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Identifying factors that predict higher levels of children's subjective well-being (SWB) is imperative for practice and policy implications. The current study explored latent subgroups of risks characterized by various dimensions of child well-being and investigated whether the latent risk groups were associated with children's SWB across 16 nations. The moderating role of subjective child rights as a protective factor in the relationship between latent risk profiles and children's SWB was also examined. Data of children aged 12 years from the second wave of the International Survey of Children's Well-Being (N = 19,212) was analyzed. Latent profile analysis was used to identify risk profiles based on children's different risk experiences, and subsequently, multilevel regression analysis was used to identify whether group membership predicted SWB. Five latent profiles were identified: low, moderate, dual, material, and victimization risk groups. Findings revealed the concurrent nature of risks in children's lives, as they are often exposed to deficiencies across multiple domains, rather than just one. Multilevel regression analysis results signified that membership in any risk profile is linked with lower SWB of children when compared to the low risk group and highlighted the significant conditioning role of subjective child rights in the relationship between the risk profiles and SWB. Policymakers should be aware of the co-experience of multiple risk factors and devise policies that meet the needs of various groups of children at risk and advocate children as rights holders to further help children with co-occurring risks attain a higher level of SWB. [ABSTRACT FROM AUTHOR]

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]

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]

Objective: To find an association between cognitive-perceptual problems of older drivers and unsafe driving performance during simulated automobile driving in a virtual environment. Design: Cross-sectional study. Setting: A driver evaluation clinic in a rehabilitation hospital. Participants: Fifty-five drivers aged 65 years or older and 48 drivers in their late twenties to early forties. Methods: All participants underwent evaluation of cognitive-perceptual function and driving performance, and the results were compared between older and younger drivers. The association between cognitive-perceptual function and driving performance was analyzed. Main Outcome Measurements: Cognitive-perceptual function was evaluated with the Cognitive Perceptual Assessment for Driving (CPAD), a computer-based assessment tool consisting of depth perception, sustained attention, divided attention, the Stroop test, the digit span test, field dependency, and trail-making test A and B. Driving performance was evaluated with use of a virtual reality–based driving simulator. During simulated driving, car crashes were recorded, and an occupational therapist observed unsafe performances in controlling speed, braking, steering, vehicle positioning, making lane changes, and making turns. Results: Thirty-five older drivers did not pass the CPAD test, whereas all of the younger drivers passed the test. When using the driving simulator, a significantly greater number of older drivers experienced car crashes and demonstrated unsafe performance in controlling speed, steering, and making lane changes. CPAD results were associated with car crashes, steering, vehicle positioning, and making lane changes. Older drivers who did not pass the CPAD test are 4 times more likely to experience a car crash, 3.5 times more likely to make errors in steering, 2.8 times more likely to make errors in vehicle positioning, and 6.5 times more likely to make errors in lane changes than are drivers who passed the CPAD test. Conclusion: Unsafe driving performance and car crashes during simulated driving were more prevalent in older drivers than in younger drivers. Unsafe performance in steering, vehicle positioning, making lane changes, and car crashes were associated with cognitive-perceptual dysfunction. [Copyright &y& Elsevier]

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]

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]