ABSTRACT
BACKGROUND: Dysregulated serum calcium and FGF23 are associated with increased mortality and morbidity rates in patients receiving hemodialysis. Preliminary data suggest serum calcium regulates FGF23 secretion independently of serum phosphate, parathyroid hormone, and 25-OH vitamin D. It is unclear to what extent dietary and prescription sources of calcium influence calcium and FGF23 levels, and whether they confound this relationship. In this cross-sectional analysis of a multi-ethnic cohort of prevalent hemodialysis patients, association of dietary calcium and prescribed calcium were examined against serum calcium and FGF23. Bi- and multivariable linear regression was used for all analyses. RESULTS: 81 patients (mean age 58 years, dialysis vintage 2 years, 51 men) participated. Dietary calcium was inversely associated with FGF23 (p = 0.04) however association of FGF23 with prescribed calcium did not reach statistical significance (0.08). In multivariable models, dietary calcium and prescribed calcium were associated in opposing directions with serum calcium (prescribed calcium; ß-coefficient = -0.35, p = 0.005 versus dietary calcium; ß-coefficient = 0.35, p = 0.03). FGF23 was independently associated with serum calcium (p = 0.007). CONCLUSIONS: We found differing, sometimes opposing, associations between serum calcium and FGF23 levels when considering prescribed versus dietary sources of calcium. Serum calcium and FGF23 were strongly correlated regardless of possible confounders examined in this hemodialysis cohort. Dietary calcium was associated with higher serum calcium and lower FGF23 concentrations, while prescribed calcium was only inversely associated with serum calcium. Further studies are required to confirm these associations and determine causality.
ABSTRACT
INTRODUCTION: Though computed tomographic angiography has very high sensitivity and specificity to diagnose acute aortic dissection, false-negative studies can occur and secondary tests may be required to make the diagnosis. CASE PRESENTATION: We report the case of a 57-year-old Caucasian man with a typical presentation for acute type A aortic dissection in whom the initial non-cardiac gated computed tomographic angiogram was negative, leading to a delay in surgical management. Transesophageal echocardiography and post hoc 3D reconstruction of the original computed tomographic scan revealed a dissection flap confined to the aortic root, immediately superior to the sinuses of Valsalva and masquerading as part of the aortic valve apparatus. CONCLUSION: This case demonstrates that false-negative computed tomographic angiograms taken to rule out type A aortic dissection can occur and that secondary imaging tests, such as echocardiography, should be performed in cases in which the pre-test probability of aortic dissection is high. Cardiac gating of computed tomographic angiograms to exclude aortic dissection may enhance diagnostic accuracy.
ABSTRACT
Type III secretion systems are present in many pathogenic bacteria and mediate the translocation of bacterial effectors into host cells. Identification of host targets of these effectors is crucial for understanding bacterial virulence. IcsB, a type III secretion effector, helps Shigella to evade the host autophagy defense system by binding to the autophagy protein, Atg5. Here, we show that IcsB is able to interact specifically with cholesterol. The cholesterol binding domain (CBD) of IcsB is located between residues 288 and 351. Specific mutations of single tyrosine residues Y297 or Y340 of IcsB by phenylalanine (F) slightly reduced cholesterol binding, whereas deletion of the entire CBD or double mutation Y297F-Y340F strongly abolished interactions with cholesterol. To determine whether Shigella expressing IcsB variants could evade autophagy as effectively as the wild-type Shigella, we infected MDAMC cells stably expressing the autophagy marker LC3 fused to GFP and bacterial autophagosome formation was quantified using fluorescence microscopy. Mutation Y297F or Y340F slightly impaired IcsB function, whereas complete removal of CBD or mutation Y297F-Y340F significantly impaired autophagy evasion. Furthermore, we report that BopA, the counterpart of IcsB in Burkholderia pseudomallei with similar autophagy-evading properties, contains the CBD domain and is also able to bind cholesterol.
