Bariatric Surgery Outcomes in Patients with Inflammatory Bowel Disease in the United States: An Analysis of the Nationwide Readmissions Database.

PURPOSE: Bariatric surgery has been reported to produce durable weight loss in the management of obesity; sleeve gastrectomy (SG) is the most common bariatric procedure. Obesity is a common comorbidity of inflammatory bowel disease (IBD), and the impact of IBD on short-term SG outcomes has not been widely reported. This study assessed whether IBD was associated with adverse post-SG outcomes. MATERIALS AND METHODS: Hospitalizations of patients undergoing SG in the United States were identified using the 2010-2020 Nationwide Readmissions Database (NRD) and stratified by IBD diagnosis. The SG cohort was propensity-matched based on age, biological sex, body mass index (BMI), comorbid diabetes, hypertension, depression, chronic obstructive pulmonary disease, and discharge in quarter four. Primary aims were to compare in-hospital mortality, post-operative complications, and all-cause 90-day readmission between patients with and without IBD. Secondary outcomes were length of stay (LOS) and total hospital cost. RESULTS: A total of 2030 hospitalizations were matched. The odds of complication were 48% higher for hospitalizations of patients with IBD (11.1% vs. 7.8%; aOR 1.48, aOR 95% CI 1.10-2.00, p = .009). The most common complication was nausea (4.9% vs. 3.7%, p = .187). No statistically significant difference was observed for all-cause 90-day readmissions, LOS, or hospital cost. CONCLUSION: Hospitalizations of patients with IBD who underwent SG experienced significantly higher post-operative complication rates. However, the similar lengths of stay and readmission rates compared to propensity-matched SG hospitalizations without IBD suggest many complications were minor. SG remains a safe weight loss procedure for patients suffering from IBD and obesity.

Antenatal mesenchymal stromal cell extracellular vesicle treatment preserves lung development in a model of bronchopulmonary dysplasia due to chorioamnionitis.

Antenatal stressors such as chorioamnionitis (CA) increase the risk for bronchopulmonary dysplasia (BPD). Studies have shown that experimental BPD can be ameliorated by postnatal treatment with mesenchymal stromal cell-derived extracellular vesicles (MEx). However, the antenatal efficacy of MEx to prevent BPD is unknown. To determine whether antenatal MEx therapy attenuates intrauterine inflammation and preserves lung growth in a rat model of CA-induced BPD. At embryonic day (E)20, rat litters were treated with intra-amniotic injections of saline, endotoxin (ETX) to model chorioamnionitis, MEx, or ETX plus MEx followed by cesarean section delivery with placental harvest at E22. Placental and lung evaluations were conducted at day 0 and day 14, respectively. To assess the effects of ETX and MEx on lung growth in vitro, E15 lung explants were imaged for distal branching. Placental tissues from ETX-exposed pregnancies showed increased expression of inflammatory markers NLRP-3 and IL-1ß and altered spiral artery morphology. In addition, infant rats exposed to intrauterine ETX had reduced alveolarization and pulmonary vessel density (PVD), increased right ventricular hypertrophy (RVH), and decreased lung mechanics. Intrauterine MEx therapy of ETX-exposed pups reduced inflammatory cytokines, normalized spiral artery architecture, and preserved distal lung growth and mechanics. In vitro studies showed that MEx treatment enhanced distal lung branching and increased VEGF and SPC gene expression. Antenatal MEx treatment preserved distal lung growth and reduced intrauterine inflammation in a model of CA-induced BPD. We speculate that MEx may provide a novel therapeutic strategy to prevent BPD due to antenatal inflammation.

Electronic control of DNA polymerase binding and unbinding to single DNA molecules.

DNA polymerases catalyze template-dependent genome replication. The assembly of a high affinity ternary complex between these enzymes, the double strand-single strand junction of their DNA substrate, and the deoxynucleoside triphosphate (dNTP) complementary to the first template base in the polymerase active site is essential to this process. We present a single molecule method for iterative measurements of DNA-polymerase complex assembly with high temporal resolution, using active voltage control of individual DNA substrate molecules tethered noncovalently in an alpha-hemolysin nanopore. DNA binding states of the Klenow fragment of Escherichia coli DNA polymerase I (KF) were diagnosed based upon their ionic current signature, and reacted to with submillisecond precision to execute voltage changes that controlled exposure of the DNA substrate to KF and dNTP. Precise control of exposure times allowed measurements of DNA-KF complex assembly on a time scale that superimposed with the rate of KF binding. Hundreds of measurements were made with a single tethered DNA molecule within seconds, and dozens of molecules can be tethered within a single experiment. This approach allows statistically robust analysis of the assembly of complexes between DNA and RNA processing enzymes and their substrates at the single molecule level.

Feedback control of a DNA molecule tethered in a nanopore to repeatedly probe DNA-binding enzymes.

This paper demonstrates feedback voltage control of a single DNA molecule tethered in a biological nanopore. The nanopore device monitors ionic current through a single protein pore inserted in a lipid bilayer. The limiting aperture of the pore is just sufficient (1.5 nm diameter) to accommodate single-stranded DNA. The tethered DNA is double stranded on each end, with a single stranded segment that traverses the pore. Voltage control is used to regulate the motion of the tethered DNA, for repeated capture and subsequent voltage-promoted dissociation of DNA-binding enzymes above the nanopore. In initial experiments using the Klenow fragment of Escherichia coli DNA polymerase I, control of 8 independent tethered DNA molecules yielded 337 dissociation events in a period of 380 seconds. The resulting distribution of DNA-protein dissociation times can be used to model the free energy profile of dissociation. Moreover, the approach is applicable to numerous enzymes that bind or modify DNA or RNA including exonucleases, kinases, and other polymerases.

Sequence-specific detection of individual DNA polymerase complexes in real time using a nanopore.

Nanoscale pores have potential to be used as biosensors and are an established tool for analysing the structure and composition of single DNA or RNA molecules. Recently, nanopores have been used to measure the binding of enzymes to their DNA substrates. In this technique, a polynucleotide bound to an enzyme is drawn into the nanopore by an applied voltage. The force exerted on the charged backbone of the polynucleotide by the electric field is used to examine the enzyme-polynucleotide interactions. Here we show that a nanopore sensor can accurately identify DNA templates bound in the catalytic site of individual DNA polymerase molecules. Discrimination among unbound DNA, binary DNA/polymerase complexes, and ternary DNA/polymerase/deoxynucleotide triphosphate complexes was achieved in real time using finite state machine logic. This technique is applicable to numerous enzymes that bind or modify DNA or RNA including exonucleases, kinases and other polymerases.