Born with a solitary kidney: at risk of hypertension

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Failure to thrive in children with tubulopathies increases the risk of overweight later in life

: Failure to thrive (FTT) is an inadequate growth in young children. It can increase the risk of overweight or obesity later in life. Patients with renal tubulopathies can present FTT due to solute losses in the urine. We aimed to test our hypothesis that children with tubulopathies have an increased risk of overweight and obesity due to rebound following FTT that could complicate these conditions. We enrolled 26 patients with tubulopathies and evaluated for the first time within the first 12 months of life (mean age: 4.8 months ± 2.6 SDS). FTT was evident in 17 out of 26 patients (65.4%). The mean age at the last follow-up was 14.1 years ± 5.5 SDS. The mean age at overweight/obesity onset was 9.0 years ± 3.6 SDS. The prevalence of overweight/obesity was 73.1% (19/26). Among the patients with FTT, 15 (88.2%) developed overweight/obesity compared to 4 out of the 9 patients (44.4%) without FFT (p = 0.028). The presence of FTT determined an OR for obesity/overweight of 9.4 (95% CI: 1.3-67.6; p = 0.026). FTT continued to be significantly associated with obesity/overweight also after adjustment for preterm birth and birth weight <10th percentile (OR = 23.3; 95% CI: 1.95-279.4; p = 0.01). In conclusion, in our series, patients with tubulopathies presented an increased risk of overweight/obesity due to the FTT that can complicate these conditions

Image-Assisted Microvessel-on-a-Chip Platform for Studying Cancer Cell Transendothelial Migration Dynamics.

With the push to reduce in vivo approaches, the demand for microphysiological models that recapitulate the in vivo settings in vitro is dramatically increasing. Here, we present an extracellular matrix-integrated microfluidic chip with a rounded microvessel of ~100 µm in diameter. Our system displays favorable characteristics for broad user adaptation: simplified procedure for vessel creation, minimised use of reagents and cells, and the ability to couple live-cell imaging and image analysis to study dynamics of cell-microenvironment interactions in 3D. Using this platform, the dynamic process of single breast cancer cells (LM2-4175) exiting the vessel lumen into the surrounding extracellular matrix was tracked. Here, we show that the presence of endothelial lining significantly reduced the cancer exit events over the 15-hour imaging period: there were either no cancer cells exiting, or the fraction of spontaneous exits was positively correlated with the number of cancer cells in proximity to the endothelial barrier. The capability to map the z-position of individual cancer cells within a 3D vessel lumen enabled us to observe cancer cell transmigration 'hot spot' dynamically. We also suggest the variations in the microvessel qualities may lead to the two distinct types of cancer transmigration behaviour. Our findings provide a tractable in vitro model applicable to other areas of microvascular research

Effect of ROCK inhibition studied by single cell morphological statistics.

<p>(a),(b),(k)&(l) Histograms of frequency distribution of cell orientation for untreated cells on NFES gelatin patterns (NF-0), ROCK-inhibited cells on NFES gelatin patterns (NF-I(5 M)), untreated cells on PDMS (PDMS-0), and ROCK inhibited cells on PDMS (PDMS-I(5 M)). (c),(f),(g)&(j) The corresponding histograms of frequency distribution of cell perimeters. (d,e,h,i) The corresponding scatter plots of the cell perimeter <i>vs</i> cell orientation.</p

Dependence of cell morphology w.r.t. H1152 concentration.

<p>(a–d) Scatter plots of cell perimeter <i>vs.</i> orientation for ECs subject to no ROCK inhibition, and H1152 concentration at 2.5 M, 25 M, and 50 M respectively. (e–h) Scatter plots of cell perimeter <i>vs.</i> area for ECs subjected to the same treatment.</p

Versatile gelatin fibril patterns can be formed by near-field electrospinning over a large area.

<p>(a) Scheme of the NFES patterning process. (b) A 2 inch PDMS sheet containing arrays of gelatin patterns. (c)–(e) Confocal images of fibril patterns with bead-on-strings, coils, and uniform straight fibrils respectively. (f)–(h) Scanning electron micrographs showing typical regions of the fibril patterns illustrated in (c)–(e).</p

Physical and chemical properties of gelatin fibrils.

<p>(a) FTIR spectra of as-received gelatin powder (P), a cast gelatin film (F), the crosslinked gelatin film (Fx), NFES gelatin fibrils (NF), crosslinked NFES gelatin fibrils (NFx), and crosslinked gelatin films post cell culturing for 18 hrs (Fx(C18)). (b) AFM profiles of a crosslinked gelatin fibril before being immersed in water (left), and after being immersed in water for 24 hrs and dried (right). (c) Cross-sectional profile of the fibrils presented in (b). (d) In-situ AFM imaging of a hydrated gelatin fibril. (e) Young's modulus mapping of a central fibril region. (f) Histogram showing the range of Young's modulus values for the gelatin fibril and PDMS respectively.</p

Fibril assay elucidating the drug effectiveness of H1152.

<p>Plot of and <i>Orientation Deviation</i> w.r.t. H1152 concentration for the ECs interfaced with the gelatin fibril assay. Immunofluorescence images for the selected inhibition experiments are included as examples.</p

Solution properties controls global fibril morphology.

<p>Different solution properties are plotted against the total acid-acyl contents (A.A.E.A.) for (a) conductivity, (b) pH, and (c) surface tension. The approximate regimes of fibril morphology are highlighted in each graph. For (b) and (c), a pair of blue lines are drawn to enclose the range of conditions which resulted in the formation of straight fibers. It is to note that for G10-A70, the A.A.∶E.A. ratios of 1, 1.5 and 4 were tested, and this can be seen as the increase in conductivity in (a).</p

Expanding Phenotype of Schimke Immuno-Osseous Dysplasia: Congenital Anomalies of the Kidneys and of the Urinary Tract and Alteration of NK Cells

Schimke immuno-osseous dysplasia (SIOD) is a rare multisystemic disorder with a variable clinical expressivity caused by biallelic variants in SMARCAL1. A phenotype-genotype correlation has been attempted and variable expressivity of biallelic SMARCAL1 variants may be associated with environmental and genetic disturbances of gene expression. We describe two siblings born from consanguineous parents with a diagnosis of SIOD revealed by whole exome sequencing (WES). Results: A homozygous missense variant in the SMARCAL1 gene (c.1682G>A; p.Arg561His) was identified in both patients. Despite carrying the same variant, the two patients showed substantial renal and immunological phenotypic differences. We describe features not previously associated with SIOD-both patients had congenital anomalies of the kidneys and of the urinary tract and one of them succumbed to a classical type congenital mesoblastic nephroma. We performed an extensive characterization of the immunophenotype showing combined immunodeficiency characterized by a profound lymphopenia, lack of thymic output, defective IL-7R alpha expression, and disturbed B plasma cells differentiation and immunoglobulin production in addition to an altered NK-cell phenotype and function. Conclusions: Overall, our results contribute to extending the phenotypic spectrum of features associated with SMARCAL1 mutations and to better characterizing the underlying immunologic disorder with critical implications for therapeutic and management strategies