Properdin acts as an essential positive regulator of the alternative pathway of complement by stabilizing enzymatic convertases. Identical properdin monomers form head-to-tail associations of oligomers in a reported 20:54:26 ratio (most often described as an approximate 1:2:1 ratio) of tetramers (P), trimers (P), and dimers (P), in blood, under normal physiological conditions. Oligomeric size is proportional to properdin function with tetramers being more active, followed by trimers and dimers.
View Article and Find Full Text PDFExtracellular sulfatase-2 (Sulf-2) influences receptor-ligand binding and subsequent signaling by chemokines and growth factors, yet Sulf-2 remains unexplored in inflammatory cytokine signaling in the context of rheumatoid arthritis (RA). In the present study, we characterized Sulf-2 expression in RA and investigated its potential role in TNF-α-induced synovial inflammation using primary human RA synovial fibroblasts (RASFs). Sulf-2 expression was significantly higher in serum and synovial tissues from patients with RA and in synovium and serum from hTNFtg mice.
View Article and Find Full Text PDFTo investigate the utility of AngioVac-assisted vegetation debulking (AVD) in right sided infective endocarditis (RSIE). AngioVac is a vacuum-based device that was approved in 2014 for the percutaneous removal of undesirable materials from the intravascular system. Although there are multiple reports on the use of the AngioVac device to aspirate right-sided heart chamber thrombi, data on its use to treat RSIE is limited.
View Article and Find Full Text PDFA significant number of postural orthostatic tachycardia syndrome (POTS) patients have platelet delta granule storage pool deficiency (δ-SPD). The etiology of POTS is unknown but a number of laboratories, including ours, have reported elevations of G-protein-coupled adrenergic receptor and muscarinic acetylcholine receptor autoantibodies in POTS patients, detected by a variety of techniques, suggesting that the disorder is an autoimmune condition. Thus, it could also be considered an inflammatory disease.
View Article and Find Full Text PDFRheumatoid arthritis synovial fibroblasts (RASFs) contribute to synovial inflammation and bone destruction by producing a pleiotropic cytokine interleukin-6 (IL-6). However, the molecular mechanisms through which IL-6 propels RASFs to contribute to bone loss are not fully understood. In the present study, we investigated the effect of IL-6 and IL-6 receptor (IL-6/IL-6R)-induced trans-signaling in human RASFs.
View Article and Find Full Text PDFBackground: Direct oral anticoagulants (DOACs) have been increasingly preferred over warfarin; however, The International Society of Thrombosis and Hemostasis recommended avoiding the use of DOACs in morbidly obese patients (body mass index >40 or weight >120 kg) because of limited clinical data.
Study Question: Are DOACs effective and safe in morbidly obese patients with nonvalvular atrial fibrillation (NVAF).
Data Sources: We performed a comprehensive search for published studies indexed in PubMed/MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials that evaluated the efficacy and safety of DOACs in morbidly obese patients with NVAF.
Background/purpose: Home healthcare (HHC) utilization is associated with higher rates of rehospitalization in patients with heart failure and transcatheter mitral valve repair. This study sought to assess the utilization, predictors, and the association of HHC with 30-day readmission in patients undergoing transcatheter aortic valve replacement (TAVR).
Methods/materials: We queried the Nationwide Readmission Database from January 2012 to December 2017 for TAVR discharges with and without HHC referral.
Background The prognostic value of echocardiographic evaluation of right ventricular (RV) function in patients undergoing left-sided valvular surgery has not been well described. The objective of this study is to determine the role of broad echocardiographic assessment of RV function in predicting short-term outcomes after valvular surgery. Methods and Results Preoperative echocardiographic data, perioperative adverse outcomes, and 30-day mortality were analyzed in patients who underwent left-sided valvular surgery from 2006 to 2014.
View Article and Find Full Text PDFBackground: Data comparing the effect of age on outcomes of patients who underwent either endovascular coiling (EVC) or neurosurgical clipping (NSC) for ruptured intracranial aneurysms remains limited.
Objective: To better elucidate the preferred intervention for ruptured aneurysm management by presenting the results of our systematic review of the literature that evaluated the potential advantages of the two interventions between different age groups.
Methods: Systematic review of PubMed and Embase was performed (2002 - June 10, 2019) following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2013 guidelines.
Background: Standardized Nucleic Acid Quantification for SEQuencing (SNAQ-SEQ) is a novel method that utilizes synthetic DNA internal standards spiked into each sample prior to next generation sequencing (NGS) library preparation. This method was applied to analysis of normal appearing airway epithelial cells (AEC) obtained by bronchoscopy in an effort to define a somatic mutation field effect associated with lung cancer risk. There is a need for biomarkers that reliably detect those at highest lung cancer risk, thereby enabling more effective screening by annual low dose CT.
View Article and Find Full Text PDFObjective: Hyperglycemia is an independent risk factor in hospitalized patients for adverse outcomes, even if patients are not diabetic. We used continuous glucose monitoring to evaluate whether glycemic control (hyperglycemia) in the first 72 h after an intensive care admission was associated with the need for admission to a post discharge long-term medical facility.
Results: We enrolled 59 coronary artery bypass grafting patients.
Background: There is a need for more powerful methods to identify low-effect SNPs that contribute to hereditary COPD pathogenesis. We hypothesized that SNPs contributing to COPD risk through cis-regulatory effects are enriched in genes comprised by bronchial epithelial cell (BEC) expression patterns associated with COPD.
Methods: To test this hypothesis, normal BEC specimens were obtained by bronchoscopy from 60 subjects: 30 subjects with COPD defined by spirometry (FEV1/FVC < 0.
Background: Middle cerebral artery division (M2) occlusion was significantly underrepresented in recent mechanical thrombectomy (MT) randomized controlled trials, and the approach to this disease remains heterogeneous.
Objective: To conduct a systematic review and meta-analysis of outcomes at 90 days among patients undergoing MT for M2 middle cerebral artery (MCA) occlusions.
Methods: Five clinical databases were searched from inception through September 2016.
Background: Systemic sclerosis (SSc) is a multisystem disease associated with significant morbidity and increased mortality. The prevalence of different gastrointestinal (GI) manifestations has been investigated in multiple, but mainly small, retrospective studies. In this study, we investigated the prevalence and risk for a broad spectrum of GI disorders and malignancies in a large sample of inpatients with SSc in the United States.
View Article and Find Full Text PDFOvarian cancer is the gynecological cancer with the poorest prognosis. One significant reason is the development of resistance to the chemotherapeutic drugs used in its treatment. The large GTPase, hGBP-1, has been implicated in paclitaxel resistance in ovarian cell lines.
View Article and Find Full Text PDFIntroduction: There is a paucity of data regarding autonomic dysfunction (AD) in Guillain-Barré Syndrome (GBS). Concern exists regarding inpatient mortality risk in GBS. We sought to identify the prevalence of AD in GBS inpatients.
View Article and Find Full Text PDFBackground: Postoperative state is characterized by increased thrombotic risk by virtue of platelet activation. Whether aspirin ameliorates this risk in patients with established coronary artery disease undergoing cardiac or noncardiac surgery is unknown. We conducted a systematic review and meta-analysis to compare the risk of major adverse cardiac events (MACE) and the risk of bleeding in patients with early (3-5 or more days before surgery) vs.
View Article and Find Full Text PDFFrancisella tularensis is the causative agent of the lethal disease tularemia. Despite decades of research, little is understood about why F. tularensis is so virulent.
View Article and Find Full Text PDFExcision repair cross-complementation group 5 (ERCC5) gene plays an important role in nucleotide excision repair, and dysregulation of ERCC5 is associated with increased lung cancer risk. Haplotype and diplotype analyses were conducted in normal bronchial epithelial cells (NBEC) to better understand mechanisms responsible for interindividual variation in transcript abundance regulation of ERCC5 We determined genotypes at putative ERCC5 cis-regulatory SNPs (cis-rSNP) rs751402 and rs2296147, and marker SNPs rs1047768 and rs17655. ERCC5 allele-specific transcript abundance was assessed by a recently developed targeted sequencing method.
View Article and Find Full Text PDFBackground: The number of aging human immunodeficiency virus-infected (HIV+) individuals living in the United States has substantially grown over the past two decades. Advanced age and HIV infection both increase susceptibility to infection due to B cell dysfunction. The combined impact of these factors on pneumococcal vaccine responses remains unknown.
View Article and Find Full Text PDFBackground: Members of the Tumor Necrosis Factor (TNF)-superfamily have speculated roles in the response against T-independent type II antigens (TI-II) including pneumococcal polysaccharides (PPS). Dysregulation in their expression is associated with an enhanced risk for pneumococcal disease in neonates but their expression in other high-risk populations including HIV-positive individuals remains to be elucidated.
Objective: To investigate signals that contribute towards PPS-response and identify potential anomalies that may account for diminished serological response in HIV-positive individuals post Pneumovax (PPV23) immunization.
Background: Advanced age and human immunodeficiency virus (HIV) infection are associated with increased pneumococcal disease risk. The impact of these factors on cellular responses to vaccination is unknown.
Methods: HIV-infected (HIV+) individuals 50-65 years old with CD4(+) Tcells/μl (CD4) >200 on antiretroviral therapy (ART) ≥1 year received either the 13-valent pneumococcal conjugate vaccine followed by the 23-valent pneumococcal polysaccharide vaccine (PCV/PPV) or PPV only.
The extensive invasive capacity of glioblastoma (GBM) makes it resistant to surgery, radiotherapy, and chemotherapy and thus makes it lethal. In vivo, GBM invasion is mediated by Rho GTPases through unidentified downstream effectors. Mammalian Diaphanous (mDia) family formins are Rho-directed effectors that regulate the F-actin cytoskeleton to support tumor cell motility.
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