Data_Sheet_1_Outcome of CPAP Titration for Moderate-to-Severe OSA Under Drug-Induced Sleep Endoscopy: A Randomized Controlled Crossover Trial.PDF

BackgroundThe titration pressure of continuous positive airway pressure (CPAP) is important in patients with obstructive sleep apnea (OSA). This study aimed to understand the difference between drug-induced sleep endoscopy (DISE)-guided CPAP titration and conventional sleep center (CSC) CPAP titration in patients with OSA.MethodsIn this randomized, controlled, and single-blind crossover trial, we compared the effects of 1-month CPAP treatment in patients with OSA with either DISE-guided CPAP titration or CSC CPAP titration. Twenty-four patients with OSA were recruited for the study. All patients underwent polysomnography, DISE-guided CPAP titration, and accommodation. Initially, patients were randomly assigned to receive either DISE-guided CPAP titration or CSC CPAP treatment for the first month. They were then switched to other treatments in the second month. The Epworth sleepiness scale (ESS) score was recorded at baseline, 1 and 2 months.ResultsThe upper limit of the pressure of DISE-guided titration and CSC CPAP titration was not significantly different (13.9 ± 0.7 vs. 13.5 ± 0.5 cm H2O; P = 0.92). The residual apnea-hypopnea index and compliance were also not significantly different between the groups. ESS score significantly improved from baseline to 1 month after CPAP treatment in both groups. Both epiglottis (anterior-posterior collapse) and tongue base collapse were significantly associated with 95% CPAP pressure (P = 0.031 and 0.038, respectively). After multivariate regression analyses, the epiglottis (anterior-posterior collapse) was an independent factor for 95% CPAP pressure. The incidence rate of bradycardia was 58.3%, which is a safety concern for DISE. Despite the high incidence of bradycardia, all patients with bradycardia recovered with proper management.ConclusionBoth modalities were comparable in terms of establishing the pressure settings required to treat patients. Further large-scale studies are required to confirm these results.Trial registrationhttps://clinicaltrials.gov/, NCT03523013.</p

Gemini Lipopeptide Bearing an Ultrashort Peptide for Enhanced Transfection Efficiency and Cancer-Cell-Specific Cytotoxicity

Cationic gemini lipopeptides are a relatively new class of amphiphilic compounds to be used for gene delivery. Through the possibility of incorporating short peptides with cell-penetrating functionalities, these lipopeptides may be advantageous over traditional cationic lipids. Herein, we report the design, synthesis, and application of a novel cationic gemini lipopeptide for gene delivery. An ultrashort peptide, containing four amino acids, arginine–cysteine–cysteine–arginine, serves as a cationic head group, and two α-tocopherol moieties act as hydrophobic anchoring groups. The new lipopeptide (ATTA) is incorporated into the conventional liposomes, containing 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 1,2-dioleoyl-sn-glycerol-3-phosphoethanolamine (DOPE), at different molar ratios. The formulated liposomes are characterized and screened for better transfection efficiency. Transfection activity in multiple human cell lines from cancerous and noncancerous origins indicates that the inclusion of an optimal ratio of ATTA in the liposomes substantially enhances the transfection efficiency, superior to that of a traditional liposome, DOTAP–DOPE. Cytotoxicity of ATTA-containing formulations against multiple cell lines indicates potentially distinct activity between cancer and noncancer cell lines. Furthermore, lipoplexes of the ATTA-containing formulations with anticancer therapeutic gene, plasmid encoding tumor necrosis factor-related apoptosis-inducing ligand (pTRAIL), induce obviously more cytotoxicity than conventional formulations. The results indicate that arginine-rich cationic lipopeptide appears to be a promising ingredient in gene delivery vector formulations to enhance transfection efficiency and cell-selective cytotoxicity

A Simplified Screening Questionnaire for Detecting Severe OSA in Chronic Obstructive Airway Disease in Asian Population

The aim of this study was to develop a simplified screening questionnaire to detect the existence of severe obstructive sleep apnea (OSA) in chronic obstructive pulmonary disease (COPD) patients to reduce mortality and hospitalization rates. Seventy-seven stable Asian COPD patients aged 69.2 ± 11.5 years were retrospectively analyzed into the development group. The simplified screening questionnaire was developed from factors identified from sleep surveys and demographic data to predict severe OSA. Receiver operating characteristic (ROC) curve analysis was used to validate the simplified screening questionnaire. Data from another 78 stable COPD patients were used for validation. The apnea-hypopnea index was similar between the development and validation groups (26.3 ± 21.9 and 27.6 ± 21.1, respectively). After logistic regression analysis in the development group, snoring, body mass index ≥27.5 kg/m2, witnessed apnea and coronary artery disease were incorporated into the screening questionnaire to predict OSA. When this questionnaire was applied to the validation group, the results were similar. The simplified screening questionnaire developed is useful in identifying severe OSA in COPD patients.</p

Hybrid Polyethylenimine and Polyacrylic Acid-Bound Iron Oxide as a Magnetoplex for Gene Delivery

Low transfection efficiency is always an issue when cationic polymers are used as a nonviral gene vector in the physiological condition, especially in the presence of proteins. A cationic magnetic nanoparticle (MNP) may be an alternative to solve this problem because a magnetic field can help to attract the MNP and internalize it into cells. The aim of this study was to determine the potency of polyethylenimine (PEI)-decorated MNPs for efficiently complexing and delivering plasmid DNA in vitro with the help of a magnetic field. PEI is associated with poly­(acrylic acid)-bound superparamagnetic iron oxide (PAAIO) through electrostatic interactions (PEI-PAAIO). PEI-PAAIO formed stable polyplexes with pDNA in the presence and absence of 10% fetal bovine serum (FBS) and could be used for magnetofection. The effect of a static magnetic field on the cytotoxicity, cellular uptake, and transfection efficiency of PEI-PAAIO/pDNA was evaluated with and without 10% FBS. Magnetofection efficacy in HEK 293T cells and U87 cells containing 10% FBS was significantly improved in the presence of an external magnetic field. The amount of internalized iron was quantitatively measured using an inductively coupled plasma-optical emission spectrometer and directly visualized using Prussian blue staining. The internalized pDNA was visualized using a confocal laser scanning microscope

The time-frequency (TF) representation of the PTT (blue curve) determined by the de-shape short-time Fourier transform of subjects from the CGMH database.

Left figure shows the PTT from a subject and its TF representation. Right figure shows the average TF representation over 22 subjects. It is clear that there is a dominant line at 0.01Hz. This indicates a regular oscillation of 0.01Hz in most PTT signals.</p

Chemically Conjugating Polyethylenimine with Chondroitin Sulfate to Promote CD44-Mediated Endocytosis for Gene Delivery

Polyethylenimine (PEI) is one of the most potent synthetic gene delivery vectors because of its high transfection efficiency. Although PEI has been used as a delivery vehicle for a long while, its toxicity is always an issue for clinical applications. In this study, we introduced a low molecular weight PEI of 10 kilodaltons to chondroitin sulfate (CS) via a Michael addition method. By adjusting weight ratios between cationic PEI and anionic CS, the intermolecular or intramolecular, or both, electrostatic interactions of CS-modified PEI (CP) maintained good water solubility but lost some ability to permeate cell membranes. Thus, the cytotoxicity of PEI decreased without sacrificing its gene transfection efficiency. Three CP copolymers with different PEI contents were synthesized and used to prepare polyplexes with plasmid DNA. The pDNA-formed polyplex with a low PEI content (CP­(L)) was least cytotoxic and had a transfection efficiency comparable to Lipofectamine/pDNA. The good uptake of CP­(L)/pDNA into U87 cells was primarily based on clatherin-dependent and CD44-mediated endocytosis

An illustration of removing the sawtooth artifact by the manifold learning tool.

The black tracking is the original PTT signal (with the unit shown on the left ticks), while the blue one is the corrected PTT signal (with the unit shown on the right ticks).</p

The pulse transit time (PTT) of subjects in the CGMH database are shown in the first subplot, and their associated power spectra are shown in the second subplot.

The PTT signals and the power spectra are shifted to enhance visualization. Note that compared with Fig 2, in this database the signal is of only 5 minutes long, so the sawtooth artifact is stretched and there are only few sawtooth cycles. The black line in the second subplot indicates 0.01 Hz. a.u. = arbitrary unit.</p

The time-frequency (TF) representation of the PTT (blue curve) determined by the de-shape short-time Fourier transform of subjects from the SKWHSMH database.

Left figure shows the PTT from a subject and its TF representation. Right figure shows the average TF representation over 35 subjects. It is clear that there is a dominant line at 0.01 Hz and a line slightly below 0.1 Hz. This indicates a regular oscillation of 0.01 Hz, or a regular oscillation of about 0.1 Hz in most of PTT signals.</p

The pulse transit time (PTT) during the entire laparoscopic cholecystectomy procedure of all enrolled subjects in the SKWHSMH database is shown in the top subplot, and their associated power spectra are shown in the bottom subplot.

The PTT signals and the power spectra are shifted to enhance visualization. The black dash line and red dash line in the bottom subplot denote the frequencies of 0.01 Hz and 0.095 Hz, respectively. a.u. = arbitrary unit.</p