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

Meeting abstrac

The microRNA processor DROSHA is a candidate gene for a severe progressive neurological disorder

DROSHA encodes a ribonuclease that is a subunit of the Microprocessor complex and is involved in the first step of microRNA (miRNA) biogenesis. To date, DROSHA has not yet been associated with a Mendelian disease. Here, we describe two individuals with profound intellectual disability, epilepsy, white matter atrophy, microcephaly and dysmorphic features, who carry damaging de novo heterozygous variants in DROSHA. DROSHA is constrained for missense variants and moderately intolerant to loss-of-function (o/e = 0.24). The loss of the fruit fly ortholog drosha causes developmental arrest and death in third instar larvae, a severe reduction in brain size and loss of imaginal discs in the larva. Loss of drosha in eye clones causes small and rough eyes in adult flies. One of the identified DROSHA variants (p.Asp1219Gly) behaves as a strong loss-of-function allele in flies, while another variant (p.Arg1342Trp) is less damaging in our assays. In worms, a knock-in that mimics the p.Asp1219Gly variant at a worm equivalent residue causes loss of miRNA expression and heterochronicity, a phenotype characteristic of the loss of miRNA. Together, our data show that the DROSHA variants found in the individuals presented here are damaging based on functional studies in model organisms and likely underlie the severe phenotype involving the nervous system

The microRNA processor DROSHA is a candidate gene for a severe progressive neurological disorder

DROSHA encodes a ribonuclease that is a subunit of the Microprocessor complex and is involved in the first step of microRNA (miRNA) biogenesis. To date, DROSHA has not yet been associated with a Mendelian disease. Here, we describe two individuals with profound intellectual disability, epilepsy, white matter atrophy, microcephaly and dysmorphic features, who carry damaging de novo heterozygous variants in DROSHA. DROSHA is constrained for missense variants and moderately intolerant to loss-of-function (o/e = 0.24). The loss of the fruit fly ortholog drosha causes developmental arrest and death in third instar larvae, a severe reduction in brain size and loss of imaginal discs in the larva. Loss of drosha in eye clones causes small and rough eyes in adult flies. One of the identified DROSHA variants (p.Asp1219Gly) behaves as a strong loss-of-function allele in flies, while another variant (p.Arg1342Trp) is less damaging in our assays. In worms, a knock-in that mimics the p.Asp1219Gly variant at a worm equivalent residue causes loss of miRNA expression and heterochronicity, a phenotype characteristic of the loss of miRNA. Together, our data show that the DROSHA variants found in the individuals presented here are damaging based on functional studies in model organisms and likely underlie the severe phenotype involving the nervous system

Insights into the role of hydration in protein structure and stability obtained through hydrostatic pressure studies

A thorough understanding of protein structure and stability requires that we elucidate the molecular basis for the effects of both temperature and pressure on protein conformational transitions. While temperature effects are relatively well understood and the change in heat capacity upon unfolding has been reasonably well parameterized, the state of understanding of pressure effects is much less advanced. Ultimately, a quantitative parameterization of the volume changes (at the basis of pressure effects) accompanying protein conformational transitions will be required. The present report introduces a qualitative hypothesis based on available model compound data for the molecular basis of volume change upon protein unfolding and its dependence on temperature

Arte, conhecimento geográfico e leitura de imagens: O geógrafo, de Vermeer Art, geographical knowledge and image reading: Vermeer's "Geographer"

O quadro O geógrafo, do pintor holandês Johannes Vermeer, é uma imagem freqüentemente escolhida para capas de livros em geografia. Desenhada na segunda metade do século XVII, a pintura não apenas pode ser considerada um retrato de como pensar e fazer geografia naquela época, mas também representa uma obra de arte com forte carga simbólica para estimular uma discussão metodológica sobre a leitura geográfica de imagens. Neste texto, objetiva-se refletir sobre as linguagens deste quadro dentro do seu contexto sociocultural, econômico e político e em relação aos diversos processos de construir conhecimento geográfico.<br>The painting The Geographer by the Dutch artist Johannes Vermeer is an image that is frequently selected as a cover for geography books. Drawn in the second half of the 17th century, the picture must not only be considered as a portrait of how to think and do geography at that time; it can also be seen as a piece of art with a heavy symbolic load to stimulate a methodological debate on geographic readings of images. The present text aims to reflect about the languages of this painting, considering its sociocultural, economic and political contexts and its relation to the different processes of constructing geographic knowledge

Basics of Micro/Nano Fluidics and Biology

International audienceMastering the basics of theoretical and experimental aspects of fluidics and biology is an obvious requirement for the design and evaluation of micro/nano biosystems. This chapter provides a review of the phyics of micro/nano fluidics systems as well as basics of biochemistry and biological functions. It also gives detailed information on common experimental techniques used to characterize fluidic and biological systems as well as tyical examples of application

Incidence and management of pleural effusions in patients with Wilms tumor: A Pediatric Surgical Oncology Research Collaborative study

Wilms tumor (WT) is the most common renal malignancy in children. Children with favorable histology WT achieve survival rates of over 90%. Twelve percent of patients present with metastatic disease, most commonly to the lungs. The presence of a pleural effusion at the time of diagnosis of WT may be noted on staging imaging; however, minimal data exist regarding the significance and prognostic importance of this finding. The objectives of our study are to identify the incidence of pleural effusions in patients with WT, and to determine the potential impact on oncologic outcomes. A multi-institutional retrospective review was performed from January 2009 to December 2019, including children with WT and a pleural effusion on diagnostic imaging treated at Pediatric Surgical Oncology Research Collaborative (PSORC) participating institutions. Of 1259 children with a new WT diagnosis, 94 (7.5%) had a pleural effusion. Patients with a pleural effusion were older than those without (median 4.3 vs 3.5 years; P = .004), and advanced stages were more common (local stage III 85.9% vs 51.9%; P < .0001). Only 14 patients underwent a thoracentesis for fluid evaluation; 3 had cytopathologic evidence of malignant cells. Event-free and overall survival of all children with WT and pleural effusions was 86.2% and 91.5%, respectively. The rate and significance of malignant cells present in pleural fluid is unknown due to low incidence of cytopathologic analysis in our cohort; therefore, the presence of an effusion does not appear to necessitate a change in therapy. Excellent survival can be expected with current stage-specific treatment regimens.What’s new?Some Wilms tumor (WT) patients have fluid around the lungs, or pleural effusion, at diagnosis, but its effect on outcomes is not well known. Here, the authors evaluated data from 1259 children with WT from 21 hospitals in North America. Pleural effusion was present in 7.5% of patients, higher than the previously reported rate of 4.3%, and management was not standardized among different hospitals. The authors also report that patients with pleural effusion were more likely to present with advanced stage tumors and to have their preoperative tumor rupture, but their outcomes were not significantly worse than other patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/174970/1/ijc34188_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/174970/2/ijc34188.pd