Comparison of a second TNFi vs other biologic or targeted synthetic DMARD following an initial TNFi.

Patients with rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, or ulcerative colitis may require treatment with a biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD). Often, a tumor necrosis factor inhibitor (TNFi) is the initial b/tsDMARD. The TNFi may not be effective or may not be well tolerated, so patients will opt for a different TNFi or switch to a non-TNFi b/tsDMARD.

Mapping enzyme catalysis with metabolic biosensing.

Enzymes are represented across a vast space of protein sequences and structural forms and have activities that far exceed the best chemical catalysts; however, engineering them to have novel or enhanced activity is limited by technologies for sensing product formation. Here, we describe a general and scalable approach for characterizing enzyme activity that uses the metabolism of the host cell as a biosensor by which to infer product formation. Since different products consume different molecules in their synthesis, they perturb host metabolism in unique ways that can be measured by mass spectrometry.

Real-world treatment, clinical outcomes and healthcare resource utilization among persons with hemophilia A by age.

Examine real-world characteristics, treatment patterns, and outcomes among treated persons with hemophilia A (PwHA) stratified by age. This study utilized US claims data from 1 January 2007-31 July 2018 from the Humana Research Database. Unadjusted comparisons were conducted across PwHA (<18, 18-55, 56-89 years) enrolled in commercial or Medicare Advantage Prescription Drug plans.

Preserved and variable spatial-chemical changes of lipids across tomato leaves in response to central vein wounding reveals potential origin of linolenic acid in signal transduction cascade.

Membrane lipids serve as substrates for the generation of numerous signaling lipids when plants are exposed to environmental stresses, and jasmonic acid, an oxidized product of 18-carbon unsaturated fatty acids (e.g., linolenic acid), has been recognized as the essential signal in wound-induced gene expression.

Dynamic Range Expansion by Gas-Phase Ion Fractionation and Enrichment for Imaging Mass Spectrometry.

In the analysis of biological tissue by imaging mass spectrometry (IMS), the limit of detection and dynamic range are of paramount importance in obtaining experimental results that provide insight into underlying biological processes. Many important biomolecules are present in the tissue milieu in low concentrations and in complex mixtures with other compounds of widely ranging abundances, challenging the limits of analytical technologies. In many IMS experiments, the ion signal can be dominated by a few highly abundant ion species.

Rapid MALDI mass spectrometry imaging for surgical pathology.

Matrix assisted laser desorption ionization mass spectrometry imaging (MALDI MSI) is an emerging analytical technique, which generates spatially resolved proteomic and metabolomic images from tissue specimens. Conventional MALDI MSI processing and data acquisition can take over 30 min, limiting its clinical utility for intraoperative diagnostics. We present a rapid MALDI MSI method, completed under 5 min, including sample preparation and analysis, providing a workflow compatible with the clinical frozen section procedure.

Impact of a transposon insertion in phzF2 on the specialized metabolite production and interkingdom interactions of Pseudomonas aeruginosa.

In microbiology, gene disruption and subsequent experiments often center on phenotypic changes caused by one class of specialized metabolites (quorum sensors, virulence factors, or natural products), disregarding global downstream metabolic effects. With the recent development of mass spectrometry-based methods and technologies for microbial metabolomics investigations, it is now possible to visualize global production of diverse classes of microbial specialized metabolites simultaneously. Using imaging mass spectrometry (IMS) applied to the analysis of microbiology experiments, we can observe the effects of mutations, knockouts, insertions, and complementation on the interactive metabolome.

Interkingdom metabolic transformations captured by microbial imaging mass spectrometry.

In polymicrobial infections, microbes can interact with both the host immune system and one another through direct contact or the secretion of metabolites, affecting disease progression and treatment options. The thick mucus in the lungs of patients with cystic fibrosis is highly susceptible to polymicrobial infections by opportunistic pathogens, including the bacterium Pseudomonas aeruginosa and the fungus Aspergillus fumigatus. Unravelling the hidden molecular interactions within such polymicrobial communities and their metabolic exchange processes will require effective enabling technologies applied to model systems.

Comparison of hepatitis C virus treatment between incarcerated and community patients.

Unlabelled: The prevalence of chronic hepatitis C virus (HCV) infection among incarcerated individuals in the United States is estimated to be between 12% and 31%. HCV treatment during incarceration is an attractive option because of improved access to health care and directly observed therapy. We compared incarcerated and nonincarcerated HCV-infected patients evaluated for treatment at a single academic center between January 1, 2002 and December 31, 2007.

Metastatic Kaposi's Sarcoma with Perirectal Involvement Diagnosed with Endoscopic Ultrasound-Guided EchoBrush Cytology Sampling.

AIDS-related Kaposi's sarcoma (KS) is a low-grade vascular tumor that occurs in association with human herpesvirus 8 infection. Here we report the case of a 21-year-old male with recently diagnosed cutaneous KS who presented with rectal bleeding and anal pruritus. Initial endoscopic evaluation was nondiagnostic.

The causes and outcome of acute pancreatitis associated with serum lipase >10,000 u/l.

Objectives: Our objective was to investigate the use of serum lipase levels >10,000 U/L as a tool for predicting the etiology of acute pancreatitis (AP) and to further address the relationship between lipase elevation and disease severity.

Methods: We compared patients with AP and serum lipase >10,000 U/L (HL) with patients with AP and lower serum lipase levels (855-10,000 U/L). The etiology and severity of AP were recorded.

Normalization in MALDI-TOF imaging datasets of proteins: practical considerations.

Normalization is critically important for the proper interpretation of matrix-assisted laser desorption/ionization (MALDI) imaging datasets. The effects of the commonly used normalization techniques based on total ion count (TIC) or vector norm normalization are significant, and they are frequently beneficial. In certain cases, however, these normalization algorithms may produce misleading results and possibly lead to wrong conclusions, e.

Screening colonoscopy and detection of neoplasia in asymptomatic, average-risk, solid organ transplant recipients: case-control study.

The aim of this study was to evaluate the detection of colonic neoplasia in an average-risk population of SOT recipients. Studies regarding colonic neoplasia in solid organ transplantation (SOT) recipients have demonstrated mixed results due to the inclusion of above average-risk patients. We performed a case-control study of 102 average-risk SOT recipients who underwent screening colonoscopy, compared with an average-risk, age and sex-matched control group (n=287).

From whole-body sections down to cellular level, multiscale imaging of phospholipids by MALDI mass spectrometry.

Significant progress in instrumentation and sample preparation approaches have recently expanded the potential of MALDI imaging mass spectrometry to the analysis of phospholipids and other endogenous metabolites naturally occurring in tissue specimens. Here we explore some of the requirements necessary for the successful analysis and imaging of phospholipids from thin tissue sections of various dimensions by MALDI time-of-flight mass spectrometry. We address methodology issues relative to the imaging of whole-body sections such as those cut from model laboratory animals, sections of intermediate dimensions typically prepared from individual organs, as well as the requirements for imaging areas of interests from these sections at a cellular scale spatial resolution.

Utility of colonoscopy in the evaluation of diarrhea in solid organ transplant recipients.

Background: Diarrhea is common in solid organ transplant recipients. Colonoscopy with random biopsies is performed frequently in the diagnostic evaluation of the posttransplant population with diarrhea. The purpose of this study was to determine the sensitivity of colonoscopy with random biopsy in determining a specific diagnosis and changing management in solid organ transplant recipients with diarrhea.

High-throughput profiling of formalin-fixed paraffin-embedded tissue using parallel electrophoresis and matrix-assisted laser desorption ionization mass spectrometry.

Analysis of formalin-fixed paraffin-embedded tissues (FFPE) is increasingly recognized as a strategy for the discovery and validation of clinically useful biomarker candidates. Large tissue collections including tissue microarrays (TMAs) are available, but current analytical strategies for their characterization have limited throughput. In this report, we describe a workflow for rapid analysis of hundreds of FFPE tissue specimens.

Spatial and temporal alterations of phospholipids determined by mass spectrometry during mouse embryo implantation.

Molecular events involved in successful embryo implantation are not well understood. In this study, we used MALDI imaging mass spectrometry (IMS) technologies to characterize the spatial and temporal distribution of phospholipid species associated with mouse embryo implantation. Molecular images showing phospholipid distribution within implantation sites changed markedly between distinct cellular areas during days 4-8 of pregnancy.

MALDI-FTICR imaging mass spectrometry of drugs and metabolites in tissue.

A new approach is described for imaging mass spectrometry analysis of drugs and metabolites in tissue using matrix-assisted laser desorption ionization-Fourier transform ion cyclotron resonance (MALDI-FTICR). The technique utilizes the high resolving power to produce images from thousands of ions measured during a single mass spectrometry (MS)-mode experiment. Accurate mass measurement provides molecular specificity for the ion images on the basis of elemental composition.

Findings on optical colonoscopy after positive CT colonography exam.

Background & Aims: The aim of this study is to evaluate the findings on optical colonoscopy (OC) after a positive CT colonography (CTC) exam and characterize the type of polyps seen on OC but not reported by CTC.

Methods: Over an 18-month period a total of 159 asymptomatic adults had polyps seen on computed tomography colonography examination and subsequently underwent planned therapeutic optical colonoscopy. The colonoscopists were aware of the findings on CT colonography prior to further evaluation of the colon.

Solvent-free matrix dry-coating for MALDI imaging of phospholipids.

A fast and simple, solvent-free matrix deposition protocol was developed for positive ionization mode phospholipid analysis in tissues. Finely ground 2,5-dihydroxybenzoic acid was deposited onto sagittal mouse brain sections using a dry-coating technique, in which solid matrix particles were filtered directly onto the tissue through a 20-microm stainless steel sieve. Phospholipid signals were obtained directly off these sections, allowing acquisition of high-resolution MS images.

Identification of dimethyldioctadecylammonium ion (m/z 550.6) and related species (m/z 522.6, 494.6) as a source of contamination in mass spectrometry.

Chemical contamination can be one of the more common problems encountered when performing trace-level analysis regardless of the analytical technique. Minimizing or eliminating background interferences can be a difficult task, so knowledge of the chemical composition of these contaminants can prove invaluable when it comes to identifying the source. Once the source is identified, proper steps may be taken to reduce or eliminate it.

Integrating spatially resolved three-dimensional MALDI IMS with in vivo magnetic resonance imaging.

We have developed a method for integrating three dimensional-volume reconstructions of spatially resolved matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) ion images of whole mouse heads with high-resolution images from other modalities in an animal-specific manner. This approach enabled us to analyze proteomic profiles from MALDI IMS data with corresponding in vivo data provided by magnetic resonance imaging.