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Jinghui Zhang, Kelly McCastlain, Hiroki Yoshihara, Beisi Xu, Yunchao Chang, Michelle L Churchman, Gang Wu, Yongjin Li, Lei Wei, Ilaria Iacobucci, Yu Liu, Chunxu Qu, Ji Wen, Michael Edmonson, Debbie Payne-Turner, Kerstin B Kaufmann, Shin-Ichiro Takayanagi, Erno Wienholds, Esmé Waanders, Panagiotis Ntziachristos, Sofia Bakogianni, Jingjing Wang, Iannis Aifantis, Kathryn G Roberts, Jing Ma, Guangchun Song, John Easton, Heather L Mulder, Xiang Chen, Scott Newman, Xiaotu Ma, Michael Rusch, Pankaj Gupta, Kristy Boggs, Bhavin Vadodaria, James Dalton, Yanling Liu, Marcus L Valentine, Li Ding, Charles Lu, Robert S Fulton, Lucinda Fulton, Yashodhan Tabib, Kerri Ochoa, Meenakshi Devidas, Deqing Pei, Cheng Cheng, Jun Yang, William E Evans, Mary V Relling, Ching-Hon Pui, Sima Jeha, Richard C Harvey, I-Ming L Chen, Cheryl L Willman, Guido Marcucci, Clara D Bloomfield, Jessica Kohlschmidt, Krzysztof Mrózek, Elisabeth Paietta, Martin S Tallman, Wendy Stock, Matthew C Foster, Janis Racevskis, Jacob M Rowe, Selina Luger, Steven M Kornblau, Sheila A Shurtleff, Susana C Raimondi, Elaine R Mardis, Richard K Wilson, John E Dick, Stephen P Hunger, Mignon L Loh, James R Downing, Charles G Mullighan
Chromosomal rearrangements deregulating hematopoietic transcription factors are common in acute lymphoblastic leukemia (ALL). Here we show that deregulation of the homeobox transcription factor gene DUX4 and the ETS transcription factor gene ERG is a hallmark of a subtype of B-progenitor ALL that comprises up to 7% of B-ALL. DUX4 rearrangement and overexpression was present in all cases and was accompanied by transcriptional deregulation of ERG, expression of a novel ERG isoform, ERGalt, and frequent ERG deletion...
October 24, 2016: Nature Genetics
Hsin-Hua Liu, Zheng He, Christine T O Nguyen, Algis J Vingrys, Bang V Bui
PURPOSE: This pilot study considered whether intraocular pressure (IOP) lowering could reverse ganglion cell dysfunction in a rat model of chronic ocular hypertension. METHODS: A circumlimbal suture was applied in one eye to induce ocular hypertension (n = 7) in Long-Evans rats. The contralateral eye served as an untreated control. After 8 weeks of IOP elevation the suture was removed to lower IOP for the remaining 7 weeks. Electroretinogram (ERG) and optical coherence tomography (OCT) were measured at baseline, 2, 4, 8, 12 and 15 weeks...
October 24, 2016: Ophthalmic & Physiological Optics: the Journal of the British College of Ophthalmic Opticians (Optometrists)
Ewa Langwinska-Wosko, Marta Skowronska, Tomasz Kmiec, Anna Czlonkowska
BACKGROUND: Mitochondrial membrane protein-associated neurodegeneration (MPAN) is an neurodegeneration with brain iron accumulation (NBIA) subtype with mutation of C19orf12. Optic atrophy is one of the core symptoms in almost all MPAN cases, but the detailed ophthalmologic features of MPAN patients have not yet been described. METHODS: All consecutive symptomatic, gene proven MPAN patients underwent a detailed ophthalmological examination: best corrected visual acuity (BCVA), slit lamp examination, dilated fundus examination, tonometry, optical coherent tomography (OCT) and electrophysiological examinations...
November 15, 2016: Journal of the Neurological Sciences
Adriana C Vidal, Stephen J Freedland
CONTEXT: In 2012, we published a detailed review on obesity and prostate cancer. Since then, new studies have brought further understanding regarding the role of obesity in selecting active surveillance candidates, and differing associations between obesity and prostate cancer as a function of race and molecular subtype of prostate cancer. OBJECTIVE: To review new manuscripts on these new concepts for which there were limited data before 2012. EVIDENCE ACQUISITION: A PubMed search from July 2012 to March 2016 was performed using the terms "prostate cancer" and "obesity"...
October 19, 2016: European Urology
Benjamin Kearns, Abdullah Pandor, Matt Stevenson, Jean Hamilton, Duncan Chambers, Mark Clowes, John Graham, M Satish Kumar
As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the company that manufactures cabazitaxel (Jevtana(®), Sanofi, UK) to submit evidence for the clinical and cost effectiveness of cabazitaxel for treatment of patients with metastatic hormone-relapsed prostate cancer (mHRPC) previously treated with a docetaxel-containing regimen. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG)...
October 22, 2016: PharmacoEconomics
Ester Fernandez-Salas, Shaomeng Wang, Arul M Chinnaiyan
Castration resistant prostate cancer (CRPC) is a deadly disease with few therapeutic options once patients become resistant to second generation drugs targeting the AR-transcriptional program. The BET-BRD readers of chromatin are key regulators of AR-, ERG-, and c-Myc-mediated transcription in CRPC. BET-BRD inhibitors have demonstrated pre-clinical efficacy in models of CRPC and are currently being evaluated in several clinical trials. These novel drugs have the potential to transform the way we treat CRPC in the near future...
March 2016: Drug Discovery Today. Technologies
Jimmy A Irwin, W Peter Maksym, Gregory R Sivakoff, Aaron J Romanowsky, Dacheng Lin, Tyler Speegle, Ian Prado, David Mildebrath, Jay Strader, Jifeng Liu, Jon M Miller
A flaring X-ray source was found near the galaxy NGC 4697 (ref. 1). Two brief flares were seen, separated by four years. During each flare, the flux increased by a factor of 90 on a timescale of about one minute. There is no associated optical source at the position of the flares, but if the source was at the distance of NGC 4697, then the luminosities of the flares were greater than 10(39) erg per second. Here we report the results of a search of archival X-ray data for 70 nearby galaxies looking for similar flares...
October 19, 2016: Nature
Soumyarwit Manna, James J Augsburger, Zelia M Correa, Marwan F Al-Rjoub, Marepalli B Rao, Rupak K Banerjee
PURPOSE: The purpose of this study is to noninvasively evaluate the safety and toxicity of a chitosan (CS) and polylactic acid (PLA)-based sustained-release methotrexate (MTX) intravitreal microimplant in normal rabbit eyes using electroretinography (ERG). METHODS: PLA-coated CS-based microimplants containing 400 μg of MTX and placebo microimplants (without drug) were surgically implanted in the vitreous of the right and the left eyes, respectively, in each of the 8 New Zealand rabbits using minimally invasive technique...
October 18, 2016: Journal of Ocular Pharmacology and Therapeutics
Yuan Ma, Xiangxian Feng, Jing Zhang, Haijun Wang, Jianhui Yuan, Zhifang Li, Yanbo Han, Jianbin Zhang, Feng J He, Graham MacGregor, Yangfeng Wu
OBJECTIVE: To identify the social determinants shaping children's behaviour on salt reduction from a network perspective. DESIGN AND METHOD: School-EduSalt is a cluster-randomized controlled trial carried out in 28 primary schools in northern China involving 279 families (279 children aged 10.1 ± 0.5yrs and 553 adults). A 3.5-month education on salt reduction was delivered to the 14 schools (classes) in the intervention group, of which children and their families achieved a significant reduction in salt intake as measured by 24-hour urine sodium...
September 2016: Journal of Hypertension
Nobuhiro Nagai, Satoru Iwata, Hirokazu Kaji, Kaori Sampei, Yuki Katsukura, Hideyuki Onami, Matsuhiko Nishizawa, Toru Nakazawa, Yukihiko Mashima, Toshiaki Abe
It has been suggested that unoprostone isopropyl (UNO) has potent neuroprotective activity in the retina. The effect of sustained transscleral UNO delivery to the posterior segment of the eye on photoreceptor degeneration was evaluated. UNO was loaded into a device made of poly(ethyleneglycol) dimethacrylate by polydimethylsiloxane mold-based UV-curing. The amount of UNO diffusing from these devices was measured using high-performance liquid chromatography. The polymeric devices that released UNO at 1.8 μg/day were implanted on the sclerae of S334ter rats at postnatal 21 days, and electroretinograms (ERGs) were compared with those of topical application and placebo devices...
November 2016: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
Milan S Geybels, Karen D McCloskey, Ian G Mills, Janet L Stanford
BACKGROUND: Calcium channel blockers (CCBs) may affect prostate cancer (PCa) growth by various mechanisms including those related to androgens. The fusion of the androgen-regulated gene TMPRSS2 and the oncogene ERG (TMPRSS2:ERG or T2E) is common in PCa, and prostate tumors that harbor the gene fusion are believed to represent a distinct disease subtype. We studied the association of CCB use with the risk of PCa, and molecular subtypes of PCa defined by T2E status. METHODS: Participants were residents of King County, Washington, recruited for population-based case-control studies (1993-1996 or 2002-2005)...
October 18, 2016: Prostate
Irina A Tikhonova, Martin W Hoyle, Tristan M Snowsill, Chris Cooper, Joanna L Varley-Campbell, Claudius E Rudin, Ruben E Mujica Mota
The National Institute for Health and Care Excellence (NICE) invited the manufacturer of azacitidine (Celgene) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of acute myeloid leukaemia with more than 30 % bone marrow blasts in adults who are not eligible for haematopoietic stem cell transplantation, as part of the NICE's Single Technology Appraisal process. The Peninsula Technology Assessment Group was commissioned to act as the Evidence Review Group (ERG). The ERG produced a critical review of the evidence contained within the company's submission to NICE...
October 17, 2016: PharmacoEconomics
Tapasi Rana, Pravallika Kotla, Roderick Fullard, Marina Gorbatyuk
Expression of T17M rhodopsin (T17M) in rods activates the Unfolded Protein Response (UPR) and leads to the development of autosomal dominant retinitis pigmentosa (adRP). The rod death occurs in adRP retinas prior to cone photoreceptor death, so the mechanism by which cone photoreceptors die remains unclear. Therefore, the goal of the study was to verify whether UPR in rods induces TNFa-mediated signaling to the cones and to determine whether the TNFa deficit could prevent adRP cone cell death. Primary rod photoreceptors and cone-derived 661W cells transfected with siRNA against TNFa were treated with tunicamycin to mimic activation of UPR in T17M retinas expressing normal and reduced TNFa levels...
October 14, 2016: Biochimica et Biophysica Acta
Reza Ashrafi, Marianne Yon, Lucy Pickavance, Joseph Yanni Gerges, Gershan Davis, John Wilding, Kun Jian, Henggui Zhang, George Hart, Mark Boyett
Introduction. Obesity is increasingly common and is associated with an increased prevalence of cardiac arrhythmias. The aim of this study was to see whether in obesity there is proarrhythmic gene expression of ventricular ion channels and related molecules. Methods and Results. Rats were fed on a high-fat diet and compared to control rats on a normal diet (n = 8). After 8 weeks, rats on the high-fat diet showed significantly greater weight gain and higher adiposity. Left ventricle samples were removed at 8 weeks and mRNA expression of ion channels and other molecules was measured using qPCR...
2016: Journal of Obesity
Frédéric Chamberland, Tristan Maurina, Séverine Degano-Valmary, Thierry Spicarolen, Loïc Chaigneau
Angiosarcomas are one of the rarest subtypes of sarcomas; those are malignant vascular tumors arising from vascular endothelial cells. Occurrence of intra-oral angiosarcoma is extremely rare (0.0077% of all cancers in Europe). We present here, to our knowledge, the first case of a 83-year-old man with gingival and both palatine tonsils localization of a grade-two angiosarcoma discovered after a two months history of a painful lesion followed by hematoma and spontaneous bleeding. Chemotherapy with paclitaxel and hemostatic radiotherapy were inefficient and he died seven months after the first symptoms...
September 5, 2016: Rare Tumors
Laura Contreras, Laura Ramirez, Jianhai Du, James B Hurley, Jorgina Satrústegui, Pedro de la Villa
PURPOSE: To characterize the vision phenotype of mice lacking Aralar/AGC1/Slc25a12, the mitochondrial aspartate-glutamate carrier mutated in global cerebral hypomyelination (OMIM 612949). METHODS: We tested overnight dark-adapted control and aralar-deficient mice for the standard full electroretinogram (ERG) response. The metabolic stress of dark-adaptation was reduced by 5 min illumination after which the ERG response was monitored in darkness. We used the electrical response to two identical saturating light flashes (paired-flash stimulation) to isolate the inner retina and photoreceptor responses...
2016: Molecular Vision
Stephanie Kletke, Vaishnavi Batmanabane, Tianyang Dai, Ajoy Vincent, Shuning Li, Karen A Gordon, Blake C Papsin, Sharon L Cushing, Elise Héon
The co-occurrence of hearing impairment and visual dysfunction is devastating. Most deaf-blind etiologies are genetically determined, the commonest being Usher syndrome (USH). While studies of the congenitally deaf population reveal a variable degree of visual problems, there are no effective ophthalmic screening guidelines. We hypothesized that children with congenital sensorineural hearing loss (SNHL) and vestibular impairment were at an increased risk of having Usher syndrome. A retrospective chart review of 33 cochlear implants recipients for severe to profound SNHL and measured vestibular dysfunction was done to determine the ocular phenotype...
October 15, 2016: Clinical Genetics
Oleksandr N Kryvenko, Sean R Williamson, Kiril Trpkov, Nilesh S Gupta, Daniel Athanazio, Martin K Selig, Paul Taylor Smith, Cristina Magi-Galluzzi, Merce Jorda
Small cell-like change (SCLC) is a rare prostate lesion which has been described in only two previous studies (total of eight cases). Its relation to possible neuroendocrine differentiation remained unclear. We evaluated 11 SCLC cases with immunohistochemistry and electron microscopy. SCLC was characterized by crowded hyperchromatic small nuclei with scant cytoplasm, rosette-like structures, finely granular chromatin with indistinct nucleoli, and lack of mitoses, apoptoses, and necroses. In nine cases, SCLC was admixed with high-grade cancer, and in two cases, it represented a separate intraductal process, spatially remote from a low-volume Gleason score 6 (grade group 1) cancer...
October 14, 2016: Virchows Archiv: An International Journal of Pathology
Sâmia Georgia Dantas Linhares, João Carlos Das-Neves Pereira, Paulo Manuel Pêgo Fernades, José Ribas Milanez de Campos
PURPOSE: The aim of this study was to compare the functional exercise capacity and the lung function among patients undergoing early rehabilitation with those submitted to the conventional care after pectus excavatum repair using the Nuss procedure. METHOD: Patients were randomly allocated to the early rehabilitation group (ERG) who started rehabilitation after surgery and the group of the conventional care (CG) received routine care of the institution. They were evaluated before surgery (preoperative) and in hospital discharge day (postoperative)...
October 13, 2016: Pediatric Surgery International
Kuo-Cheng Huang, Andrew Evans, Bryan Donnelly, Tarek A Bismar
SPINK1 is proposed as potential prognostic marker in prostate cancer (PCA). However, its relation to PTEN and ERG in localized PCA remains unclear. The study population consisted of two independent cohorts of men treated by radical prostatectomy for localized PCA (discovery n = 218 and validation n = 129). Patterns of association between SPINK1 and each of ERG and PTEN were evaluated by immunohistochemistry and fluorescence in situ hybridization. Associations between SPINK1 expression and various pathologic parameters and clinical outcome were also investigated...
October 13, 2016: Pathology Oncology Research: POR
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