Real-World Evaluation of the Safety and Effectiveness of 2.3% Hypertonic Saline Soft Mist Spray for Sino-Nasal Symptoms.

Introduction and aims Mildly hypertonic saline is more effective in relieving symptoms of nasal congestion compared to placebo or isotonic saline. Recently, a unique device, delivering a soft mist of 2.3% hypertonic sea-salt saline (Nasoclear PureHaleTM; Zydus Healthcare Ltd., India) has been introduced in India. The device uses a power-less manual technique to release the saline as a soft mist at 1 ml/min. Methods This is a retrospective, multi-centric, single-arm study to evaluate the safety and effectiveness of 2.3% hypertonic sea-salt saline nasal irrigation delivered through a soft mist device in patients with sino-nasal symptoms. This is an analysis of data of 130 patients collected from the medical records of 11 practicing pediatricians across India. Results The mean age of the patients was 5.23 ± 4.24 years; 63 % were boys and 37% were girls (n = 130). The mean reduction in total nasal symptom score (TNSS) at follow-up from baseline was 6.28 ± 0.18 (median days = 7) (95% CI = 5.92 to 6.64; p<0.0001; mean TNSS at baseline = 7.75 ± 2.01, mean TNSS at follow-up = 1.47± 1.30). Out of 130 patients, 33 patients (25.3%) showed complete improvement in TNSS, 93 patients (71.5%) had ≥ 50% improvement in TNSS while 4 patients (3.07%) showed <50% improvement in TNSS. The effectiveness of the device was rated as excellent (75%-100% improvement) and very good (50%-75% improvement) in 41 and 74 patients, respectively. It was rated as very easy to use and easy to use by 62 patients and 57 patients, respectively. One hundred nineteen patients (91.5%) were compliant with the prescribed frequency of the device and 110 patients (84.6%) were compliant with the prescribed duration of use of the device. No serious adverse events were reported; two patients reported mild side effects - stinging and irritation of the throat. Conclusions The 2.3% hypertonic sea-salt saline nasal irrigation delivered through the soft mist device was found to be well-tolerated and effective in patients with sino-nasal symptoms in real-world clinical settings. Clinical trial number The clinical trial number of this study is CTRI/2022/07/043751.

ATOMDANCE: Kernel-based denoising and choreographic analysis for protein dynamic comparison.

Comparative methods in molecular evolution and structural biology rely heavily upon the site-wise analysis of DNA sequence and protein structure, both static forms of information. However, it is widely accepted that protein function results from nanoscale nonrandom machine-like motions induced by evolutionarily conserved molecular interactions. Comparisons of molecular dynamics (MD) simulations conducted between homologous sites representative of different functional or mutational states can potentially identify local effects on binding interaction and protein evolution. In addition, comparisons of different (i.e., nonhomologous) sites within MD simulations could be employed to identify functional shifts in local time-coordinated dynamics indicative of logic gating within proteins. However, comparative MD analysis is challenged by the large fraction of protein motion caused by random thermal noise in the surrounding solvent. Therefore, properly denoised MD comparisons could reveal functional sites involving these machine-like dynamics with good accuracy. Here, we introduce ATOMDANCE, a user-interfaced suite of comparative machine learning-based denoising tools designed for identifying functional sites and the patterns of coordinated motion they can create within MD simulations. ATOMDANCE-maxDemon4.0 employs Gaussian kernel functions to compute site-wise maximum mean discrepancy between learned features of motion, thereby assessing denoised differences in the nonrandom motions between functional or evolutionary states (e.g., ligand bound versus unbound, wild-type versus mutant). ATOMDANCE-maxDemon4.0 also employs maximum mean discrepancy to analyze potential random amino acid replacements allowing for a site-wise test of neutral versus nonneutral evolution on the divergence of dynamic function in protein homologs. Finally, ATOMDANCE-Choreograph2.0 employs mixed-model analysis of variance and graph network to detect regions where time-synchronized shifts in dynamics occur. Here, we demonstrate ATOMDANCE's utility for identifying key sites involved in dynamic responses during functional binding interactions involving DNA, small-molecule drugs, and virus-host recognition, as well as understanding shifts in global and local site coordination occurring during allosteric activation of a pathogenic protease.

Statistical machine learning for comparative protein dynamics with the DROIDS/maxDemon software pipeline.

Comparative analysis of protein structure or sequence alignments often ignores the protein dynamics and function. We offer a graphical user interface to a computing pipeline, complete with molecular visualization, enabling the biophysical simulation and statistical comparison of two-state functional protein dynamics (i.e., single unbound state vs. complex with a ligand, DNA, or protein). We utilize multi-agent machine learning classifiers to identify functionally conserved dynamic motions and compare them in genetic or drug-class variants. For complete details on the use and execution of this profile, please refer to Babbitt et al. (2020b, 2020a, 2018) and Rynkiewicz et al. (2021).