Aquatic models of human ciliary diseases

Cilia are microtubule‐based structures that either transmit information into the cell or move fluid outside of the cell. There are many human diseases that arise from malfunctioning cilia. Although mammalian models provide vital insights into the underlying pathology of these diseases, aquatic organisms such as Xenopus and zebrafish provide valuable tools to help screen and dissect out the underlying causes of these diseases. In this review we focus on recent studies that identify or describe different types of human ciliopathies and outline how aquatic organisms have aided our understanding of these diseases.     

Iron homeostasis and methionine-centred redox cycle in nasal polyposis

Abstract

Nasal polyposis is a multifactorial disease with a strong inflammatory component. Its pathogenesis is often associated with ROS production catalysed by redox-active iron. This study aimed to characterize the roles of iron homeostasis and redox status in the pathogenesis of polyposis. Nasal polyps (NP) from asthmatics and non-asthmatics and turbinates from controls and NP-patients were analysed for ferritin, ferritin-bound iron (FBI) and levels of methionine-centred redox cycle proteins. The ferritin content in both NPs was significantly higher than in adjacent turbinates. No differences in FBI were observed between both NP groups and both turbinates groups, while in NPs it was significantly higher. In NP-turbinates the highest levels of redox proteins were observed. In conclusion, re-distribution of iron occurs upon the development of NP. While FBI is elevated in NPs, the adjacent turbinate remain iron-poor and low-inflammatory, suggesting the formation of virtual boundary between these tissues.     

Thermally Triggered Mucoadhesive In Situ Gel of Loratadine: β-Cyclodextrin Complex for Nasal Delivery

The aim of the present study was to increase the solubility of an anti-allergic drug loratadine by making its inclusion complex with β-cyclodextrin and to develop it’s thermally triggered mucoadhesive in situ nasal gel so as to overcome first-pass effect and consequently enhance its bioavailability. A total of eight formulations were prepared by cold method and optimized by 2³ full factorial design. Independent variables (concentration of poloxamer 407, concentration of carbopol 934 P, and pure drug or its inclusion complex) were optimized in order to achieve desired gelling temperature with sufficient mucoadhesive strength and maximum permeation across experimental nasal membrane. The design was validated by extra design checkpoint formulation (F9) and Pareto charts were used to help eliminate terms that did not have a statistically significant effect. The response surface plots and possible interactions between independent variables were analyzed using Design Expert Software 8.0.2 (Stat Ease, Inc., USA). Faster drug permeation with zero-order kinetics and target flux was achieved with formulation containing drug: β-cyclodextrin complex rather than those made with free drug. The optimized formulation (F8) with a gelling temperature of 28.6 ± 0.47°C and highest mucoadhesive strength of 7,676.0 ± 0.97 dyn/cm² displayed 97.74 ± 0.87% cumulative drug permeation at 6 h. It was stable for over 3 months and histological examination revealed no remarkable damage to the nasal tissue.     

Human immune responses elicited by an intranasal inactivated H5 influenza vaccine

Intranasally administered influenza vaccines could be more effective than injected vaccines, because intranasal vaccination can induce virus-specific immunoglobulin A (IgA) antibodies in the upper respiratory tract, which is the initial site of infection. In this study, immune responses elicited by an intranasal inactivated vaccine of influenza A(H5N1) virus were evaluated in healthy individuals naive for influenza A(H5N1) virus. Three doses of intranasal inactivated whole-virion H5 influenza vaccine induced strong neutralizing nasal IgA and serum IgG antibodies. In addition, a mucoadhesive excipient, carboxy vinyl polymer, had a notable impact on the induction of nasal IgA antibody responses but not on serum IgG antibody responses. The nasal hemagglutinin (HA)-specific IgA antibody responses clearly correlated with mucosal neutralizing antibody responses, indicating that measurement of nasal HA-specific IgA titers could be used as a surrogate for the mucosal antibody response. Furthermore, increased numbers of plasma cells and vaccine antigen-specific Th cells in the peripheral blood were observed after vaccination, suggesting that peripheral blood biomarkers may also be used to evaluate the intranasal vaccine-induced immune response. However, peripheral blood immune cell responses correlated with neutralizing antibody titers in serum samples but not in nasal wash samples. Thus, analysis of the peripheral blood immune response could be a surrogate for the systemic immune response to intranasal vaccination but not for the mucosal immune response. The current study suggests the clinical potential of intranasal inactivated vaccines against influenza A(H5N1) viruses and highlights the need to develop novel means to evaluate intranasal vaccine-induced mucosal immune responses.     

Diurnal Variation in the Symptoms of Colds and Influenza

The present research examined diurnal variation in the severity of symptoms of experimentally-induced colds and influenza. Nasal secretion was greatest in the morning, decreased over the day, and then showed a slight increase in the late evening. Colds did not change the average temperature, nor did they alter the temperature rhythm. Similar, negative results were found with alertness ratings.

Influenza B illnesses produced an increase in nasal secretion and systemic effects. The average temperature increased during this illness and subjects reported that they felt more drowsy. Diurnal variation in the severity of local and central symptoms was observed, with nasal secretion and the temperature increase being greatest in the early morning. These results have important implications for the assessment and treatment of the illnesses.     

Nasal and oral calls in mother and young trunk-nosed saiga antelopes,Saiga tatarica

The trunk-like nose of the saiga antelope Saiga tatarica is a striking example of an exaggerated trait, assumed to having evolved as a dust filter for inhaled air. In addition, it functions to elongate the vocal tract in harem saiga males for producing low-formant calls that serve as a cue to body size for conspecifics. This study applies the source–filter theory to the acoustics of nasal, oral and nasal-and-oral calls that were recorded from a captive herd of 24 mother and 32 neonate saigas within the first 10 days postpartum. Anatomical measurements of the nasal and oral vocal tracts of two specimens (one per age class) helped to establish the settings for the analysis of formants. In both mother and young, the lower formants of nasal calls/call parts were in agreement with the source–filter theory, which suggests lower formants for the longer nasal vocal tract than for the shorter oral vocal tract. Similar fundamental frequencies of the nasal and oral parts of nasal-and-oral calls were also in agreement with the source–filter theory, which postulates the independence of source and filter. However, the fundamental frequency was higher in oral than in nasal calls, probably due to the higher emotional arousal during the production of oral calls. We discuss production mechanisms and the ontogeny of formant patterns of oral and nasal calls among bovid and cervid species with and without a trunk-like nose.     

Estimation of Respiratory Nasal Pressure and Flow Rate Signals Using Different Respiratory Sound Features

BackgroundRespiratory sounds are associated with the flow rate, nasal flow pressure, and physical characteristics of airways. In this study, we aimed to develop the flow rate and nasal flow pressure estimation models for the clinical application, and find out the optimal feature set for estimation to achieve the optimal model performance.MethodsRespiratory sounds and flow rate were acquired from nine healthy volunteers. Respiratory sounds and nasal flow pressure were acquired from twenty-three healthy volunteers. Four types of respiratory sound features were extracted for flow rate and nasal flow pressure estimation using different estimation models. Effects of estimations using these features were evaluated using Bland-Altman analysis, estimation error, and respiratory sound feature calculation time. Besides, expiratory and inspiratory phases divided estimation errors were compared with united estimation errors.ResultsThe personalized logarithm model was selected as the optimal flow rate estimation model. Respiratory nasal flow pressure estimation based on this model was also performed. For the four different respiratory sound features, there is no statistically significant difference in flow rate and pressure estimation errors. LogEnvelope was, therefore, chosen as the optimal feature because of the lowest computational cost. In addition, for any type of respiratory sound feature, no statistically significant difference was observed between divided and united estimation errors (flow rate and pressure).ConclusionRespiratory flow rate and nasal flow pressure can be estimated accurately using respiratory sound features. Expiratory and inspiratory phases united estimation using respiratory sounds is a more reasonable estimation method than divided estimation. LogEnvelope can be used for this united respiratory flow rate and nasal flow pressure estimation with minimum computational cost and acceptable estimation error.     

Nasal Staphylococcus aureus and S. pseudintermedius carriage in healthy dogs and cats: a systematic review of their antibiotic resistance,virulence and genetic lineages of zoonotic relevance

The molecular ecology of Staphylococcus aureus, Staphylococcus pseudintermedius and their methicillin-resistant strains in healthy dogs and cats could serve as good models to understand the concept of bacterial zoonosis due to animal companionship. This study aims to provide insights into pooled prevalence, genetic lineages, virulence and antimicrobial resistance (AMR) among healthy dogs and cats. Original research and brief communication articles published from 2001 to 2021 that reported the nasal detection of S. aureus and S. pseudintermedius in healthy dogs and cats in the community, homes and outside veterinary clinics were examined and analysed. Forty-nine studies were eligible and included in this systematic review. The pooled prevalence of nasal carriage of S. aureus/methicillin-resistant S. aureus (MRSA) in healthy dogs and cats were 10.9% (95% CI: 10.1–11.9)/2.8% (95% CI: 2.4–3.2) and 3.2% (95% CI: 1.9–4.8)/0.5% (95% CI: 0.0–1.1), respectively. Conversely, the pooled prevalence of S. pseudintermedius/methicillin-resistant S. pseudintermedius (MRSP) in healthy dogs and cats were 18.3% (95% CI: 17.1–19.7)/3.1% (95% CI: 2.5–3.7) and 1.3% (95% CI: 0.6–2.4)/1.2% (95% CI: 0.6–2.3), respectively. Although highly diverse genetic lineages of S. aureus were detected in healthy dogs and cats, MSSA-CC1/CC5/CC22/CC45/CC121/CC398 and MRSA-CC5/CC93/CC22/CC30 were mostly reported in dogs; and MSSA-CC5/CC8/CC15/CC48 and MRSA-CC22/CC30/CC80 in cats. Of note, MSSA-CC398 isolates (spa-types t034 and t5883) were detected in dogs. Genetic lineages often associated with MSSP/MRSP were ST20/ST71, highlighting the frequent detection of the epidemic European MRSP-ST71 clone in dogs. S. aureus isolates carrying the luk-S/F-PV, tst, eta, etb and etd genes were seldomly detected in dogs, and luk-S/F-PV was the unique virulence factor reported in isolates of cats. S. pseudintermedius isolates harbouring the luk-S/F-I, seint and expA genes were frequently found, especially in dogs. High and diverse rates of AMR were noted, especially among MRSA/MRSP isolates. There is a need for additional studies on the molecular characterization of isolates from countries with under-studied nasal staphylococci isolates.