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Author Howard, C.M.; Valluri, J.; Alberico, A.; Julien, T.; Mazagri, R.; Marsh, R.; Alastair, H.; Cortese, A.; Griswold, M.; Wang, W.; Denning, K.; Brown, L.; Claudio, P.P. url  doi
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  Title Analysis of Chemopredictive Assay for Targeting Cancer Stem Cells in Glioblastoma Patients Type Journal Article
  Year 2017 Publication Translational Oncology Abbreviated Journal Transl Oncol  
  Volume 10 Issue 2 Pages (up) 241-254  
  Keywords  
  Abstract INTRODUCTION: The prognosis of glioblastoma (GBM) treated with standard-of-care maximal surgical resection and concurrent adjuvant temozolomide (TMZ)/radiotherapy remains very poor (less than 15 months). GBMs have been found to contain a small population of cancer stem cells (CSCs) that contribute to tumor propagation, maintenance, and treatment resistance. The highly invasive nature of high-grade gliomas and their inherent resistance to therapy lead to very high rates of recurrence. For these reasons, not all patients with similar diagnoses respond to the same chemotherapy, schedule, or dose. Administration of ineffective anticancer therapy is not only costly but more importantly burdens the patient with unnecessary toxicity and selects for the development of resistant cancer cell clones. We have developed a drug response assay (ChemoID) that identifies the most effective chemotherapy against CSCs and bulk of tumor cells from of a panel of potential treatments, offering great promise for individualized cancer management. Providing the treating physician with drug response information on a panel of approved drugs will aid in personalized therapy selections of the most effective chemotherapy for individual patients, thereby improving outcomes. A prospective study was conducted evaluating the use of the ChemoID drug response assay in GBM patients treated with standard of care. METHODS: Forty-one GBM patients (mean age 54 years, 59% male), all eligible for a surgical biopsy, were enrolled in an Institutional Review Board-approved protocol, and fresh tissue samples were collected for drug sensitivity testing. Patients were all treated with standard-of-care TMZ plus radiation with or without maximal surgery, depending on the status of the disease. Patients were prospectively monitored for tumor response, time to recurrence, progression-free survival (PFS), and overall survival (OS). Odds ratio (OR) associations of 12-month recurrence, PFS, and OS outcomes were estimated for CSC, bulk tumor, and combined assay responses for the standard-of-care TMZ treatment; sensitivities/specificities, areas under the curve (AUCs), and risk reclassification components were examined. RESULTS: Median follow-up was 8 months (range 3-49 months). For every 5% increase in in vitro CSC cell kill by TMZ, 12-month patient response (nonrecurrence of cancer) increased two-fold, OR=2.2 (P=.016). Similar but somewhat less supported associations with the bulk tumor test were seen, OR=2.75 (P=.07) for each 5% bulk tumor cell kill by TMZ. Combining CSC and bulk tumor assay results in a single model yielded a statistically supported CSC association, OR=2.36 (P=.036), but a much attenuated remaining bulk tumor association, OR=1.46 (P=.472). AUCs and [sensitivity/specificity] at optimal outpoints (>40% CSC cell kill and >55% bulk tumor cell kill) were AUC=0.989 [sensitivity=100/specificity=97], 0.972 [100/89], and 0.989 [100/97] for the CSC only, bulk tumor only, and combined models, respectively. Risk categorization of patients was improved by 11% when using the CSC test in conjunction with the bulk test (risk reclassification nonevent net reclassification improvement [NRI] and overall NRI=0.111, P=.030). Median recurrence time was 20 months for patients with a positive (>40% cell kill) CSC test versus only 3 months for those with a negative CSC test, whereas median recurrence time was 13 months versus 4 months for patients with a positive (>55% cell kill) bulk test versus negative. Similar favorable results for the CSC test were observed for PFS and OS outcomes. Panel results across 14 potential other treatments indicated that 34/41 (83%) potentially more optimal alternative therapies may have been chosen using CSC results, whereas 27/41 (66%) alternative therapies may have been chosen using bulk tumor results. CONCLUSIONS: The ChemoID CSC drug response assay has the potential to increase the accuracy of bulk tumor assays to help guide individualized chemotherapy choices. GBM cancer recurrence may occur quickly if the CSC test has a low in vitro cell kill rate even if the bulk tumor test cell kill rate is high.  
  Address Department of BioMolecular Sciences, National Center for Natural Products Research, University of Mississippi, University, MS; Department of Radiation Oncology, University of Mississippi Medical Center Cancer Institute, Jackson, MS 39216. Electronic address: pclaudio@olemiss.edu  
  Corporate Author Thesis  
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  Language English Summary Language Original Title  
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  Series Volume Series Issue Edition  
  ISSN 1936-5233 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28199863 Approved no  
  Call Number ref @ user @ Serial 96608  
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Author LaGrone, L.N.; Isquith-Dicker, L.N.; Huaman Egoavil, E.; Rodriguez Castro, M.J.A.; Allagual, A.; Revoredo, F.; Mock, C.N. url  doi
openurl 
  Title Surgeons' and Trauma Care Physicians' Perception of the Impact of the Globalization of Medical Education on Quality of Care in Lima, Peru Type Observational Study
  Year 2017 Publication JAMA Surgery Abbreviated Journal JAMA Surg  
  Volume 152 Issue 3 Pages (up) 251-256  
  Keywords *Attitude of Health Personnel; *Developing Countries; Education, Distance; *Education, Medical; Faculty, Medical/psychology; General Surgery/*education/standards; Humans; International Educational Exchange; Internationality; Internship and Residency; Interviews as Topic; Perception; Peru; Qualitative Research; *Quality of Health Care; Surgeons/*psychology; *Traumatology  
  Abstract Importance: The globalization of medical education-the process by which trainees in any region gain access to international training (electronic or in-person)-is a growing trend. More data are needed to inform next steps in the responsible stewardship of this process, from the perspective of trainees and institutions at all income levels, and for use by national and international policymakers. Objective: To describe the impact of the globalization of medical education on surgical care in Peru from the perspective of Peruvian surgeons who received international training. Design, Setting, and Participants: Observational study of qualitative interviews conducted from September 2015 to January 2016 using grounded theory qualitative research methods. The study was conducted at 10 large public institutions that provide most of the trauma care in Lima, Peru, and included urban resident and faculty surgery and trauma care physicians. Exposures: Access to international surgical rotations and medical information. Main Outcomes and Measures: Outcome measures defining the impact of globalization on surgical care were developed as part of simultaneous data collection and analysis during qualitative research as part of a larger project on trauma quality improvement practices in Peru. Results: Fifty qualitative interviews of surgeons and emergency medicine physicians were conducted at 10 hospitals, including multiple from the public and social security systems. A median of 4 interviews were conducted at each hospital, and fewer than 3 interviews were conducted at only 1 hospital. From the broader theme of globalization emerged subthemes of an eroded sense of agency and a perception of inadequate training on the adaptation of international standards as negative effects of globalization on surgical care in Peru. Access to research funds, provision of incentives for acquisition of advanced clinical training, increased expectations for patient outcomes, and education in quality improvement skills are ways in which globalization positively affected surgeons and their patients in Peru. Conclusions and Relevance: Short-term overseas training of surgeons from low- and middle-income countries may improve care in the surgeons' country of origin through the acquisition of skills and altered expectations for excellence. Prioritization of evidence-based medical education is necessary given widespread internet access and thus clinician exposure to variable quality medical information. Finally, the establishment of centers of excellence in low- and middle-income countries may address the eroded sense of agency attributable to globalization and offer a local example of world-class surgical outcomes, diminishing surgeons' most frequently cited reason for emigration: access to better surgical training.  
  Address University of Washington, Seattle  
  Corporate Author Thesis  
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  Language English Summary Language Original Title  
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  Series Volume Series Issue Edition  
  ISSN 2168-6254 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:27893012 Approved no  
  Call Number ref @ user @ Serial 97649  
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Author Mercatelli, N.; Galardi, S.; Ciafre, S.A. url  doi
openurl 
  Title MicroRNAs as Multifaceted Players in Glioblastoma Multiforme Type Journal Article
  Year 2017 Publication International Review of Cell and Molecular Biology Abbreviated Journal Int Rev Cell Mol Biol  
  Volume 333 Issue Pages (up) 269-323  
  Keywords Biomarker; Cancer stem cells; Glioblastoma; MicroRNAs; Microenvironment; OncomomiRs; Therapy; Tumor suppressors  
  Abstract Glioblastoma multiforme (GBM) is the most common and inevitably lethal primary brain tumor, with a median survival rate of only 15 months from diagnosis. The current standard treatment involves maximal surgical resection flanked by radiotherapy and chemotherapy with the alkylating agent temozolomide. However, even such aggressive treatment is never curative, and recurrent tumors always arise, commonly in more aggressive, chemo- and radio-resistant forms, leading to untreatable and deadly tumors. MicroRNAs, recognized major players in cancer, are deeply involved in GBM, as shown by more than a decade of studies. In this review, we revise the main milestones of MicroRNA studies in GBM, and the latest relevant discoveries in this field. Examples are given of MicroRNAs working as “oncomiRs” or tumor suppressors, with specific connections with GBM clinical subtypes, patients' survival, and resistance to therapies. As the interaction of GBM cells with the microenvironment was proven as a key determinant of tumor growth, the role of MicroRNAs in GBM microenvironment, tumor angiogenesis, and tumor-secreted microvesicles is also reviewed. Finally, we discuss the latest findings presenting MicroRNAs as possible therapeutic targets for GBM, or their use as circulating biomarkers in diagnosis and prognosis.  
  Address Department of Biomedicine and Prevention, University of Rome “Tor Vergata”, Rome, Italy  
  Corporate Author Thesis  
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  Language English Summary Language Original Title  
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  Series Volume Series Issue Edition  
  ISSN 1937-6448 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28729027 Approved no  
  Call Number ref @ user @ Serial 96577  
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Author Griboff, J.; Horacek, M.; Wunderlin, D.A.; Monferran, M.V. url  doi
openurl 
  Title Bioaccumulation and trophic transfer of metals, As and Se through a freshwater food web affected by antrophic pollution in Cordoba, Argentina Type Journal Article
  Year 2017 Publication Ecotoxicology and Environmental Safety Abbreviated Journal Ecotoxicol Environ Saf  
  Volume 148 Issue Pages (up) 275-284  
  Keywords Aquatic organisms; As; Biomagnification; Food web; Metals; Stable isotopes  
  Abstract The concentration of metals (Al, Cr, Mn, Fe, Ni, Cu, Zn, Ag, Cd, Hg, Pb, U), As and Se in different ecosystem components (water, sediment, plankton, shrimp, and fish muscle) has been determined in a eutrophic reservoir in the Province of Cordoba (Argentina). Los Molinos Lake (LML) was sampled during the dry (DS) and wet seasons (WS) in order to examine the bioaccumulation and transfer of these inorganic elements through the food web. Stable nitrogen isotope (delta15N) was used to investigate trophic interactions. According to this, samples were divided into three categories: plankton, shrimp (Palaemonetes argentinus) and fish (Silverside, Odontesthes bonariensis). The bioaccumulation factor (BAF) was calculated for the organisms, and it was determined that the elements analyzed undergo bioaccumulation, especially in organisms such as plankton. The invertebrates were characterized by the highest BAF for Cu and Zn in both seasons, As (DS), and Cd and Hg (WS). The fish muscle was characterized by the highest BAF for Se (WS), Ag and Hg (DS). On the other hand, a significant decrease in Al, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Cd and U concentrations through the analyzed trophic web during both seasons was observed. Moreover, a significant increase in Hg levels was observed with increasing trophic levels in the DS, indicating its biomagnification. Despite the increasing impact of metals, As and Se pollution in the studied area due to urban growth and agricultural and livestock activities, no previous study has focused on the behavior and relationships of these pollutants with the biotic and abiotic components of this aquatic reservoir. We expect that these findings may be used for providing directions or guidance for future monitoring and environmental protection policies.  
  Address ICYTAC, Instituto de Ciencia y Tecnologia de Alimentos Cordoba, CONICET and Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Bv. Dr. Juan Filloy s/n, Ciudad Universitaria, 5000 Cordoba, Argentina. Electronic address: mmonferran@fcq.unc.edu.ar  
  Corporate Author Thesis  
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  Language English Summary Language Original Title  
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  Series Volume Series Issue Edition  
  ISSN 0147-6513 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:29078130 Approved no  
  Call Number ref @ user @ Serial 98006  
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Author Cole, D.C.; Giordano, C.R.; Vasilopoulos, T.; Fahy, B.G. url  doi
openurl 
  Title Resident Physicians Improve Nontechnical Skills When on Operating Room Management and Leadership Rotation Type Journal Article
  Year 2017 Publication Anesthesia and Analgesia Abbreviated Journal Anesth Analg  
  Volume 124 Issue 1 Pages (up) 300-307  
  Keywords  
  Abstract BACKGROUND: Anesthesiology residency primarily emphasizes the development of medical knowledge and technical skills. Yet, nontechnical skills (NTS) are also vital to successful clinical practice. Elements of NTS are communication, teamwork, situational awareness, and decision making. METHODS: The first 10 consecutive senior residents who chose to participate in this 2-week elective rotation of operating room (OR) management and leadership training were enrolled in this study, which spanned from March 2013 to March 2015. Each resident served as the anesthesiology officer of the day (AOD) and was tasked with coordinating OR assignments, managing care for 2 to 4 ORs, and being on call for the trauma OR; all residents were supervised by an attending AOD. Leadership and NTS techniques were taught via a standardized curriculum consisting of leadership and team training articles, crisis management text, and daily debriefings. Resident self-ratings and attending AOD and charge nurse raters used the Anaesthetists' Non-Technical Skills (ANTS) scoring system, which involved task management, situational awareness, teamwork, and decision making. For each of the 10 residents in their third year of clinical anesthesiology training (CA-3) who participated in this elective rotation, there were 14 items that required feedback from resident self-assessment and OR raters, including the daily attending AOD and charge nurse. Results for each of the items on the questionnaire were compared between the beginning and the end of the rotation with the Wilcoxon signed-rank test for matched samples. Comparisons were run separately for attending AOD and charge nurse assessments and resident self-assessments. Scaled rankings were analyzed for the Kendall coefficient of concordance (omega) for rater agreement with associated chi and P value. RESULTS: Common themes identified by the residents during debriefings were recurrence of challenging situations and the skills residents needed to instruct and manage clinical teams. For attending AOD and charge nurse assessments, resident performance of NTS improved from the beginning to the end of the rotation on 12 of the 14 NTS items (P < .05), whereas resident self-assessment improved on 3 NTS items (P < .05). Interrater reliability (across the charge nurse, resident, and AOD raters) ranged from omega = .36 to .61 at the beginning of the rotation and omega = .27 to .70 at the end of the rotation. CONCLUSIONS: This rotation allowed for teaching and resident assessment to occur in a way that facilitated resident education in several of the skills required to meet specific milestones. Resident physicians are able to foster NTS and build a framework for clinical leadership when completing a 2-week senior elective as an OR manager.  
  Address From the Department of Anesthesiology, University of Florida, College of Medicine, Gainesville, Fla  
  Corporate Author Thesis  
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  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0003-2999 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:27918336 Approved no  
  Call Number ref @ user @ Serial 95061  
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