Neighborhood Social Context and Kidney Function Over Time: The Multi-Ethnic Study of Atherosclerosis

Although socioeconomic status has been associated with chronic kidney disease (CKD), little is known about its relationship to residential neighborhood context.

http://bit.ly/2Cl6Vgx

Cancers, Vol. 11, Pages 84: Macrovascular Networks on Contrast-Enhanced Magnetic Resonance Imaging Improves Survival Prediction in Newly Diagnosed Glioblastoma

Cancers, Vol. 11, Pages 84: Macrovascular Networks on Contrast-Enhanced Magnetic Resonance Imaging Improves Survival Prediction in Newly Diagnosed Glioblastoma

Cancers doi: 10.3390/cancers11010084

Authors: Josep Puig Carles Biarnés Pepus Daunis-i-Estadella Gerard Blasco Alfredo Gimeno Marco Essig Carme Balaña Angel Alberich-Bayarri Ana Jimenez-Pastor Eduardo Camacho Santiago Thio-Henestrosa Jaume Capellades Javier Sanchez-Gonzalez Marian Navas-Martí Blanca Domenech-Ximenos Sonia Del Barco Montserrat Puigdemont Carlos Leiva-Salinas Max Wintermark Kambiz Nael Rajan Jain Salvador Pedraza

A higher degree of angiogenesis is associated with shortened survival in glioblastoma. Feasible morphometric parameters for analyzing vascular networks in brain tumors in clinical practice are lacking. We investigated whether the macrovascular network classified by the number of vessel-like structures (nVS) visible on three-dimensional T1-weighted contrast–enhanced (3D-T1CE) magnetic resonance imaging (MRI) could improve survival prediction models for newly diagnosed glioblastoma based on clinical and other imaging features. Ninety-seven consecutive patients (62 men; mean age, 58 ± 15 years) with histologically proven glioblastoma underwent 1.5T-MRI, including anatomical, diffusion-weighted, dynamic susceptibility contrast perfusion, and 3D-T1CE sequences after 0.1 mmol/kg gadobutrol. We assessed nVS related to the tumor on 1-mm isovoxel 3D-T1CE images, and relative cerebral blood volume, relative cerebral flow volume (rCBF), delay mean time, and apparent diffusion coefficient in volumes of interest for contrast-enhancing lesion (CEL), non-CEL, and contralateral normal-appearing white matter. We also assessed Visually Accessible Rembrandt Images scoring system features. We used ROC curves to determine the cutoff for nVS and univariate and multivariate cox proportional hazards regression for overall survival. Prognostic factors were evaluated by Kaplan-Meier survival and ROC analyses. Lesions with nVS > 5 were classified as having highly developed macrovascular network; 58 (60.4%) tumors had highly developed macrovascular network. Patients with highly developed macrovascular network were older, had higher volumeCEL, increased rCBFCEL, and poor survival; nVS correlated negatively with survival (r = −0.286; p = 0.008). On multivariate analysis, standard treatment, age at diagnosis, and macrovascular network best predicted survival at 1 year (AUC 0.901, 83.3% sensitivity, 93.3% specificity, 96.2% PPV, 73.7% NPV). Contrast-enhanced MRI macrovascular network improves survival prediction in newly diagnosed glioblastoma.

http://bit.ly/2AKcvsR

Ultraspiracle-independent anti-apoptotic function of ecdysone receptors is required for the survival of larval peptidergic neurons via suppression of grim expression in Drosophila melanogaster

Abstract

In Drosophila melanogaster a significant number of heterogenous larval neurons in the central nervous system undergo metamorphosis-associated programmed cell death, termed metamorphoptosis. Interestingly distinct groups of doomed larval neurons are eliminated at different metamorphic phases. Although ecdysone hormonal signaling via nuclear ecdysone receptors (EcRs) is known to orchestrate the neuronal metamorphoptosis, little is known about how this signaling controls such diverse neuronal responses. Crustacean cardioactive peptide (CCAP)-producing neurons in the ventral nerve cord are developmentally programmed to die shortly after adult emergence. In this study, we show that disruption of endogenous EcR function by ectopic expression of dominant negative forms of EcRs (EcR^DN) causes premature death of larval CCAP neurons in a caspase-dependent manner. This event is rescued by co-expression of individual EcR isoforms. Furthermore, larval CCAP neurons are largely normal in ecr mutants lacking either EcR-A or EcR-B isoforms, suggesting that EcR isoforms redundantly function to protect larval CCAP neurons. Of surprise, a role of Ultraspiracle (Usp), a canonical partner of EcR, is dispensable in the protection of CCAP neurons, whereas both EcR and Usp are required for inducing metamorphoptosis of vCrz neurons shortly after prepupal formation. As a downstream, grim is an essential cell death gene for the EcR^DN-mediated CCAP neuronal death, while either hid or rpr function is dispensable. Together, our results suggest that Usp-independent EcR actions protect CCAP neurons from their premature death by repressing grim expression until their normally scheduled apoptosis at post-emergence. Our studies highlight two opposite roles played by EcR function for metamorphoptosis of two different peptidergic neuronal groups, proapoptotic (vCrz) versus antiapoptotic (CCAP), and propose that distinct death timings of doomed larval neurons are determined by differential signaling mechanisms involving EcR.

http://bit.ly/2CjiZio

3D Electrophysiological Measurements on Cells Embedded within Fiber‐Reinforced Matrigel

Melt electrowriting of scaffolds is used to reinforce Matrigel and allow 3D electrophysiology on transfected fibroblast cells. A square pore spacing of 200 µm allows proper cell growth, handling during cell staining, and good cell accessibility by the recording electrode. This approach provides a fundamental milestone to further develop electrophysiology in 3D neuronal networks.

Abstract

2D electrophysiology is often used to determine the electrical properties of neurons. In the brain however, neurons form extensive 3D networks. Thus, performing electrophysiology in a 3D environment provides a closer situation to the physiological condition and serves as a useful tool for various applications in the field of neuroscience. In this study, 3D electrophysiology is established within a fiber‐reinforced matrix to enable fast readouts from transfected cells, which are often used as model systems for 2D electrophysiology. Using melt electrowriting (MEW) of scaffolds to reinforce Matrigel, 3D electrophysiology is performed on a glycine receptor‐transfected Ltk‐11 mouse fibroblast cell line. The glycine receptor is an inhibitory ion channel associated when mutated with impaired neuromotor behavior. The average thickness of the MEW scaffold is 141.4 ± 5.7 µm, using 9.7 ± 0.2 µm diameter fibers, and square pore spacings of 100, 200, and 400 µm. For the first time, the electrophysiological characterization of glycine receptor‐transfected cells is demonstrated with respect to agonist efficacy and potency in a 3D matrix. With the MEW scaffold reinforcement not interfering with the electrophysiological measurement, this approach can now be further adapted and developed for different kinds of neuronal cultures to study and understand pathological mechanisms under disease conditions.

http://bit.ly/2D7XMJD

Oncocytic poorly differentiated (insular) thyroid carcinoma mimicking metastatic adenocarcinoma. A case report and review of the literature

Abstract

We report the cytohistologic and immunohistochemical findings of an oncocytic variant of poorly differentiated thyroid carcinoma in a 76‐year old man with a prior history of prostatic adenocarcinoma. The man complained of a palpable nodule in the right thyroid lobe and cervical lymph node. Fine‐needle aspiration (FNA) in both cases yielded solid clusters of cells/insulae, microfollicles, and isolated atypical cells. Considering the patient's past history, an initial diagnosis of metastasis from prostate adenocarcinoma was considered. However, immunohistochemical staining of liquid‐based cytology specimens (Thin‐Prep) showed diffuse positive results for TTF‐1 and thyroglobulin. The patient underwent total thyroidectomy with bilateral neck dissection. Histologic and immunohistochemical evaluation showed a poorly differentiated oncocytic thyroid carcinoma with lymphovascular invasion and lymph node metastases. To our knowledge, this is the first description of the immunocytochemical evaluation of this rare variant of poorly differentiated thyroid carcinoma using FNA and liquid based cytology.

http://bit.ly/2THWuKS

Erratum to: Development and validation of the Charcot-Marie-Tooth Disease Infant Scale

Melissa R. Mandarakas, Manoj P. Menezes, Kristy J. Rose, Rosemary Shy, Kate Eichinger, Maria Foscan, Timothy Estilow, Rachel Kennedy, Karen Herbert, Paula Bray, Kathryn Refshauge, Monique M. Ryan, Eppie M. Yiu, Michelle Farrar, Hugo Sampaio, Isabella Moroni, Emanuela Pagliano, Davide Pareyson, Sabrina W. Yum, David N. Herrmann, Gyula Acsadi, Michael E. Shy, Joshua Burns and Oranee Sanmaneechai for the Inherited Neuropathies Consortium. Development and validation of the Charcot-Marie-Tooth Disease Infant Scale. Brain 2018; 141: 3319–3330; doi:10.1093/brain/awy280.

http://bit.ly/2QItHnv

A biallelic mutation links MYORG to autosomal-recessive primary familial brain calcification

Sir,

http://bit.ly/2VNIpNU