Am J Obstet Gynecol MFM
September 2022
Background: Preeclampsia is a hypertensive disease unique to pregnancy and has a significant impact on maternal and neonatal morbidity and mortality. Daily aspirin has been demonstrated to reduce the risk of preeclampsia. The American College of Obstetricians and Gynecologists recommends daily low-dose aspirin, ideally before 16 weeks' gestation, in at-risk patients for preeclampsia risk reduction.
View Article and Find Full Text PDFDirect pathogen detection in blood to diagnose active tuberculosis (TB) has been difficult due to low levels of circulating antigens or due to the lack of specific, high-affinity binding reagents and reliable assays with adequate sensitivity. We sought to determine whether slow off-rate modified aptamer (SOMAmer) reagents with subnanomolar affinity for proteins (antigens 85A, 85B, 85C, GroES, GroEL2, DnaK, CFP10, KAD, CFP2, RplL, and Tpx) could be useful to diagnose tuberculosis. When incorporated into the multiplexed, array-based proteomic SOMAscan assay, limits of detection reached the subpicomolar range in 40% serum.
View Article and Find Full Text PDFNew non-sputum biomarker tests for active tuberculosis (TB) diagnostics are of the highest priority for global TB control. We performed in-depth proteomic analysis using the 4,000-plex SOMAscan assay on 1,470 serum samples from seven countries where TB is endemic. All samples were from patients with symptoms and signs suggestive of active pulmonary TB that were systematically confirmed or ruled out for TB by culture and clinical follow-up.
View Article and Find Full Text PDFHtrA serine proteases are highly conserved and essential ATP-independent proteases with chaperone activity. Bacteria express a variable number of HtrA homologues that contribute to the virulence and pathogenicity of bacterial pathogens. Lyme disease spirochetes possess a single HtrA protease homologue, Borrelia burgdorferi HtrA (BbHtrA).
View Article and Find Full Text PDFBorrelia burgdorferi synthesizes an HtrA protease (BbHtrA) which is a surface-exposed, conserved protein within Lyme disease spirochetes with activity toward CheX and BmpD of Borrelia spp, as well as aggrecan, fibronectin and proteoglycans found in skin, joints and neural tissues of vertebrates. An antibody response against BbHtrA is observed in Lyme disease patients and in experimentally infected laboratory mice and rabbits. Given the surface location of BbHtrA on B.
View Article and Find Full Text PDFUnderstanding the functions of multi-cellular organs in terms of the molecular networks within each cell is an important step in the quest to predict phenotype from genotype. B-lymphocyte population dynamics, which are predictive of immune response and vaccine effectiveness, are determined by individual cells undergoing division or death seemingly stochastically. Based on tracking single-cell time-lapse trajectories of hundreds of B cells, single-cell transcriptome, and immunofluorescence analyses, we constructed an agent-based multi-modular computational model to simulate lymphocyte population dynamics in terms of the molecular networks that control NF-κB signaling, the cell cycle, and apoptosis.
View Article and Find Full Text PDFCompendial methods determining dry powder inhaler (DPI)-emitted aerosol aerodynamic particle size distribution (APSD) collect a 4-L air sample containing the aerosol bolus, where the flow, which propagates through the cascade impactor (CI) measurement system from the vacuum source, is used to actuate the inhaler. A previous article described outcomes with two CIs (Andersen eight-stage cascade impactor (ACI) and Next-Generation Pharmaceutical Impactor (NGI)) when the air sample volume was ≤4 L with moderate-resistance DPIs. This article extends that work, examining the hypothesis that DPI flow resistance may be a factor in determining outcomes.
View Article and Find Full Text PDFThe Lyme disease spirochaete, Borrelia burgdorferi, causes damage to diverse host tissues and induces inflammation but the mechanisms of injury are poorly understood. We recently reported that a surface-exposed B. burgdorferi protease, which is expressed during human disease and is conserved within the major Lyme disease spirochaete species, degrades the extracellular matrix proteoglycan, aggrecan.
View Article and Find Full Text PDFA novel method of culturing spirochetes from the serum of U.S. Lyme disease patients was recently reported by Sapi and colleagues to have 94% sensitivity and 100% specificity for Borrelia species as assessed by microscopy and DNA sequence analysis of the pyrG gene (E.
View Article and Find Full Text PDFConnective tissues are the most common area of colonization for the Lyme disease spirochaete Borrelia burgdorferi. Colonization is aided by the interaction between numerous bacterial adhesins with components of the extracellular matrix (ECM). Here we describe a novel interaction between B.
View Article and Find Full Text PDFBackground: The Abbreviated Impactor Measurement (AIM) concept simplifies determination of aerodynamic size metrics for inhaler quality control testing. A similar approach is needed to compare in vitro particle size distribution metrics with human respiratory tract (HRT) deposition.
Methods: An abbreviated impactor based on the Andersen eight-stage cascade impactor (ACI) was developed having two size-fractionating stages with cut-points at 4.
The CD8+ T-cell is a key mediator of antiviral immunity, potentially contributing to control of pathogenic lentiviral infection through both innate and adaptive mechanisms. We studied viral dynamics during antiretroviral treatment of simian immunodeficiency virus (SIV) infected rhesus macaques following CD8+ T-cell depletion to test the importance of adaptive cytotoxic effects in clearance of cells productively infected with SIV. As previously described, plasma viral load (VL) increased following CD8+ T-cell depletion and was proportional to the magnitude of CD8+ T-cell depletion in the GALT, confirming a direct relationship between CD8+ T-cell loss and viral replication.
View Article and Find Full Text PDFJ Adolesc Health
January 2004
Purpose: To examine and explain the relationship between work intensity (number of hours worked per week) and heavy alcohol use among adolescents.
Methods: Analyses were conducted with two waves of in-home interview data provided by a representative sample of adolescents who participated in the National Longitudinal Study of Adolescent Health. Multinomial logistic regression analyses were conducted to determine whether a higher level of work intensity at Wave 1 predicted a higher level of past-year heavy drinking approximately 1 year later at Wave 2, and the degree to which the relationship between work intensity and heavy drinking persisted after adjusting for demographic characteristics, alcohol use before Wave 1, and psychosocial risk and protective factors in family, school, and peer-individual domains.