University of Colorado Denver

About: University of Colorado Denver is a education organization based out in Denver, Colorado, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 27444 authors who have published 57213 publications receiving 2539937 citations. The organization is also known as: CU Denver & UCD.

Potential Public Health Hazards, Exposures and Health Effects from Unconventional Natural Gas Development

Abstract: The rapid increase in unconventional natural gas (UNG) development in the United States during the past decade has brought wells and related infrastructure closer to population centers. This review evaluates risks to public health from chemical and nonchemical stressors associated with UNG, describes likely exposure pathways and potential health effects, and identifies major uncertainties to address with future research. The most important occupational stressors include mortality, exposure to hazardous materials and increased risk of industrial accidents. For communities near development and production sites the major stressors are air pollutants, ground and surface water contamination, truck traffic and noise pollution, accidents and malfunctions, and psychosocial stress associated with community change. Despite broad public concern, no comprehensive population-based studies of the public health effects of UNG operations exist. Major uncertainties are the unknown frequency and duration of human exposure,...

Clinical Mechanism of the Cystic Fibrosis Transmembrane Conductance Regulator Potentiator Ivacaftor in G551D-mediated Cystic Fibrosis

Abstract: Rationale: Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator recently approved for patients with CF age 6 and older with the G551D mutation. Objectives: To evaluate ivacaftor in a postapproval setting and determine mechanism of action and response of clinically relevant markers. Methods: We conducted a longitudinal cohort study in 2012–2013 in G551D CF patients age 6 and older with no prior exposure to ivacaftor. Study assessments were performed at baseline, 1, 3, and 6 months after ivacaftor initiation. Substudies evaluated mucociliary clearance, β-adrenergic sweat secretion rate, gastrointestinal pH, and sputum inflammation and microbiology Measurements and Main Results: A total of 151 of 153 subjects were prescribed ivacaftor and 88% completed the study through 6 months. FEV1 % predicted improved from baseline to 6 months (mean absolute change, 6.7%; P < 0.001). Similarly, body mass index improved from baseline to 6 months (mean change, 0.8 kg/m2; P < 0.001). Sweat chloride decreased from baseline to 6 months (mean change, −53.8 mmol/L; 95% confidence interval, −57.7 to −49.9; P < 0.001), reflecting augmented CFTR function. There was significant improvement in hospitalization rate (P < 0.001) and Pseudomonas aeruginosa burden (P < 0.01). Significant improvements in mucociliary clearance (P < 0.001), gastrointestinal pH (P = 0.001), and microbiome were also observed, providing clinical mechanisms underlying the therapeutic benefit of ivacaftor. Conclusions: Significant clinical and physiologic improvements were observed on initiation of ivacaftor in a broad patient population, including reduced infection with P. aeruginosa. Biomarker studies substantially improve the understanding of the mechanistic consequences of CFTR modulation on pulmonary and gastrointestinal physiology.

Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjogren's syndrome.

Abstract: Sjogren's syndrome is a common autoimmune disease (affecting ∼0.7% of European Americans) that typically presents as keratoconjunctivitis sicca and xerostomia. Here we report results of a large-scale association study of Sjogren's syndrome. In addition to strong association within the human leukocyte antigen (HLA) region at 6p21 (Pmeta = 7.65 × 10(-114)), we establish associations with IRF5-TNPO3 (Pmeta = 2.73 × 10(-19)), STAT4 (Pmeta = 6.80 × 10(-15)), IL12A (Pmeta = 1.17 × 10(-10)), FAM167A-BLK (Pmeta = 4.97 × 10(-10)), DDX6-CXCR5 (Pmeta = 1.10 × 10(-8)) and TNIP1 (Pmeta = 3.30 × 10(-8)). We also observed suggestive associations (Pmeta < 5 × 10(-5)) with variants in 29 other regions, including TNFAIP3, PTTG1, PRDM1, DGKQ, FCGR2A, IRAK1BP1, ITSN2 and PHIP, among others. These results highlight the importance of genes that are involved in both innate and adaptive immunity in Sjogren's syndrome.