Inflammation, Senescence and MicroRNAs in Chronic Kidney Disease.

BACKGROUND: Patients with chronic kidney disease (CKD) show a chronic microinflammatory state that promotes premature aging of the vascular system. Currently, there is a growth interest in the search of novel biomarkers related to vascular aging to identify CKD patients at risk to develop cardiovascular complications. METHODS: Forty-five CKD patients were divided into three groups according to CKD-stages [predialysis (CKD4-5), hemodialysis (HD) and kidney transplantation (KT)]. In all these patients, we evaluated the quantitative changes in microRNAs (miRNAs), CD14+C16++ monocytes number, and microvesicles (MV) concentration [both total MV, and monocytes derived MV (CD14+Annexin V+CD16+)]. To understand the molecular mechanism involved in senescence and osteogenic transdifferentation of vascular smooth muscle cells (VSMC), these cells were stimulated with MV isolated from THP-1 monocytes treated with uremic toxins (txMV). RESULTS: A miRNA array was used to investigate serum miRNAs profile in CKD patients. Reduced expression levels of miRNAs-126-3p, -191-5p and -223-3p were observed in CKD4-5 and HD patients as compared to KT. This down-regulation disappeared after KT, even when lower glomerular filtration rates (eGFR) persisted. Moreover, HD patients had higher percentage of proinflammatory monocytes (CD14+CD16++) and MV derived of proinflammatory monocytes (CD14+Annexin V+CD16+) than the other groups. In vitro studies showed increased expression of osteogenic markers (BMP2 and miRNA-223-3p), expression of cyclin D1, ß-galactosidase activity and VSMC size in those cells treated with txMV. CONCLUSION: CKD patients present a specific circulating miRNAs expression profile associated with the microinflammatory state. Furthermore, microvesicles generated by monocytes treated with uremic toxins induce early senescence and osteogenic markers (BMP2 and miRNA-223-3p) in VSMC.

Exceptional coprolite association from the Early Cretaceous continental Lagerstätte of Las Hoyas, Cuenca, Spain.

Coprolites are some of the most abundant fossils at the Las Hoyas site, a well-known Early Cretaceous Konservat-Lagerstätte located in Cuenca, central Spain. The coprolite association is described, introducing taphonomic features and sedimentological properties. This study is based on a subsample of 433 fossils selected from some 2000 specimens collected. The taphonomic features of the coprolites show that their integrity, absence of desiccation marks, and volume are congruent with faeces produced and deposited in an aquatic ecosystem, which were immediately covered by microbial mats. The highest abundance of coprolites, 96%, occurs in layers linked to the presence of microbial mats. Consequently, it is likely that coprolites are taphonomically autochthonous. A dichotomous key has been made in order to delimit the morphotypes. The key is based on (1) presence/absence of spiral marks, (2) morphology of coprolite ends, including polarity, expansion, and surface, and (3) overall shape, outline, diameter, and constrictions. Twelve different morphotypes are distinguished: spiral, circular, irregular, elongated, rosary, ellipsoidal, cylinder, bump-headed lace, fir-tree, cone, straight lace, and thin lace. The association is dominated by thin-lace and cylinder morphotypes. The sizes, inclusions, and EDX analyses indicate that the Las Hoyas coprolites correspond mostly to carnivorous producers with ichthyophagous diets, as crocodiles, urodelans and different kind of fishes.

Phylogenetic relationships of Chanidae (Teleostei: Gonorynchiformes) as impacted by Dastilbe moraesi, from the Sanfranciscana basin, Early Cretaceous of Brazil

Fossil gonorynchiform fishes range from the Lower Cretaceous to the early Miocene, and are represented by a few dozen living species. The order is currently divided into two major clades: Gonorynchoidei, which includes the families Gonorynchidae and Kneriidae, and Chanoidei, encompassing a single family, Chanidae, with a single recent species, the Indo-Pacific Chanos chanos, and several fossil taxa. Chanidae includes some poorly known taxa, such as Dastilbe moraesi, described from the Aptian (Lower Cretaceous) of the Areado Formation, Sanfranciscana basin, Brazil. This species is currently considered to be a junior synonym of the type species of its genus, Dastilbe crandalli, from Santana Formation, Aptian, northeastern Brazil. The analysis of abundant D. moraesi specimens revealed several new morphological features, many of which had previously been misinterpreted. Dastilbe moraesi was incorporated into a gonorynchiform character matrix as revised and modified for the Chanidae. We obtained a single most parsimonious tree in which D. moraesi is distinct and phylogenetically apart from D. crandalli. According our analysis, D. moraesi forms a sister pair with Chanos, a clade which is closely related to Tharrhias, all composing the tribe Chanini.(AU)

Gonorynchiformes fósseis ocorrem desde do Cretáceo inferior ao Mioceno inferior, e são representados por alguns representantes viventes. A ordem está dividida atualmente em dois clados principais: Gonorynchoidei, que inclui as famílias Gonorynchidae e Kneriidae, e Chanoidei, compreendendo uma única família, Chanidae, com uma única espécie vivente, Chanos chanos, do Indo-Pacífico, além de vários representantes fósseis. Chanidae inclui alguns táxons problemáticos, tais como Dastilbe moraesi, descrito do Aptiano (Cretáceo Inferior) da Formação Areado, bacia Sanfranciscana, Brasil. Esta espécie é atualmente considerada um sinônimo júnior da espécie-tipo de seu gênero, Dastilbe crandalli, da Formação Santana, Aptiano do nordeste do Brasil. A análise de abundante material de D. moraesi revelou várias novas características anatômicas, muitas das quais haviam sido previamente mal interpretadas. Dastilbe moraesi foi incorporado em uma matriz revisada de caracteres da família Chanidae. Nós obtivemos uma única árvore mais parcimoniosa na qual D. moraesi é distinto e filogeneticamente distante de D. crandalli. De acordo com nossa análise, D. moraesi é o grupo-irmão de Chanos, um clado intimamente relacionado a Tharrhias, com todos compondo a tribo Chanini.(AU)

Análisis de la gestión de recursos humanos en los modelos de salud familiar, comunitaria e intercultural de los países andinos / Analysis of human resources management in family health, community and intercultural models in Andean countries

Introducción: Junto con destacar la importancia de contar con trabajadores sanitarios en cantidad y calidad suficientes, los Estados miembros del Organismo Andino de Salud - Convenio Hipólito Unanue (ORAS/CONHU), han impulsado iniciativas orientadas a generar y diseminar conocimiento sobre políticas, estrategias y modelos de gestión de recursos humanos. Objetivo: Analizar el componente de Gestión de Recursos Humanos de Salud, identificando los modelos aplicados y su contribución a la instalación de un sistema de salud basado en atención primaria. Diseño: Estudio cualitativo. Lugar: Ministerios de Salud de los países andinos. Participantes: Gestores de Recursos Humanos. Intervenciones: Diseño y aplicación de instrumento para el análisis cualitativo. Resultados: Los países han logrado avances en el desarrollo de los sistemas de gestión de recursos humanos de salud, reconociéndose que los problemas persistentes son la escasez e inadecuada distribución del personal, así como, perfiles profesionales de egreso que no se ajustan plenamente a las necesidades de salud derivadas del cambio epidemiológico y de un creciente compromiso por avanzar hacia el acceso y cobertura universales de salud. Conclusiones: Estrategias innovadoras de planificación, formación y gestión del desempeño, podrían contribuir a enfrentar los problemas de recursos humanos de salud, en un contexto adecuado de liderazgo y gobernanza.

Introduction: While stressing the importance of health workers in sufficient quantity and quality, the member states of the Andean Health Organization -Hipólito Unanue Agreement (ORAS / CONHU) have launched initiatives aimed at generating and disseminating knowledge on policies, strategies and models of human resource management. Objective: To analyze the component of Human Resources for Health Management, identifying models used and their contribution to the set up of a health system based on primary care. Design: Qualitative study. Location: Ministries of Health of the Andean countries. Participants: Managers of Human Resources. Interventions: Design and implementation of a tool for qualitative analysis. Results: Countries have made progress in developing systems for managing human resources for health. They acknowledge that persistent problems include staff shortage and maldistribution, as well as professional graduate profiles not fully meeting population health needs derived from epidemiological change and a growing commitment to universal health coverage. Conclusions: Innovative strategies for planning, training and performance management could help to address the problems of human resources for health in a proper context of leadership and governance.

Post-dilution high convective transport improves microinflammation and endothelial dysfunction independently of the technique.

BACKGROUND/AIMS: We examined the effects of different online hemodiafiltration techniques on microinflammation and endothelial damage/repair. METHODS: The study was designed as a prospective crossover study. Flow cytometry was used to measure CD14(+)CD16(+) monocytes, apoptotic endothelial microparticles (EMPs), and endothelial progenitor cells (EPCs). RESULTS: Patients treated with high-flux hemodialysis showed a marked chronic inflammatory state (HF-HD 11 ± 2) versus healthy subjects (HS 3.9 ± 2.3; p < 0.05). High convective transport, independent of the technique used, improves microinflammatory parameters (OL-HDF 7.3 ± 2.1 or MID 6.5 ± 3.4; p < 0.05) and the endothelial damage/repair balance compared to HF-HD (EPCs HF-HD 0.3 ± 0.2), with no differences found between the two modalities (EPCs OL-HDF 0.6 ± 0.1, MID 0.6 ± 0.2; p < 0.05). CONCLUSION: An increase in convective transport improves the microinflammatory state and the endothelial damage/repair of these patients independently of the technique used.

Cinacalcet treatment for secondary hyperparathyroidism in dialysis patients: an observational study in routine clinical practice.

BACKGROUND: Cinacalcet reduces intact parathyroid hormone (iPTH), Ca and P serum levels in patients with secondary hyperparathyroidism (SHPT). METHODS: This Spanish, multicenter, observational, retrospective study collected data from SHPT dialysis patients 12 weeks before and up to 72 weeks after starting cinacalcet in clinical practice. RESULTS: Data from 428 patients with uncontrolled SHPT despite receiving standard of care (29% with baseline iPTH 501-800 pg/ml; 51% with >800 pg/ml) were collected. Percentages of patients within National Kidney Foundation Kidney Disease Outcomes Quality Initiative targets at baseline and 72 weeks were: iPTH, 0 versus 32.5% (p < 0.05); Ca, 40.1 versus 50% (p < 0.05); P, 47.7 versus 53.8% (p = 0.162). Vitamin D sterol use decreased from 53.3% at baseline to 36.7% at 72 weeks (p < 0.05). The mean ± SD cinacalcet dose at 72 weeks was 44.0 ± 25.8, 51.7 ± 31.3 and 57.1 ± 37.0 mg for patients with baseline iPTH 301-500, 501-800 or >800 pg/ml, respectively. The main adverse reactions were nausea (5.4%), dyspepsia (5.1%) and vomiting (3.7%). CONCLUSIONS: The introduction of cinacalcet improved the routine clinical management of SHPT in a large cohort of Spanish dialysis patients. Cinacalcet is effective and well tolerated regardless of disease severity, and maintains its efficacy over 72 weeks.

Spontaneous remission of nephrotic syndrome in idiopathic membranous nephropathy.

Spontaneous remission is a well known characteristic of idiopathic membranous nephropathy, but contemporary studies describing predictors of remission and long-term outcomes are lacking. We conducted a retrospective, multicenter cohort study of 328 patients with nephrotic syndrome resulting from idiopathic membranous nephropathy that initially received conservative therapy. Spontaneous remission occurred in 104 (32%) patients: proteinuria progressively declined after diagnosis until remission of disease at 14.7 +/- 11.4 months. Although spontaneous remission was more frequent with lower levels of baseline proteinuria, it also frequently occurred in patients with massive proteinuria: 26% among those with baseline proteinuria 8 to 12 g/24 h and 22% among those with proteinuria >12 g/24 h. Baseline serum creatinine and proteinuria, treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists, and a >50% decline of proteinuria from baseline during the first year of follow-up were significant independent predictors for spontaneous remission. Only six patients (5.7%) experienced a relapse of nephrotic syndrome. The incidence of death and ESRD were significantly lower among patients with spontaneous remission. In conclusion, spontaneous remission is common among patients with nephrotic syndrome resulting from membranous nephropathy and carries a favorable long-term outcome with a low incidence of relapse. A decrease in proteinuria >50% from baseline during the first year predicts spontaneous remission.