Fibroblast Growth Factor 23 and Incident Cardiovascular Disease and Mortality in Middle-Aged Adults.

Background Higher circulating fibroblast growth factor 23 (FGF23) associates with greater risk of cardiovascular disease (CVD) and mortality in older adults. The association of FGF23 with cardiovascular outcomes in younger populations has been incompletely explored. Methods and Results We measured C-terminal FGF23 (cFGF23) and intact FGF23 (iFGF23) in 3151 middle-aged adults (mean age, 45±4) who participated in the year 20 examination of the CARDIA (Coronary Artery Risk Development in Young Adults) study.

Acupuncture for chronic pain in adults with sickle cell disease: a mixed-methods pilot study.

Objective: Chronic pain is a common symptom experienced among patients with sickle cell disease (SCD). Our aims were to assess the feasibility and acceptability of performing acupuncture for the treatment of chronic pain in adults with SCD.

Methods: This was a single-arm, prospective pilot study of six adults with SCD.

Unraveling the genomic basis of congenital heart disease.

The genetic, epigenetic, and environmental etiologic basis of congenital heart disease (CHD) for most heart anomalies remains unexplained. In this issue of the JCI, Lahm et al. performed the largest genome-wide association study (GWAS) to date of European individuals with CHD and clinical subtypes.

Association of tubular solute clearances with the glomerular filtration rate and complications of chronic kidney disease: the Chronic Renal Insufficiency Cohort study.

Background: The secretion of organic solutes by the proximal tubules is an essential intrinsic kidney function. The degree to which secretory solute clearance corresponds with the glomerular filtration rate (GFR) and potential metabolic implications of net secretory clearance are largely unknown.

Methods: We evaluated 1240 participants with chronic kidney disease (CKD) from the multicenter Chronic Renal Insufficiency Cohort (CRIC) Study.

Effects of ferric carboxymaltose on markers of mineral and bone metabolism: A single-center prospective observational study of women with iron deficiency.

Background: Two weekly infusions of ferric carboxymaltose (FCM) are commonly prescribed for treatment of iron-deficiency anemia. However, administration of FCM increases intact levels of fibroblast growth factor 23 (FGF23), which causes hypophosphatemia due to renal phosphate wasting, calcitriol deficiency and secondary hyperparathyroidism. The adverse effects of FCM on mineral metabolism and bone health emerged from case reports and secondary analyses of trials.

Kidney Clearance of Secretory Solutes Is Associated with Progression of CKD: The CRIC Study.

Background: The secretion of organic solutes by the proximal tubules is an essential intrinsic kidney function. However, the clinical significance of the kidney's clearance of tubular secretory solutes is uncertain.

Methods: In this prospective cohort study, we evaluated 3416 participants with CKD from the Chronic Renal Insufficiency Cohort (CRIC) study.

Phenylethanolamine -methyltransferase gene polymorphisms associate with crisis pain in sickle cell disease patients.

Phenylethanolamine methyltransferase (PNMT) catalyzes the conversion of sympathetic neurotransmitter norepinephrine to epinephrine. We examined the association of polymorphisms with acute and chronic pain in sickle cell disease (SCD). Utilization of emergency care owing to painful crisis was used as a marker for acute pain in 131 patients with SCD.

Serial Fibroblast Growth Factor 23 Measurements and Risk of Requirement for Kidney Replacement Therapy: The CRIC (Chronic Renal Insufficiency Cohort) Study.

Rationale & Objective: Studies using a single measurement of fibroblast growth factor 23 (FGF-23) suggest that elevated FGF-23 levels are associated with increased risk for requirement for kidney replacement therapy (KRT) in patients with chronic kidney disease. However, the data do not account for changes in FGF-23 levels as kidney disease progresses.

Study Design: Case-cohort study.

Longitudinal Evolution of Markers of Mineral Metabolism in Patients With CKD: The Chronic Renal Insufficiency Cohort (CRIC) Study.

Rationale & Objective: The pathogenesis of disordered mineral metabolism in chronic kidney disease (CKD) is largely informed by cross-sectional studies of humans and longitudinal animal studies. We sought to characterize the longitudinal evolution of disordered mineral metabolism during the course of CKD.

Study Design: Retrospective analysis nested in a cohort study.

Randomized clinical trial of computerized PAINRelieveIt® for patients with sickle cell disease: PAINReportIt® and PAINUCope®.

Objective: To compare effects of a tailored multimedia education program versus usual-care on barriers to pain management of adult patients with SCD.

Methods: Pretest/posttest randomized controlled trial (RCT) of 228 outpatients with SCD randomized to the tablet-based PAINUCope intervention focused on barriers to pain management, pain, and analgesic adherence or selection of games (control). Outcomes were barriers to pain management, pain, and analgesic adherence.

Precautions and Monitoring of Patients Taking Phosphodiesterase Type 5 Inhibitors Who are at Risk of Increased Intraocular Pressure.

Phosphodiesterase type 5 inhibitors (PDE5Is) may increase intraocular pressure (IOP) by increasing blood flow to the ciliary body. Although clinical studies of changes in IOP after single and multiple doses of PDE5Is show variable results, most are limited by small sample sizes, absence of control groups and blinding, and use of normal patient volunteers who have no risk factors for glaucoma. However, multiple case reports of glaucoma have been published, and one epidemiologic analysis of the National Health and Nutrition Examination Survey (NHANES) database of US respondents suggested a significant association of prolonged sildenafil use and self-reported glaucoma.

A Pilot Randomized Trial of Ferric Citrate Coordination Complex for the Treatment of Advanced CKD.

Background: Researchers have yet to determine the optimal care of patients with advanced CKD. Evidence suggests that anemia and CKD-related disordered mineral metabolism (including abnormalities in phosphate and fibroblast growth factor 23 [FGF23]) contribute to adverse outcomes in this population.

Methods: To investigate whether fixed-dose ferric citrate coordination complex favorably affects multiple biochemical parameters in patients with advanced CKD, we randomly assigned 203 patients with eGFR≤20 ml/min per 1.

Beta2-Adrenergic Receptor Polymorphisms and Haplotypes Associate With Chronic Pain in Sickle Cell Disease.

Pain in sickle cell disease (SCD) is severe, variable, and inadequately comprehended. The β2-adrenergic receptor () is critical in mediating neurotransmitter response in the sympathetic nervous system. In this association study, we examined 16 single nucleotide polymorphisms (SNPs) covering 5'-UTR and coding regions of for pain variability in SCD.

Associations of Fenofibrate Therapy With Incidence and Progression of CKD in Patients With Type 2 Diabetes.

Introduction: Abnormalities in lipid metabolism may contribute to the development and progression of chronic kidney disease (CKD) in patients with type 2 diabetes. Fenofibrate induces early and reversible reduction in estimated glomerular filtration rate (eGFR), but it may have protective effects on microvascular complications of diabetes. We hypothesized that randomization to fenofibrate versus placebo would be associated with beneficial long-term effects on kidney outcomes in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial participants.

A New Role of OmpR in Acid and Osmotic Stress in and .

Bacteria survive and respond to diverse environmental conditions and during infection inside the host by systematic regulation of stress response genes. and . Typhimurium can undergo large changes in intracellular osmolality (up to 1.

The role of acid stress in Salmonella pathogenesis.

After uptake by epithelial cells or engulfment by macrophages, Salmonella resides in an acidic vacuole. Salmonella senses this acidic compartment through the action of the EnvZ/OmpR two-component regulatory system. OmpR, in turn, represses the cadC/BA system, preventing neutralization of the bacterial cytoplasm.

A single molecule analysis of H-NS uncouples DNA binding affinity from DNA specificity.

Heat-stable nucleoid structuring protein (H-NS) plays a crucial role in gene silencing within prokaryotic cells and is important in pathogenesis. It was reported that H-NS silences nearly 5% of the genome, yet the molecular mechanism of silencing is not well understood. Here, we employed a highly-sensitive single-molecule counting approach, and measured the dissociation constant (KD) of H-NS binding to single DNA binding sites.

Glucocorticoid receptor single nucleotide polymorphisms are associated with acute crisis pain in sickle cell disease.

Aim: Pain in sickle cell disease patients is heterogeneous and genetic polymorphisms may predispose an individual to varied vulnerability to painful events. We studied the association of SNPs in the glucocorticoid receptor gene (NR3C1) with pain in sickle cell disease.

Method: Acute pain was scored as the number of utilizations due to crisis pain in a 12-month period.

Genetic variants of GCH1 associate with chronic and acute crisis pain in African Americans with sickle cell disease.

The multidimensional nature of pain in sickle cell disease (SCD) has rendered its therapeutic management extremely challenging. In this study, we explored the role of five single nucleotide polymorphisms (SNPs) of candidate gene GCH1 in SCD pain. Composite pain index (CPI) scores and acute care utilization rates were used as phenotype markers.

Sleep disordered breathing and fibroblast growth factor 23 in the Hispanic Community Health Study/Study of Latinos.

Preclinical data suggest that hypoxia stimulates fibroblast growth factor 23 (FGF23) transcription and cleavage in osteocytes, resulting in elevated circulating c-terminal (cFGF23) levels but normal intact FGF23 (iFGF23) levels. We conducted a case-control study within the Hispanic Community Health Study/Study of Latinos to investigate whether sleep disordered breathing, as a model of hypoxemia, is independently associated with elevated cFGF23 levels in the general population and with elevated cFGF23 and iFGF23 levels in patients with chronic kidney disease (CKD), in whom FGF23 cleavage may be impaired. Cases (n = 602) had severe sleep disordered breathing defined as an apnea/hypopnea index (AHI) of ≥30.