Chronic VEGF Blockade Worsens Glomerular Injury in the Remnant Kidney Model

VEGF inhibition can promote renal vascular and parenchymal injury, causing proteinuria, hypertension and thrombotic microangiopathy. The mechanisms underlying these side effects are unclear. We investigated the renal effects of the administration, during 45 days, of sunitinib (Su), a VEGF receptor inhibitor, to rats with 5/6 renal ablation (Nx). Adult male Munich-Wistar rats were distributed among groups S+V, sham-operated rats receiving vehicle only; S+Su, S rats given Su, 4 mg/kg/day; Nx+V, Nx rats receiving V; and Nx+Su, Nx rats receiving Su. Su caused no change in Group S. Seven and 45 days after renal ablation, renal cortical interstitium was expanded, in association with rarefaction of peritubular capillaries. Su did not worsen hypertension, proteinuria or interstitial expansion, nor did it affect capillary rarefaction, suggesting little angiogenic activity in this model. Nx animals exhibited glomerulosclerosis (GS), which was aggravated by Su. This effect could not be explained by podocyte damage, nor could it be ascribed to tuft hypertrophy or hyperplasia. GS may have derived from organization of capillary microthrombi, frequently observed in Group Nx+Su. Treatment with Su did not reduce the fractional glomerular endothelial area, suggesting functional rather than structural cell injury. Chronic VEGF inhibition has little effect on normal rats, but can affect glomerular endothelium when renal damage is already present

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Variants of the human NRAMP1 gene and altered human immunodeficiency virus infection susceptibility

International audienceno abstrac

Structural Insights into Rotavirus Entry.

To initiate infection, non-enveloped viruses must recognize a target cell and penetrate the cell membrane by pore formation or membrane lysis. Rotaviruses are non-enveloped dsRNA viruses that infect the mature intestinal epithelium. They are major etiologic agents of diarrheal disease in human infants, as well as in young individuals of various avian and mammalian species. Rotavirus entry into the cell is a complex multistep process initiated by the interaction of the tip of the viral spike with glycan ligands at the cell surface, and driven by conformational changes of the proteins present in the outer protein capsid, the viral machinery for entry. This review feeds on the abundant structural information produced for rotavirus during the past 30 years and focuses on the structure and the dynamics of the rotavirus entry machinery. We survey the current models for rotavirus entry into cells.S

El componente educativo en el abordaje integral del asma bronquial The educational component in an integrated approach to bronchial asthma

El asma bronquial es una enfermedad inflamatoria crónica de las vías respiratorias cuya prevalencia está aumentando en el mundo. Actualmente no se dispone de un tratamiento curativo, y el objetivo principal de todo abordaje es el control de la enfermedad y la optimización de la calidad de vida de los pacientes. En este sentido, durante las últimas décadas se han estado implementando y evaluando programas de intervención complementarios a los tratamientos médicos convencionales. Gran parte de éstos consisten en intervenciones educativas o incluyen algún tipo de componente educativo. El objetivo del presente trabajo fue analizar las características y el impacto de las intervenciones educativas en el asma, a través de: a) revisión actualizada sobre los diferentes tipos de intervenciones educativas desarrolladas e implementadas para el asma; b) identificación de aspectos comunes a todas estas intervenciones; c) análisis de los hallazgos de la investigación referidos a su impacto sobre la salud y la calidad de vida de los pacientes. Se concluye que las intervenciones educativas son efectivas para mejorar la salud y la calidad de vida de los pacientes con asma, y para reducir el uso y el costo de recursos sanitarios. Estos hallazgos señalan la importancia de incluir el componente educativo como parte esencial del abordaje integral de esta población clínica. Asimismo, la complejidad inherente al proceso educativo pone de manifiesto la necesidad del trabajo conjunto y complementario entre diferentes profesionales de la salud.<br>Bronchial asthma is an inflammatory chronic disease of the respiratory tract whose prevalence is increasing worldwide. Since there is no curative treatment available, the principal objective of every approach is to control the disease and to improve the quality of life of patients. Over the last few decades, intervention programs supplementing conventional medical treatments have been tested and implemented. The majority of such programs consist of educational interventions or include some type of educational component. In this study, we attempted to determine the characteristics and the impact of educational interventions on asthma by means of the following: a) an updated review of the various educational interventions developed and implemented for asthma patients; b) the identification of aspects that are common to all of these interventions; and c) the analysis of the findings in the literature regarding the impact that these interventions have on the health and quality of life of patients. We conclude that educational interventions are effective in improving the health and quality of life of asthma patients, as well as in reducing the use and costs of health resources. These findings indicate the importance of including an educational component as part of an integrated approach to this population. Likewise, the inherent complexity of the educational process highlights the importance of a complementary joint effort including various health professionals