Spectrum of Renal Biopsy Findings in TRIDENT Cohort

Introduction: Diabetic kidney disease is the most common cause of chronic end stage renal failure in the USA. Kidney biopsy is the gold standard diagnostic criteria; however, it is an invasive procedure; not everyone undergoes diagnostic biopsy. The relationship between histological and clinical parameters and prognosis in DKD is incompletely understood. TRIDENT, (Transformative research in diabetic nephropathy) plans to enroll 400 diabetic subjects undergoing clinically indicated renal biopsies and performs multi-omics characterization of subjects to identify pathways associated with kidney function decline. Genetic studies indicated that podocytes influence albuminuria and diabetic kidney disease development. We seek to understand whether podocyte and basement membrane changes correlate with kidney function, degree of albuminuria, and histopathologic features of diabetic nephropathy using electron microscopy and digital light microscopy. Methods: I performed quantitative characterization of podocyte foot process morphology using TRIDENT subject biopsies. Podocyte foot process width (FPW) was measured using electron micrographs in ImageJ and calculated: FPW = (π/4) × (ΣGBM length/Σfoot process). Results: In our cohort, the average FPW was 1.624μm, and the glomerular basement membrane (GBM) average thickness was 773.27μm. The average FPW and GBM thickness ranged from 519μm-4.806μm and 200μm-3230μm per patient, respectively. Using a Pearson’s correlation coefficient: GBM thickness positively correlates with RPS Class (.424240229), %interstitial fibrosis (.203720183), arteriolar hyalinosis (0.307801899), proteinuria (.639114291). Discussion: Podocyte features such as FPW and GBM thickness showed stronger correlation with proteinuria than other parameters. Some samples were collected in patients with advanced DKD; collecting samples earlier in the disease process may represent more accurate correlations between EM findings and disease severity. Overall podocyte structural changes strongly correlate with proteinuria, indicating the key role of podocytes in proteinuria

Content Matters: Neuroimaging Investigation of Brain and Behavioral Impact of Televised Anti-Tobacco Public Service Announcements

Televised public service announcements are video ads that are a key component of public health campaigns against smoking. Understanding the neurophysiological correlates of anti-tobacco ads is an important step toward novel objective methods of their evaluation and design. In the present study, we used functional magnetic resonance imaging (fMRI) to investigate the brain and behavioral effects of the interaction between content ( argument strength, AS) and format ( message sensation value, MSV) of anti-smoking ads in humans. Seventy-one nontreatment-seeking smokers viewed a sequence of 16 high or 16 low AS ads during an fMRI scan. Dependent variables were brain fMRI signal, the immediate recall of the ads, the immediate change in intentions to quit smoking, and the urine levels of a major nicotine metabolite cotinine at a 1 month follow-up. Whole-brain ANOVA revealed that AS and MSV interacted in the inferior frontal, inferior parietal, and fusiform gyri; the precuneus; and the dorsomedial prefrontal cortex (dMPFC). Regression analysis showed that the activation in the dMPFC predicted the urine cotinine levels 1 month later. These results characterize the key brain regions engaged in the processing of persuasive communications and suggest that brain fMRI response to anti-smoking ads could predict subsequent smoking severity in nontreatment-seeking smokers. Our findings demonstrate the importance of the quality of content for objective ad outcomes and suggest that fMRI investigation may aid the prerelease evaluation of televised public health ads

Low Message Sensation Health Promotion Videos Are Better Remembered and Activate Areas of the Brain Associated with Memory Encoding - Table 1

a<p>Location of the clusters and the local maxima of the BOLD fMRI signal change. <i>Z</i>>2.3 cluster corrected at <i>p</i><0.05.</p>b<p>Brodmann area.</p>c<p>Number of voxels.</p>d<p><i>Z</i>-MAX values represent peak activation for the cluster.</p>e<p>Talairach (1988) coordinates.</p>f<p>Hemisphere.</p><p><i>For clarity, clusters with less than 150 voxels are not reported in this table.</i></p><p>Low Message Sensation Health Promotion Videos Are Better Remembered and Activate Areas of the Brain Associated with Memory Encoding - Table 1 </p

Brain response to safe-sex video messages.

<p>Middle temporal gyrus (MTG) and inferior frontal gyri (IFG) (red) have increased response for Low MSV>High MSV items. Occipital cortex (OCC) (blue) has increased response for High MSV>Low MSV ads. Statistical maps are displayed over the Montreal Neurological Institute (MNI) brain template and thresholded at Z = 2.3, cluster-corrected for multiple comparisons at p<0.05. Coordinates converted to Talairach space <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0113256#pone.0113256-Talairach1" target="_blank">[45]</a>.</p

Design of the video message task.

<p>The actual task displays 16 video messages (8 high MSV and 8 low MSV) in pseudorandom order (the order presented above is one possible organization).</p

Urinary Single-Cell Profiling Captures the Cellular Diversity of the Kidney.

BACKGROUND: Microscopic analysis of urine sediment is probably the most commonly used diagnostic procedure in nephrology. The urinary cells, however, have not yet undergone careful unbiased characterization. METHODS: Single-cell transcriptomic analysis was performed on 17 urine samples obtained from five subjects at two different occasions, using both spot and 24-hour urine collection. A pooled urine sample from multiple healthy individuals served as a reference control. In total 23,082 cells were analyzed. Urinary cells were compared with human kidney and human bladder datasets to understand similarities and differences among the observed cell types. RESULTS: Almost all kidney cell types can be identified in urine, such as podocyte, proximal tubule, loop of Henle, and collecting duct, in addition to macrophages, lymphocytes, and bladder cells. The urinary cell-type composition was subject specific and reasonably stable using different collection methods and over time. Urinary cells clustered with kidney and bladder cells, such as urinary podocytes with kidney podocytes, and principal cells of the kidney and urine, indicating their similarities in gene expression. CONCLUSIONS: A reference dataset for cells in human urine was generated. Single-cell transcriptomics enables detection and quantification of almost all types of cells in the kidney and urinary tract