Salbutamol is a primary bronchodilator for feline asthma management. However, comprehensive data on its cardiovascular safety in cats are limited despite its widespread clinical use. This study aimed to characterize the acute cardiovascular and respiratory responses following nebulized salbutamol administration in healthy feline subjects, with an emphasis on clinical safety assessment. Twenty healthy adult cats received nebulized salbutamol (3.75 mg per 20 min). A comprehensive cardiovascular evaluation, including vital signs monitoring, electrocardiography, and echocardiography, was performed before and 15 min after treatment. Salbutamol administration was associated with minimal physiological alterations. Heart rate increased from a mean of 204.10 ± 33.09 to 218.35 ± 4.84 beats per min. The E-wave/A-wave ratio increased from 2.44 ± 0.33 to 3.05 ± 0.56. Normal sinus rhythm was maintained in all subjects (100%). Sinus tachycardia was observed in 65.00% of cats, transient PR interval shortening in 25.00%, and isolated premature atrial contractions in 15.00%. No pathological arrhythmias or significant conduction blocks were detected. Respiratory rate showed a minor increase from 38.05 ± 5.87 to 40.05 ± 5.96 breaths/min, while blood pressure and body temperature remained stable. Nebulized salbutamol demonstrates a high margin of cardiovascular safety in healthy cats. The preservation of normal sinus rhythm and clinically insignificant nature of the observed physiological changes support its continued use as a first-line bronchodilator in feline respiratory medicine.

Background: Aerosol delivery during nasal high-flow (NHF) therapy occurs within a heated and humidified environment where formulation composition, NHF rate, and Next Generation Impactor (NGI)/system temperature may jointly influence aerosol behavior. However, their combined effects following NHF-conditioned transport remain incompletely characterized. Methods: A balanced 4 × 2 × 2 full-factorial design evaluated NGI/system temperature (5, 21, 37, and 40 °C), formulation (isotonic and 3% hypertonic salbutamol formulations), and NHF rate (30 and 50 L·min[-1]). Aerosols generated using a vibrating mesh nebulizer integrated within an NHF system were transported through an adult nasal replica coupled to an NGI. Particle-size, fine-particle, delivery-efficiency, and regional-deposition metrics were analyzed using factorial ANOVA. Results: NHF rate exerted the greatest influence on downstream aerosol delivery, with increasing NHF rate reducing delivery efficiency, Fine Particle Dose (FPD), and NGI deposition while increasing NHF circuit retention. Significant Temperature × Formulation × Flow interactions were observed for MMAD (p = 0.0055), D16 (p < 0.0001), GSD (p = 0.0009), Fine Particle Fraction (FPF) (p = 0.0042), and dose-normalized FPD (p = 0.0149). The hypertonic formulation exhibited greater thermal sensitivity across several particle metrics. Although increasing NGI/system temperature generally reduced MMAD, D16, and D84, similar reductions in MMAD frequently produced markedly different responses in FPF, FPD, delivery efficiency, and regional deposition. All aerosols remained within ranges commonly associated with pulmonary deposition. Conclusions: Aerosol characteristics during NHF are governed by interacting effects of flow, formulation, and NGI/system temperature. Measurements conducted at NGI/system temperatures approaching body temperature provide additional mechanistic insight, particularly for hypertonic aerosols, and support integrated assessment of particle-size, delivery, and deposition outcomes rather than APSD metrics alone.

Acute hyperkalaemia is a medical emergency requiring rapid clinical evaluation. Point-of-care blood gas analysis may overestimate serum potassium concentration and should be confirmed with a laboratory sample unless urgent treatment is required. When ECG (electrocardiogram) changes are present, immediate cardiac protection is a priority. Current guidelines recommend administering intravenous 10% calcium gluconate to restore cardiac conduction velocity. Intravenous insulin rapidly shifts potassium into cells. It is given with intravenous dextrose to reduce the risk of hypoglycaemia. A reduced insulin dose can be considered in patients with significant kidney dysfunction. Salbutamol shifts potassium into cells and has a synergistic effect with insulin. Nebulised salbutamol administration offers similar efficacy to intravenous delivery with fewer adverse effects. The routine use of intravenous sodium bicarbonate or oral potassium binders is not recommended for immediate lowering of serum potassium in acute hyperkalaemia. Sodium bicarbonate should be reserved as an adjunctive treatment for patients with concurrent metabolic acidosis. Post-acute care focuses on addressing reversible triggers and, once hyperkalaemia resolves, restarting important drugs that can increase potassium concentrations, if their benefit outweighs the risk (e.g. renin-angiotensin-aldosterone system inhibitors).

G protein-coupled receptors (GPCRs) are central physiological signal transducers and represent a primary class of therapeutic targets. While emerging evidence highlights a critical link between ligand-induced receptor conformations and pharmacological outcomes, the structural diversity dictating GPCR-G protein interface interactions remains incompletely understood. High-resolution structural studies reveal discrete, ligand-stabilized states, but these static snapshots do not fully capture the dynamic processes underlying GPCR activation and ligand efficacy. To address this, we established a native mass spectrometry (nMS) platform to probe ligand-induced conformational heterogeneity at the GPCR intracellular interface. Using the β1-adrenergic receptor (β1AR) as a model, we demonstrated a strong correlation between ligand efficacy and receptor complex formation with diverse active-state-specific nanobodies. Notably, leveraging the quantitative capacity of nMS, we uncovered distinct propensities of two highly similar nanobodies, Nb80 and Nb6B9, and showed that Nb6B9 engages weak-agonist-stabilized receptor states more effectively than Nb80. These interactions indicate that Nb6B9 recognizes ligand-specific conformations distinct from active states induced by full agonists. To gain structural insights, we utilized Nb6B9 chimeras with exchanged complementarity-determining regions (CDRs) and identified CDR1 and CDR3 as the primary drivers for ligand-specific recognition, implicating the involvement of receptor transmembrane motifs TM5 and TM6 in this conformational diversity. Finally, we demonstrated that nanobody-based nMS can distinguish receptor responses induced by the two salbutamol enantiomers, implying stereochemistry-dependent intracellular interface heterogeneity. Together, our study highlights the utility of nanobody-based nMS for evaluating the structural heterogeneity and dynamic landscapes of GPCRs.

Background and Clinical Significance: Cystic fibrosis may remain undiagnosed until adolescence, when recurrent respiratory infections and bronchiectasis are attributed to a previous severe infection. Case Presentation: We report the case of a male adolescent in whom approximately five years elapsed between microbiologically confirmed pulmonary tuberculosis in July 2021 and recognition of cystic fibrosis in August 2026. Archived records documented two sputum specimens that were acid-fast bacilli smear-positive (1+) and culture-positive (1+) for Mycobacterium tuberculosis complex. During adolescence, persistent bronchiectasis, recurrent Gram-negative respiratory infections, digital clubbing, and repeated Pseudomonas aeruginosa isolation prompted etiologic reassessment. A single documented sweat chloride concentration was 114 mmol/L. CFTR analysis of blood collected on 18 August 2026, reported on 16 September 2026, identified homozygous c.1521_1523delCTT (p.Phe508del; F508del), providing molecular confirmation. Spirometry showed FEV1 2.69 L (79.6% predicted), FVC 3.73 L (91.56% predicted), and FEV1/FVC 72.01% (z-score -2.58), consistent with airflow obstruction; without total lung capacity measurements, restriction or a mixed ventilatory defect could not be confirmed. The previously recorded azithromycin regimen was 500 mg orally three times weekly. Tobramycin inhalation solution 300 mg/5 mL was prescribed as one ampoule twice daily for 28 days, followed by 28 days off, with three planned cycles and salbutamol 15 min before administration. Management of cystic fibrosis also included airway-clearance therapy, dornase alfa 2.5 mg once daily, a high-calorie diet, pancreatic enzyme replacement, and vitamin supplementation. Longitudinal post-treatment spirometry, anthropometry, and validated quality-of-life measurements were not available. Conclusions: Previous pulmonary tuberculosis should not terminate etiologic investigation when bronchiectasis, repeated Pseudomonas aeruginosa isolation, digital clubbing, or progressive structural lung disease persists. Earlier recognition may permit earlier coordinated cystic fibrosis care and genotype-appropriate CFTR-modulator assessment.

A proof-of-concept differential dual-modal aptamer array was developed for clenbuterol (CLB) and salbutamol (SAL) screening in artificial urine. A CLB-selective aptamer and AP-Ago, a broad β2-agonist aptamer, were coupled to graphene-oxide fluorescence resonance energy transfer and to methylene-blue/ferrocene-labelled gold electrodes. Their four responses formed an analyte fingerprint by combining CLB-selective recognition with the broader response of AP-Ago. Seventy-two blind-coded samples represented six matrices, four screening classes and three independent preparation batches. Batches 1-2 (n = 48) supported model development, whereas batch 3 (n = 24; six samples per class) was locked for external assessment. Weighted calibration gave provisional procedural limits of detection of 0.083 ng mL[-1] for CLB and 0.164 ng mL[-1] for SAL. Mean external prediction-to-reference ratios were approximately 96% for CLB and 81% for SAL, distinct from controlled spike recoveries; intraday precision was 3.7% and interbatch precision was 5.8%. Against isotope-dilution LC-MS/MS, concordance correlation coefficients were 0.939 for CLB and 0.793 for SAL. A regularized multinomial logistic model achieved external balanced accuracy of 0.833, macro-F1 of 0.836 and Matthews correlation coefficient of 0.791. The reported bootstrap 95% confidence interval for balanced accuracy was 0.656-0.969, reflecting the small external set. The results support a candidate front-end triage strategy within the tested artificial matrices: differential signals identify presumptive CLB, SAL-associated high-response and mixed patterns, while any presumptive positive is referred for confirmatory LC-MS/MS rather than used for an anti-doping adjudication.