BackgroundMedical treatment has been the mainstay of chronic rhinitis management. Meanwhile, innovative minimally invasive nasal surgery has shown promising results. The therapeutic outcomes of these surgical interventions compared with medical treatment in chronic rhinitis have not been discussed previously.ObjectiveThis study aimed to evaluate the efficacy of radiofrequency ablation of the inferior turbinate of the intraturbinate segment of the posterior nasal nerve (RAPN) in comparison with intranasal corticosteroid spray (INCS) plus oral antihistamines for the treatment of chronic rhinitis.MethodsA retrospective cohort study was conducted on patients with chronic rhinitis who had an inadequate response to medication. Inclusion criteria included a 24-h Reflective Total Nasal Symptom Score (rTNSS) ≥4 and a rhinorrhea score ≥1. Patients with prior nasal surgeries, caudal septal deviation, or acute/chronic rhinosinusitis were excluded. The primary endpoint was the change in 24-h rTNSS and Nasal Obstruction Symptom Evaluation (NOSE) scores at the 3-month follow-up.ResultsA total of 64 patients were included: 44 received RAPN, and 20 received INCS. Baseline rTNSS was 7.3 ± 2.1 for RAPN and 6.9 ± 2.3 for INCS (p = .497). Both groups showed significant improvement in rTNSS and NOSE scores at 1 and 3 months (p < .001). However, the RAPN group demonstrated significantly greater improvement than the INCS group at 1 to 3 months of follow-up (p = .001). Subscore analysis revealed that rhinorrhea (at 1 and 3 months) and sneezing (at 1 month) did not differ significantly between groups. One case of postoperative anterior epistaxis was noted in the RAPN group.ConclusionsBoth INCS and RAPN are highly effective in alleviating chronic rhinitis symptoms. Although RAPN does not establish definitive superiority over medical therapy across all neurogenic domains, it provides comparable, sustained symptom control with the distinct advantage of drug-free maintenance, offering a valuable therapeutic alternative.

Allergic rhinitis is a prevalent chronic inflammatory disorder of the nasal mucosa, imposing substantial medical and socioeconomic burdens. Thus, there is an urgent need to develop novel agents capable of both symptom relief and immune modulation. This study elucidates the mechanism by which tetrandrine alleviates allergic rhinitis through REV-ERBα activation and cholinergic pathway suppression. In ovalbumin-induced allergic rhinitis mice, intranasal tetrandrine significantly reduced sneezing frequency and nasal scratching versus controls, while decreasing serum histamine and substance P levels. Mechanistically, tetrandrine dose-dependently upregulated the mRNA and protein expression of REV-ERBα in nasal mucosa, enhancing its transcriptional repression in Gal4 reporter assays. Genetic ablation of Rev-erbα abolished tetrandrine's efficacy, exacerbating allergic rhinitis symptoms and inflammatory mediators. Crucially, tetrandrine suppressed choline acetyltransferase expression in nasal mucosa, reducing the level of acetylcholine; this effect was diminished by α-NETA (choline acetyltransferase inhibitor) pretreatment. This confirmed the essential role of REV-ERBα-dependent suppression of choline acetyltransferase-mediated acetylcholine synthesis in tetrandrine's therapeutic effect on allergic rhinitis. These findings establish tetrandrine as a novel agent targeting the circadian clock pathway and the circadian-allergy crosstalk, providing a new therapeutic strategy for allergic rhinitis.

Signaling via tropomyosin-related kinase receptor B (TrkB) plays an important role in synaptic function and plasticity at the neuromuscular junction. Multiple conditions show selective effects on the most forceful and fatigable motor units that require high frequency activation and are necessary for maximal force generation. The goal of the present study is to investigate the effects of inhibiting TrkB kinase activity on neuromuscular transmission in mouse diaphragm muscle during repeated stimulation at frequencies that reflect the recruitment of different motor units (10 vs. 75 Hz). TrkB[F616A] mice, which possess a mutation that renders TrkB kinase activity susceptible to rapid inhibition by 1NMPP1, were used at 6-8 months old (n = 12; 6 females). Neuromuscular transmission failure (NMTF) was estimated in diaphragm-phrenic nerve preparations following 1 hour treatment with 1NMPP1 or vehicle by assessing the difference in forces evoked by 2 min of repetitive nerve and muscle stimulation at either 10 or 75 Hz. There was no effect of 1NMPP1 on muscle contractile properties, but there was a frequency-dependent effect of 1NMPP1 treatment on the extent of NMTF. At 10 Hz stimulation, 1NMPP1 decreased the extent of NMTF compared to vehicle by 35%. At 75 Hz, 1NMPP1 increased the extent of NMTF compared to vehicle by 28%. The greater negative effect of TrkB kinase inhibition during higher frequency stimulation suggests reliance on TrkB signaling for sustained activation predominantly at higher force, more fatigable motor units which are responsible for the high forces necessary for airway clearance (i.e., coughing and sneezing).

BACKGROUND Allergic rhinitis (AR) is a common inflammatory disorder of the nasal mucosa triggered by allergens and characterized by sneezing, nasal congestion, and itching. This study aimed to identify and validate potential biomarkers associated with immune dysregulation in AR via bioinformatics analyses initiated with chemokine-related genes. MATERIAL AND METHODS AR-related datasets (GSE75011 and GSE50223) and 69 chemokine-related genes were analyzed via differential expression analysis and weighted gene co-expression network analysis to identify candidate genes. Random forest analysis was used to select optimal features. Expression analysis identified potential immunoregulatory biomarkers that were downregulated in AR samples. A nomogram incorporating these biomarkers was constructed as an exploratory tool to estimate individual AR probability and support future diagnostic model development. RESULTS Early growth response protein 2 (EGR2) and transforming growth factor-β1 (TGFB1) were identified as chemokine-related biomarkers in AR. Immune infiltration analysis showed significant correlations between TGFB1 and M2 macrophages, as well as activated memory CD4+ T cells. Drug prediction identified tretinoin as a potential therapeutic agent targeting both biomarkers; molecular docking confirmed stable binding of the 3 top-ranked predicted drugs with TGFB1. Pilot reverse transcription-quantitative polymerase chain reaction analysis demonstrated downregulation of EGR2 and TGFB1 in AR samples, providing preliminary supportive evidence. Gene set enrichment analysis indicated involvement in the MAPK and p53 signaling pathways, suggesting roles in cell proliferation, apoptosis, cell cycle regulation, and stress responses. CONCLUSIONS EGR2 and TGFB1 offer potential immunoregulatory biomarkers for AR diagnosis and may provide preliminary insights into AR pathogenesis and potential treatment strategies.

Cough is a purposeful airway defensive reflex, but in chronic cough it no longer provides a clear physiological benefit and markedly impairs patient's quality of life. Currently available antitussive drugs have limited efficacy and may cause severe side effects. Thus, further research is needed to find reliable treatments. It has been shown that acetylcholine (ACh) downregulates cough via muscarinic ACh receptor (mAChRs) in the rabbit caudal portion of the nucleus tractus solitarii (cNTS), with a major involvement of the M4 receptor subtype. The identification of cholinergic agents modulating ACh depressant effects on coughing could be of considerable interest for the development of novel therapeutic strategies. Here we tested the hypothesis that increasing synaptic ACh levels by inhibiting acetylcholinesterase activity may downregulate the cough reflex. In anesthetized, spontaneously breathing rabbits, we investigated the effect of donepezil, a brain-penetrant, potent and selective acetylcholinesterase inhibitor, on the modulation of the cough reflex induced by mechanical and chemical stimulation of the tracheobronchial tree and on the sneeze reflex. Efferent respiratory and electromyographic activities were recorded from phrenic nerves and abdominal muscles, respectively. Donepezil, either systemically administered (5 mg/kg; subcutaneously) or bilaterally microinjected (5 mM; 30-50 nl) into the cNTS, induced strong depressant effects up to the complete abolition of the mechanically-induced cough, without affecting sneezing. Donepezil also decreased expiratory activity even to complete suppression, while transient increases in respiratory frequency were observed only after local application. These findings support further investigation on donepezil and related centrally acting cholinergic agents as candidate antitussive therapies.

Quantifying human exposure to airborne respiratory viruses is essential for infection risk assessment modeling and evidence-based infection control policies. However, accurate size and time resolved estimates of airborne viral RNA copies in indoor spaces are often hindered by existing models that compress complex droplet physics into too simplified processes. Therefore, we present a size-resolved framework that couples saliva-specific evaporation and residue formation with gravitational settling to compute airborne viral RNA covering 1-2000 µm under varied temperature, relative humidity, and ambient pressure (101.325 and 75.3 kPa). Our framework also combines particle volume contribution considering saliva mass uncertainty, viral load, viral half-life, exhalation mechanisms (talking, coughing, sneezing), and ventilation effects. Under literature-based half-life inputs and volume-proportional RNA allocation, viral load and size-resolved airborne lifetime dominated the simulated RNA-copy trends, although the role of viral half-life may vary if RNA decay differs from infectivity decay or if viral RNA concentrates in long-suspended fine aerosols. Talking dominates persistence of airborne RNA copies since coughing and sneezing produce larger droplets that settle quickly. Also, model predictions are compared with hospital air-sampling datasets. The 50-percentile of saliva mass provides the closest match, with most samples falling within roughly one order of magnitude and central tendency close to unbiased. Our model is designed to serve as (1) pre-processor that supplies inputs for infection-risk assessment modeling studies and (2) decision-making support tool, facilitating public-health intervention. Therefore, we also provide an online web tool that allows users to directly adjust inputs and immediately analyze scenario-specific outcomes.

This study evaluated the efficacy and safety of a sedation protocol through the nares combining dexmedetomidine with midazolam and butorphanol in cockatiels. Six adults were enrolled in a randomized, 4 treatment, 4 period crossover trial comparing a control regimen (midazolam 3 mg/kg and butorphanol 3 mg/kg) with three combinations including dexmedetomidine at 0.04, 0.06, or 0.08 mg/kg, administered through the nares. The volume of all treatments was standardized to the volume of the highest dose of dexmedetomidine administered (2 mL/kg) with sterile saline solution. Sedation scores, respiratory rate, heart rate, and cloacal temperature were recorded for 10 min after drug administration and during 15 min of manual restraint, followed by flumazenil and atipamezole via the nares for reversal. All birds completed all treatments; mild sneezing occurred but no clinically relevant respiratory complications were observed. Medium and high dose dexmedetomidine produced higher sedation scores and lower respiratory rate, heart rate, and body temperature during restraint than the control regimen, whereas the control group showed increased respiratory rate, suggesting insufficient suppression of restraint induced stress. In all groups, sedation and physiological variables returned to near baseline values within 15 min after reversal, and no serious adverse events occurred. These findings indicate that administration through the nares dexmedetomidine at 0.06 or 0.08 mg/kg combined with midazolam and butorphanol provides deeper, more stable, and reversible sedation and improved control of stress responses in cockatiels and may represent a clinically useful protocol in this species.