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Fibroblast Growth Factorâ23 and Cardiac Structure and Function
Background: Fibroblast growth factorâ23 (FGFâ23) is a phosphaturic factor previously associated with left ventricular hypertrophy and systolic dysfunction among individuals with chronic kidney disease. Whether FGFâ23 acts directly to induce left ventricular hypertrophy, potentially independent of its klotho coreceptor, remains uncertain. We investigated associations of FGFâ23 with cardiac structural abnormalities among individuals with a broad range of kidney function and explored potential biological mechanisms using cardiac magnetic resonance imaging and histology in klothoânull mice, an established model of constitutively elevated FGFâ23. Methods and Results: Among 887 participants with coronary artery disease in the Heart and Soul Study, FGFâ23 was modestly associated with worse left ventricular ejection fraction (â1.0% per standard deviation increase in lnFGFâ23; standard error, 0.4%), but was not associated with the overall prevalence of concentric hypertrophy (odds ratio, 1.5; CI, 0.9 to 2.4) or eccentric hypertrophy (odds ratio, 1.1; CI, 0.9 to 1.3). FGFâ23 was only associated with concentric hypertrophy among individuals with diminished kidney function (eGFR <60 mL/min per 1.73 m2; odds ratio, 2.3; CI, 1.0 to 5.3; Pâinteraction=0.28). Comparing klothoânull with wildâtype mice, null mice did not have greater left ventricular mass (P=0.37) or a lower ejection fraction (P=0.94). Conclusions: Together, our results suggest that FGFâ23 is unlikely to have major effects on cardiovascular structure and function among patients free of substantial chronic kidney disease, and these effects may not be independent of the klotho coreceptor
Population-Based Limits of Urine Creatinine Excretion
Introduction: The validity of a timed urine collection is typically judged by measurement of urine creatinine excretion, but prevailing limits may be unreliable. We sought to empirically derive population-based limits of excretion for evaluating the validity of a timed urine collection. Methods: Covariate and 24-hour urine data were obtained from 3582 participants in the Chronic Renal Insufficiency Cohort (CRIC) study, 814 participants in the Modification of Diet in Renal Disease (MDRD) study, 1010 participants in the Jackson Heart Study (JHS), and 8536 participants in the Prevention of Renal Vascular End Stage Disease (PREVEND) study. Weight, height, age, sex, and serum creatinine concentrations were evaluated as potential predictors of urine creatinine excretion using Akaike Information Criteria, R-squared values, and deviance. Bias and precision of the fitted models were assessed by analyses of residuals. Agreement between 24-hour creatinine clearance and 125I-iothalamate clearance was assessed before and after exclusion of potentially invalid urine samples. Results: A best-fitting model to predict 24-hour urine creatinine excretion among the 9199 discovery cohort members included sex-specific terms for weight, height, and age (R-squared = 0.328). This model had a median bias of +4.3 mg creatinine/day (95% confidence interval â5.6, +13.3 mg/day) in 4599 validation cohort members, and 82% of observed values were within 30% of predicted model. Serum creatinine concentrations only marginally improved model precision but reduced bias in persons with advanced chronic kidney disease (CKD). Conclusion: The limits of urine creatinine excretion derived here represent the most valid and representative data for appraising the adequacy of a timed urine collection
Vitamin D and the risk of dementia and Alzheimer disease
OBJECTIVE: To determine whether low vitamin D concentrations are associated with an increased risk of incident all-cause dementia and Alzheimer disease. METHODS: One thousand six hundred fifty-eight elderly ambulatory adults free from dementia, cardiovascular disease, and stroke who participated in the US population-based Cardiovascular Health Study between 1992-1993 and 1999 were included. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were determined by liquid chromatography-tandem mass spectrometry from blood samples collected in 1992-1993. Incident all-cause dementia and Alzheimer disease status were assessed during follow-up using National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria. RESULTS: During a mean follow-up of 5.6 years, 171 participants developed all-cause dementia, including 102 cases of Alzheimer disease. Using Cox proportional hazards models, the multivariate adjusted hazard ratios (95% confidence interval [CI]) for incident all-cause dementia in participants who were severely 25(OH)D deficient (<25 nmol/L) and deficient (â„25 to <50 nmol/L) were 2.25 (95% CI: 1.23-4.13) and 1.53 (95% CI: 1.06-2.21) compared to participants with sufficient concentrations (â„50 nmol/L). The multivariate adjusted hazard ratios for incident Alzheimer disease in participants who were severely 25(OH)D deficient and deficient compared to participants with sufficient concentrations were 2.22 (95% CI: 1.02-4.83) and 1.69 (95% CI: 1.06-2.69). In multivariate adjusted penalized smoothing spline plots, the risk of all-cause dementia and Alzheimer disease markedly increased below a threshold of 50 nmol/L. CONCLUSION: Our results confirm that vitamin D deficiency is associated with a substantially increased risk of all-cause dementia and Alzheimer disease. This adds to the ongoing debate about the role of vitamin D in nonskeletal conditions.National Heart, Lung, and Blood InstituteNational Institute of Neurological Disorders and StrokeNational Institute on AgingAlzheimer's AssociationMary Kinross Charitable TrustJames Tudor FoundationHalpin TrustAge Related Diseases and Health TrustNorman Family Charitable TrustUK National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for the South West Peninsul
O2â03â02: Vitamin D and the risk of developing neuroimaging abnormalities
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152624/1/alzjjalz201507143.pd
Vitamin D and the risk of dementia and Alzheimer disease
Objective: To determine whether low vitamin D concentrations are associated with an increased risk of incident all-cause dementia and Alzheimer disease. Methods: One thousand six hundred fifty-eight elderly ambulatory adults free from dementia, cardiovascular disease, and stroke who participated in the US population?based Cardiovascular Health Study between 1992?1993 and 1999 were included. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were determined by liquid chromatography-tandem mass spectrometry from blood samples collected in 1992?1993. Incident all-cause dementia and Alzheimer disease status were assessed during follow-up using National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer\u27s Disease and Related Disorders Association criteria. Results: During a mean follow-up of 5.6 years, 171 participants developed all-cause dementia, including 102 cases of Alzheimer disease. Using Cox proportional hazards models, the multivariate adjusted hazard ratios (95% confidence interval [CI]) for incident all-cause dementia in participants who were severely 25(OH)D deficient (\u3c25 nmol/L) and deficient (?25 to \u3c50 nmol/L) were 2.25 (95% CI: 1.23?4.13) and 1.53 (95% CI: 1.06?2.21) compared to participants with sufficient concentrations (?50 nmol/L). The multivariate adjusted hazard ratios for incident Alzheimer disease in participants who were severely 25(OH)D deficient and deficient compared to participants with sufficient concentrations were 2.22 (95% CI: 1.02?4.83) and 1.69 (95% CI: 1.06?2.69). In multivariate adjusted penalized smoothing spline plots, the risk of all-cause dementia and Alzheimer disease markedly increased below a threshold of 50 nmol/L. Conclusion: Our results confirm that vitamin D deficiency is associated with a substantially increased risk of all-cause dementia and Alzheimer disease. This adds to the ongoing debate about the role of vitamin D in nonskeletal conditions
Predicting prescribed magnification
Aim: To determine the best method of estimating the optimum magnification needed by visually impaired patients. Methods: The magnification of low vision aids prescribed to 187 presbyopic visually impaired patients for reading newspapers or books was compared with logMAR distance and near acuity (at 25 cm) and magnification predicted by +4 D step near additions. Results: Distance letter (r = 0.58) and near word visual acuity (r = 0.67) were strongly correlated to the prescribed magnification as were predictive formulae based on these measures. Prediction using the effect of proximal magnification resulted in a similar correlation (r = 0.67) and prediction was poorer in those who did not benefit from proximal magnification. The difference between prescribed and predicted magnification was found to be unrelated to the condition causing visual impairment (F = 2.57, p = 0.08), the central visual field status (F = 0.57, p = 0.57) and patient psychology (F = 0.44, p = 0.51), but was higher in those prescribed stand magnifiers than high near additions (F = 5.99, p < 0.01). Conclusions: The magnification necessary to perform normal visual tasks can be predicted in the majority of cases using visual acuity measures, although measuring the effect of proximal magnification demonstrates the effect of stronger glasses and identifies those in whom prescribed magnification is more difficult to predict
Impact of Vitamin D Supplementation on Arterial Vasomotion, Stiffness and Endothelial Biomarkers in Chronic Kidney Disease Patients
Background: Cardiovascular events are frequent and vascular endothelial function is abnormal in patients with chronic
kidney disease (CKD). We demonstrated endothelial dysfunction with vitamin D deficiency in CKD patients; however the impact of cholecalciferol supplementation on vascular stiffness and vasomotor function, endothelial and bone biomarkers in CKD patients with low 25-hydroxy vitamin D [25(OH)D] is unknown, which this study investigated.
Methods: We assessed non-diabetic patients with CKD stage 3/4, age 17â80 years and serum 25(OH)D ,75 nmol/L. Brachial
artery Flow Mediated Dilation (FMD), Pulse Wave Velocity (PWV), Augmentation Index (AI) and circulating blood biomarkers were evaluated at baseline and at 16 weeks. Oral 300,000 units cholecalciferol was administered at baseline and 8-weeks.
Results: Clinical characteristics of 26 patients were: age 50614 (mean61SD) years, eGFR 41611 ml/min/1.73 m2, males
73%, dyslipidaemia 36%, smokers 23% and hypertensives 87%. At 16-week serum 25(OH)D and calcium increased (43616
to 84629 nmol/L, p,0.001 and 2.3760.09 to 2.4260.09 mmol/L; p = 0.004, respectively) and parathyroid hormone
decreased (10.868.6 to 7.464.4; p = 0.001). FMD improved from 3.163.3% to 6.163.7%, p = 0.001. Endothelial biomarker
concentrations decreased: E-Selectin from 566662123 to 525662058 pg/mL; p = 0.032, ICAM-1, 3.4560.01 to
3.1061.04 ng/mL; p = 0.038 and VCAM-1, 54633 to 42633 ng/mL; p = 0.006. eGFR, BP, PWV, AI, hsCRP, von Willebrand
factor and Fibroblast Growth Factor-23, remained unchanged.
Conclusion: This study demonstrates for the first time improvement of endothelial vasomotor and secretory functions with vitamin D in CKD patients without significant adverse effects on arterial stiffness, serum calcium or FGF-23.
Trial Registration: ClinicalTrials.gov NCT0200571
Dietary Phosphorus, Blood Pressure, and Incidence of Hypertension in the Atherosclerosis Risk in Communities Study and the Multi-Ethnic Study of Atherosclerosis
Greater phosphorus intake has been associated with lower levels of blood pressure in cross-sectional studies. This association, however, has not been assessed prospectively. We studied 13444 participants from the Atherosclerosis Risk in Communities cohort and the Multi-Ethnic Study of Atherosclerosis, with diet assessed at baseline using validated food frequency questionnaires. Blood pressure and use of antihypertensive medication were determined at baseline and during follow-up visits. Compared to individuals in the lowest quintile of phosphorus intake at baseline, those in the highest quintile had lower baseline systolic and diastolic blood pressure after adjustment for dietary and non-dietary confounders (â2.0 mmHg, 95% confidence interval â3.6, â0.5; p for trend=0.01; and â0.6, 95% confidence interval â1.6, +0.3, p for trend=0.20, respectively). During an average 6.2 years of follow-up, 3345 cases of hypertension were identified. Phosphorus intake was associated with the risk of hypertension (hazard ratio 0.80, 95% confidence interval 0.80-1.00, comparing extreme quintiles; p for trend=0.02) after adjustment for non-dietary factors, but not after additional adjustment for dietary variables (hazard ratio 1.01, 95% confidence interval 0.82-1.23, p for trend=0.88). Phosphorus from dairy products but not from other sources was associated with lower baseline blood pressure and reduced risk of incident hypertension. Hazard ratios (95% confidence interval) comparing extreme quintiles were 0.86 (0.76-0.97), p for trend=0.01, for phosphorus from dairy foods and 1.04 (0.93-1.17), p for trend=0.48, for phosphorus from other foods. These findings could indicate an effect of phosphorus in conjunction with other dairy constituents or of dairy itself without involvement of phosphorus
Pulsar-wind nebulae and magnetar outflows: observations at radio, X-ray, and gamma-ray wavelengths
We review observations of several classes of neutron-star-powered outflows:
pulsar-wind nebulae (PWNe) inside shell supernova remnants (SNRs), PWNe
interacting directly with interstellar medium (ISM), and magnetar-powered
outflows. We describe radio, X-ray, and gamma-ray observations of PWNe,
focusing first on integrated spectral-energy distributions (SEDs) and global
spectral properties. High-resolution X-ray imaging of PWNe shows a bewildering
array of morphologies, with jets, trails, and other structures. Several of the
23 so far identified magnetars show evidence for continuous or sporadic
emission of material, sometimes associated with giant flares, and a few
possible "magnetar-wind nebulae" have been recently identified.Comment: 61 pages, 44 figures (reduced in quality for size reasons). Published
in Space Science Reviews, "Jets and Winds in Pulsar Wind Nebulae, Gamma-ray
Bursts and Blazars: Physics of Extreme Energy Release
Search for Chargino-Neutralino Associated Production at the Fermilab Tevatron Collider
We have searched in collisions at = 1.8 TeV for events
with three charged leptons and missing transverse energy. In the Minimal
Supersymmetric Standard Model, we expect trilepton events from
chargino-neutralino (\chione \chitwo) pair production, with subsequent decay
into leptons. We observe no candidate , ,
or events in 106 pb integrated
luminosity. We present limits on the sum of the branching ratios times cross
section for the four channels: \sigma_{\chione\chitwo}\cdot
BR(\chione\chitwo\to 3\ell+X) 81.5 \mgev\sp and
M_\chitwo > 82.2 \mgev\sp for , ~\mgev\sp and
M_\squark= M_\gluino.Comment: 9 pages and 3 figure
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