Chorioretinal thinning in chronic kidney disease links to inflammation and endothelial dysfunction

BACKGROUND. Chronic kidney disease (CKD) is strongly associated with cardiovascular disease and there is an established association between vasculopathy affecting the kidney and eye. Optical coherence tomography (OCT) is a novel, rapid method for high-definition imaging of the retina and choroid. Its use in patients at high cardiovascular disease risk remains unexplored. METHODS. We used the new SPECTRALIS OCT machine to examine retinal and retinal nerve fiber layer (RNFL) thickness, macular volume, and choroidal thickness in a prospective cross-sectional study in 150 subjects: 50 patients with hypertension (defined as a documented clinic BP greater than or equal to 140/90 mmHg (prior to starting any treatment) with no underlying cause identified); 50 with CKD (estimated glomerular filtration rate (eGFR) 8–125 ml/min/1.73 m(2)); and 50 matched healthy controls. We excluded those with diabetes. The same, masked ophthalmologist carried out each study. Plasma IL-6, TNF-α , asymmetric dimethylarginine (ADMA), and endothelin-1 (ET-1), as measures of inflammation and endothelial function, were also assessed. RESULTS. Retinal thickness, macular volume, and choroidal thickness were all reduced in CKD compared with hypertensive and healthy subjects (for retinal thickness and macular volume P < 0.0001 for CKD vs. healthy and for CKD vs. hypertensive subjects; for choroidal thickness P < 0.001 for CKD vs. healthy and for CKD vs. hypertensive subjects). RNFL thickness did not differ between groups. Interestingly, a thinner choroid was associated with a lower eGFR (r = 0.35, P <0.0001) and, in CKD, with proteinuria (r = –0.58, P < 0.001) as well as increased circulating C-reactive protein (r = –0.57, P = 0.0002), IL-6 (r = –0.40, P < 0.01), ADMA (r = –0.37, P = 0.02), and ET-1 (r = –0.44, P < 0.01). Finally, choroidal thinning was associated with renal histological inflammation and arterial stiffness. In a model of hypertension, choroidal thinning was seen only in the presence of renal injury. CONCLUSIONS. Chorioretinal thinning in CKD is associated with lower eGFR and greater proteinuria, but not BP. Larger studies, in more targeted groups of patients, are now needed to clarify whether these eye changes reflect the natural history of CKD. Similarly, the associations with arterial stiffness, inflammation, and endothelial dysfunction warrant further examination. TRIAL REGISTRATION. Registration number at www.clinicalTrials.gov: NCT02132741. SOURCE OF FUNDING. TR was supported by a bursary from the Erasmus Medical Centre, Rotterdam. JJMHvB was supported by a bursary from the Utrecht University. JRC is supported by a Rowling Scholarship. SB was supported by a Wellcome Trust funded clinical research fellowship from the Scottish Translational Medicine and Therapeutics Initiative, and by a Rowling Scholarship, at the time of this work. ND is supported by a British Heart Foundation Intermediate Clinical Research Fellowship (FS/13/30/29994)

Chorioretinal thinning in chronic kidney disease links to inflammation and endothelial dysfunction

The Engineering and Sciences Library was formed in 1990,incorporating the C. S. Davis Mathematics Library and the Thomas Parnell Memorial Physics Library. In 1997 the library was refurbished and merged with the Geology Library collection. The library was named the Dorothy Hill Physical Sciences and Engineering Library, after the late Professor Dorothy Hill, and opened officially on 26 August 1997. In 2011, the name was changed to the Dorothy Hill Engineering and Sciences Library, when the collections were merged with those of the Biological Sciences Library

Asymmetric dimethylarginine, homoarginine levels and atrial fibrillation in oesophagectomy patients

No abstract available

The Correlation of radiographic findings and patient symptomatology in cervical degenerative joint disease : a cross-sectional study

Background: There are few known studies investigating the correlation of symptomatology with the specific subtypes of cervical spine degenerative joint disease demonstrated on radiograph. The aim of this study was to assess the correlation and diagnostic test accuracy of specific symptoms in determining the presence, type and severity of degenerative joint disease on radiograph. Methods: A retrospective cross-sectional design was used to correlate cervical radiographic findings with neck pain and related symptomatology. Radiographs of 322 patients from April 2010 to June 2012 were assessed and evidence of radiographic cervical degenerative joint disease was extracted. Clinical data for each patient was obtained from their patient files including: pain using a VAS, presence of neck stiffness, presence of headaches, presence of shoulder referral, presence of hand radiculopathy and presence of hand numbness. Measures of diagnostic test accuracy and regression analysis were used to assess for any correlation between symptoms and radiographic findings. Results: Referral of pain to the shoulder and neck stiffness showed small degrees of correlation with cervical degenerative joint disease, however, these correlations were not maintained when age was accounted for. Only age showed consistent statistical significance as a predictor for degree of disc degeneration (correlation coefficient (95% confidence interval): 0.06 (0.055, 0.066)); the presence of facet hypertrophy (odds ratio (95% confidence interval): 1.12 (1.09, 1.15)); or uncinate process hypertrophy (odds ratio (95% confidence interval): 1.15 (1.12, 1.18)). Neck stiffness demonstrated a small degree of diagnostic test accuracy for the degree of cervical disc degeneration (area under the curve (95%CI): 0.62 (0.56, 0.68)) and the presence of either facet (diagnostic OR (95%CI):1.69 (1.04, 2.76)) and uncinated process hypertrophy (LR+ (95%CI): 1.17 (1.00, 1.38)). Conclusion: The results of this study indicate that clinical symptoms such as pain level, headaches, shoulder referral and hand radiculopathy or numbness are not reliably correlated with radiographic findings of degenerative joint disease in the cervical spine. A small increase in diagnostic accuracy between the presence of neck stiffness and all forms of cervical degenerative joint disease is shown, however, this increase is not at the level expected to change clinical practice.7 page(s

Assessment of asymmetrical dimethylarginine metabolism in patients with critical illness

Background Critically ill patients experience metabolic disorders including hypercatabolic state and hyperglycaemia and these are associated with poor outcome. Hyperglycaemia and asymmetric dimethylarginine (ADMA) are reported to have significant influences on endothelial dysfunction. The aim of the present study was to examine the relationship between plasma asymmetric dimethylarginine (ADMA) and related arginine metabolism in patients with critical illness. Materials and Methods Two venous blood samples (EDTA) (104 patients), on admission and follow up sample in the last day in ICU (died or discharge sample median 7, IQR 6-8, range 5-15). Plasma ADMA, arginine, homoarginine and symmetrical dimethylarginine (SDMA) were measured by high-performance liquid chromatography (HPLC). Result ADMA (p&lt;0.01) and SDMA (p&lt;0.05) were elevated and homoarginine was decreased (p&lt;0.05) in non-survivors and were directly associated with predicted mortality rate (p&lt;0.05 and p&lt;0.001), SOFA (p&lt;0.05, p&lt;0.001), ICU stay (p&lt;0.05, p&lt;0.001) and mortality (p&lt;0.01, p&lt;0.05). ADMA was directly associated with SDMA (p&lt;0.001), albumin (p&lt;0.05), ICU stay and mortality (p&lt;0.01). SDMA was directly associated with creatinine (p&lt;0.001) and APACHE II score (p&lt;0.001). In the follow up measurements there was a significant decrease in SOFA score (p&lt;0.01), homoarginine (p&lt;0.01), ALT (p&lt;0.01), Lab-Glucose (p&lt;0.01), and albumin (p&lt;0.01). In contrast, there was an increase in arginine ((p&lt;0.01), ADMA (p&lt;0.01), ADMA:SDMA ratio (p&lt;0.01), and the norepinephrine administration (p&lt;0.01). Conclusion In the present longitudinal study ADMA metabolism was altered in patients with critical illness and was associated with disease severity and mortality

New tools for “hot-wiring” clathrin-mediated endocytosis with temporal and spatial precision

Clathrin-mediated endocytosis (CME) is the major route of receptor internalization at the plasma membrane. Analysis of constitutive CME is difficult because the initiation of endocytic events is unpredictable. When and where a clathrin-coated pit will form and what cargo it will contain are difficult to foresee. Here we describe a series of genetically encoded reporters that allow the initiation of CME on demand. A clathrin-binding protein fragment (“hook”) is inducibly attached to an “anchor” protein at the plasma membrane, which triggers the formation of new clathrin-coated vesicles. Our design incorporates temporal and spatial control by the use of chemical and optogenetic methods for inducing hook–anchor attachment. Moreover, the cargo is defined. Because several steps in vesicle creation are bypassed, we term it “hot-wiring.” We use hot-wired endocytosis to describe the functional interactions between clathrin and AP2. Two distinct sites on the β2 subunit, one on the hinge and the other on the appendage, are necessary and sufficient for functional clathrin engagement

The High-Altitude water cherenkov (HAWC) observatory in México: The primary detector

The High-Altitude Water Cherenkov (HAWC) observatory is a second-generation continuously operated, wide field-of-view, TeV gamma-ray observatory. The HAWC observatory and its analysis techniques build on experience of the Milagro experiment in using ground-based water Cherenkov detectors for gamma-ray astronomy. HAWC is located on the Sierra Negra volcano in México at an elevation of 4100 meters above sea level. The completed HAWC observatory principal detector (HAWC) consists of 300 closely spaced water Cherenkov detectors, each equipped with four photomultiplier tubes to provide timing and charge information to reconstruct the extensive air shower energy and arrival direction. The HAWC observatory has been optimized to observe transient and steady emission from sources of gamma rays within an energy range from several hundred GeV to several hundred TeV. However, most of the air showers detected are initiated by cosmic rays, allowing studies of cosmic rays also to be performed. This paper describes the characteristics of the HAWC main array and its hardware.UCR::Vicerrectoría de Docencia::Ciencias Básicas::Facultad de Ciencias::Escuela de Físic