On the relationship between proteinuria and plasma phosphate.

Albuminuria is strongly associated with renal and cardiovascular outcomes independently of renal function level. However, the pathophysiology of these associations is debated. In chronic kidney disease (CKD), phosphate retention participates in cardiovascular events and increased cardiovascular mortality. We hypothesised that albuminuria may modulate tubular phosphate handling by the kidney. To verify this hypothesis, we first studied the association between phosphataemia and albuminuria in children with nephrotic syndrome and in adults with CKD. In both cases, higher albuminuria was associated with higher phosphate level, independently of glomerular filtration rate. We further tried to decipher the molecular mechanisms of these observations. Using animal models of nephrotic proteinuria, we could show that albuminuric rats and mice had abnormally elevated sodium-phosphate apical co-transporter expression, despite elevated fibroblast growth factor 23 (FGF23). The FGF23 downstream pathway was inhibited despite elevated FGF23 levels. Klotho protein expression was also lower in proteinuric animals compared to controls. Finally, albumin had no direct effects on phosphate transport in cells. Altogether, we show that albuminuria induces alteration of phosphate tubular handling, independently of glomerular filtration rate. The mechanisms involved appear to include Klotho down-regulation and resistance to FGF23. This observation may link albuminuria to increased cardiovascular disease via altered phosphate handling. Finally, this observation opens up further opportunities to better understand the link between albuminuria, Klotho, FGF23 and phosphate handling

Parafoveal OCT Angiography Features in Diabetic Patients without Clinical Diabetic Retinopathy: A Qualitative and Quantitative Analysis

Purpose. To evaluate the capacity of OCT angiography (OCTA) for detecting infraclinical lesions in parafoveal capillaries in diabetic patients without diabetic retinopathy (DR). Methods. This prospective observational cross-sectional case-control study analyzed the superficial and deep capillary plexuses (SCP and DCP) on macular OCTA scans (3 × 3 mm) centered on the fovea. We compared 22 diabetic patients (34 eyes included) without DR diagnosis on color fundus photographs, with 22 age- and gender-matched nondiabetic controls (40 eyes included). Qualitative analysis concerned morphological ischemic capillary alterations. Quantitative analysis measured foveal avascular zone (FAZ) size, parafoveal capillary density, and enlargement coefficient of FAZ between SCP and DCP. Results. Neither the qualitative nor quantitative parameters were significantly different between both groups. No microaneurysms or venous tortuosity was observed in any of the analyzed images. On the SCP, the mean FAZ area was 0.322 ± 0.125 mm2 in diabetic patients and 0.285 ± 0.150 mm2 in controls, P=0.31. On the DCP, the mean FAZ area was 0.444 ± 0.153 mm2 in cases and 0.398 ± 0.138 mm2 in controls, P=0.20. Conclusion. OCTA did not detect infraclinical qualitative or quantitative differences in parafoveal capillaries of diabetic patients without DR in comparison with nondiabetic controls

Multi-objective optimization of gate location and processing conditions in injection molding using MOEAs: experimental assessment

The definition of the gate location in injection molding is one of the most important factors in achieving dimensionally accuracy of the parts. This paper presents an optimization methodology for addressing this problem based on a Multi-objective Evolutionary Algorithm (MOEA). The algorithm adopted here is named Reduced Pareto Set Genetic Algorithm (RPSGA) and was used to create a balanced filling pattern using weld line characterization. The optimization approach proposed in this paper is an integration of evolutionary algorithms with Computer-Aided Engineering (CAE) software (Autodesk Moldflow Plastics software). The performance of the proposed optimization methodology was illustrated with an example consisting in the injection of a rectangular part with a non-symmetrical hole. The numerical results were experimentally assessed. Physical meaning was obtained which guaranteed a successful process optimization.This work was supported by the Portuguese Fundação para a Ciência e Tecnologia under grant SFRH/BD/28479/2006 and IPC/I3N – Institute for Polymers and Composites, University of Minho.info:eu-repo/semantics/publishedVersio

Localization and function of the renal calcium-sensing receptor

The ability to monitor changes in the ionic composition of the extracellular environment is a crucial feature that has evolved in all living organisms. The cloning and characterization of the extracellular calcium-sensing receptor (CaSR) from the mammalian parathyroid gland in the early 1990s provided the first description of a cellular, ion-sensing mechanism. This finding demonstrated how cells can detect small, physiological variations in free ionized calcium (Ca 2+) in the extracellular fluid and subsequently evoke an appropriate biological response by altering the secretion of parathyroid hormone (PTH) that acts on PTH receptors expressed in target tissues, including the kidney, intestine, and bone. Aberrant Ca 2+ sensing by the parathyroid glands, as a result of altered CaSR expression or function, is associated with impaired divalent cation homeostasis. CaSR activators that mimic the effects of Ca 2+ (calcimimetics) have been designed to treat hyperparathyroidism, and CaSR antagonists (calcilytics) are in development for the treatment of hypercalciuric disorders. The kidney expresses a CaSR that might directly contribute to the regulation of many aspects of renal function in a PTH-independent manner. This Review discusses the roles of the renal CaSR and the potential impact of pharmacological modulation of the CaSR on renal function

Simulation of a generalized Newtonian fluid by the Lattice Boltzmann Method

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Segmentation of Giant Cerebral Aneurysm Using a Multilevel Object Detection Scheme Based on Lattice Boltzmann Method

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Blood flow simulation within Stented Intracranial Aneurysm

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High-Resolution MRI Visualization of Aneurysmal Thrombosis after Flow Diverter Stent Placement

International audienceFlow-diverter stents are the new promising tools in the treatment of intracranial aneurysms allowing progressive aneurysm occlusion. Here, we report a case where high-resolution magnetic resonance imaging showed thrombus at fundus of the aneurysm sac, indicating a progressive intraaneurysmal thrombosis after flow-diverter placement

Blood flow simulation within Stented Intracranial Aneurysm

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