Mechanisms of pulmonary arterial hypertension-induced atrial fibrillation: insights from multi-scale models of the human atria.

This study aimed to use multi-scale atrial models to investigate pulmonary arterial hypertension (PAH)-induced atrial fibrillation mechanisms. The results of our computer simulations revealed that, at the single-cell level, PAH-induced remodelling led to a prolonged action potential (AP) (ΔAPD: 49.6 ms in the right atria (RA) versus 41.

Evidence for the formation of fused aromatic ring structures in an organic soil profile in the early diagenesis.

The presence of fused aromatic ring (FAR) structures in soil define the stability of the recalcitrant soil organic matter (RSOM). FAR are important skeletal features in RSOM that contribute to its extended residence time. During the early diagenesis, FAR structures are formed through condensation and polymerization of biomolecules produced during plant residue and microbial product decay.

Circulating Tumor Cell Enumeration for Serial Monitoring of Treatment Outcomes for Locally Advanced Esophageal Squamous Cell Carcinoma.

We aim to reveal the clinical significance and potential usefulness of dynamic monitoring of CTCs to track therapeutic responses and improve survival for advanced ESCC patients. Peripheral blood (PB) ( = 389) and azygos vein blood (AVB) ( = 13) samplings were recruited prospectively from 88 ESCC patients undergoing curative surgery from 2017 to 2022. Longitudinal CTC enumeration was performed with epithelial (EpCAM/pan-cytokeratins/MUC1) and mesenchymal (vimentin) markers at 12 serial timepoints at any of the pre-treatment, all of the post-treatments/pre-surgery, post-surgery follow-ups for 3-year, and relapse.

Mechanisms underlying pro-arrhythmic abnormalities arising from Pitx2-induced electrical remodelling: an in silico intersubject variability study.

Background: Electrical remodelling as a result of the homeodomain transcription factor 2 (Pitx2)-dependent gene regulation induces atrial fibrillation (AF) with different mechanisms. The purpose of this study was to identify Pitx2-induced changes in ionic currents that cause action potential (AP) shortening and lead to triggered activity.

Methods: Populations of computational atrial AP models were developed based on AP recordings from sinus rhythm (SR) and AF patients.

In Silico Assessment of Class I Antiarrhythmic Drug Effects on -Induced Atrial Fibrillation: Insights from Populations of Electrophysiological Models of Human Atrial Cells and Tissues.

Electrical remodelling as a result of homeodomain transcription factor 2 (Pitx2)-dependent gene regulation was linked to atrial fibrillation (AF) and AF patients with single nucleotide polymorphisms at chromosome 4q25 responded favorably to class I antiarrhythmic drugs (AADs). The possible reasons behind this remain elusive. The purpose of this study was to assess the efficacy of the AADs disopyramide, quinidine, and propafenone on human atrial arrhythmias mediated by Pitx2-induced remodelling, from a single cell to the tissue level, using drug binding models with multi-channel pharmacology.

In Silico Assessment of Genetic Variation in PITX2 Reveals the Molecular Mechanisms of Calcium-Mediated Cellular Triggered Activity in Atrial Fibrillation.

Genome-wide association studies have identified genetic variants including rs13143308T in the homeobox gene Pitx2 associated with atrial fibrillation (AF) populations. However, the molecular mechanisms leading to AF due to the rs13143308T variant are poorly understood. Therefore, this study aims to investigate the effects of this variant-induced alteration in calcium handling on properties of Ca-transients (CaT) and spontaneous calcium-release events (SCaEs).

Afterdepolarizations and abnormal calcium handling in atrial myocytes with modulated SERCA uptake: a sensitivity analysis of calcium handling channels.

Delayed afterdepolarizations (DADs) and spontaneous depolarizations (SDs) are typically triggered by spontaneous diastolic Ca release from the sarcoplasmic reticulum (SR) which is caused by an elevated SR Ca-ATPase (SERCA) uptake and dysfunctional ryanodine receptors. However, recent studies on the T-box transcription factor gene (TBX5) demonstrated that abnormal depolarizations could occur despite a reduced SERCA uptake. Similar findings have also been reported in experimental or clinical studies of diabetes and heart failure.

PITX2 upregulation increases the risk of chronic atrial fibrillation in a dose-dependent manner by modulating and -insights from human atrial modelling.

Background: Functional analysis has shown that the paired-like homeodomain transcription factor 2 (PITX2) overexpression associated with atrial fibrillation (AF) leads to the slow delayed rectifier K current ( ) increase and the L-type Ca current ( ) reduction observed in isolated right atrial myocytes from chronic AF (CAF) patients. Through multiscale computational models, this study aimed to investigate the functional impact of the PITX2 overexpression on atrial electrical activity.

Methods: The well-known Courtemanche-Ramirez-Nattel (CRN) model of human atrial action potentials (APs) was updated to incorporate experimental data on alterations in and due to the PITX2 overexpression.

In silico investigation of the mechanisms underlying atrial fibrillation due to impaired Pitx2.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is a major cause of stroke and morbidity. Recent genome-wide association studies have shown that paired-like homeodomain transcription factor 2 (Pitx2) to be strongly associated with AF. However, the mechanisms underlying Pitx2 modulated arrhythmogenesis and variable effectiveness of antiarrhythmic drugs (AADs) in patients in the presence or absence of impaired Pitx2 expression remain unclear.

Proarrhythmia in the p.Met207Val PITX2c-Linked Familial Atrial Fibrillation-Insights From Modeling.

Functional analysis has shown that the p.Met207Val mutation was linked to atrial fibrillation and caused an increase in transactivation activity of PITX2c, which caused changes in mRNA synthesis related to ionic channels and intercellular electrical coupling. We assumed that these changes were quantitatively translated to the functional level.

A biradical-tagged phospholipid as a polarizing agent for solid-state MAS Dynamic Nuclear Polarization NMR of membrane proteins.

A novel Dynamic Nuclear Polarization (DNP) NMR polarizing agent ToSMTSL-PTE representing a phospholipid with a biradical TOTAPOL tethered to the polar head group has been synthesized, characterized, and employed to enhance solid-state Nuclear Magnetic Resonance (SSNMR) signal of a lipid-reconstituted integral membrane protein proteorhodopsin (PR). A matrix-free PR formulation for DNP improved the absolute sensitivity of NMR signal by a factor of ca. 4 compared to a conventional preparation with TOTAPOL dispersed in a glassy glycerol/water matrix.

Intraoperative ketorolac dose of 15mg versus the standard 30mg on early postoperative pain after spine surgery: A randomized, blinded, non-inferiority trial.

Study Objective: The primary aim of this study is to show the non-inferiority of 15mg intraoperative dose of ketorolac as compared to the standard 30mg ketorolac by looking at the visual analog scale pain (VAS) scores 4h after an adult spine surgery.

Design: The study design is a prospective randomized non-inferiority clinical trial looking at non-inferiority of intraoperative 15mg ketorolac from the standard 30mg dose.

Setting: Quaternary care center.

Anterior Segment Biometry Changes with Cycloplegia in Myopic Adults.

Purpose: To determine the effect of cycloplegia on corneal thickness, corneal curvature, anterior chamber depth (ACD), angle-to-angle (ATA) and white-to-white (WTW) distances, and axial length (AL).

Methods: Changes in corneal thickness, corneal curvature, ACD, ATA and WTW distances, and AL with and without cycloplegia were analyzed in 31 eyes of 31 young myopic adults, aged 26.4 ± 3.

Proteomics Characterization of Primary Human Oral Epithelial Cells Using a Novel Culture Technique for Use in Tissue Regeneration.

Oral mucosa keratinocytes are widely used in regenerative medicine. The unique cultured cell population "Epithelial-derived Pop-Up Keratinocytes (ePUKs)" was previously reported as undifferentiated cells. Gravity Assisted Cell Sorting (GACS) was used to isolate a small-sized population of undifferentiated cells enriched ePUKs.

Glycoprotein biomarker panel for pancreatic cancer discovered by quantitative proteomics analysis.

Pancreatic cancer is a lethal disease where specific early detection biomarkers would be very valuable to improve outcomes in patients. Many previous studies have compared biosamples from pancreatic cancer patients with healthy controls to find potential biomarkers. However, a range of related disease conditions can influence the performance of these putative biomarkers, including pancreatitis and diabetes.

Label-free relative quantification of alpha-2-macroglobulin site-specific core-fucosylation in pancreatic cancer by LC-MS/MS.

We describe a label-free relative quantification LC-MS/MS method for core-fucosylation in alpha-2-macroglobulin (A2MG) immunoprecipitated from human sera. The method utilizes endoglycosidase F partial deglycosylation to reduce glycosylation microheterogeneity, while retaining the innermost N-acetylglucosamine (GlcNAc) and core fucose. Precursor ion peak areas of partially deglycosylated peptides were obtained and site-specific core-fucosylation ratios based on the peak areas of core-fucosylated and nonfucosylated counterparts were calculated and evaluated for assay development.

Diagnostic criteria for distinguishing endometrial adenocarcinoma from complex atypical endometrial hyperplasia.

Morphologic criteria for distinguishing endometrial adenocarcinoma from complex atypical endometrial hyperplasia have been described previously, but they have not been examined extensively for their individual ability for predicting endometrial adenocarcinoma as determined by subsequent hysterectomy. We examined endometrial biopsies diagnosed in the spectrum of complex atypical endometrial hyperplasia to well-differentiated endometrial adenocarcinoma for various morphologic features that may be predictive for the presence of myoinvasive endometrial adenocarcinoma in subsequent hysterectomy. Cases diagnosed as FIGO grade I endometrial adenocarcinoma or complex atypical endometrial hyperplasia in endometrial biopsies seen at New York University Medical Center from 2003 to 2006 were analyzed for the presence of various morphologic features without the knowledge of hysterectomy findings.

Quantitative high-speed laryngoscopic analysis of vocal fold vibration in fatigued voice of young karaoke singers.

Purpose: The present study aimed to determine whether there were physiological differences in the vocal fold vibration between nonfatigued and fatigued voices using high-speed laryngoscopic imaging and quantitative analysis.

Methods: Twenty participants aged from 18 to 23 years (mean, 21.2 years; standard deviation, 1.

Analytical performance of reciprocal isotope labeling of proteome digests for quantitative proteomics and its application for comparative studies of aerobic and anaerobic Escherichia coli proteomes.

Due to limited sample amounts, instrument time considerations, and reagent costs, only a small number of replicate experiments are typically performed for quantitative proteome analyses. Generation of reproducible data that can be readily assessed for consistency within a small number of datasets is critical for accurate quantification. We report our investigation of a strategy using reciprocal isotope labeling of two comparative samples as a tool for determining proteome changes.

Automation of dimethylation after guanidination labeling chemistry and its compatibility with common buffers and surfactants for mass spectrometry-based shotgun quantitative proteome analysis.

Isotope labeling liquid chromatography-mass spectrometry (LC-MS) is a major analytical platform for quantitative proteome analysis. Incorporation of isotopes used to distinguish samples plays a critical role in the success of this strategy. In this work, we optimized and automated a chemical derivatization protocol (dimethylation after guanidination, 2MEGA) to increase the labeling reproducibility and reduce human intervention.

Isobaric protein-level labeling strategy for serum glycoprotein quantification analysis by liquid chromatography-tandem mass spectrometry.

While peptide-level labeling using isobaric tag reagents has been widely applied for quantitative proteomics experiments, there are comparatively few reports of protein-level labeling. Intact protein labeling could be broadly applied to quantification experiments utilizing protein-level separations or enrichment schemes. Here, protein-level isobaric labeling was explored as an alternative strategy to peptide-level labeling for serum glycoprotein quantification.

An N-glycosylation Analysis of Human Alpha-2-Macroglobulin Using an Integrated Approach.

Assignment of glycosylation sites and site microheterogeneity is of both biological and clinical significance. Herein, the detailed N-glycosylation pattern of human serum alpha-2-macroglobulin was studied using an integrative approach, including permethylation of N-glycans, collision induced dissociation (CID) and electron transfer dissociation (ETD) of chymotryptic N-glycopeptides, and partial deglycosylation of chymotryptic N-glycopeptides with endo-β-N-acetylglucosaminidase F3 (Endo F3). Three N-glycosylation sites were found to be occupied by four biantennary complex type N-glycans using N-glycan analysis and the ETD/CID method.

Prognostic implications of the magnetic resonance imaging appearance in papillary renal cell carcinoma.

Objective: To evaluate the prognostic implications of the MRI appearance and pathological features of papillary renal cell carcinoma (pRCC).

Methods: A total of 128 pRCC in 115 patients who underwent preoperative MRI were characterised in terms of pathological type (type 1 vs. type 2), MRI appearance (focal vs.

Local structures of mesoporous bioactive glasses and their surface alterations in vitro: inferences from solid-state nuclear magnetic resonance.

We review the benefits of using (29)Si and (1)H magic angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy for probing the local structures of both bulk and surface portions of mesoporous bioactive glasses (MBGs) of the CaO-SiO(2)-(P(2)O(5)) system. These mesoporous materials exhibit an ordered pore arrangement, and are promising candidates for improved bone and tooth implants. We discuss experimental MAS NMR results from three MBGs displaying different Ca, Si and P contents: the (29)Si NMR spectra were recorded either directly by employing radio-frequency pulses to (29)Si, or by magnetization transfers from neighbouring protons using cross polarization, thereby providing quantitative information about the silicate speciation present in the pore wall and at the MBG surface, respectively.

Carbapenem resistance via the blaKPC-2 gene in Enterobacter cloacae blood culture isolate.

An Enterobacter cloacae blood culture isolate expressing carbapenem resistance via the Klebsiella pneumoniae carbapenemase KPC-2 gene is reported. To our knowledge, this is the first report of a nosocomial isolate with carbapenemase-mediated resistance causing infection in a patient from Tennessee.