Causality Network of Infectious Disease Revealed With Causal Decomposition.

Causal inference in the field of infectious disease attempts to gain insight into the potential causal nature of an association between risk factors and diseases. Simulated causality inference experiments have shown preliminary promise in improving understanding of the transmission of infectious diseases but still lack sufficient quantitative causal inference studies based on real-world data. Here, we investigate the causal interactions between three different infectious diseases and related factors, using causal decomposition analysis, to characterize the nature of infectious disease transmission. We show that the complex interactions between infectious disease and human behavior have a quantifiable impact on transmission efficiency of infectious diseases. Our findings, by shedding light on the underlying transmission mechanism of infectious diseases, suggest that causal inference analysis is a promising approach to determine epidemiological interventions.

Colonization of nasal cavities by Staphylococcus epidermidis mitigates SARS-CoV-2 nucleocapsid phosphoprotein-induced interleukin (IL)-6 in the lung.

Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can trigger excessive interleukin (IL)-6 signalling, leading to a myriad of biological effects including a cytokine storm that contributes to multiple organ failure in severe coronavirus disease 2019 (COVID-19). Using a mouse model, we demonstrated that nasal inoculation of nucleocapsid phosphoprotein (NPP) of SARS-CoV-2 increased IL-6 content in bronchoalveolar lavage fluid (BALF). Nasal administration of liquid coco-caprylate/caprate (LCC) onto Staphylococcus epidermidis (S. epidermidis)-colonized mice significantly attenuated NPP-induced IL-6. Furthermore, S. epidermidis-mediated LCC fermentation to generate electricity and butyric acid that promoted bacterial colonization and activated free fatty acid receptor 2 (Ffar2) respectively. Inhibition of Ffar2 impeded the effect of S. epidermidis plus LCC on the reduction of NPP-induced IL-6. Collectively, these results suggest that nasal S. epidermidis is part of the first line of defence in ameliorating a cytokine storm induced by airway infection of SARS-CoV-2.

Effectiveness of Digital Cognitive Behavioral Therapy for Insomnia in Young People: Preliminary Findings from Systematic Review and Meta-Analysis.

Various forms of cognitive behavioral therapy for insomnia (CBT-i) have been developed to improve its scalability and accessibility for insomnia management in young people, but the efficacy of digitally-delivered cognitive behavioral therapy for insomnia (dCBT-i) remains uncertain. This study systematically reviewed and evaluated the effectiveness of dCBT-i among young individuals with insomnia. We conducted comprehensive searches using four electronic databases (PubMed, Cochrane Library, PsycINFO, and Embase; until October 2021) and examined eligible records. The search strategy comprised the following three main concepts: (1) participants were adolescents or active college students; (2) dCBT-I was employed; (3) standardized tools were used for outcome measurement. Four randomized controlled trials qualified for meta-analysis. A significant improvement in self-reported sleep quality with a medium-to-large effect size after treatment (Hedges's g = -0.58~-0.80) was noted. However, a limited effect was detected regarding objective sleep quality improvement (total sleep time and sleep efficiency measured using actigraphy). These preliminary findings from the meta-analysis suggest that dCBT-i is a moderately effective treatment in managing insomnia in younger age groups, and CBT-i delivered through the web or a mobile application is an acceptable approach for promoting sleep health in young people.

Gut probiotic Lactobacillus rhamnosus attenuates PDE4B-mediated interleukin-6 induced by SARS-CoV-2 membrane glycoprotein.

Membrane glycoprotein is the most abundant protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but its role in coronavirus disease 2019 (COVID-19) has not been fully characterized. Mice intranasally inoculated with membrane glycoprotein substantially increased the interleukin (IL)-6, a hallmark of the cytokine storm, in bronchoalveolar lavage fluid (BALF), compared to mice inoculated with green fluorescent protein (GFP). The high level of IL-6 induced by membrane glycoprotein was significantly diminished in phosphodiesterase 4 (PDE4B) knockout mice, demonstrating the essential role of PDE4B in IL-6 signaling. Mycelium fermentation of Lactobacillus rhamnosus (L. rhamnosus) EH8 strain yielded butyric acid, which can down-regulate the PDE4B expression and IL-6 secretion in macrophages. Feeding mice with mycelia increased the relative abundance of commensal L. rhamnosus. Two-week supplementation of mice with L. rhamnosus plus mycelia considerably decreased membrane glycoprotein-induced PDE4B expression and IL-6 secretion. The probiotic activity of L. rhamnosus plus mycelia against membrane glycoprotein was abolished in mice treated with GLPG-0974, an antagonist of free fatty acid receptor 2 (Ffar2). Activation of Ffar2 in the gut-lung axis for down-regulation of the PDE4B-IL-6 signalling may provide targets for development of modalities including probiotics for treatment of the cytokine storm in COVID-19.