Daño real inducido por la hematuria de origen glomerular

La enfermedad renal crónica (ERC) es una patología con una prevalencia en aumento por lo que ha sido reconocida como un problema de salud pública a nivel mundial. Aunque han sido identificados algunos factores de riesgo implicados en la progresión de la ERC, como la proteinuria, la hipertensión arterial, y los niveles de fósforo, factor de crecimiento fibroblástico 23 [FGF-23] y parathormona séricos, aún se desconoce gran parte de su patogenia. Por otro lado, la biopsia renal se considera el mejor método para diagnosticar enfermedades renales. La biopsia renal nos permite estimar el pronóstico basándose en una gradación de la actividad o cronicidad de las lesiones histológicas encontradas, para así guiar el tratamiento. Sin embargo, dado que la biopsia renal es un procedimiento invasivo, ésta se debe reservar para casos justificados en los que el beneficio de los hallazgos de la biopsia sea superior a los riesgos. Por ello, es necesario conocer de forma precisa los mecanismos implicados en la progresión de la enfermedad renal crónica para poder controlar sus factores de riesgo. La hematuria se define como la presencia de sangre en la orina en cantidades superiores a lo normal (ie. > 3 hematíes por campo), dado que en condiciones fisiológicas no existen hematíes en la orina. La hematuria glomerular es aquella producida por la extravasación de los hematíes desde el capilar glomerular al espacio urinario. Esta se diagnostica por la presencia de hematíes con contornos irregulares en la orina, por ello la hematuria glomerular es un signo de disfunción de la barrera de filtración glomerular..

Haematuria on the spanish registry of glomerulonephritis

Recent studies suggest a pathogenic role for glomerular haematuria among renal function. However, there is no data on the prevalence of haematuria from a large renal biopsy registry. We analysed the prevalence of gross (GH) and microscopic (mH) haematuria in 19,895 patients that underwent native renal biopsies from the Spanish Registry of Glomerulonephritis. Haematuria's overall incidence was 63% (GH 8.6% and mH 55.1%), being more frequent in males (64.7% vs. 62.4%). GH was more prevalent in patients <18 years (21.3% vs. 7.7%). The commonest clinical presentation associated with GH was acute kidney injury (31.5%) and IgA Nephropathy (IgAN) (33.6%) was the most frequent histological finding. GH patients showed a significantly (p < 0.05) lower eGFR and proteinuria levels as compared with patients with mH and without haematuria. Moreover, mH was more prevalent in adults (56.3%). Nephrotic syndrome was the commonest clinical presentation in mH patients (32.2%) and IgAN (18.5%) the most frequent histological finding. In conclusion, haematuria, is a frequent urinalysis finding in patients underwent native renal biopsy. The most frequent histological finding in both GH and mH is IgAN. Whereas, GH is more frequent in young males with acute kidney injury, mH is commoner among adults with nephrotic syndrome.This work has been supported by grants from FIS (Programa Miguel Servet: CP10/00479, PI13/00802 and PI14/00883), Fundación Renal Iñigo Alvarez de Toledo and Spanish Society of Nephrology to JA

Haematuria increases progression of advanced proteinuric kidney disease

Background Haematuria has been traditionally considered as a benign hallmark of some glomerular diseases; however new studies show that haematuria may decrease renal function. Objective To determine the influence of haematuria on the rate of chronic kidney disease (CKD) progression in 71 proteinuric patients with advanced CKD (baseline eGFR <30 mL/min) during 12 months of follow-up. Results The mean rate of decline in eGFR was higher in patients with both haematuria and proteinuria (haemoproteinuria, HP, n=31) than in patients with proteinuria alone (P patients, n=40) (-3.8±8.9 vs 0.9±9.5 mL/min/1.73m2/year, p<0.05, respectively). The deleterious effect of haematuria on rate of decline in eGFR was observed in patients <65 years (-6.8±9.9 (HP) vs. 0.1±11.7 (P) mL/min/1.73m2/year, p65 years (-1.2±6.8 (HP) vs. 1.5±7.7 (P) mL/min/1.73m2/year). Furthermore, the harmful effect of haematuria on eGFR slope was found patients with proteinuria >0.5 g/24 h (-5.8±6.4 (HP) vs. -1.37± 7.9 (P) mL/min/1.73m2/year, p<0.05), whereas no significant differences were found in patients with proteinuria < 0.5 g/24 h (-0.62±7.4 (HP) vs. 3.4±11.1 (P) mL/min/1.73m2/year). Multivariate analysis reported that presence of haematuria was significantly and independently associated with eGFR deterioration after adjusting for traditional risk factors, including age, serum phosphate, mean proteinuria and mean serum PTH (β=-4.316, p=0.025) Conclusions The presence of haematuria is closely associated with a faster decrease in renal function in advanced proteinuric CKD patients, especially in younger CKD patients with high proteinuria levels; therefore this high risk subgroup of patients would benefit of intensive medical surveillance and treatmentThis work was supported by grants from FIS (Programa Miguel Servet: CP10/00479, PI13/ 00802 and PI14/00883) and Spanish Society of Nephrology to Juan Antonio Moreno. Fundacion Lilly, FRIAT (Fundación Renal Iñigo Alvarez de Toledo) and ISCIII fund PI14/00386 to Jesus Egid

Nrf2 Plays a Protective Role Against Intravascular Hemolysis-Mediated Acute Kidney Injury

Massive intravascular hemolysis is associated with acute kidney injury (AKI). Nuclear factor erythroid-2-related factor 2 (Nrf2) plays a central role in the defense against oxidative stress by activating the expression of antioxidant proteins. We investigated the role of Nrf2 in intravascular hemolysis and whether Nrf2 activation protected against hemoglobin (Hb)/heme-mediated renal damage in vivo and in vitro. We observed renal Nrf2 activation in human hemolysis and in an experimental model of intravascular hemolysis promoted by phenylhydrazine intraperitoneal injection. In wild-type mice, Hb/heme released from intravascular hemolysis promoted AKI, resulting in decreased renal function, enhanced expression of tubular injury markers (KIM-1 and NGAL), oxidative and endoplasmic reticulum stress (ER), and cell death. These features were more severe in Nrf2-deficient mice, which showed decreased expression of Nrf2-related antioxidant enzymes, including heme oxygenase 1 (HO-1) and ferritin. Nrf2 activation with sulforaphane protected against Hb toxicity in mice and cultured tubular epithelial cells, ameliorating renal function and kidney injury and reducing cell stress and death. Nrf2 genotype or sulforaphane treatment did not influence the severity of hemolysis. In conclusion, our study identifies Nrf2 as a key molecule involved in protection against renal damage associated with hemolysis and opens novel therapeutic approaches to prevent renal damage in patients with severe hemolytic crisis. These findings provide new insights into novel aspects of Hb-mediated renal toxicity and may have important therapeutic implications for intravascular hemolysis-related diseases.Supported by FIS/FEDER CP14/00008, CP16/00014, CP16/00017, PI15/00448, PI16/00735, PI16/02057, PI17/00130, PI17/01495, PI17/01700, ISCIII-RETIC REDinREN RD012/0021, RD016/0009 FEDER funds, Spanish Ministry of Economy and Competitiveness (RYC-2017-22369), Sociedad Española de Nefrología, Fundacion Renal Iñigo Álvarez de Toledo (FRIAT), Comunidad de Madrid CIFRA2 B2017/BMD-3686 and BMD-3827, Fundacion La Caixa, CaixaImpulse program CI17-00048, and Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM).S

The emergence of functional microcircuits in visual cortex.

Sensory processing occurs in neocortical microcircuits in which synaptic connectivity is highly structured and excitatory neurons form subnetworks that process related sensory information. However, the developmental mechanisms underlying the formation of functionally organized connectivity in cortical microcircuits remain unknown. Here we directly relate patterns of excitatory synaptic connectivity to visual response properties of neighbouring layer 2/3 pyramidal neurons in mouse visual cortex at different postnatal ages, using two-photon calcium imaging in vivo and multiple whole-cell recordings in vitro. Although neural responses were already highly selective for visual stimuli at eye opening, neurons responding to similar visual features were not yet preferentially connected, indicating that the emergence of feature selectivity does not depend on the precise arrangement of local synaptic connections. After eye opening, local connectivity reorganized extensively: more connections formed selectively between neurons with similar visual responses and connections were eliminated between visually unresponsive neurons, but the overall connectivity rate did not change. We propose a sequential model of cortical microcircuit development based on activity-dependent mechanisms of plasticity whereby neurons first acquire feature preference by selecting feedforward inputs before the onset of sensory experience--a process that may be facilitated by early electrical coupling between neuronal subsets--and then patterned input drives the formation of functional subnetworks through a redistribution of recurrent synaptic connections

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

Hippocampal biomarkers of fear memory in an animal model of generalized anxiety disorder

Generalized anxiety disorder (GAD) is highly prevalent and incapacitating. Here we used the Carioca High-Conditioned Freezing (CHF) rats, a previously validated animal model for GAD, to identify biomarkers and structural changes in the hippocampus that could be part of the underlying mechanisms of their high-anxiety profile. Spatial and fear memory was assessed in the Morris water maze and passive avoidance test. Serum corticosterone levels, immunofluorescence for glucocorticoid receptors (GR) in the dentate gyrus (DG), and western blotting for hippocampal brain derived neurotrophic factor (BDNF) were performed. Immunohistochemistry for markers of cell proliferation (bromodeoxiuridine/Ki-67), neuroblasts (doublecortin), and cell survival were undertaken in the DG, along with spine staining (Golgi) and dendritic arborization tracing. Hippocampal GABA release was assessed by neurochemical assay. Fear memory was higher among CHF rats whilst spatial learning was preserved. Serum corticosterone levels were increased, with decreased GR expression. No differences were observed in hippocampal cell proliferation/survival, but the number of newborn neurons was decreased, along with their number and length of tertiary dendrites. Increased expression of proBDNF and dendritic spines was observed; lower ratio of GABA release in the hippocampus was also verified. These findings suggest that generalized anxiety/fear could be associated with different hippocampal biomarkers, such as increased spine density, possibly as a compensatory mechanism for the decreased hippocampal number of neuroblasts and dendritic arborization triggered by high corticosterone. Disruption of GABAergic signaling and BDNF impairment are also proposed as part of the hippocampal mechanisms possibly underlying the anxious phenotype of this model

Masoterapia 1: Roce Superficial y Profundo

El presente material audiovisual didáctico, constituye un apoyo para el aprendizaje de técnicas de Masoterapia en alumnos de Grado en Fisioterapia. El uso de vídeo sin audio, con paradas y repeticiones para centralizar la atención en los detalles importantes y el empleo de texto esquemático, junto con flechas que muestran presas y líneas de dirección de movimiento, suponen una innovación en este tipo de materiales y un refuerzo en la consolidación a medio-largo plazo de las destrezas y conocimientos adquiridos. En concreto, este vídeo describe la realización de la técnica de Roce Superficial y Profundo. Este material es para uso exclusivo de alumnos de Fisioterapia. La implementación de estas técnicas en pacientes debe ser ejecutada por un fisioterapeuta experto tras la elaboración del diagnóstico de Fisioterapia a través de un adecuado razonamiento clínico

Masoterapia 2: Roce Profundo Interóseo

El presente material audiovisual didáctico, constituye un apoyo para el aprendizaje de técnicas de Masoterapia en alumnos de Grado en Fisioterapia. El uso de vídeo sin audio, con paradas y repeticiones para centralizar la atención en los detalles importantes y el empleo de texto esquemático, junto con flechas que muestran presas y líneas de dirección de movimiento, suponen una innovación en este tipo de materiales y un refuerzo en la consolidación a medio-largo plazo de las destrezas y conocimientos adquiridos. En concreto, este vídeo describe la realización de la técnica de Roce Profundo Interóseo. Este material es para uso exclusivo de alumnos de Fisioterapia. La implementación de estas técnicas en pacientes debe ser ejecutada por un fisioterapeuta experto tras la elaboración del diagnóstico de Fisioterapia a través de un adecuado razonamiento clínico