Adrenergic Autoantibody-Induced Postural Tachycardia Syndrome in Rabbits.

Background Previous studies have demonstrated that functional autoantibodies to adrenergic receptors may be involved in the pathogenesis of postural tachycardia syndrome. The objective of this study was to examine the impact of these autoantibodies on cardiovascular responses to postural changes and adrenergic orthosteric ligand infusions in immunized rabbits. Methods and Results Eight New Zealand white rabbits were coimmunized with peptides from the α1-adrenergic receptor and β1-adrenergic receptor (β1AR).

Stroke Incidence and Survival in American Indians, Blacks, and Whites: The Strong Heart Study and Atherosclerosis Risk in Communities Study.

Background American Indians ( AIs ) have high stroke morbidity and mortality. We compared stroke incidence and mortality in AI s, blacks, and whites. Methods and Results Pooled data from 2 cardiovascular disease cohort studies included 3182 AI s from the SHS (Strong Heart Study), aged 45 to 74 years at baseline (1988-1990) and 3765 blacks and 10 413 whites from the ARIC (Atherosclerosis Risk in Communities) Study, aged 45 to 64 years at baseline (1987-1989).

Thrombotic thrombocytopenic purpura: Toward targeted therapy and precision medicine.

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy characterized by severe congenital or immune-mediated deficiency in ADAMTS13, the enzyme that cleaves von Willebrand factor multimers. This rare condition leads invariably and rapidly to a fatal outcome in the absence of treatment, and therefore raises multiple diagnostic and therapeutic challenges. The novel concepts and mechanisms identified in the laboratory for this disease have been rapidly and successfully translated into the clinic for the benefit of patients, making TTP an archetypal disease that has benefited from targeted therapies.

Elevated Sera sST2 Is Associated With Heart Failure in Men ≤50 Years Old With Myocarditis.

Background Myocarditis is an important cause of acute and chronic heart failure. Men with myocarditis have worse recovery and an increased need for transplantation compared with women, but the reason for the sex difference remains unclear. Elevated sera soluble (s) ST2 predicts mortality from acute and chronic heart failure, but has not been studied in myocarditis patients.

Role of ADTRP (Androgen-Dependent Tissue Factor Pathway Inhibitor Regulating Protein) in Vascular Development and Function.

Background The physiological function of ADTRP (androgen-dependent tissue factor pathway inhibitor regulating protein) is unknown. We previously identified ADTRP as coregulating with and supporting the anticoagulant activity of tissue factor pathway inhibitor in endothelial cells in vitro. Here, we studied the role of ADTRP in vivo, specifically related to vascular development, stability, and function.

Enteric infection coupled with chronic Notch pathway inhibition alters colonic mucus composition leading to dysbiosis, barrier disruption and colitis.

Intestinal mucus layer disruption and gut microflora modification in conjunction with tight junction (TJ) changes can increase colonic permeability that allows bacterial dissemination and intestinal and systemic disease. We showed previously that Citrobacter rodentium (CR)-induced colonic crypt hyperplasia and/or colitis is regulated by a functional cross-talk between the Notch and Wnt/β-catenin pathways. In the current study, mucus analysis in the colons of CR-infected (108 CFUs) and Notch blocker Dibenzazepine (DBZ, i.

Heterogeneity in association of remote herpesvirus infections and pediatric MS.

Objective: While prior Epstein-Barr virus (EBV) infection has been consistently associated with subsequent risk of developing multiple sclerosis (MS), the association with other common herpesviruses has been more controversial. Our objectives were to determine whether remote infection with EBV and other common herpesviruses affect the susceptibility to pediatric MS and if there are interactions between genetic and demographic factors and viral infections.

Methods: Cases with pediatric-onset MS or clinically isolated syndrome within 4 years of disease onset, and controls were recruited from 16 American pediatric MS centers.

The first case of deafness-dystonia syndrome due to compound heterozygous variants in .

We report the second known family affected by deafness-dystonia syndrome associated with loss of function of . Our patient is compound heterozygous for pathogenic variants, while affected siblings in the first report were homozygous. This case provides evidence that this novel genetic disorder is associated with autosomal recessive inheritance.

Focusing in on use of pharmacokinetic profiles in routine hemophilia care.

Background: Emergence of population pharmacokinetic models for prediction of individual pharmacokinetic (PK) profiles facilitates individualization of prescribed prophylactic therapy for patients with hemophilia A and B and may have a favorable impact on clinical outcomes and annual factor utilization. How providers approach the integration and application of these data into routine clinical practice is not clear.

Objective: To explore the potential application of and barriers to incorporating PK profiles into current hemophilia prophylaxis decision making.

Global public awareness about atrial fibrillation.

Background: Atrial fibrillation (AF) is an important cause of ischemic stroke that often remains undetected until stroke occurs. Awareness of the risk factors and symptoms is important so that AF can be diagnosed and thromboprophylaxis given. However, the extent of public awareness of AF is uncertain.

Impact of World Thrombosis Day campaign.

Thrombosis is an underlying cause of one in four deaths globally. The International Society on Thrombosis and Haemostasis established the inaugural World Thrombosis Day on October 13, 2014. The World Thrombosis Day campaign aims to 1) highlight the disease burden from thrombosis, 2) increase public awareness of the risks, signs, and symptoms of thromboembolic conditions, 3) empower individuals to discuss their thrombosis risk with their healthcare provider, 4) galvanize organizations across the globe, and 5) advocate for "systems of care" to prevent, diagnose, and treat venous thromboembolism and atrial fibrillation.

Impact of ranolazine on ventricular arrhythmias - A systematic review.

Ranolazine is a new medication for the treatment of refractory angina. However, except its anti-anginal properties, it has been found to act as an anti-arrhythmic. The aim of our systematic review is to present the existing data about the impact of ranolazine in ventricular arrhythmias.

The crossed frontal aslant tract: A possible pathway involved in the recovery of supplementary motor area syndrome.

Introduction: Supplementary motor area (SMA) syndrome is a constellation of temporary symptoms that may occur following tumors of the frontal lobe. Affected patients develop akinesia and mutism but often recover within weeks to months. With our own case examples and with correlations to fiber tracking validated by gross anatomical dissection as ground truth, we describe a white matter pathway through which recovery may occur.

A structural equation modeling approach to understanding pathways that connect socioeconomic status and smoking.

The inverse association between socioeconomic status and smoking is well established, yet the mechanisms that drive this relationship are unclear. We developed and tested four theoretical models of the pathways that link socioeconomic status to current smoking prevalence using a structural equation modeling (SEM) approach. Using data from the 2013 National Health Interview Survey, we selected four indicator variables (poverty ratio, personal earnings, educational attainment, and employment status) that we hypothesize underlie a latent variable, socioeconomic status.

Bioactive Antimicrobial Peptides as Therapeutics for Corneal Wounds and Infections.

More than 2 million eye injuries and infections occur each year in the United States that leave civilians and military members with reduced or complete vision loss due to the lack of effective therapeutics. Severe ocular injuries and infections occur in varied settings including the home, workplace, and battlefields. In this review, we discuss the potential of developing antimicrobial peptides (AMPs) as therapeutics for the treatment of corneal wounds and infections for which the current treatment options are inadequate.

White matter connections of the inferior parietal lobule: A study of surgical anatomy.

Introduction: Interest in the function of the inferior parietal lobule (IPL) has resulted in increased understanding of its involvement in visuospatial and cognitive functioning, and its role in semantic networks. A basic understanding of the nuanced white-matter anatomy in this region may be useful in improving outcomes when operating in this region of the brain. We sought to derive the surgical relationship between the IPL and underlying major white-matter bundles by characterizing macroscopic connectivity.

Clinical report: variable phenotypic expression in a large sibling cohort with a deletion of 4p16.1.

We report a half-sibling cohort with deletion of 4p16.1, astigmatism, gross and fine motor delay, variable intellectual disability, and variable behavioral concerns. However, two siblings without the deletion also had learning delays and psychological concerns.

Simultaneous targeting of 5-LOX-COX and ODC block NNK-induced lung adenoma progression to adenocarcinoma in A/J mice.

Lung cancer is the leading cause of cancer deaths worldwide. Targeting complementary pathways will achieve better treatment efficacy than a single agent high-dose strategy that could increase risk of side effects and tumor resistance. To target COX-2, 5-LOX, and ODC simultaneously, we tested the effects of a dual 5-LOX-COX inhibitor, licofelone, and an ODC inhibitor, DFMO, alone and in combination, on NNK-induced lung tumors in female A/J mice.

TP53 modulating agent, CP-31398 enhances antitumor effects of ODC inhibitor in mouse model of urinary bladder transitional cell carcinoma.

Mutations of the tumor suppressor p53 and elevated levels of polyamines are known to play key roles in urothelial tumorigenesis. We investigated the inhibition of polyamines biosynthesis and the restoration of p53 signaling as a possible means of preventing muscle invasive urothelial tumors using DFMO, an ODC-inhibiting agent, and CP-31398 (CP), a p53 stabilizing agent. Transgenic UPII-SV40T male mice at 6weeks age (n=15/group) were fed control diet (AIN-76A) or experimental diets containing DFMO (1000 and 2000 ppm) or 150 ppm CP or both.