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Michelle J Wilkinson, Henry G Smith, Gráinne McEntee, Joan Kyula-Currie, Tim D Pencavel, David C Mansfield, Aadil A Khan, Victoria Roulstone, Andrew J Hayes, Kevin J Harrington
Advanced extremity melanoma and sarcoma present a significant therapeutic challenge, requiring multimodality therapy to treat or even palliate disease. These aggressive tumours are relatively chemo-resistant, therefore new treatment approaches are urgently required. We have previously reported on the efficacy of oncolytic virotherapy (OV) delivered by isolated limb perfusion. In this report, we have improved therapeutic outcomes by combining OV with radiotherapy. In vitro, the combination of oncolytic vaccinia virus (GLV-1h68) and radiotherapy demonstrated synergistic cytotoxicity...
October 22, 2016: Oncotarget
Akiko Harada, Junji Uchino, Taishi Harada, Noriaki Nakagaki, Junko Hisasue, Masaki Fujita, Koichi Takayama
Malignant mesothelioma (MM) incidence is increasing drastically worldwide as an occupational disease resulting from asbestos exposure. However, no curative treatment for MM of advanced stage is available. Thus, new therapeutic approaches for MM are required. Because malignant pleural mesothelioma (MPM) cells spread along the pleural surface in most patients, MPM can be targeted using intrapleural therapeutic approaches. In this study, we investigated the effectiveness of the intrapleural instillation of a replication-competent adenovirus as an oncolytic agent against MPM...
October 26, 2016: Cancer Science
Solimar Figueroa, Julie Gardner, Jose Irizarry, Tanya Cohn
BACKGROUND: The transition to practice for new graduate nurses poses distinct challenges at the point of care. The complicated work environment necessitates a preceptorship model that maintains safety at all times. METHOD: This study used survey, focus groups, and interviews to assess the effects of the married state preceptorship model (MSPM) on the experiences and perceptions of the new nurses and preceptors in a hospital setting. RESULTS: The result validated the original findings from the new nurses' survey, indicating all (N = 28, 100%) of the new nurses found the MSPM to be beneficial, promote safety, and lessen anxiety, and 27 (96%) thought it helped them to assume a full patient load...
November 1, 2016: Journal of Continuing Education in Nursing
James Weger-Lucarelli, Claudia Rückert, Nunya Chotiwan, Chilinh Nguyen, Selene M Garcia Luna, Joseph R Fauver, Brian D Foy, Rushika Perera, William C Black, Rebekah C Kading, Gregory D Ebel
In 2015, Zika virus (ZIKV; Flaviviridae; Flavivirus) emerged in the Americas, causing millions of infections in dozens of countries. The rapid spread of the virus and the association with disease outcomes such as Guillain-Barré syndrome and microcephaly make understanding transmission dynamics essential. Currently, there are no reports of vector competence (VC) of American mosquitoes for ZIKV isolates from the Americas. Further, it is not clear whether ZIKV strains from other genetic lineages can be transmitted by American Aedes aegypti populations, and whether the scope of the current epidemic is in part facilitated by viral factors such as enhanced replicative fitness or increased vector competence...
October 2016: PLoS Neglected Tropical Diseases
Olga Volotskova, Larisa Dubrovsky, Michael Keidar, Michael Bukrinsky
Cold atmospheric plasma (CAP) is a specific type of partially ionized gas that is less than 104°F at the point of application. It was recently shown that CAP can be used for decontamination and sterilization, as well as anti-cancer treatment. Here, we investigated the effects of CAP on HIV-1 replication in monocyte-derived macrophages (MDM). We demonstrate that pre-treatment of MDM with CAP reduced levels of CD4 and CCR5, inhibiting virus-cell fusion, viral reverse transcription and integration. In addition, CAP pre-treatment affected cellular factors required for post-entry events, as replication of VSV-G-pseudotyped HIV-1, which by-passes HIV receptor-mediated fusion at the plasma membrane during entry, was also inhibited...
2016: PloS One
Nanna Hellum Nielsen, Ahmed Jahoor, Jens Due Jensen, Jihad Orabi, Fabio Cericola, Vahid Edriss, Just Jensen
Genomic selection was recently introduced in plant breeding. The objective of this study was to develop genomic prediction for important seed quality parameters in spring barley. The aim was to predict breeding values without expensive phenotyping of large sets of lines. A total number of 309 advanced spring barley lines tested at two locations each with three replicates were phenotyped and each line was genotyped by Illumina iSelect 9Kbarley chip. The population originated from two different breeding sets, which were phenotyped in two different years...
2016: PloS One
Shivani K Mhatre, Omar Serna, Shubhada Sansgiry, Marc L Fleming, E James Essien, Sujit S Sansgiry
BACKGROUND: Low adherence to oral antidiabetic drugs (OADs) in the Medicare population can greatly reduce Centers for Medicare & Medicaid Services (CMS) star ratings for managed care organizations (MCOs). OBJECTIVE: To develop and validate a risk assessment tool (Prescription Medication Adherence Prediction Tool for Diabetes Medications [RxAPT-D]) to predict nonadherence to OADs using Medicare claims data. METHODS: In this retrospective observational study, claims data for members enrolled in a Medicare Advantage Prescription Drug (MA-PD) program in Houston, Texas, were used...
November 2016: Journal of Managed Care & Specialty Pharmacy
Xingyue Ji, Jinhua Chen, Guang-Hui Zheng, Meng-Hao Huang, Lei Zhang, Jie Jin, Hong Yi, Jian-Dong Jiang, Zong-Gen Peng, Zhuo-Rong Li
There still remains a need to develop new anti-HCV agents with distinct mechanism of action (MOA) due to the occurrence of resistance to direct-acting antiviral agents (DAAs). Cajanine, a stilbenic component isolated from Cajanus cajan L., was identified as a potent HCV inhibitor by phenotypic screening in this work (EC50 = 3.17±0.75 μM). The intensive structure optimization provided significant insights into the structure-activity relationships. Furthermore, the MOA study revealed that cajanine inhibited HCV replications via down-regulating a cellular protein chondroitin sulfate N-acetylgalactosaminyltransferase 1...
October 26, 2016: Journal of Medicinal Chemistry
Paola Sebastiani, Bharat Thyagarajan, Fangui Sun, Lawrence S Honig, Nicole Schupf, Stephanie Cosentino, Mary F Feitosa, Mary Wojczynski, Anne B Newman, Monty Montano, Thomas T Perls
OBJECTIVES: To determine reference values for laboratory tests in individuals aged 85 and older. DESIGN: Cross-sectional cohort study. SETTING: International. PARTICIPANTS: Long Life Family Study (LLFS) participants (N~5,000, age: range 25-110, median 67, 45% male). MEASUREMENTS: Serum biomarkers were selected based on association with aging-related diseases and included complete blood count, lipids (triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol), 25-hydroxyvitamin D2 and D3, vitamin D epi-isomer, diabetes mellitus-related biomarkers (adiponectin, insulin, insulin-like growth factor 1, glucose, glycosylated hemoglobin, soluble receptor for advanced glycation endproduct), kidney disease-related biomarkers (albumin, creatinine, cystatin), endocrine biomarkers (dehydroepiandrosterone, sex-hormone binding globulin, testosterone), markers of inflammation (interleukin 6, high-sensitivity C-reactive protein, N-terminal pro b-type natriuretic peptide), ferritin, and transferrin...
October 26, 2016: Journal of the American Geriatrics Society
Rodolfo Furlan Damiano, Luciana Maria de Andrade Ribeiro, Amanda Guedes Dos Santos, Barbara Almeida da Silva, Giancarlo Lucchetti
The purpose of this study was to investigate the influence of spirituality, religiosity, personal beliefs, and previous contact with health issues on the level of empathy in medical students. Jefferson Scale of Empathy-Student Version, WHOQOL-Spirituality, Religiousness and Personal Beliefs, and Duke University Religion Index were applied to 285 Brazilian medical students. The findings suggest that meaning of life and previous mental health treatment but not Religiosity were positively related to empathy. We suggest that more attention should be given for prevention and treatment of mental health issues, and further studies are needed to understand and replicate these findings...
October 25, 2016: Journal of Religion and Health
Kit Man Wong, Lindsey N Micel, Heather M Selby, Aik Choon Tan, Todd M Pitts, Stacey M Bagby, Anna Spreafico, Peter J Klauck, Stephen J Blakemore, Peter F Smith, Alice McDonald, Allison Berger, John J Tentler, S Gail Eckhardt
Background The neddylation pathway conjugates NEDD8 to cullin-RING ligases and controls the proteasomal degradation of specific proteins involved in essential cell processes. Pevonedistat (MLN4924) is a selective small molecule targeting the NEDD8-activating enzyme (NAE) and inhibits an early step in neddylation, resulting in DNA re-replication, cell cycle arrest and death. We investigated the anti-tumor potential of pevonedistat in preclinical models of melanoma. Methods Melanoma cell lines and patient-derived tumor xenografts (PDTX) treated with pevonedistat were assessed for viability/apoptosis and tumor growth, respectively, to identify sensitive/resistant models...
October 25, 2016: Investigational New Drugs
Gabor Kiraly, Athene S Simonyi, Melinda Turani, Istvan Juhasz, Gabor Nagy, Gaspar Banfalvi
In early S phase the newly replicated DNA is folded back to increasingly compact structures. The process of chromatin condensation inside the nucleus starts with the formation of a micronucleus observed in five established cell lines (K562, CHO, Indian muntjac, murine preB and SCC). Supercoiling of chromatin generates a polarized end-plate region extruded from the nucleus. The extruded chromatin is turned around itself forming the head portion (micronucleus) visible by fluorescence microscopy until the middle of S phase when chromatin structures are succeeded by distinguishable early forms of chromosomes...
October 25, 2016: Apoptosis: An International Journal on Programmed Cell Death
Tanja Stachon, Krasimir Kolev, Zsuzsa Flaskó, Berthold Seitz, Achim Langenbucher, Nóra Szentmáry
PURPOSE: Keratoconus (KC) is a disease characterized by thinning and deformation of the cornea, but its etiology remains unknown. Seventy percent of the corneal stroma consists of collagen, which is composed of three intertwined polypeptide chains with glycine-hydroxyproline-proline repeats along their sequence. Arginase is a cytoplasmatic enzyme and catalyzes the conversion of arginine to urea and ornithine, which serves as a precursor for the endogenous synthesis of proline and hydroxyproline...
October 25, 2016: Graefe's Archive for Clinical and Experimental Ophthalmology
Ziqiang Wang, Ping Fan, Yiwan Zhao, Shikuan Zhang, Jinhua Lu, Weidong Xie, Yuyang Jiang, Fan Lei, Naihan Xu, Yaou Zhang
Nuclear paraspeckle assembly transcript 1 (NEAT1) is the crucial structural platform of paraspeckles, which is one type of nuclear bodies. As a stress-induced lncRNA, the expression of NEAT1 increases in response to viral infection, but little is known about the role of NEAT1 or paraspeckles in the replication of herpes simplex virus-1 (HSV-1). Here, we demonstrate that HSV-1 infection increases NEAT1 expression and paraspeckle formation in a STAT3-dependent manner. NEAT1 and other paraspeckle protein components, P54nrb and PSPC1, can associate with HSV-1 genomic DNA...
October 25, 2016: Cellular and Molecular Life Sciences: CMLS
Alina Rudnicka, Yohei Yamauchi
Viruses are obligatory cellular parasites. Their mission is to enter a host cell, to transfer the viral genome, and to replicate progeny whilst diverting cellular immunity. The role of ubiquitin is to regulate fundamental cellular processes such as endocytosis, protein degradation, and immune signaling. Many viruses including influenza A virus (IAV) usurp ubiquitination and ubiquitin-like modifications to establish infection. In this focused review, we discuss how ubiquitin and unanchored ubiquitin regulate IAV host cell entry, and how histone deacetylase 6 (HDAC6), a cytoplasmic deacetylase with ubiquitin-binding activity, mediates IAV capsid uncoating...
October 24, 2016: Viruses
Jiaqian Pan, Shuangmei Tong, Lei Kang, Jing Tang
PURPOSE OF REVIEW: Although available therapies can effectively inhibit hepatitis B virus (HBV) replication in patients with active chronic hepatitis B (CHB) infection, therapeutic efficacy is limited because of potential drug resistance, and an inability to mediate viral clearance and to rectify immune impairment in CHB patients. This review will summarize the state-of-the-art for anti-HBV drugs and focus on potential drugs and targets under development and evaluation. RECENT FINDINGS: New developing drugs are evaluated for their antiviral effects in the areas of interference with the viral replication cycle, elimination of covalently closed circular DNA, modulation of host immunity and identification of the La protein and its regulator casein kinase as possible targets for the development of anti-HBV therapies...
December 2016: Current Opinion in Infectious Diseases
Ryan A Whitehead, Nicholas L Lam, Melody S Sun, Joshua Sanchez, Shahani Noor, Arden G Vanderwall, Timothy R Petersen, Hugh B Martin, Erin D Milligan
BACKGROUND: Animal models of peripheral neuropathy produced by a number of manipulations are assessed for the presence of pathologic pain states such as allodynia. Although stimulus-induced behavioral assays are frequently used and important to examine allodynia (ie, sensitivity to light mechanical touch; von Frey fiber test), other measures of behavior that reflect overall function are not only complementary to stimulus-induced responsive measures, but are also critical to gain a complete understanding of the effects of the pain model on quality of life, a clinically relevant aspect of pain on general function...
October 24, 2016: Anesthesia and Analgesia
Giovanni A Salum, Karin Mogg, Brendan P Bradley, Argyris Stringaris, Ary Gadelha, Pedro M Pan, Luis A Rohde, Guilherme V Polanczyk, Gisele G Manfro, Daniel S Pine, Ellen Leibenluft
BACKGROUND: Irritability, a frequent complaint in children with psychiatric disorders, reflects increased predisposition to anger. Preliminary work in pediatric clinical samples links irritability to attention bias to threat, and the current study examines this association in a large population-based sample. METHODS: We studied 1,872 children (ages 6-14) using the Development and Well-Being Assessment (DAWBA), Childhood Behavior Checklist (CBCL), and dot-probe tasks...
October 26, 2016: Journal of Child Psychology and Psychiatry, and Allied Disciplines
Enrico Girardi, Antonella d'Arminio Monforte, Laura Camoni, Patrizio Pezzotti, Giovanni Guaraldi, Adriana Ammassari, Andrea Antinori, Stefano Bonora, Cristina Mussini, Antonella Cingolani, Giulio Maria Corbelli, Silvia Adami, Luca Degli Esposti, Margherita Andretta
HIV disease has dramatically changed in the last two decades from a progressive, lethal disease to a chronic manageable condition. These changes are due to the availability of potent antiretroviral combination therapy, which also have the potential to contribute significantly to the control of the epidemic. Among persons living with HIV, incidence of immunosuppression-related opportunistic illnesses has clearly decreased, while an increase was observed in the prevalence of age-related noncommunicable comorbidities, including cardiovascular, metabolic, renal, bone and hepatic disease, due to chronic inflammatory state and to an overall aging of the population of persons with HIV...
October 2016: Recenti Progressi in Medicina
Wim Trypsteen, Pejman Mohammadi, Clarissa Van Hecke, Pieter Mestdagh, Steve Lefever, Yvan Saeys, Pieter De Bleser, Jo Vandesompele, Angela Ciuffi, Linos Vandekerckhove, Ward De Spiegelaere
Studying the effects of HIV infection on the host transcriptome has typically focused on protein-coding genes. However, recent advances in the field of RNA sequencing revealed that long non-coding RNAs (lncRNAs) add an extensive additional layer to the cell's molecular network. Here, we performed transcriptome profiling throughout a primary HIV infection in vitro to investigate lncRNA expression at the different HIV replication cycle processes (reverse transcription, integration and particle production). Subsequently, guilt-by-association, transcription factor and co-expression analysis were performed to infer biological roles for the lncRNAs identified in the HIV-host interplay...
October 26, 2016: Scientific Reports
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