Histopathologic Analysis of Lung Cancer Incidence Associated with Radon Exposure among Ontario Uranium Miners

Although radon is a well-established contributor to lung cancer mortality among uranium miners, the effects of radon decay products on different histopathologies of lung carcinoma are not well established. Using a retrospective cohort design, this study aims to examine the risks of lung cancer by histological subtypes associated with exposure to radon decay products among the Ontario Uranium Miners cohort. Cases were stratified by histological groups, and associated risks were estimated for cumulative radon exposure after adjustment for attained age and calendar period. Between 1969 and 2005, 1274 incident cases of primary lung cancer were identified. Of these, 1256 diagnoses (99%) contained information on histology. Squamous cell carcinoma was most common (31%), followed by adenocarcinoma (20%), large cells (18%), small cell lung carcinoma (14%), and other or unspecified cell types (17%). Of the histological sub-groups, small cell lung carcin

Angiomatous meningiomas have a distinct genetic profile with multiple chromosomal polysomies including polysomy of chromosome 5

Meningiomas are a diverse group of tumors with a broad spectrum of histologic features. There are over 12 variants of meningioma, whose genetic features are just beginning to be described. Angiomatous meningioma is a World Health Organization (WHO) meningioma variant with a predominance of blood vessels. They are uncommon and confirming the histopathologic classification can be challenging. Given a lack of biomarkers that define the angiomatous subtype and limited understanding of the genetic changes underlying its tumorigenesis, we compared the genomic characteristics of angiomatous meningioma to more common meningioma subtypes. While typical grade I meningiomas demonstrate monosomy of chromosome 22 or lack copy number aberrations, 13 of 14 cases of angiomatous meningioma demonstrated a distinct copy number profile – polysomies of at least one chromosome, but often of many, especially in chromosomes 5, 13, and 20. WHO grade II atypical meningiomas with angiomatous features have both polysomies and genetic aberrations characteristic of other atypical meningiomas. Sequencing of over 560 cancer-relevant genes in 16 cases of angiomatous meningioma showed that these tumors lack common mutations found in other variants of meningioma. Our study demonstrates that angiomatous meningiomas have distinct genomic features that may be clinically useful for their diagnosis

Myeloid-derived miR-223 regulates intestinal inflammation via repression of the NLRP3 inflammasome

MicroRNA (miRNA)-mediated RNA interference regulates many immune processes, but how miRNA circuits orchestrate aberrant intestinal inflammation during inflammatory bowel disease (IBD) is poorly defined. Here, we report that miR-223 limits intestinal inflammation by constraining the nlrp3 inflammasome. miR-223 was increased in intestinal biopsies from patients with active IBD and in preclinical models of intestinal inflammation. miR-223-/y mice presented with exacerbated myeloid-driven experimental colitis with heightened clinical, histopathological, and cytokine readouts. Mechanistically, enhanced NLRP3 inflammasome expression with elevated IL-1β was a predominant feature during the initiation of colitis with miR-223 deficiency. Depletion of CCR2+ inflammatory monocytes and pharmacologic blockade of IL-1β or NLRP3 abrogated this phenotype. Generation of a novel mouse line, with deletion of the miR-223 binding site in the NLRP3 3′ untranslated region, phenocopied the characteristics of miR-223-/y mice. Finally, nanoparticle-mediated overexpression of miR-223 attenuated experimental colitis, NLRP3 levels, and IL-1β release. Collectively, our data reveal a previously unappreciated role for miR-223 in regulating the innate immune response during intestinal inflammation

Rethinking place-making: aligning placeness factors with perceived urban design qualities (PUDQs) to improve the built environment in historical district

Understanding the concept of place is critically important for urban design and place-making practice, and this research attempted to investigate the pathways by which perceived urban design qualities (PUDQs) influence placeness factors in the Chinese context. Twelve hypotheses were developed and combined in a structural equation model for validation. The Tanhualin historical district in Wuhan, China was selected for the analysis. As a result, place attachment was verified as a critical bridge factor that mediated the influence of PUDQs on place satisfaction. Among the five selected PUDQs, walkability and space quality were revealed as the most influential factors associated with place attachment and place satisfaction. Accessibility was actually indirectly beneficial to place-making via the mediation of walkability. Corresponding implications and strategies were discussed to maintain the sense of place for historic districts

Risk of iatrogenic peripheral retinal breaks in 20-G pars plana vitrectomy.

PURPOSE: To estimate the frequency and risk factors for entry site and other peripheral iatrogenic retinal breaks in eyes undergoing standard 20-G 3-port pars plana vitrectomy. DESIGN: Single-center, retrospective, interventional case series. PARTICIPANTS: A total of 645 eyes undergoing pars plana vitrectomy at Moorfields Eye Hospital during the period June 1, 2005, to June 1, 2006, for indications excluding rhegmatogenous retinal detachment. METHODS: Case note review. Exclusion criteria were preexisting retinal breaks or rhegmatogenous retinal detachment, previously vitrectomized eyes, and iatrogenic breaks posterior to the equator. MAIN OUTCOME MEASURES: Frequency, anatomic location, and risk factors associated with iatrogenic peripheral retinal breaks and rate of postoperative rhegmatogenous retinal detachment. RESULTS: Iatrogenic peripheral retinal breaks occurred in 98 of 645 eyes (15.2%) intraoperatively. Eleven of 645 cases (1.7%) experienced postoperative rhegmatogenous retinal detachment caused by undetected or new peripheral retinal breaks. Breaks were most common during surgery for tractional retinal detachment (22.2%), macular hole (18.1%), dislocated intraocular lens implants (16.7%), and epiretinal membrane (13.9%). Overall, breaks were more common in the superior retina (P<0.01), with 41.5% occurring in the 10 and 2 o'clock positions. Eyes requiring surgical induction of a posterior vitreous detachment had 2.9 times greater odds of developing iatrogenic peripheral retinal breaks (95% confidence interval, 1.8-4.7, P<0.001) than eyes with preexisting posterior vitreous detachment. Similarly, phakic eyes had 2.4 times higher odds (95% confidence interval, 1.42-3.96, P = 0.001) of break formation. CONCLUSIONS: Iatrogenic peripheral retinal breaks caused by vitrectomy are more common than previously indicated. Approximately 4 in 10 breaks are related to traction at sclerotomy entry sites. Eyes undergoing surgery for tractional retinal detachment seemed to have the highest risk for break formation. Similarly, phakic eyes and eyes that require induction of a posterior vitreous detachment have more than double the risk for break formation

Histopathologic Analysis of Lung Cancer Incidence Associated with Radon Exposure among Ontario Uranium Miners

Although radon is a well-established contributor to lung cancer mortality among uranium miners, the effects of radon decay products on different histopathologies of lung carcinoma are not well established. Using a retrospective cohort design, this study aims to examine the risks of lung cancer by histological subtypes associated with exposure to radon decay products among the Ontario Uranium Miners cohort. Cases were stratified by histological groups, and associated risks were estimated for cumulative radon exposure after adjustment for attained age and calendar period. Between 1969 and 2005, 1274 incident cases of primary lung cancer were identified. Of these, 1256 diagnoses (99%) contained information on histology. Squamous cell carcinoma was most common (31%), followed by adenocarcinoma (20%), large cells (18%), small cell lung carcinoma (14%), and other or unspecified cell types (17%). Of the histological sub-groups, small cell lung carcinoma had the strongest association with cumulative radon exposure; compared to the reference group (&lt;1 cumulative working level months (WLM)), the highest exposure category (&gt;60 cumulative WLM) had a relative risk (RR) of 2.76 (95% CI: 1.67&#8315;4.57). Adenocarcinoma had the lowest risk and was not significantly associated with exposure to radon decay products (RR = 1.49, 95% CI: 0.96&#8315;2.31). An increasing, linear trend in relative risk was noted with increasing cumulative WLM across small cell, squamous cell, and large cell lung carcinomas (Ptrend &lt; 0.05). Similarly, the excess relative risk (ERR) per WLM was highest for small cell lung carcinoma (ERR/WLM = 0.15, p &lt; 0.01), followed by squamous cell carcinoma (ERR/WLM = 0.12, p &lt; 0.01). Non-statistically significant excess risk was observed for adenocarcinoma (ERR/WLM = 0.004, p = 0.07). Our analysis of the Ontario Uranium Miners cohort data shows differences in the magnitude of the risks across four histological subtypes of lung carcinoma; the strongest association was noted for small cell lung carcinoma, followed by squamous cell, large cell, and lastly adenocarcinoma, which showed no significant associations with exposure to radon decay products

Anti-inflammatory effect of Heliotropium indicum Linn on lipopolysaccharide-induced uveitis in New Zealand white rabbits

AIM: To investigate the anti-inflammatory effect of an aqueous whole plant extract of Heliotropium indicum (HIE) on endotoxin-induced uveitis in New Zealand white rabbits. METHODS: Clinical signs of uveitis including flares, iris hyperemia and miosis, were sought for and scored in 1.0 mg/kg lipopolysaccharide (LPS) -induced uveitic rabbits treated orally with HIE (30-300 mg/kg), prednisolone (30 mg/kg), or normal saline (10 mL/kg). The number of polymorphonuclear neutrophils infiltrating, the protein concentration, as well as levels of tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2), and monocyte chemmoattrant protein-1 (MCP-1) in the aqueous humor after the various treatments were also determined. A histopathological study of the anterior uveal was performed. RESULTS: The extract and prednisolone-treatment significantly reduced (P≤0.001) both the clinical scores of inflammation (1.0-1.8 compared to 4.40±0.40 in the normal saline-treated rabbits) and inflammatory cells infiltration. The level of protein, and the concentrations of TNF-α, PGE2 and MCP-1 in the aqueous humor were also significantly reduced (P≤0.001). Histopathological studies showed normal uveal morphology in the HIE and prednisolone-treated rabbits while normal saline-treated rabbits showed marked infiltration of inflammatory cells. CONCLUSION: The HIE exhibits anti-inflammatory effect on LPS-induced uveitis possibly by reducing the production of pro-inflammatory mediators

Residual Convolutional Neural Network for the Determination of IDH Status in Low- and High-Grade Gliomas from MR Imaging

Purpose: Isocitrate dehydrogenase (IDH) mutations in glioma patients confer longer survival and may guide treatment decision making. We aimed to predict the IDH status of gliomas from MR imaging by applying a residual convolutional neural network to preoperative radiographic data.Experimental Design: Preoperative imaging was acquired for 201 patients from the Hospital of University of Pennsylvania (HUP), 157 patients from Brigham and Women's Hospital (BWH), and 138 patients from The Cancer Imaging Archive (TCIA) and divided into training, validation, and testing sets. We trained a residual convolutional neural network for each MR sequence (FLAIR, T2, T1 precontrast, and T1 postcontrast) and built a predictive model from the outputs. To increase the size of the training set and prevent overfitting, we augmented the training set images by introducing random rotations, translations, flips, shearing, and zooming.Results: With our neural network model, we achieved IDH prediction accuracies of 82.8% (AUC = 0.90), 83.0% (AUC = 0.93), and 85.7% (AUC = 0.94) within training, validation, and testing sets, respectively. When age at diagnosis was incorporated into the model, the training, validation, and testing accuracies increased to 87.3% (AUC = 0.93), 87.6% (AUC = 0.95), and 89.1% (AUC = 0.95), respectively.Conclusions: We developed a deep learning technique to noninvasively predict IDH genotype in grade II-IV glioma using conventional MR imaging using a multi-institutional data set. (C) 2017 AACR