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Author McCloskey, M.L.; Tarazona-Meza, C.E.; Jones-Smith, J.C.; Miele, C.H.; Gilman, R.H.; Bernabe-Ortiz, A.; Miranda, J.J.; Checkley, W. url  doi
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  Title (up) Disparities in dietary intake and physical activity patterns across the urbanization divide in the Peruvian Andes Type Journal Article
  Year 2017 Publication The International Journal of Behavioral Nutrition and Physical Activity Abbreviated Journal Int J Behav Nutr Phys Act  
  Volume 14 Issue 1 Pages 90  
  Keywords 24-h recall; Chronic diseases; Low- and middle income countries; Nutrition transition; Overweight; Urbanization  
  Abstract BACKGROUND: Diet and activity are thought to worsen with urbanization, thereby increasing risk of obesity and chronic diseases. A better understanding of dietary and activity patterns across the urbanization divide may help identify pathways, and therefore intervention targets, leading to the epidemic of overweight seen in low- and middle-income populations. Therefore, we sought to characterize diet and activity in a population-based study of urban and rural residents in Puno, Peru. METHODS: We compared diet and activity in 1005 (503 urban, 502 rural) participants via a lifestyle questionnaire. We then recruited an age- and sex-stratified random sample of 50 (25 urban, 25 rural) participants to further characterize diet and activity. Among these participants, diet composition and macronutrient intake was assessed by three non-consecutive 24-h dietary recalls and physical activity was assessed using Omron JH-720itc pedometers. RESULTS: Among 1005 participants, we found that urban residents consumed protein-rich foods, refined grains, sugary items, and fresh produce more frequently than rural residents. Among the 50 subsample participants, urban dwellers consumed more protein (47 vs. 39 g; p = 0.05), more carbohydrates (280 vs. 220 g; p = 0.03), more sugary foods (98 vs. 48 g, p = 0.02) and had greater dietary diversity (6.4 vs 5.8; p = 0.04). Rural subsample participants consumed more added salt (3.1 vs 1.7 g, p = 0.006) and tended to consume more vegetable oil. As estimated by pedometers, urban subsample participants burned fewer calories per day (191 vs 270 kcal, p = 0.03). CONCLUSIONS: Although urbanization is typically thought to increase consumption of fat, sugar and salt, our 24-h recall results were mixed and showed lower levels of obesity in rural Puno were not necessarily indicative of nutritionally-balanced diets. All subsample participants had relatively traditional lifestyles (low fat intake, limited consumption of processed foods and frequent walking) that may play a role in chronic disease outcomes in this region.  
  Address Biomedical Research Unit, A.B. PRISMA, Lima, Peru. wcheckl1@jhmi.edu  
  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 1479-5868 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28693514 Approved no  
  Call Number ref @ user @ Serial 98015  
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Author Voss, D.M.; Spina, R.; Carter, D.L.; Lim, K.S.; Jeffery, C.J.; Bar, E.E. url  doi
openurl 
  Title (up) Disruption of the monocarboxylate transporter-4-basigin interaction inhibits the hypoxic response, proliferation, and tumor progression Type Journal Article
  Year 2017 Publication Scientific Reports Abbreviated Journal Sci Rep  
  Volume 7 Issue 1 Pages 4292  
  Keywords  
  Abstract We have previously shown that glioblastoma stem cells (GSCs) are enriched in the hypoxic tumor microenvironment, and that monocarboxylate transporter-4 (MCT4) is critical for mediating GSC signaling in hypoxia. Basigin is involved in many physiological functions during early stages of development and in cancer and is required for functional plasma membrane expression of MCT4. We sought to determine if disruption of the MCT-Basigin interaction may be achieved with a small molecule. Using a cell-based drug-screening assay, we identified Acriflavine (ACF), a small molecule that inhibits the binding between Basigin and MCT4. Surface plasmon resonance and cellular thermal-shift-assays confirmed ACF binding to basigin in vitro and in live glioblastoma cells, respectively. ACF significantly inhibited growth and self-renewal potential of several glioblastoma neurosphere lines in vitro, and this activity was further augmented by hypoxia. Finally, treatment of mice bearing GSC-derived xenografts resulted in significant inhibition of tumor progression in early and late-stage disease. ACF treatment inhibited intratumoral expression of VEGF and tumor vascularization. Our work serves as a proof-of-concept as it shows, for the first time, that disruption of MCT binding to their chaperon, Basigin, may be an effective approach to target GSC and to inhibit angiogenesis and tumor progression.  
  Address Department of Neurological Surgery, Case Western Reserve University School of Medicine and The Case Comprehensive Cancer Center, Cleveland, OH, USA. eli.bar@case.edu  
  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 2045-2322 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28655889 Approved no  
  Call Number ref @ user @ Serial 96580  
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Author Souza, R.L.; Mugabe, V.A.; Paploski, I.A.D.; Rodrigues, M.S.; Moreira, P.S.D.S.; Nascimento, L.C.J.; Roundy, C.M.; Weaver, S.C.; Reis, M.G.; Kitron, U.; Ribeiro, G.S. url  doi
openurl 
  Title (up) Effect of an intervention in storm drains to prevent Aedes aegypti reproduction in Salvador, Brazil Type Journal Article
  Year 2017 Publication Parasites & Vectors Abbreviated Journal Parasit Vectors  
  Volume 10 Issue 1 Pages 328  
  Keywords Aedes aegypti; Arboviruses; Catch basin; Disease vectors; Entomology; Epidemiology; Insect vectors; Mosquitoes; Storm drain  
  Abstract BACKGROUND: Aedes aegypti, the principal vector for dengue, chikungunya and Zika viruses, is a synanthropic species that uses stagnant water to complete its reproductive cycle. In urban settings, rainfall water draining structures, such as storm drains, may retain water and serve as a larval development site for Aedes spp. reproduction. Herein, we describe the effect of a community-based intervention on preventing standing water accumulation in storm drains and their consequent infestation by adult and immature Ae. aegypti and other mosquitoes. METHODS: Between April and May of 2016, local residents association of Salvador, Brazil, after being informed of water accumulation and Ae. aegypti infestation in the storm drains in their area, performed an intervention on 52 storm drains. The intervention consisted of placing concrete at the bottom of the storm drains to elevate their base to the level of the outflow tube, avoiding water accumulation, and placement of a metal mesh covering the outflow tube to avoid its clogging with debris. To determine the impact of the intervention, we compared the frequency at which the 52 storm drains contained water, as well as adult and immature mosquitoes using data from two surveys performed before and two surveys performed after the intervention. RESULTS: During the pre-intervention period, water accumulated in 48 (92.3%) of the storm drains, and immature Ae. aegypti were found in 11 (21.2%) and adults in 10 (19.2%). After the intervention, water accumulated in 5 (9.6%) of the storm drains (P < 0.001), none (0.0%) had immatures (P < 0.001), and 3 (5.8%) contained adults (P = 0.039). The total number of Ae. aegypti immatures collected decreased from 109 to 0 (P < 0.001) and adults decreased from 37 to 8 (P = 0.011) after the intervention. Collection of immature and adult non-Aedes mosquitoes (mainly Culex spp.) in the storm drains also decreased after the intervention. CONCLUSION: This study exemplifies how a simple intervention targeting storm drains can result in a major reduction of water retention, and, consequently, impact Ae. aegypti larval populations. Larger and multi-center evaluations are needed to confirm the potential of citywide structural modifications of storm drains to reduce Aedes spp. infestation level.  
  Address Instituto de Saude Coletiva, Universidade Federal da Bahia, Salvador, Bahia, Brazil. guilherme.ribeiro@bahia.fiocruz.br  
  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 1756-3305 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28697811 Approved no  
  Call Number ref @ user @ Serial 97633  
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Author Jensen, S.S.; Petterson, S.A.; Halle, B.; Aaberg-Jessen, C.; Kristensen, B.W. url  doi
openurl 
  Title (up) Effects of the lysosomal destabilizing drug siramesine on glioblastoma in vitro and in vivo Type Journal Article
  Year 2017 Publication BMC Cancer Abbreviated Journal BMC Cancer  
  Volume 17 Issue 1 Pages 178  
  Keywords Brain slice cultures; Cancer stem cell; Glioblastoma; Lysosomes; Siramesine; Spheroids  
  Abstract BACKGROUND: Glioblastoma is the most frequent and most malignant brain tumor with the patients having a median survival of only 14.6 months. Although glioblastoma patients are treated with surgery, radiation and chemotherapy recurrence is inevitable. A stem-like population of radio- and chemoresistant brain tumor-initiating cells combined with the invasive properties of the tumors is believed to be critical for treatment resistance. In the present study, the aim was to investigate the effect of a novel therapeutic strategy using the lysosomotropic detergent siramesine on glioblastomas. METHODS: Standard glioma cell lines and patient-derived spheroids cultures with tumor-initiating stem-like cells were used to investigate effects of siramesine on proliferation and cell death. Responsible mechanisms were investigated by inhibitors of caspases and cathepsins. Effects of siramesine on migrating tumor cells were investigated by a flat surface migration assay and by implanting spheroids into organotypic rat brain slice cultures followed by confocal time-lapse imaging. Finally the effect of siramesine was investigated in an orthotopic mouse glioblastoma model. Results obtained in vitro and in vivo were confirmed by immunohistochemical staining of histological sections of spheroids, spheroids in brain slice cultures and tumors in mice brains. RESULTS: The results showed that siramesine killed standard glioma cell lines in vitro, and loss of acridine orange staining suggested a compromised lysosomal membrane. Co-treatment of the cell lines with inhibitors of caspases and cathepsins suggested differential involvement in cell death. Siramesine caused tumor cell death and reduced secondary spheroid formation of patient-derived spheroid cultures. In the flat surface migration model siramesine caused tumor cell death and inhibited tumor cell migration. This could not be reproduced in the organotypic three dimensional spheroid-brain slice culture model or in the mice xenograft model. CONCLUSIONS: In conclusion the in vitro results obtained with tumor cells and spheroids suggest a potential of lysosomal destabilizing drugs in killing glioblastoma cells, but siramesine was without effect in the organotypic spheroid-brain slice culture model and the in vivo xenograft model.  
  Address Institute of Clinical Research, University of Southern Denmark, Winslowparken 19.3, 5000, Odense C, Denmark. bjarne.winther.kristensen@rsyd.dk  
  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 1471-2407 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28270132 Approved no  
  Call Number ref @ user @ Serial 96603  
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Author Goncalves, D.P.N.; Rodriguez, R.D.; Kurth, T.; Bray, L.J.; Binner, M.; Jungnickel, C.; Gur, F.N.; Poser, S.W.; Schmidt, T.L.; Zahn, D.R.T.; Androutsellis-Theotokis, A.; Schlierf, M.; Werner, C. url  doi
openurl 
  Title (up) Enhanced targeting of invasive glioblastoma cells by peptide-functionalized gold nanorods in hydrogel-based 3D cultures Type Journal Article
  Year 2017 Publication Acta Biomaterialia Abbreviated Journal Acta Biomater  
  Volume 58 Issue Pages 12-25  
  Keywords 3D culture; Cancer stem cells; Glioblastoma Multiforme; Gold nanorods; Photothermolysis  
  Abstract Cancer stem cells (CSCs) are responsible for drug resistance, tumor recurrence, and metastasis in several cancer types, making their eradication a primary objective in cancer therapy. Glioblastoma Multiforme (GBM) tumors are usually composed of a highly infiltrating CSC subpopulation, which has Nestin as a putative marker. Since the majority of these infiltrating cells are able to elude conventional therapies, we have developed gold nanorods (AuNRs) functionalized with an engineered peptide capable of specific recognition and selective eradication of Nestin positive infiltrating GBM-CSCs. These AuNRs generate heat when irradiated by a near-infrared laser, and cause localized cell damage. Nanoparticle internalization assays performed with GBM-CSCs or Nestin negative cells cultured as two-dimensional (2D) monolayers or embedded in three-dimensional (3D) biodegradable-hydrogels of tunable mechanical properties, revealed that the AuNRs were mainly internalized by GBM-CSCs, and not by Nestin negative cells. The AuNRs were taken up via energy-dependent and caveolae-mediated endocytic mechanisms, and were localized inside endosomes. Photothermal treatments resulted in the selective elimination of GBM-CSCs through cell apoptosis, while Nestin negative cells remained viable. Results also indicated that GBM-CSCs embedded in hydrogels were more resistant to AuNR photothermal treatments than when cultured as 2D monolayers. In summary, the combination of our engineered AuNRs with our tunable hydrogel system has shown the potential to provide an in vitro platform for the evaluation and screening of AuNR-based cancer therapeutics, leading to a substantial advancement in the application of AuNRs for targeted GBM-CSC therapy. STATEMENT OF SIGNIFICANCE: There is an urgent need for reliable and efficient therapies for the treatment of Glioblastoma Multiforme (GBM), which is currently an untreatable brain tumor form with a very poor patient survival rate. GBM tumors are mostly comprised of cancer stem cells (CSCs), which are responsible for tumor reoccurrence and therapy resistance. We have developed gold nanorods functionalized with an engineered peptide capable of selective recognition and eradication of GBM-CSCs via heat generation by nanorods upon NIR irradiation. An in vitro evaluation of nanorod therapeutic activities was performed in 3D synthetic-biodegradable hydrogel models with distinct biomechanical cues, and compared to 2D cultures. Results indicated that cells cultured in 3D were more resistant to photothermolysis than in 2D systems.  
  Address Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, Hohe Strasse 6, 01069 Dresden, Germany  
  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 1742-7061 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28576716 Approved no  
  Call Number ref @ user @ Serial 96583  
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