A Case of Type II Achalasia Presenting With Markedly Elevated Troponins.

Achalasia is an esophageal motility disorder that presents with dysphagia to solids and liquids and regurgitation of undigested food. Cardiac troponin (cTn) is a sensitive biomarker for myocardial injury, and elevated levels suggest an increased risk of mortality from acute coronary syndrome (ACS). Non-cardiac gastrointestinal (GI) causes of troponin elevation are rare and have generally been described in cases of critical illness (e.g., significant gastrointestinal bleeding (GIB) or acute liver failure). We report a rare case of type II achalasia presenting with markedly elevated troponins. This case illustrates an important GI-related mimic of ACS that should be considered by frontline providers and gastroenterologists.

The Impact of the Colonoscopy Starting Position and Its Potential Outcomes.

Based on the literature review, many studies have been inconclusive in regards to adenoma detection and procedural positioning during a colonoscopy. Scope looping can make cecal intubation challenging, changing the positioning of the patient and application of external abdominal pressure can overcome this difficulty. A colonoscopy in a prone position can overcome these challenges and reduce cecal intubation time. It can thus improve the safety of the patient and the staff by minimizing the movement of a sedated patient.

A Study of Proton Pump Inhibitors and Other Risk Factors in Warfarin-Associated Gastrointestinal Bleeding.

Background Warfarin users are at increased risk for gastrointestinal bleeding (GIB). History of GIB, stroke, cardiovascular or chronic kidney disease, age greater than 65 years, and drug interaction with proton pump inhibitors (PPI) have previously been identified as risk factors for GIB in warfarin users. We hypothesized that concomitant use of warfarin and PPI would increase the incidence of GIB relative to warfarin use alone. Methods We did a retrospective review of medical records of 626 patients taking warfarin for at least two weeks. Parameters including age, concomitant medication use (non-steroidal anti-inflammatory drugs (NSAID), aspirin, selective serotonin reuptake inhibitors (SSRIs), PPI, and anti-platelet drug), history of GIB, chronic renal failure (CRF), and peptic ulcer disease (PUD) prior to warfarin use were analyzed. Results Variables that increase the likelihood of bleeding in warfarin users included aspirin, PPI, history of PUD, history of previous GIB, CRF, and elevated prothrombin time (PT)/international normalized ratio (INR) values. Concomitant antiplatelet use showed a slight increase in GIB but this was not statistically significant (p=0.082). NSAID use and SSRI use were not associated with a higher risk of GIB among warfarin users. Patients who are on PPI and warfarin simultaneously are more likely to be on acetylsalicylic acid (ASA) or have a history of PUD, GIB, or CRF, all of which are associated with increased incidences of GIB. Conclusions Although concomitant use of warfarin and PPI appears to be associated with an increased incidence of GIB, these patients are more likely to have other risk factors that also increase the risk of a GIB outcome. Therefore, the interaction between PPI and warfarin is clinically insignificant.

Multiplexed target detection using DNA-binding dye chemistry in droplet digital PCR.

Two years ago, we described the first droplet digital PCR (ddPCR) system aimed at empowering all researchers with a tool that removes the substantial uncertainties associated with using the analogue standard, quantitative real-time PCR (qPCR). This system enabled TaqMan hydrolysis probe-based assays for the absolute quantification of nucleic acids. Due to significant advancements in droplet chemistry and buoyed by the multiple benefits associated with dye-based target detection, we have created a "second generation" ddPCR system compatible with both TaqMan-probe and DNA-binding dye detection chemistries. Herein, we describe the operating characteristics of DNA-binding dye based ddPCR and offer a side-by-side comparison to TaqMan probe detection. By partitioning each sample prior to thermal cycling, we demonstrate that it is now possible to use a DNA-binding dye for the quantification of multiple target species from a single reaction. The increased resolution associated with partitioning also made it possible to visualize and account for signals arising from nonspecific amplification products. We expect that the ability to combine the precision of ddPCR with both DNA-binding dye and TaqMan probe detection chemistries will further enable the research community to answer complex and diverse genetic questions.

High-throughput droplet digital PCR system for absolute quantitation of DNA copy number.

Digital PCR enables the absolute quantitation of nucleic acids in a sample. The lack of scalable and practical technologies for digital PCR implementation has hampered the widespread adoption of this inherently powerful technique. Here we describe a high-throughput droplet digital PCR (ddPCR) system that enables processing of ~2 million PCR reactions using conventional TaqMan assays with a 96-well plate workflow. Three applications demonstrate that the massive partitioning afforded by our ddPCR system provides orders of magnitude more precision and sensitivity than real-time PCR. First, we show the accurate measurement of germline copy number variation. Second, for rare alleles, we show sensitive detection of mutant DNA in a 100,000-fold excess of wildtype background. Third, we demonstrate absolute quantitation of circulating fetal and maternal DNA from cell-free plasma. We anticipate this ddPCR system will allow researchers to explore complex genetic landscapes, discover and validate new disease associations, and define a new era of molecular diagnostics.

Interfacial and physico-chemical properties of polymer-supported CdSZnS nanocomposites and their role in the visible-light mediated photocatalytic splitting of water.

Nano-composite CdSZnS moieties coated over polyester strip were found to exhibit better visible-light-mediated photo-activity for splitting of water, as compared to corresponding pure CdS or ZnS containing coupons. This increase in activity depended upon the mol ratio of the two component sulphides in a particular sample. HRTEM experiments revealed the presence of 1-3 nm size CdS particles embedded over larger size ZnS clusters, the composite samples thus functioning as a highly dispersed guest-host system. In the case of CdS and ZnS dispersed individually over polyester, average crystallite size was found to be around 5 and 15 nm, respectively. A blue shift was observed in the UV-vis absorption spectrum of CdS on addition of ZnS, in conformation with the quantum size effects. Powder XRD, electron diffraction and XPS studies showed that the nanocomposites were comprised of the face-centered cubic (alpha) phases of both CdS and ZnS in a close contact with each other. At the same time, certain solid solution phases, i.e. Cd(1-x)Zn(x)S, were generated at the interfaces of these two semiconductors. Our study demonstrates that the increase in the number of reaction sites due to smaller size of CdS particles and the micro-structural properties associated with the nanostructured CdS or CdS/ZnS interfaces may together play a vital role in the augmented catalytic activity of CdSZnS composite photocatalysts.

Intramolecular epitope spreading in Heymann nephritis.

Immunization with megalin induces active Heymann nephritis, which reproduces features of human idiopathic membranous glomerulonephritis. Megalin is a complex immunological target with four discrete ligand-binding domains (LBDs) that may contain epitopes to which pathogenic autoantibodies are directed. Recently, a 236-residue N-terminal fragment, termed "L6," that spans the first LBD was shown to induce autoantibodies and severe disease. We used this model to examine epitope-specific contributions to pathogenesis. Sera obtained from rats 4 weeks after immunization with L6 demonstrated reactivity only with the L6 fragment on Western blot, whereas sera obtained after 8 weeks demonstrated reactivity with all four recombinant fragments of interest (L6 and LBDs II, III, and IV). We demonstrated that the L6 immunogen does not contain the epitopes responsible for the reactivity to the LBD fragments. Therefore, the appearance of antibodies directed at LBD fragments several weeks after the primary immune response suggests intramolecular epitope spreading. In vivo, we observed a temporal association between increased proteinuria and the appearance of antibodies to LBD fragments. These data implicate B cell epitope spreading in antibody-mediated pathogenesis of active Heymann nephritis, a model that should prove valuable for further study of autoimmune dysregulation.