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Frontiers in Pharmacology 2023Postoperative sore throat (POST) is one of the most reported complications after general anesthesia with an incidence of as high as 60% which may impact patient... (Review)
Review
Postoperative sore throat (POST) is one of the most reported complications after general anesthesia with an incidence of as high as 60% which may impact patient satisfaction and increase the cost of treatment. The aim of this review is to summarize the currently accepted approaches and new trends intended to reduce the risk and increase the treatment efficacy of POST. Difficult intubation, traumatic intubation, and several other factors contribute to the development of POST. Endotracheal intubation using a stylet-loaded tube exerts excessive pressure on the anterior tracheal wall predisposing to mucosal trauma and contributing to development of POST. Pharmacological interventions are aimed at prevention, amelioration of symptoms, and treatment of POST. Medications suggested for this purpose include corticosteroids, topical sprays and creams, non-steroidal anti-inflammatory drugs (NSAID), and N-methyl-D-aspartate (NMDA) receptor antagonists. The use of video-laryngoscopes (VL) for endotracheal intubation improves the glottic view and increases the success rates with less force required to ensure adequate laryngoscopic view. Nevertheless, despite advances in laryngoscopic devices, the incidence of POST remains high. A novel intubation technique with endotracheal tube (ETT) rotation 180 degrees (ETT 180°) has been suggested to overcome stylet related injury and, possibly, decrease the POST. To date, no clinical trials have been conducted to test the efficacy of ETT 180° in reducing the incidence of POST. Undoubtedly, the suggested method deserves further investigation to determine its role in patient care.
PubMed: 38074131
DOI: 10.3389/fphar.2023.1284071 -
NPJ Vaccines Aug 2023Mycoplasma synoviae (M. synoviae) is a serious avian pathogen that causes significant economic losses to chicken and turkey producers worldwide. The currently available...
Mycoplasma synoviae (M. synoviae) is a serious avian pathogen that causes significant economic losses to chicken and turkey producers worldwide. The currently available live attenuated and inactivated vaccines provide limited protection. The objective of this study was to identify potential subunit vaccine candidates using immunoproteomics and reverse vaccinology analyses and to evaluate their preliminary protection. Twenty-four candidate antigens were identified, and five of them, namely RS01790 (a putative sugar ABC transporter lipoprotein), BMP (a substrate-binding protein of the BMP family ABC transporter), GrpE (a nucleotide exchange factor), RS00900 (a putative nuclease), and RS00275 (an uncharacterized protein), were selected to evaluate their immunogenicity and preliminary protection. The results showed that all five antigens had good immunogenicity, and they were localized on the M. synoviae cell membrane. The antigens induced specific humoral and cellular immune responses, and the vaccinated chickens exhibited significantly greater body weight gain and lower air sac lesion scores and tracheal mucosal thicknesses. Additionally, the vaccinated chickens had lower M. synoviae loads in throat swabs than non-vaccinated chickens. The protective effect of the RS01790, BMP, GrpE, and RS00900 vaccines was better than that of the RS00275 vaccine. In conclusion, our study demonstrates the potential of subunit vaccines as a new approach to developing M. synoviae vaccines, providing new ideas for controlling the spread of M. synoviae worldwide.
PubMed: 37582795
DOI: 10.1038/s41541-023-00721-y -
Mucosal Immunology Oct 2023Although high-affinity immunoglobulin (Ig)E receptor (FcεRI) expression is upregulated in type 2 (T2)-high asthmatic airway epithelium, its functional role in airway...
Although high-affinity immunoglobulin (Ig)E receptor (FcεRI) expression is upregulated in type 2 (T2)-high asthmatic airway epithelium, its functional role in airway epithelial dysfunction has not been elucidated. Here we report the upregulated expression of FcεRI and p-EGFR (Epidermal Growth Factor Receptor), associated with decreased expression of E-cadherin and claudin-18 in bronchial biopsies of severe T2-high asthmatics compared to mild allergic asthmatics and non-T2 asthmatics. Monomeric IgE (mIgE) decreased the expression of junction proteins, E-cadherin, claudin-18, and ZO-1, and increased alarmin messenger RNA and protein expression in cultured primary bronchial epithelial cells from T2-high asthmatics. Epithelial FcεRI ligation with mIgE decreased transepithelial electric resistance in air-liquid interface cultured epithelial cells. FcεRI ligation with mIgE or IgE- Dinitrophenyl or serum of high-level allergen-specific IgE activated EGFR and Akt via activation of Src family kinases, mediating alarmin expression, junctional protein loss, and increased epithelial permeability. Furthermore, tracheal instillation of mIgE in house dust mite-sensitized mice induced airway hyper-responsiveness, junction protein loss, epithelial cell shedding, and increased epithelial permeability. Thus, our results suggest that IgE-FcεRI cross-linking in the airway epithelium is a potential and unnoticed mechanism for impaired barrier function, increased mucosal permeability, and EGFR-mediated alarmin production in T2-high asthma.
PubMed: 37536562
DOI: 10.1016/j.mucimm.2023.07.003 -
Nature Feb 2024A limitation of current SARS-CoV-2 vaccines is that they provide minimal protection against infection with current Omicron subvariants, although they still provide... (Comparative Study)
Comparative Study
A limitation of current SARS-CoV-2 vaccines is that they provide minimal protection against infection with current Omicron subvariants, although they still provide protection against severe disease. Enhanced mucosal immunity may be required to block infection and onward transmission. Intranasal administration of current vaccines has proven inconsistent, suggesting that alternative immunization strategies may be required. Here we show that intratracheal boosting with a bivalent Ad26-based SARS-CoV-2 vaccine results in substantial induction of mucosal humoral and cellular immunity and near-complete protection against SARS-CoV-2 BQ.1.1 challenge. A total of 40 previously immunized rhesus macaques were boosted with a bivalent Ad26 vaccine by the intramuscular, intranasal and intratracheal routes, or with a bivalent mRNA vaccine by the intranasal route. Ad26 boosting by the intratracheal route led to a substantial expansion of mucosal neutralizing antibodies, IgG and IgA binding antibodies, and CD8 and CD4 T cell responses, which exceeded those induced by Ad26 boosting by the intramuscular and intranasal routes. Intratracheal Ad26 boosting also led to robust upregulation of cytokine, natural killer, and T and B cell pathways in the lungs. After challenge with a high dose of SARS-CoV-2 BQ.1.1, intratracheal Ad26 boosting provided near-complete protection, whereas the other boosting strategies proved less effective. Protective efficacy correlated best with mucosal humoral and cellular immune responses. These data demonstrate that these immunization strategies induce robust mucosal immunity, suggesting the feasibility of developing vaccines that block respiratory viral infections.
Topics: Animals; Humans; Administration, Intranasal; Antibodies, Neutralizing; Antibodies, Viral; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; COVID-19; COVID-19 Vaccines; Cytokines; Immunity, Mucosal; Immunization, Secondary; Immunoglobulin A; Immunoglobulin G; Injections, Intramuscular; Killer Cells, Natural; Lung; Macaca mulatta; mRNA Vaccines; SARS-CoV-2; Trachea
PubMed: 38096903
DOI: 10.1038/s41586-023-06951-3 -
Journal of Virology Jun 2023Influenza C virus (ICV) is increasingly associated with community-acquired pneumonia (CAP) in children and its disease severity is worse than the influenza B virus, but...
Influenza C virus (ICV) is increasingly associated with community-acquired pneumonia (CAP) in children and its disease severity is worse than the influenza B virus, but similar to influenza A virus associated CAP. Despite the ubiquitous infection landscape of ICV in humans, little is known about its replication and pathobiology in animals. The goal of this study was to understand the replication kinetics, tissue tropism, and pathogenesis of human ICV (huICV) in comparison to the swine influenza D virus (swIDV) in guinea pigs. Intranasal inoculation of both viruses did not cause clinical signs, however, the infected animals shed virus in nasal washes. The huICV replicated in the nasal turbinates, soft palate, and trachea but not in the lungs while swIDV replicated in all four tissues. A comparative analysis of tropism and pathogenesis of these two related seven-segmented influenza viruses revealed that swIDV-infected animals exhibited broad tissue tropism with an increased rate of shedding on 3, 5, and 7 dpi and high viral loads in the lungs compared to huICV. Seroconversion occurred late in the huICV group at 14 dpi, while swIDV-infected animals seroconverted at 7 dpi. Guinea pigs infected with huICV exhibited mild to moderate inflammatory changes in the epithelium of the soft palate and trachea, along with mucosal damage and multifocal alveolitis in the lungs. In summary, the replication kinetics and pathobiological characteristics of ICV in guinea pigs agree with the clinical manifestation of ICV infection in humans, and hence guinea pigs could be used to study these distantly related influenza viruses. Similar to influenza A and B, ICV infections are seen associated with bacterial and viral co-infections which complicates the assessment of its real clinical significance. Further, the antivirals against influenza A and B viruses are ineffective against ICV which mandates the need to study the pathobiological aspects of this virus. Here we demonstrated that the respiratory tract of guinea pigs possesses specific viral receptors for ICV. We also compared the replication kinetics and pathogenesis of huICV and swIDV, as these viruses share 50% sequence identity. The tissue tropism and pathology associated with huICV in guinea pigs are analogous to the mild respiratory disease caused by ICV in humans, thereby demonstrating the suitability of guinea pigs to study ICV. Our comparative analysis revealed that huICV and swIDV replicated differentially in the guinea pigs suggesting that the type-specific genetic differences can result in the disparity of the viral shedding and tissue tropism.
Topics: Animals; Guinea Pigs; Humans; Administration, Intranasal; Gammainfluenzavirus; Orthomyxoviridae Infections; Thogotovirus; Disease Models, Animal; Receptors, Virus
PubMed: 37199648
DOI: 10.1128/jvi.00356-23 -
BioRxiv : the Preprint Server For... Jul 2023Excessive alcohol use is thought to increase the risk of respiratory infections by impairing mucociliary clearance (MCC). In this study, we investigate the hypothesis...
UNLABELLED
Excessive alcohol use is thought to increase the risk of respiratory infections by impairing mucociliary clearance (MCC). In this study, we investigate the hypothesis that alcohol reduces the function of CFTR, the protein that is defective in individuals with cystic fibrosis, thus altering mucus properties to impair MCC and the airway's defense against inhaled pathogens.
METHODS
Sprague Dawley rats with wild type CFTR (+/+), matched for age and sex, were administered either a Lieber-DeCarli alcohol diet or a control diet with the same number of calories for eight weeks. CFTR activity was measured using nasal potential difference (NPD) assay and Ussing chamber electrophysiology of tracheal tissue samples. In vivo MCC was determined by measuring the radiographic clearance of inhaled Tc99 particles and the depth of the airway periciliary liquid (PCL) and mucus transport rate in excised trachea using micro-optical coherence tomography (μOCT). The levels of rat lung MUC5b and CFTR were estimated by protein and mRNA analysis.
RESULTS
Alcohol diet was found to decrease CFTR ion transport in the nasal and tracheal epithelium and . This decrease in activity was also reflected in partially reduced full-length CFTR protein levels but not, in mRNA copies, in the lungs of rats. Furthermore, alcohol-fed rats showed a significant decrease in MCC after 8 weeks of alcohol consumption. The trachea from these rats also showed reduced PCL depth, indicating a decrease in mucosal surface hydration that was reflected in delayed mucus transport. Diminished MCC rate was also likely due to the elevated MUC5b expression in alcohol-fed rat lungs.
CONCLUSIONS
Excessive alcohol use can decrease the expression and activity of CFTR channels, leading to reduced airway surface hydration and impaired mucus clearance. This suggests that CFTR dysfunction plays a role in the compromised lung defense against respiratory pathogens in individuals who drink alcohol excessively.
PubMed: 37502889
DOI: 10.1101/2023.07.17.548927 -
Immunologic Research Aug 2023As the leading central immune organ, the thymus is where T cells differentiate and mature, and plays an essential regulatory role in the adaptive immune response. Tuft... (Review)
Review
As the leading central immune organ, the thymus is where T cells differentiate and mature, and plays an essential regulatory role in the adaptive immune response. Tuft cells, as chemosensory cells, were first found in rat tracheal epithelial, later gradually confirmed to exist in various mucosal and non-mucosal tissues. Although tuft cells are epithelial-derived, because of their wide heterogeneity, they show functions similar to cholinergic and immune cells in addition to chemosensory ability. As newly discovered non-mucosal tuft cells, thymic tuft cells have been demonstrated to be involved in and play vital roles in immune responses such as antigen presentation, immune tolerance, and type 2 immunity. In addition to their unique functions in the thymus, thymic tuft cells have the characteristics of peripheral tuft cells, so they may also participate in the process of tumorigenesis and virus infection. Here, we review tuft cells' characteristics, distribution, and potential functions. More importantly, the potential role of thymic tuft cells in immune response, tumorigenesis, and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection was summarized and discussed.
Topics: Animals; Rats; COVID-19; SARS-CoV-2; Carcinogenesis; Antigen Presentation; Immune Tolerance
PubMed: 36961668
DOI: 10.1007/s12026-023-09372-6