Diagnosis and management of nephrotic syndrome in an adult patient: A case report

Introduction: Nephrotic syndrome is a disorder characterized by proteinuria \u3e3.5 g/24 hr, hypoalbuminemia /dL, and peripheral edema. The underlying etiology of the condition is influenced in large part by the age of the patient. In children under the age of 16, a large majority of cases are secondary to minimal change disease, whereas in adults the causes are more varied to include focal segmental glomerulosclerosis and membranous nephropathy. Case Report: A 68-year-old male with nephrotic range proteinuria who required workup with laboratory studies, immunological screening, and both light microscopy as well as electron microscopy to arrive at a diagnosis of minimal change disease. Conclusion: Also included is a review of previously published studies regarding minimal change disease and its association with non-Hodgkin lymphoma in the adult population, along with a discussion of current treatment approaches and a comparison of their efficacies

Inequality in provider continuity for children by Australian general practitioners

<p>Abstract</p> <p>Background</p> <p>There is little published on provider continuity in Australian general practice and none on its effect on inequality of care for children.</p> <p>Method</p> <p>Questionnaire administered to parents of the ACT Kindergarten Health Screen asking the name of their child's usual GP and practice address between 2001 and 2008.</p> <p>Results</p> <p>Parents of 30,789 children named 433 GPs and 141 practices. In each year, an average of 77% of parents could name both the GP and the practice, an average of 11% of parents could name only the practice, and an average of 12% of parents could name neither. In each year, 25% of parents could not name a usual GP for children of Aboriginal or Torres Straight Islander descent, or children born outside of Australia, compared to 10% of all other children (p = < 0.0001). The frequency of GPs displaying continuity of care varied over time with 19% of GPs being present in the ACT in only one year and 39% of GPs being present in every year over the eight years of study. GPs displayed two different forms of transience either by working in more than one practice in each year (5% of GPs), or by not being present in the ACT region from one year to the next (15% of GPs). Fewer parents nominated transient GPs as their child's GP compared to choosing GPs who displayed continuity (p < 0.001).</p> <p>Conclusions</p> <p>Many GPs (39%) were reported to provide continuity of care for in the ACT region and some GPs (20%) displayed transient care. Indigenous children or children born outside of Australia had less equity of access to a nominated GP than all other children. Such inequity might disappear if voluntary registration of children was adopted in Australian general practice.</p

The key role of bismuth in the magnetoelastic transitions of Ba3BiIr2O9 and Ba3BiRu2O9 as revealed by chemical doping

The key role played by bismuth in an average intermediate oxidation state in the magnetoelastic spin-gap compounds Ba3BiRu2O9 and Ba3BiIr2O9 has been confirmed by systematically replacing bismuth with La3+ and Ce4+. Through a combination of powder diffraction (neutron and synchrotron), X-ray absorption spectroscopy, and magnetic properties measurements, we show that Ru/Ir cations in Ba3BiRu2O9 and Ba3BiIr2O9 have oxidation states between +4 and +4.5, suggesting that Bi cations exist in an unusual average oxidation state intermediate between the conventional +3 and +5 states (which is confirmed by the Bi L3-edge spectrum of Ba3BiRu2O9). Precise measurements of lattice parameters from synchrotron diffraction are consistent with the presence of intermediate oxidation state bismuth cations throughout the doping ranges. We find that relatively small amounts of doping (~10 at%) on the bismuth site suppress and then completely eliminate the sharp structural and magnetic transitions observed in pure Ba3BiRu2O9 and Ba3BiIr2O9, strongly suggesting that the unstable electronic state of bismuth plays a critical role in the behaviour of these materials

mTORC1-S6K Activation by Endotoxin Contributes to Cytokine Up-Regulation and Early Lethality in Animals

Background: mTORC1 (mammalian target of rapamycin complex 1) activation has been demonstrated in response to endotoxin challenge, but the mechanism and significance are unclear. We investigated the effect of mTORC1 suppression in an animal model of endotoxemia and in a cellular model of endotoxin signaling. Methodology/Principal Findings: Mice were treated with the mTORC1 inhibitor rapamycin or vehicle prior to lethal endotoxin challenge. Mortality and cytokine levels were assessed. Cultured macrophage-like cells were challenged with endotoxin with or without inhibitors of various pathways known to be upstream of mTORC1. Activated pathways, including downstream S6K pathway, were assessed by immunoblots. We found that mTORC1-S6K suppression by rapamycin delayed mortality of mice challenged with lethal endotoxin, and was associated with dampened circulating levels of VEGF, IL-1b, IFN-c and IL-5. Furthermore, in vitro cellular studies demonstrated that LPS (lipopolysaccharide) activation of mTORC1-S6K still occurs in the presence of PI3K-Akt inhibition alone, but can be suppressed by concurrent inhibition of PI3K-Akt and MEK-ERK pathways. Conclusions/Significance: We conclude that cellular activation of mTORC1-S6K contributes to cytokine up-regulation an

Policy Adjustment in a Dynamic Economic Game

Making sequential decisions to harvest rewards is a notoriously difficult problem. One difficulty is that the real world is not stationary and the reward expected from a contemplated action may depend in complex ways on the history of an animal's choices. Previous functional neuroimaging work combined with principled models has detected brain responses that correlate with computations thought to guide simple learning and action choice. Those works generally employed instrumental conditioning tasks with fixed action-reward contingencies. For real-world learning problems, the history of reward-harvesting choices can change the likelihood of rewards collected by the same choices in the near-term future. We used functional MRI to probe brain and behavioral responses in a continuous decision-making task where reward contingency is a function of both a subject's immediate choice and his choice history. In these more complex tasks, we demonstrated that a simple actor-critic model can account for both the subjects' behavioral and brain responses, and identified a reward prediction error signal in ventral striatal structures active during these non-stationary decision tasks. However, a sudden introduction of new reward structures engages more complex control circuitry in the prefrontal cortex (inferior frontal gyrus and anterior insula) and is not captured by a simple actor-critic model. Taken together, these results extend our knowledge of reward-learning signals into more complex, history-dependent choice tasks. They also highlight the important interplay between striatum and prefrontal cortex as decision-makers respond to the strategic demands imposed by non-stationary reward environments more reminiscent of real-world tasks

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment