Glomerular sclerosis in kidneys with congenital nephrotic syndrome (NPHS1)

Congenital nephrotic syndrome of the Finnish type (NPHS1) is a rare genetic disease caused by mutations in the NPHS1 gene encoding a major podocyte slit-diaphragm protein, nephrin. Patients with NPHS1 have severe nephrotic syndrome from birth and develop renal fibrosis in early childhood. In this work, we studied the development of glomerular sclerosis in kidneys removed from 4- to 44-month-old NPHS1 patients. The pathological lesions and expression of glomerular cell markers were studied in nephrectomized NPHS1 and control kidneys using light and electron microscopy and immunohistochemistry. An analysis of 1528 glomeruli from 20 patients revealed progressive mesangial sclerosis and capillary obliteration. Although few inflammatory cells were detected in the mesangial area, paraglomerular inflammation and fibrosis was common. The podocytes showed severe ultrastructural changes and hypertrophy with the upregulation of cyclins A and D1. Podocyte proliferation, however, was rare. Apoptosis was hardly detected and the expression of antiapoptotic B-cell lymphoma-2 and proapoptotic p53 were comparable to controls. Moderate amounts of podocytes were secreted into the urine of NPHS1 patients. Shrinkage of the glomerular tuft was common, whereas occlusion of tubular opening or protrusion of the glomerular tuft into subepithelial space or through the Bowman's capsule were not detected. The results indicate that, in NPHS1 kidneys, the damaged podocytes induce progressive mesangial expansion and capillary obliteration. Podocyte depletion, glomerular tuft adhesion, and misdirected filtration, however, seem to play a minor role in the nephron destruction

Congenital nephrotic syndrome

Congenital nephrotic syndrome (CNS) is a rare kidney disorder characterized by heavy proteinuria, hypoproteinemia, and edema starting soon after birth. The majority of cases are caused by genetic defects in the components of the glomerular filtration barrier, especially nephrin and podocin. CNS may also be a part of a more generalized syndrome or caused by a perinatal infection. Immunosuppressive medication is not helpful in the genetic forms of CNS, and kidney transplantation is the only curative therapy. Before the operation, management of these infants largely depends on the magnitude of proteinuria. In severe cases, daily albumin infusions are required to prevent life-threatening edema. The therapy also includes hypercaloric diet, thyroxin and mineral substitution, prevention of thrombotic episodes, and prompt management of infectious complications. The outcome of CNS patients without major extrarenal manifestations is comparable with other patient groups after kidney transplantation

The renal cortical interstitium: morphological and functional aspects

The renal interstitial compartment, situated between basement membranes of epithelia and vessels, contains two contiguous cellular networks. One network is formed by interstitial fibroblasts, the second one by dendritic cells. Both are in intimate contact with each other. Fibroblasts are interconnected by junctions and connected to basement membranes of vessels and tubules by focal adhesions. Fibroblasts constitute the “skeleton” of the kidney. In the renal cortex, fibroblasts produce erythropoietin and are distinguished from other interstitial cells by their prominent F-actin cytoskeleton, abundance of rough endoplasmic reticulum, and by ecto-5′-nucleotidase expression in their plasma membrane. The resident dendritic cells belong to the mononuclear phagocyte system and fulfil a sentinel function. They are characterized by their expression of MHC class II and CD11c. The central situation of fibroblasts suggests that signals from tubules, vessels, and inflammatory cells converge in fibroblasts and elicit an integrated response. Following tubular damage and inflammatory signals fibroblasts proliferate, change to the myofibroblast phenotype and increase their collagen production, potentially resulting in renal fibrosis. The acquisition of a profibrotic phenotype by fibroblasts in renal diseases is generally considered a main causal event in the progression of chronic renal failure. However, it might also be seen as a repair process

A resampling strategy based on bootstrap to reduce the effect of large blunders in GPS absolute positioning

In the absence of obstacles, a GPS device is generally able to provide continuous and accurate estimates of position, while in urban scenarios buildings can generate multipath and echo-only phenomena that severely affect the continuity and the accuracy of the provided estimates. Receiver autonomous integrity monitoring (RAIM) techniques are able to reduce the negative consequences of large blunders in urban scenarios, but require both a good redundancy and a low contamination to be effective. In this paper a resampling strategy based on bootstrap is proposed as an alternative to RAIM, in order to estimate accurately position in case of low redundancy and multiple blunders: starting with the pseudorange measurement model, at each epoch the available measurements are bootstrapped---that is random sampled with replacement---and the generated a posteriori empirical distribution is exploited to derive the final position. Compared to standard bootstrap, in this paper the sampling probabilities are not uniform, but vary according to an indicator of the measurement quality. The proposed method has been compared with two different RAIM techniques on a data set collected in critical conditions, resulting in a clear improvement on all considered figures of merit

Position, Navigation, and Timing (PNT) through Low Earth Orbit (LEO) Satellites: A Survey on Current Status, Challenges, and Opportunities

Publisher Copyright: AuthorMore and more satellites are populating the sky nowadays in the Low Earth orbits (LEO). Most of the targeted applications are related to broadband and narrowband communications, Earth observation, synthetic aperture radar, and internet-of-Things (IoT) connectivity. In addition to these targeted applications, there is yet-to-be-harnessed potential for LEO and positioning, navigation, and timing (PNT) systems, or what is nowadays referred to as LEO-PNT. No commercial LEO-PNT solutions currently exist and there is no unified research on LEO-PNT concepts. Our survey aims to fill the gaps in knowledge regarding what a LEO-PNT system entails, its technical design steps and challenges, what physical layer parameters are viable solutions, what tools can be used for a LEO-PNT design (e.g., optimisation steps, hardware and software simulators, etc.), the existing models of wireless channels for satellite-to-ground and ground-to-satellite propagation, and the commercial prospects of a future LEO-PNT system. A comprehensive and multidisciplinary survey is provided by a team of authors with complementary expertise in wireless communications, signal processing, navigation and tracking, physics, machine learning, Earth observation, remote sensing, digital economy, and business models.Peer reviewe