The Use of Continuous Peritoneal Dialysis in Europe for the Treatment of Children with End-Stage Renal Failure: Data from the EDTA Registry

The demographic data on the use of continuous peritoneal dialysis in Europe for children starting renal replacement therapy under the age of 15 years was obtained from data collected by the Registry of the European Dialysis and Transplant Association—European Renal Association (EDTA Registry) on individual patient questionnaires 1980-1986. Continuous ambulatory peritoneal dialysis (CAPD) and its variants appeared to be increasingly utilised as treatment for children with end-stage renal failure (ESRF) and accounted for approximately 25% of all renal replacement therapy (RRT). Important differences in its use in various European countries are demonstrated. The proportional contribution of CAPD to treatment was higher during the first year of RRT and gradually decreased thereafter. No significant sex differences existed in the use of this treatment. Approximately 70% of all patients on CAPD were older than 6 years of age, but it is in those under 6 years that the highest proportion are put on CAPD as first method of treatment for end-stage renal failure. The most common cause of abandonment of this treatment was peritonitis, which contributed 50% of the drop-out rat

Personal body ornamentation on the Southern Iberian Meseta: An archaeomineralogical study

Beads and pendants from the Castillejo del Bonete (Terrinches, Ciudad Real) and Cerro Ortega (Villanueva de la Fuente, Ciudad Real) burials were analysed using XRD, micro-Raman and XRF in order to contribute to the current distribution map of green bead body ornament pieces on the Iberian Peninsula which, so far, remain undetailed for many regions. XRD, micro-Raman and XRF analyses showed that most of the beads from Castillejo del Bonete (Late 3rd millennium cal. BC) were made from variscite or green phyllosilicates, while Cerro Ortega's (Late 4th millenniumcal. BC) beads were made out of fossil wood or Clinochlore. Significantly enough,while XRD pointed to variscite as the main crystallo-graphic phase, the elemental composition did not match any elemental compositions of known and characterised sources, thus suggesting an unknown south-eastern source or an extra-peninsular origin of these ornamental pieces

Castillejo del Bonete (Terrinches, Ciudad Real): un complejo tumular prehistórico de la Cultura de las Motillas en el Alto Guadalquivir

Situado en las estribaciones orientales de Sierra Morena, dentro de la cuenca hidrológica del Guadalquivir, Castillejo del Bonete es un gran complejo arquitectónico que consta de una cueva monumentalizada mediante estructuras varias, entre las que destacan varios corredores megalíticos y túmulos, todos ellos asociados a contextos funerarios y depósitos de ofrendas. El presente artículo se centra en la explicación detallada de los elementos que integran este complejo constructivo para posteriormente discutir el avance que supone para la investigación de la Prehistoria Reciente en La Mancha. Castillejo del Bonete tiene el potencial de convertirse en un yacimiento clave para la comprensión de las prácticas funerarias y la creciente jerarquización social durante el tránsito del III al II milenios cal ANE

Latin America's Nitrogen Challenge

Latin America (LA) has many social indicators similar to those of highly developed economies but most frequently falls midway between least developed countries and industrialized regions. To move forward, LA must address uncontrolled urbanization, agricultural production, social inequity, and destruction of natural resources. We discuss these interrelated challenges in terms of human impact on the nitrogen (N) cycle. Human activity has caused unprecedented changes to the global N cycle; in the past century; total global fixation of reactive N (Nr) has at least doubled (1). Excess Nr leaked into the environment negatively affects soils, atmosphere, and water resources in temperate zones (1). In addition to N excess from human impact, mining of natural soil N creates N deficits in some regions (2, 3).Fil: Austin, Amy Theresa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura; ArgentinaFil: Bustamante, M. M. C.. Universidade Do Brasilia; BrasilFil: Nardoto, G. B.. Universidade Do Brasilia; BrasilFil: Mitre, S. K.. Universidade Do Brasilia; BrasilFil: Pérez, T.. Instituto Venezolano de Investigaciones Cientificas; VenezuelaFil: Ometto, J. P. H. B.. Centro de Previsao de Tempo e Estudos Climaticos. Instituto Nacional de Pesquisas Espaciais; BrasilFil: Ascarrunz, N. L.. Instituto Boliviano de Investigación Forestal; BoliviaFil: Forti, M. C.. Centro de Previsao de Tempo e Estudos Climaticos. Instituto Nacional de Pesquisas Espaciais; BrasilFil: Longo, K.. Centro de Previsao de Tempo e Estudos Climaticos. Instituto Nacional de Pesquisas Espaciais; BrasilFil: Gavito, M. E.. Universidad Nacional Autónoma de México; MéxicoFil: Enrich Prast, A.. Universidade Federal do Rio de Janeiro; BrasilFil: Martinelli, L. A.. Universidade de Sao Paulo; Brasi

Annexin A6 Is Critical to Maintain Glucose Homeostasis and Survival During Liver Regeneration in Mice

Background and Aims: Liver regeneration requires the organized and sequential activation of events that lead to restoration of hepatic mass. During this process, other vital liver functions need to be preserved, such as maintenance of blood glucose homeostasis, balancing the degradation of hepatic glycogen stores, and gluconeogenesis (GNG). Under metabolic stress, alanine is the main hepatic gluconeogenic substrate, and its availability is the rate‐limiting step in this pathway. Na+‐coupled neutral amino acid transporters (SNATs) 2 and 4 are believed to facilitate hepatic alanine uptake. In previous studies, we demonstrated that a member of the Ca2+‐dependent phospholipid binding annexins, Annexin A6 (AnxA6), regulates membrane trafficking along endo‐ and exocytic pathways. Yet, although AnxA6 is abundantly expressed in the liver, its function in hepatic physiology remains unknown. In this study, we investigated the potential contribution of AnxA6 in liver regeneration. Approach and Results: Utilizing AnxA6 knockout mice (AnxA6−/−), we challenged liver function after partial hepatectomy (PHx), inducing acute proliferative and metabolic stress. Biochemical and immunofluorescent approaches were used to dissect AnxA6−/− mice liver proliferation and energetic metabolism. Most strikingly, AnxA6−/− mice exhibited low survival after PHx. This was associated with an irreversible and progressive drop of blood glucose levels. Whereas exogenous glucose administration or restoration of hepatic AnxA6 expression rescued AnxA6−/− mice survival after PHx, the sustained hypoglycemia in partially hepatectomized AnxA6−/− mice was the consequence of an impaired alanine‐dependent GNG in AnxA6−/− hepatocytes. Mechanistically, cytoplasmic SNAT4 failed to recycle to the sinusoidal plasma membrane of AnxA6−/− hepatocytes 48 hours after PHx, impairing alanine uptake and, consequently, glucose production. Conclusions: We conclude that the lack of AnxA6 compromises alanine‐dependent GNG and liver regeneration in mice

Mitochondrial DNA disturbances and deregulated expression of oxidative phosphorylation and mitochondrial fusion proteins in sporadic inclusion body myositis

Sporadic inclusion body myositis (sIBM) is one of the most common myopathies in elderly people. Mitochondrial abnormalities at the histological level are present in these patients. We hypothesize that mitochondrial dysfunction may play a role in disease aetiology. We took the following measurements of muscle and peripheral blood mononuclear cells (PBMCs) from 30 sIBM patients and 38 age-and gender-paired controls: mitochondrial DNA (mtDNA) deletions, amount of mtDNA and mtRNA, mitochondrial protein synthesis, mitochondrial respiratory chain (MRC) complex I and IV enzymatic activity, mitochondrial mass, oxidative stress and mitochondrial dynamics (mitofusin 2 and optic atrophy 1 levels). Depletion of mtDNA was present in muscle from sIBM patients and PBMCs showed deregulated expression of mitochondrial proteins in oxidative phosphorylation. MRC complex IV/citrate synthase activity was significantly decreased in both tissues and mitochondrial dynamics were affected in muscle. Depletion of mtDNA was significantly more severe in patients with mtDNA deletions, which also presented deregulation of mitochondrial fusion proteins. Imbalance in mitochondrial dynamics in muscle was associated with increased mitochondrial genetic disturbances (both depletion and deletions), demonstrating that proper mitochondrial turnover is essential for mitochondrial homoeostasis and muscle function in these patients

The role of macrophage-inducible C-type lectin in different stages of chronic liver disease

The macrophage-inducible C-type lectin (mincle) is part of the innate immune system and acts as a pattern recognition receptor for pathogen-associated molecular patterns (PAMPS) and damage-associated molecular patterns (DAMPs). Ligand binding induces mincle activation which consequently interacts with the signaling adapter Fc receptor, SYK, and NF-kappa-B. There is also evidence that mincle expressed on macrophages promotes intestinal barrier integrity. However, little is known about the role of mincle in hepatic fibrosis, especially in more advanced disease stages. Mincle expression was measured in human liver samples from cirrhotic patients and donors collected at liver transplantation and in patients undergoing bariatric surgery. Human results were confirmed in rodent models of cirrhosis and acute-on-chronic liver failure (ACLF). In these models, the role of mincle was investigated in liver samples as well as in peripheral blood monocytes (PBMC), tissues from the kidney, spleen, small intestine, and heart. Additionally, mincle activation was stimulated in experimental non-alcoholic steatohepatitis (NASH) by treatment with mincle agonist trehalose-6,6-dibehenate (TDB). In human NASH, mincle is upregulated with increased collagen production. In ApoE deficient mice fed high-fat western diet (NASH model), mincle activation significantly increases hepatic collagen production. In human cirrhosis, mincle expression is also significantly upregulated. Furthermore, mincle expression is associated with the stage of chronic liver disease. This could be confirmed in rat models of cirrhosis and ACLF. ACLF was induced by LPS injection in cirrhotic rats. While mincle expression and downstream signaling via FC receptor gamma, SYK, and NF-kappa-B are upregulated in the liver, they are downregulated in PBMCs of these rats. Although mincle expressed on macrophages might be beneficial for intestinal barrier integrity, it seems to contribute to inflammation and fibrosis once the intestinal barrier becomes leaky in advanced stages of chronic liver disease

Annexin A6 modulates TBC1D15/Rab7/StARD3 axis to control endosomal cholesterol export in NPC1 cells

Cholesterol accumulation in late endosomes is a prevailing phenotype of Niemann-Pick type C1 (NPC1) mutant cells. Likewise, annexin A6 (AnxA6) overexpression induces a phenotype reminiscent of NPC1 mutant cells. Here, we demonstrate that this cellular cholesterol imbalance is due to AnxA6 promoting Rab7 inactivation via TBC1D15, a Rab7-GAP. In NPC1 mutant cells, AnxA6 depletion and eventual Rab7 activation was associated with peripheral distribution and increased mobility of late endosomes. This was accompanied by an enhanced lipid accumulation in lipid droplets in an acyl-CoA:cholesterol acyltransferase (ACAT)-dependent manner. Moreover, in AnxA6-deficient NPC1 mutant cells, Rab7-mediated rescue of late endosome-cholesterol export required the StAR-related lipid transfer domain-3 (StARD3) protein. Electron microscopy revealed a significant increase of membrane contact sites (MCS) between late endosomes and ER in NPC1 mutant cells lacking AnxA6, suggesting late endosome-cholesterol transfer to the ER via Rab7 and StARD3-dependent MCS formation. This study identifies AnxA6 as a novel gatekeeper that controls cellular distribution of late endosome-cholesterol via regulation of a Rab7-GAP and MCS formation