Hops bitter β-acids have antibacterial effects against sinonasal Staphylococcus aureus but also induce sinonasal cilia and mitochondrial dysfunction.

Background: Routine prescription of antibiotics to treat chronic rhinosinusitis (CRS) exacerbations may contribute to the propagation of antibiotic resistance. Hops bitter β-acids lupulone and colupulone possess potent antibacterial activities and, as T2R1, T2R14, and/or T2R40 agonists, may improve the impaired mucociliary clearance described in CRS patients. We investigated these molecules as alternative treatments to antibiotics in CRS management based on their antibacterial and T2Rs agonists properties.

Common Cold Coronavirus 229E Induces Higher Interferon Stimulating Gene Responses in Human Nasal Epithelial Cells from Patients with Chronic Rhinosinusitis with Polyposis.

Background: Viral infections have long been implicated in the development of chronic rhinosinusitis with nasal polyps (CRSwNP). Given widespread exposure to the common cold coronavirus 229E (HCoV229E), we sought to investigate how HCoV-229E is cleared and stimulates interferon pathways in air-liquid interface (ALI) cultures from patients with CRSwNP.

Objective: The objective of this study was to identify whether viral clearance and ISG expression is different in ALI cultures from donors with CRSwNP compared with controls.

Interferon signaling in the nasal epithelium distinguishes among lethal and common cold coronaviruses and mediates viral clearance.

All respiratory viruses establish primary infections in the nasal epithelium, where efficient innate immune induction may prevent dissemination to the lower airway and thus minimize pathogenesis. Human coronaviruses (HCoVs) cause a range of pathologies, but the host and viral determinants of disease during common cold versus lethal HCoV infections are poorly understood. We model the initial site of infection using primary nasal epithelial cells cultured at an air-liquid interface (ALI).

SARS-CoV-2 nsp15 endoribonuclease antagonizes dsRNA-induced antiviral signaling.

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has caused millions of deaths since its emergence in 2019. Innate immune antagonism by lethal CoVs such as SARS-CoV-2 is crucial for optimal replication and pathogenesis. The conserved nonstructural protein 15 (nsp15) endoribonuclease (EndoU) limits activation of double-stranded (ds)RNA-induced pathways, including interferon (IFN) signaling, protein kinase R (PKR), and oligoadenylate synthetase/ribonuclease L (OAS/RNase L) during diverse CoV infections including murine coronavirus and Middle East respiratory syndrome (MERS)-CoV.

Comparison of SARS-CoV-2 variants of concern in primary human nasal cultures demonstrates Delta as most cytopathic and Omicron as fastest replicating.

Unlabelled: The SARS-CoV-2 pandemic was marked with emerging viral variants, some of which were designated as variants of concern (VOCs) due to selection and rapid circulation in the human population. Here, we elucidate functional features of each VOC linked to variations in replication rate. Patient-derived primary nasal cultures grown at air-liquid interface were used to model upper respiratory infection and compared to cell lines derived from human lung epithelia.

Interferon signaling in the nasal epithelium distinguishes among lethal and common cold respiratory viruses and is critical for viral clearance.

All respiratory viruses establish primary infections in the nasal epithelium, where efficient innate immune induction may prevent dissemination to the lower airway and thus minimize pathogenesis. Human coronaviruses (HCoVs) cause a range of pathologies, but the host and viral determinants of disease during common cold versus lethal HCoV infections are poorly understood. We model the initial site of infection using primary nasal epithelial cells cultured at air-liquid interface (ALI).

SARS-CoV-2 nsp15 endoribonuclease antagonizes dsRNA-induced antiviral signaling.

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has caused millions of deaths since emerging in 2019. Innate immune antagonism by lethal CoVs such as SARS-CoV-2 is crucial for optimal replication and pathogenesis. The conserved nonstructural protein 15 (nsp15) endoribonuclease (EndoU) limits activation of double-stranded (ds)RNA-induced pathways, including interferon (IFN) signaling, protein kinase R (PKR), and oligoadenylate synthetase/ribonuclease L (OAS/RNase L) during diverse CoV infections including murine coronavirus and Middle East respiratory syndrome (MERS)-CoV.

Infection of Primary Nasal Epithelial Cells Grown at an Air-Liquid Interface to Characterize Human Coronavirus-Host Interactions.

Three highly pathogenic human coronaviruses (HCoVs) - SARS-CoV (2002), MERS-CoV (2012), and SARS-CoV-2 (2019) - have emerged and caused significant public health crises in the past 20 years. Four additional HCoVs cause a significant portion of common cold cases each year (HCoV-NL63, -229E, -OC43, and -HKU1), highlighting the importance of studying these viruses in physiologically relevant systems. HCoVs enter the respiratory tract and establish infection in the nasal epithelium, the primary site encountered by all respiratory pathogens.

Comparison of SARS-CoV-2 variants of concern in primary human nasal cultures demonstrates Delta as most cytopathic and Omicron as fastest replicating.

The SARS-CoV-2 pandemic was marked with emerging viral variants, some of which were designated as variants of concern (VOCs) due to selection and rapid circulation in the human population. Here we elucidate functional features of each VOC linked to variations in replication rate. Patient-derived primary nasal cultures grown at air-liquid-interface (ALI) were used to model upper-respiratory infection and human lung epithelial cell lines used to model lower-respiratory infection.

Infection of primary nasal epithelial cells differentiates among lethal and seasonal human coronaviruses.

The nasal epithelium is the initial entry portal and primary barrier to infection by all human coronaviruses (HCoVs). We utilize primary human nasal epithelial cells grown at air-liquid interface, which recapitulate the heterogeneous cellular population as well as mucociliary clearance functions of the in vivo nasal epithelium, to compare lethal [Severe acute respiratory syndrome (SARS)-CoV-2 and Middle East respiratory syndrome-CoV (MERS-CoV)] and seasonal (HCoV-NL63 and HCoV-229E) HCoVs. All four HCoVs replicate productively in nasal cultures, though replication is differentially modulated by temperature.

Microbial metabolite succinate activates solitary chemosensory cells in the human sinonasal epithelium.

Background: Succinate, although most famous for its role in the Krebs cycle, can be released extracellularly as a signal of cellular distress, particularly in situations of metabolic stress and inflammation. Solitary chemosensory cells (SCCs) express SUCNR1, the succinate receptor, and modulate type 2 inflammatory responses in helminth and protozoal infections in the small intestine. SCCs are the dominant epithelial source of interleukin-25, as well as an important source of cysteinyl leukotrienes in the airway, and have been implicated as upstream agents in type 2 inflammation in chronic rhinosinusitis (CRS) and asthma.

Physical activity and exercise alter cognitive abilities, and brain structure and activity in obese children.

The prevalence of childhood obesity is increasing to such an extent that it has become a major global public health problem in the 21st century. Obesity alters children's brain structure and activity and impairs their cognitive abilities. On the basis of these findings, it is necessary for educational and healthcare institutions to combat childhood obesity through preventive and therapeutic strategies.

Infection of primary nasal epithelial cells differentiates among lethal and seasonal human coronaviruses.

The nasal epithelium is the initial entry portal and primary barrier to infection by all human coronaviruses (HCoVs). We utilize primary nasal epithelial cells grown at air-liquid interface, which recapitulate the heterogeneous cellular population as well as mucociliary clearance functions of the nasal epithelium, to compare lethal (SARS-CoV-2 and MERS-CoV) and seasonal (HCoV-NL63 and HCoV-229E) HCoVs. All four HCoVs replicate productively in nasal cultures but diverge significantly in terms of cytotoxicity induced following infection, as the seasonal HCoVs as well as SARS-CoV-2 cause cellular cytotoxicity as well as epithelial barrier disruption, while MERS-CoV does not.

Lifespan developmental changes in neural substrates and functional connectivity for visual semantic processing.

Human learning and cognitive functions change with age and experience, with late-developed complex cognitive functions, particularly those served by the prefrontal cortex, showing more age-dependent variance. Reading as a complex process of constructing meaning from print uses the left prefrontal cortex and may show a similar aging pattern. In this study, we delineated the lifespan developmental changes in the neural substrates and functional connectivity for visual semantic processing from childhood (age 6) to late adulthood (age 74).

Distinct spatiotemporal patterns of syntactic and semantic processing in human inferior frontal gyrus.

Human languages are based on syntax, a set of rules which allow an infinite number of meaningful sentences to be constructed from a finite set of words. A theory associated with Chomsky and others holds that syntax is a mind-internal, universal structure independent of semantics. This theory, however, has been challenged by studies of the Chinese language showing that syntax is processed under the semantic umbrella, and is secondary and not independent.

MERS-CoV endoribonuclease and accessory proteins jointly evade host innate immunity during infection of lung and nasal epithelial cells.

Middle East respiratory syndrome coronavirus (MERS-CoV) emerged into humans in 2012, causing highly lethal respiratory disease. The severity of disease may be, in part, because MERS-CoV is adept at antagonizing early innate immune pathways—interferon (IFN) production and signaling, protein kinase R (PKR), and oligoadenylate synthetase/ribonuclease L (OAS/RNase L)—activated in response to viral double-stranded RNA (dsRNA) generated during genome replication. This is in contrast to severe acute respiratory syndrome CoV-2 (SARS-CoV-2), which we recently reported to activate PKR and RNase L and, to some extent, IFN signaling.

Myeloarchitectonic plasticity in elite golf players' brains.

Human neuroimaging studies have demonstrated that exercise influences the cortical structural plasticity as indexed by gray or white matter volume. It remains elusive, however, whether exercise affects cortical changes at the finer-grained myelination structure level. To answer this question, we scanned 28 elite golf players in comparison with control participants, using a novel neuroimaging technique-quantitative magnetic resonance imaging (qMRI).

Steroid affected cytokines in aspirin-exacerbated respiratory disease.

Background: Patients with aspirin-exacerbated respiratory disease (AERD) are among the most challenging rhinologic patients to treat. AERD has a complex inflammatory milieu of lipid mediators and cytokines. In this study we evaluated cytokine differences in the complex AERD environment at the mucus, epithelial, and tissue levels.

Is phonological deficit a necessary or sufficient condition for Chinese reading disability?

While phonological skills have been found to be correlated with reading across different writing systems, recent findings have shown that developmental dyslexia in Chinese individuals has multiple deficits, and no single factor has ever been identified as crucial for learning this writing system. To examine whether a deficit in the phonological or another cognitive domain is a necessary or sufficient condition for Chinese reading disability, this study examined the cognitive profiles of 521 good readers and 502 dyslexic readers in Chinese primary schools using a battery of behavioral measures covering phonological, visual, orthographic, visual-motor coordination and working memory skills. The results showed that among all cognitive measures, phonological skills correlated more strongly with character reading performance but that poor phonological skills did not necessarily or sufficiently lead to poor reading performance in Chinese.

MERS-CoV endoribonuclease and accessory proteins jointly evade host innate immunity during infection of lung and nasal epithelial cells.

Unlabelled: Middle East respiratory syndrome coronavirus (MERS-CoV) emerged into humans in 2012, causing highly lethal respiratory disease. The severity of disease may be in part because MERS-CoV is adept at antagonizing early innate immune pathways - interferon (IFN) production and signaling, protein kinase R (PKR), and oligoadenylate synthetase ribonuclease L (OAS/RNase L) - generated in response to viral double-stranded (ds)RNA generated during genome replication. This is in contrast to SARS-CoV-2, which we recently reported activates PKR and RNase L and to some extent, IFN signaling.

An Evaluation of the Performance of Five Burnout Screening Tools: A Multicentre Study in Anaesthesiology, Intensive Care, and Ancillary Staff.

Burnout is an important occupational hazard and early detection is paramount in preventing negative sequelae in physicians, patients, and healthcare systems. Several screening tools have been developed to replace lengthy diagnostic tools for large-scale screening, however, comprehensive head-to-head evaluation for performance and accuracy are lacking. The primary objective of this study was to compare the diagnostic performance of five burnout screening tools, including a novel rapid burnout screening tool (RBST).

Fragment-based lead discovery of indazole-based compounds as AXL kinase inhibitors.

AXL is a member of the TAM (TYRO3, AXL, MER) subfamily of receptor tyrosine kinases. It is upregulated in a variety of cancers and its overexpression is associated with poor disease prognosis and acquired drug resistance. Utilizing a fragment-based lead discovery approach, a new indazole-based AXL inhibitor was obtained.