with individuals reporting childhood NT (p < 0.0001), whereas individuals reporting teenage MT or ET had a higher probability (p < 0.0001). Furthermore, older individuals had a lower probability of reporting a chronotype change between childhood or teenage years and adulthood (p < 0.01). Conclusions Most individuals reported the same chronotype from childhood to their teenage years but a different chronotype between the teenage years and adulthood. Older age was associated with a lower probability of reporting a different chronotype during childhood or teenage years.

Respiratory syncytial virus (RSV) is a major cause of severe respiratory disease in infants and the elderly. The socioeconomic burden of RSV infection is substantial because it leads to serious respiratory problems, subsequent hospitalization, and mortality. Despite its clinical significance, a safe and effective vaccine is not yet available to prevent RSV infection. Upon RSV infection, lung dendritic cells (DCs) detecting pathogens migrate to the lymph nodes and activate the adaptive immune response. Therefore, RSV has evolved various immunomodulatory strategies to inhibit DC function. Due to the capacity of RSV to modulate defense mechanisms in hosts, RSV infection results in inappropriate activation of immune responses resulting in immunopathology and frequent reinfection throughout life. This review discusses how DCs recognize invading RSV and induce adaptive immune responses, as well as the regulatory mechanisms mediated by RSV to disrupt DC functions and ultimately avoid host defenses. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) is the leading cause of respiratory viral infection in infants and children, yet little is known about the antiviral response of plasmacytoid dendritic cells (pDCs) to RSV infection. We tracked the cellular source of interferon-β using interferon-β/yellow fluorescent protein (YFP) reporter mice and identified the signaling pathway activated by RSV that induces type I interferon production in pDCs and DCs. Results from in vitro analyses of RSV-stimulated bone marrow cells revealed that RSV induces interferon-β production in both pDCs and DCs. Kinetic analyses of interferon-β-producing cells in RSV-infected lung cells in vivo indicated that pDCs are rapidly recruited to sites of inflammation during infection. These cells produced interferon-β via the TLR7-MyD88-mediated pathway and IFNα1R-mediated pathway rather than the MAVS-mediated pathway. Moreover, pDC-ablated mice exhibited decreased interferon-γ production and the antigen specificity of CD8+ T cells. Collectively, these data indicate that pDCs play pivotal roles in cytotoxic T lymphocyte (CTL) responses and are one of producers of type I interferon during RSV infection. [ABSTRACT FROM AUTHOR]

Dynamin-like GTPase myxovirus resistance protein 1 (Mx1) is an intracellular anti-viral protein following the activation of type I and type III interferon signaling. Mx1 inhibits viral replication by blocking the transcription of viral RNA, and a deficiency in this protein enhances susceptibility to influenza infection. Thus, Mx1 could be another efficient target of anti-influenza therapy. To test our hypothesis, we fused poly-arginine cell-penetrating peptides to the C terminus of Mx1 (Mx1-9R) and examined the anti-viral activity of Mx1-9R in vitro and in vivo. Madin-Darby Canine Kidney epithelial cells internalized the Mx1-9R within 12 h. Pre-exposure Mx1-9R treatment inhibited viral replication and viral RNA expression in infected cells. Further, intranasal administration of Mx1-9R improved the survival of mice infected with the PR8 influenza viral strain. These data support the consideration of Mx1-9R as a novel therapeutic agent against mucosal influenza virus infection. [ABSTRACT FROM AUTHOR]