Kidney dysfunction, cardiorespiratory fitness, and the risk of death in women.

Background: Chronic kidney disease (CKD) is associated with increased risk of cardiovascular (CV) events and death. However, the effect of cardiorespiratory fitness on the CKD-mortality relationship remains unknown, particularly in women.

Methods: We used Cox regression to estimate hazard ratios (HR) for the effect of kidney function and fitness on all-cause mortality in a prospective cohort of 5716 women free of CKD and CV disease symptoms.

Mutant SOD1 forms ion channel: implications for ALS pathophysiology.

Point mutations in the gene encoding copper-zinc superoxide dismutase (SOD1) impart a gain-of-function to this protein that underlies 20-25% of all familial amyotrophic lateral sclerosis (FALS) cases. However, the specific mechanism of mutant SOD1 toxicity has remained elusive. Using the complementary techniques of atomic force microscopy (AFM), electrophysiology, and cell and molecular biology, here we examine the structure and activity of A4VSOD1, a mutant SOD1.

Multidimensional atomic force microscopy: a versatile novel technology for nanopharmacology research.

Nanotechnology is giving us a glimpse into a nascent field of nanopharmacology that deals with pharmacological phenomena at molecular scale. This review presents our perspective on the use of scanning probe microscopy techniques with special emphasis to multidimensional atomic force microscopy (m-AFM) to explore this new field with a particular emphasis to define targets, design therapeutics, and track outcomes of molecular-scale pharmacological interactions. The approach will be to first discuss operating principles of m-AFM and provide representative examples of studies to understand human health and disease at the molecular level and then to address different strategies in defining target macromolecules, screening potential drug candidates, developing and characterizing of drug delivery systems, and monitoring target-drug interactions.

Predictors of hypertension control in a diverse general cardiology practice.

Factors influencing hypertension (HTN) control in the United States are not well understood. The authors utilized a newly designed survey instrument to interview patients presenting to a diverse, general cardiology practice at a tertiary care center in order to identify factors associated with HTN control. The study was completed in 154 participants, and 121 (78.

Heart rate response to exercise stress testing in asymptomatic women: the st. James women take heart project.

Background: The definition of a normal heart rate (HR) response to exercise stress testing in women is poorly understood, given that most studies describing a normative response were predominately based on male data. Measures of an attenuated HR response (chronotropic incompetence) and age-predicted HR have not been validated in asymptomatic women. We investigated the association between HR response to exercise testing and age with prognosis in 5437 asymptomatic women.

Multidimensional atomic force microscopy for drug discovery: a versatile tool for defining targets, designing therapeutics and monitoring their efficacy.

Current therapeutic design involves combinatorial chemistry and system biology-based molecular synthesis and bulk pharmacological assays. Therapeutics delivery is usually non-specific to disease targets and requires excessive dosage. Efficient therapeutic discovery and delivery would require molecular level understanding of the therapeutics-effectors (e.

Adverse cardiovascular outcomes in women with nonobstructive coronary artery disease: a report from the Women's Ischemia Syndrome Evaluation Study and the St James Women Take Heart Project.

Background: Women with clinical findings suggestive of ischemia but without findings of obstructive coronary artery disease (CAD) on angiography represent a frequent clinical problem; predicting prognosis is challenging.

Methods: The Women's Ischemia Syndrome Evaluation (WISE) study examined symptomatic women referred for clinically indicated coronary angiography and followed up for a mean 5.2 years.

Regulation of the micromechanical properties of pulmonary endothelium by S1P and thrombin: role of cortactin.

Disruption of pulmonary endothelial cell (EC) barrier function is a critical pathophysiologic event in highly morbid inflammatory conditions such as sepsis and acute respiratory disease stress syndrome. Actin cytoskeleton, an essential regulator of endothelial permeability, is a dynamic structure whose stimuli-induced rearrangement is linked to barrier modulation. Here, we used atomic force microscopy to characterize structural and mechanical changes in the F-actin cytoskeleton of cultured human pulmonary artery EC in response to both barrier-enhancing (induced by sphingosine 1-phosphate (S1P)) and barrier-disrupting (induced by thrombin) conditions.

Advance directives in the cardiac care unit.

Background: Despite effective therapies, mortality for many cardiovascular diseases remains higher than for many cancers and is difficult to predict. Guidelines recommend discussing advance directives (AD), including living wills and durable powers of attorney, with heart failure patients. The Patient Self-Determination Act mandates such discussions with all hospitalized patients.

The prognostic value of a nomogram for exercise capacity in women.

Background: Recent studies have demonstrated that exercise capacity is an independent predictor of mortality in women. Normative values of exercise capacity for age in women have not been well established. Our objectives were to construct a nomogram to permit determination of predicted exercise capacity for age in women and to assess the predictive value of the nomogram with respect to survival.

Prognostic value of the duke treadmill score in asymptomatic women.

The Duke Treadmill Score (DTS) has been shown to predict mortality in women who have symptomatic heart disease, but its ability to do so in asymptomatic women is unknown, as is its comparative advantage to exercise capacity. We investigated whether a decreased DTS is associated with increased mortality in a prospective cohort of 5,636 asymptomatic women. A symptom-limited exercise treadmill test using Bruce's protocol was performed at baseline.

Exercise capacity and the risk of death in women: the St James Women Take Heart Project.

Background: Cardiovascular disease is the leading cause of death among women and accounts for more than half of their deaths. Women have been underrepresented in most studies of cardiovascular disease. Reduced physical fitness has been shown to increase the risk of death in men.