Inflammatory bowel disease and pulmonary embolism: a nationwide perspective.

OBJECTIVE: To examine the characteristics and outcomes of patients with inflammatory bowel disease (IBD) hospitalized with pulmonary embolism (PE). METHODS: This cross-sectional observational study analyzed data from the 2016 to 2019 National Inpatient Sample to investigate hospitalizations for PE in the USA, stratified by the presence or absence of IBD. Adult patients were selected using the International Classification of Diseases, Tenth Revision codes for PE, Crohn's disease, and ulcerative colitis. Data on patient demographics, comorbidities, and hospital characteristics were collected. Statistical analysis included univariable and multivariable logistic regression using Stata/BE 17.0, focusing on in-hospital mortality and complications in PE patients with and without IBD. Adjusted odds ratios (aOR) and their corresponding 95% confidence intervals (CI) were calculated when appropriate. RESULTS: PE/IBD group was younger (mean age 58.3 vs. 62.7 years; P < 0.001), had a higher proportion of white patients (81.2% vs. 70.9%; P < 0.001), and had a greater prevalence of chronic liver disease (7.54% vs. 6.02%; P = 0.002) when compared to PE/non-IBD patients. The PE/IBD group had lower prevalence rates of coronary artery disease, congestive heart failure, obesity, chronic obstructive pulmonary disease, hypertension, and diabetes. Regarding primary outcomes, there was no significant difference in in-hospital mortality between the two groups (aOR, 0.92; 95% CI, 0.77-1.09; P = 0.355). However, the IBD/PE group had a higher risk of acute kidney injury, sepsis, septic shock, cardiac arrhythmias, and deep vein thrombosis. As for secondary outcomes, PE/IBD patients had more extended hospital stays and higher healthcare costs compared with PE/non-IBD patients. CONCLUSION: Hospitalized PE patients with IBD differ demographically and have a different comorbidity profile compared to those without IBD. PE/IBD patients demonstrate greater use of healthcare resources and elevated risk of hospitalization adverse events than PE/non-IBD patients, highlighting the necessity for individualized management approaches in this population.

Microfluidic Impedance Biosensor Chips Using Sensing Layers Based on DNA-Based Self-Assembled Monolayers for Label-Free Detection of Proteins.

A microfluidic chip for electrochemical impedance spectroscopy (EIS) is presented as bio-sensor for label-free detection of proteins by using the example of cardiac troponin I. Troponin I is one of the most specific diagnostic serum biomarkers for myocardial infarction. The microfluidic impedance biosensor chip presented here consists of a microscope glass slide serving as base plate, sputtered electrodes, and a polydimethylsiloxane (PDMS) microchannel. Electrode functionalization protocols were developed considering a possible charge transfer through the sensing layer, in addition to analyte-specific binding by corresponding antibodies and reduction of nonspecific protein adsorption to prevent false-positive signals. Reagents tested for self-assembled monolayers (SAMs) on gold electrodes included thiolated hydrocarbons and thiolated oligonucleotides, where SAMs based on the latter showed a better performance. The corresponding antibody was covalently coupled on the SAM using carbodiimide chemistry. Sampling and measurement took only a few minutes. Application of a human serum albumin (HSA) sample, 1000 ng/mL, led to negligible impedance changes, while application of a troponin I sample, 1 ng/mL, led to a significant shift in the Nyquist plot. The results are promising regarding specific detection of clinically relevant concentrations of biomarkers, such as cardiac markers, with the newly developed microfluidic impedance biosensor chip.

Impaired Ribosomal Biogenesis by Noncanonical Degradation of ß-Catenin during Hyperammonemia.

Increased ribosomal biogenesis occurs during tissue hypertrophy, but whether ribosomal biogenesis is impaired during atrophy is not known. We show that hyperammonemia, which occurs in diverse chronic disorders, impairs protein synthesis as a result of decreased ribosomal content and translational capacity. Transcriptome analyses, real-time PCR, and immunoblotting showed consistent reductions in the expression of the large and small ribosomal protein subunits (RPL and RPS, respectively) in hyperammonemic murine skeletal myotubes, HEK cells, and skeletal muscle from hyperammonemic rats and human cirrhotics. Decreased ribosomal content was accompanied by decreased expression of cMYC, a positive regulator of ribosomal biogenesis, as well as reduced expression and activity of ß-catenin, a transcriptional activator of cMYC. However, unlike the canonical regulation of ß-catenin via glycogen synthase kinase 3ß (GSK3ß)-dependent degradation, GSK3ß expression and phosphorylation were unaltered during hyperammonemia, and depletion of GSK3ß did not prevent ammonia-induced degradation of ß-catenin. Overexpression of GSK3ß-resistant variants, genetic depletion of IκB kinase ß (IKKß) (activated during hyperammonemia), protein interactions, and in vitro kinase assays showed that IKKß phosphorylated ß-catenin directly. Overexpressing ß-catenin restored hyperammonemia-induced perturbations in signaling responses that regulate ribosomal biogenesis. Our data show that decreased protein synthesis during hyperammonemia is mediated via a novel GSK3ß-independent, IKKß-dependent impairment of the ß-catenin-cMYC axis.