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Author Li, M.; Xiao, A.; Floyd, D.; Olmez, I.; Lee, J.; Godlewski, J.; Bronisz, A.; Bhat, K.P.L.; Sulman, E.P.; Nakano, I.; Purow, B.
Title CDK4/6 inhibition is more active against the glioblastoma proneural subtype Type Journal Article
Year 2017 Publication Oncotarget Abbreviated Journal Oncotarget
Volume 8 Issue 33 Pages 55319-55331
Keywords Cdk4/6; glioblastoma; mesenchymal; palbociclib; proneural
Abstract Glioblastoma (GBM) is the most common and lethal brain tumor. Gene expression profiling has classified GBM into distinct subtypes, including proneural, mesenchymal, and classical, and identifying therapeutic vulnerabilities of these subtypes is an extremely high priority. We leveraged The Cancer Genome Atlas (TCGA) data, in particular for microRNA expression, to seek druggable core pathways in GBM. The E2F1-regulated miR-17 92 cluster and its analogs are shown to be highly expressed in proneural GBM and in GSC lines, suggesting the E2F cell cycle pathway might be a key driver in proneural GBM. Consistently, CDK4/6 inhibition with palbociclib preferentially inhibited cell proliferation in vitro in a majority of proneural GSCs versus those of other subtypes. Palbociclib treatment significantly prolonged survival of mice with established intracranial xenografts of a proneural GSC line. We show that most of these sensitive PN GSCs expressed higher levels of CDK6 and had intact Rb1, while two GSC lines with CDK4 overexpression and null Rb1 were highly resistant to palbociclib. Importantly, palbociclib treatment of proneural GSCs upregulated mesenchymal-associated markers and downregulated proneural-associated markers, suggesting that CDK4/6 inhibition induced proneural-mesenchymal transition and underscoring the enhanced role of the E2F cell cycle pathway in the proneural subtype. Lastly, the combination of palbociclib and N,N-diethylaminobenzaldehyde, an inhibitor of the mesenchymal driver ALDH1A3, showed strong synergistic inhibitory effects against proneural GSC proliferation. Taken together, our results reveal that proneural GBM has increased vulnerability to CDK4/6 inhibition, and the proneural subtype undergoes dynamic reprogramming upon palbociclib treatment-suggesting the need for a combination therapeutic strategy.
Address Neuro-Oncology Division, Department of Neurology, University of Virginia, Charlottesville, VA, USA
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1949-2553 ISBN Medium
Area Expedition Conference
Notes PMID:28903422 Approved no
Call Number ref @ user @ Serial 96569
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Author Gredilla, A.; Fdez-Ortiz de Vallejuelo, S.; Gomez-Nubla, L.; Carrero, J.A.; de Leao, F.B.; Madariaga, J.M.; Silva, L.F.O.
Title Are children playgrounds safe play areas? Inorganic analysis and lead isotope ratios for contamination assessment in recreational (Brazilian) parks Type Journal Article
Year 2017 Publication Environmental Science and Pollution Research International Abbreviated Journal Environ Sci Pollut Res Int
Volume 24 Issue 31 Pages 24333-24345
Keywords Chemometric analysis; Human health; Icp-Ms; Lead isotopic ratio; Metals; Normalized-and-Weighted Average Concentration; Playgrounds
Abstract In city playgrounds, there is a potential risk of harming children's health by contamination coming from anthropogenic activities. With the aim to determinate the sources and the risk of hazardous elements, soil samples were collected in 19 selected playgrounds of different urban and rural areas from the Rio Grande do Sul state (Brazil). The concentration of 23 metals and metalloids and lead isotopic ratios were determined by ICP-MS. The methodology proposed here, firstly, classified the parks according to the average metal content by means of the NWACs (Normalized-and-Weighted Average Concentrations) and assess the contamination risk determining the Contamination Factors (CFs). Finally, statistical tools (correlation analysis and principal component analysis) were used to identify the most important contamination sources. The statistical tools used, together with lead isotopic composition analysis of the samples, revealed that coal combustion is the main source of contamination in the area. Vegetation was identified as a barrier for the contamination coming from the city. Nonetheless, some of the soils present a possible toxicological risk for humans. In fact, Cr, Sb, and Pb concentrations were higher than the Residential Intervention Values (VIRs) defined by the Environmental Protection Agency of the State of Sao Paulo, also in Brazil.
Address Research Group in Environmental Management and Sustainability, Faculty of Environmental Sciences, Universidad De la Costa, Calle 58, No. 55-56, 080002, Barranquilla, Atlantico, Colombia
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0944-1344 ISBN Medium
Area Expedition Conference
Notes PMID:28889400 Approved no
Call Number ref @ user @ Serial 97629
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Author Mello, A. de C.; Carvalho, M.S.; Alves, L.C.; Gomes, V.P.; Engstrom, E.M.
Title [Food consumption and anthropometry related to the frailty syndrome in low-income community-living elderly in a large city] Type Journal Article
Year 2017 Publication Cadernos de Saude Publica Abbreviated Journal Cad Saude Publica
Volume 33 Issue 8 Pages e00188815
Keywords Aged; Aged, 80 and over; *Anthropometry; Brazil; Cross-Sectional Studies; Female; *Food; Frail Elderly/*statistics & numerical data; Geriatric Assessment; Humans; Male; Middle Aged; Nutrition Assessment; Nutrition Surveys; Socioeconomic Factors
Abstract The aim of this study was to describe anthropometric and food intake data related to the frailty syndrome in the elderly. This was a cross-sectional study in individuals >/= 60 years of age in a household survey in the Manguinhos neighborhood of Rio de Janeiro, Brazil (n = 137). Frailty syndrome was diagnosed according to Fried et al., anthropometric measures were taken, and a food frequency questionnaire was applied and the results compared to Brazilian Ministry of Health guidelines. In the pre-frail and frail groups, body mass index and measures of central adiposity showed higher levels, while lean muscle parameters showed lower values, proportional to the syndrome's gradation. Frail elderly consumed higher amounts of grains and lower amounts of beans and fruit; pre-frail elderly consumed more vegetables, dairy products, and high-sugar and high-fat foods; the two groups consumed similar amounts of meat. Thus, diagnosis of the syndrome, anthropometric evaluation, and dietary assessment should be included in health policies for the elderly, since they assist in early identification of risk and favor interventions for disease prevention and health and nutritional promotion.
Address Escola Nacional de Saude Publica Sergio Arouca, Fundacao Oswaldo Cruz, Rio de Janeiro, Brasil
Corporate Author Thesis
Publisher Place of Publication Editor
Language Portuguese Summary Language Original Title Consumo alimentar e antropometria relacionados a sindrome de fragilidade em idosos residentes em comunidade de baixa renda de um grande centro urbano
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0102-311X ISBN Medium
Area Expedition Conference
Notes PMID:28832786 Approved no
Call Number ref @ user @ Serial 98007
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Author Girardi, S.N.; Carvalho, C.L.; Maas, L.W.D.; Araujo, J.F.; Massote, A.W.; Stralen, A.C. de S. van; Souza, O.A. de
Title [Preferences for work in primary care among medical students in Minas Gerais State, Brazil: evidence from a discrete choice experiment] Type Journal Article
Year 2017 Publication Cadernos de Saude Publica Abbreviated Journal Cad Saude Publica
Volume 33 Issue 8 Pages e00075316
Keywords Brazil; *Career Choice; Choice Behavior; Female; Humans; Income; Male; *Primary Health Care; *Professional Practice Location; Sex Factors; *Students, Medical; Surveys and Questionnaires
Abstract This article presents the results of a discrete choice experiment (DCE) conducted in 2012 with 277 final-year medical students from Minas Gerais State, Brazil. The experiment tested students' preferences concerning future work as physicians in primary health care, based on hypothetical job scenarios aimed at measuring the likelihood of placement in areas with a shortage of doctors. Application of DCE involved (i) a qualitative stage to define the attributes and their respective levels to comprise the job scenarios, (ii) construction and application of the instrument, and (iii) analysis with application of multinomial logit with conditional probability to estimate the weight of attributes and to construct scenarios for choice probability. The results indicate that the job attribute that most impacted students' choice was location, followed by job conditions, pay, access to medical residency, type of employment relationship, and workload. Students from private medical schools, with higher family income, and females were generally more likely to resist job assignments in unsafe urban areas and remote areas of the countryside. The job scenarios that proved most plausible in terms of public intervention were those that combined middle-level wages, good working conditions, and 10 to 20 bonus points on medical residency exams.
Address Departamento de Matematica, Universidade Estadual do Centro-Oeste, Guarapuava, Brasil
Corporate Author Thesis
Publisher Place of Publication Editor
Language Portuguese Summary Language Original Title Preferencias para o trabalho na atencao primaria por estudantes de medicina em Minas Gerais, Brasil: evidencias de um experimento de preferencia declarada
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0102-311X ISBN Medium
Area Expedition Conference
Notes PMID:28832780 Approved no
Call Number ref @ user @ Serial 97630
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Author Saunders, M.J.; Wingfield, T.; Tovar, M.A.; Baldwin, M.R.; Datta, S.; Zevallos, K.; Montoya, R.; Valencia, T.R.; Friedland, J.S.; Moulton, L.H.; Gilman, R.H.; Evans, C.A.
Title A score to predict and stratify risk of tuberculosis in adult contacts of tuberculosis index cases: a prospective derivation and external validation cohort study Type Journal Article
Year 2017 Publication The Lancet. Infectious Diseases Abbreviated Journal Lancet Infect Dis
Volume 17 Issue 11 Pages 1190-1199
Keywords
Abstract BACKGROUND: Contacts of tuberculosis index cases are at increased risk of developing tuberculosis. Screening, preventive therapy, and surveillance for tuberculosis are underused interventions in contacts, particularly adults. We developed a score to predict risk of tuberculosis in adult contacts of tuberculosis index cases. METHODS: In 2002-06, we recruited contacts aged 15 years or older of index cases with pulmonary tuberculosis who lived in desert shanty towns in Ventanilla, Peru. We followed up contacts for tuberculosis until February, 2016. We used a Cox proportional hazards model to identify index case, contact, and household risk factors for tuberculosis from which to derive a score and classify contacts as low, medium, or high risk. We validated the score in an urban community recruited in Callao, Peru, in 2014-15. FINDINGS: In the derivation cohort, we identified 2017 contacts of 715 index cases, and median follow-up was 10.7 years (IQR 9.5-11.8). 178 (9%) of 2017 contacts developed tuberculosis during 19 147 person-years of follow-up (incidence 0.93 per 100 person-years, 95% CI 0.80-1.08). Risk factors for tuberculosis were body-mass index, previous tuberculosis, age, sustained exposure to the index case, the index case being in a male patient, lower community household socioeconomic position, indoor air pollution, previous tuberculosis among household members, and living in a household with a low number of windows per room. The 10-year risks of tuberculosis in the low-risk, medium-risk, and high-risk groups were, respectively, 2.8% (95% CI 1.7-4.4), 6.2% (4.8-8.1), and 20.6% (17.3-24.4). The 535 (27%) contacts classified as high risk accounted for 60% of the tuberculosis identified during follow-up. The score predicted tuberculosis independently of tuberculin skin test and index-case drug sensitivity results. In the external validation cohort, 65 (3%) of 1910 contacts developed tuberculosis during 3771 person-years of follow-up (incidence 1.7 per 100 person-years, 95% CI 1.4-2.2). The 2.5-year risks of tuberculosis in the low-risk, medium-risk, and high-risk groups were, respectively, 1.4% (95% CI 0.7-2.8), 3.9% (2.5-5.9), and 8.6%. (5.9-12.6). INTERPRETATION: Our externally validated risk score could predict and stratify 10-year risk of developing tuberculosis in adult contacts, and could be used to prioritise tuberculosis control interventions for people most likely to benefit. FUNDING: Wellcome Trust, Department for International Development Civil Society Challenge Fund, Joint Global Health Trials consortium, Bill & Melinda Gates Foundation, Imperial College National Institutes of Health Research Biomedical Research Centre, Foundation for Innovative New Diagnostics, Sir Halley Stewart Trust, WHO, TB REACH, and Innovation for Health and Development.
Address Section of Infectious Diseases and Immunity, Imperial College London, London, UK; Wellcome Trust Imperial College Centre for Global Health Research, London, UK; Innovation for Health and Development (IFHAD), Laboratory of Research and Development, Universidad Peruana Cayetano Heredia, Lima, Peru; Innovacion Por la Salud Y Desarrollo (IPSYD), Asociacion Benefica PRISMA, Lima, Peru
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1473-3099 ISBN Medium
Area Expedition Conference
Notes PMID:28827142 Approved no
Call Number ref @ user @ Serial 97505
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