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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 (down) 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  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  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 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
openurl 
  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 (down) 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  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  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 Spencer, D.A.; Auffinger, B.M.; Murphy, J.P.; Muroski, M.E.; Qiao, J.; Gorind, Y.; Lesniak, M.S. url  doi
openurl 
  Title Hitting a Moving Target: Glioma Stem Cells Demand New Approaches in Glioblastoma Therapy Type Journal Article
  Year 2017 Publication Current Cancer Drug Targets Abbreviated Journal Curr Cancer Drug Targets  
  Volume 17 Issue 3 Pages (down) 236-254  
  Keywords Brain Neoplasms/drug therapy/pathology; Drug Resistance, Neoplasm/drug effects; Glioblastoma/*drug therapy/pathology; Glioma/drug therapy/*pathology; Humans; Molecular Targeted Therapy/*methods; Neoplastic Stem Cells/drug effects/*pathology/radiation effects; Chemotherapy; drug targets; glioblastoma multiforme; glioma stem cells; niches; recurrence; resistance  
  Abstract BACKGROUND: Glioblastoma multiforme (GBM) continues to devastate patients and outfox investigators and clinicians despite the preponderance of research directed at its biology, pathogenesis and therapeutic advances. GBM routinely outlasts multidisciplinary treatment protocols, almost inevitably recurring in a yet more aggressive and resistant form with distinct genetic differences from the original tumor. Attempts to glean further insight into GBM point increasingly toward a subpopulation of cells with a stem-like phenotype. These cancer stem cells, similar to those now described in a variety of malignancies, are capable of tumorigenesis from a population of susceptible cells. CONCLUSIONS: Glioma stem cells have thus become a prevalent focus in GBM research for their presumed role in development, maintenance and recurrence of tumors. Glioma stem cells infiltrate the white matter surrounding tumors and often evade resection. They are uniquely suited both biochemically and environmentally to resist the best therapy currently available, intrinsically and efficiently resistant to standard chemo- and radiotherapy. These stem cells create an extremely heterogenous tumor that to date has had an answer for every therapeutic question, with continued dismal patient survival. Targeting this population of glioma stem cells may hold the long-awaited key to durable therapeutic efficacy in GBM.  
  Address Neuro-Oncology Laboratory, Department of Neurosurgery, Northwestern University, 676 N. St. Clair Street, Suite 2210, Chicago, IL60611, United States  
  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 1568-0096 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:27993114 Approved no  
  Call Number ref @ user @ Serial 96616  
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Author Hu, B.; Emdad, L.; Kegelman, T.P.; Shen, X.-N.; Das, S.K.; Sarkar, D.; Fisher, P.B. url  doi
openurl 
  Title Astrocyte Elevated Gene-1 Regulates beta-Catenin Signaling to Maintain Glioma Stem-like Stemness and Self-Renewal Type Journal Article
  Year 2017 Publication Molecular Cancer Research : MCR Abbreviated Journal Mol Cancer Res  
  Volume 15 Issue 2 Pages (down) 225-233  
  Keywords Brain Neoplasms/genetics/metabolism/*pathology; Cell Adhesion Molecules/genetics/*metabolism; Cell Line, Tumor; Glioblastoma/genetics/metabolism/*pathology; Humans; Neoplastic Stem Cells/*pathology; Signal Transduction; Tumor Cells, Cultured; beta Catenin/genetics/*metabolism  
  Abstract Glioblastoma multiforme is a common malignant brain tumor that portends extremely poor patient survival. Recent studies reveal that glioma stem-like cells (GSC) are responsible for glioblastoma multiforme escape from chemo-radiotherapy and mediators of tumor relapse. Previous studies suggest that AEG-1 (MTDH), an oncogene upregulated in most types of cancers, including glioblastoma multiforme, plays a focal role linking multiple signaling pathways in tumorigenesis. We now report a crucial role of AEG-1 in glioma stem cell biology. Primary glioblastoma multiforme cells were isolated from tumor specimens and cultured as neurospheres. Using the surface marker CD133, negative and positive cells were separated as nonstem and stem populations by cell sorting. Tissue samples and low passage cells were characterized and compared with normal controls. Functional biological assays were performed to measure stemness, self-renewal, differentiation, adhesion, protein-protein interactions, and cell signaling. AEG-1 was upregulated in all glioblastoma multiforme neurospheres compared with normal neural stem cells. Expression of AEG-1 was strongly associated with stem cell markers CD133 and SOX2. AEG-1 facilitated beta-catenin translocation into the nucleus by forming a complex with LEF1 and beta-catenin, subsequently activating Wnt signaling downstream genes. Through an AEG-1/Akt/GSK3beta signaling axis, AEG-1 controlled phosphorylation levels of beta-catenin that stabilized the protein. IMPLICATIONS: This study discovers a previously unrecognized role of AEG-1 in GSC biology and supports the significance of this gene as a potential therapeutic target for glioblastoma multiforme. Mol Cancer Res; 15(2); 225-33. (c)2016 AACR.  
  Address VCU Massey Cancer Center, School of Medicine, Virginia Commonwealth University, Richmond, Virginia  
  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 1541-7786 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:27903708 Approved no  
  Call Number ref @ user @ Serial 96619  
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Author Del Brutto, O.H.; Mera, R.M.; Zambrano, M.; Del Brutto, V.J. url  doi
openurl 
  Title Severe edentulism is a major risk factor influencing stroke incidence in rural Ecuador (The Atahualpa Project) Type Journal Article
  Year 2017 Publication International Journal of Stroke : Official Journal of the International Stroke Society Abbreviated Journal Int J Stroke  
  Volume 12 Issue 2 Pages (down) 201-204  
  Keywords Adult; Comorbidity; Ecuador/epidemiology; Female; Follow-Up Studies; Humans; Hypertension/complications/epidemiology; Incidence; Male; Middle Aged; Mouth, Edentulous/complications/*epidemiology; Prospective Studies; Risk Factors; Rural Population; Severity of Illness Index; Stroke/complications/*epidemiology; Ecuador; Stroke incidence; cohort study; edentulism; stroke risk factors  
  Abstract Background There is no information on stroke incidence in rural areas of Latin America, where living conditions and cardiovascular risk factors are different from urban centers. Aim Using a population-based prospective cohort study design, we aimed to assess risk factors influencing stroke incidence in community-dwelling adults living in rural Ecuador. Methods First-ever strokes occurring from 1 June 2012 to 31 May 2016, in Atahualpa residents aged >/=40 years, were identified from yearly door-to-door surveys and other overlapping sources. Poisson regression models adjusted for demographics, cardiovascular risk factors, edentulism and the length of observation time per subject were used to estimate stroke incidence rate ratio as well as factors influencing such incidence. Results Of 807 stroke-free individuals prospectively enrolled in the Atahualpa Project, follow-up was achieved in 718 (89%), contributing 2,499 years of follow-up (average 3.48 +/- 0.95 years). Overall stroke incidence rate was 2.97 per 100 person-years of follow-up (95% CI: 1.73-4.2), which increased to 4.77 (95% CI: 1.61-14.1) when only persons aged >/=57 years were considered. Poisson regression models, adjusted for relevant confounders, showed that high blood pressure (IRR: 5.24; 95% CI: 2.55-7.93) and severe edentulism (IRR: 5.06; 95% CI: 2.28-7.85) were the factors independently increasing stroke incidence. Conclusions Stroke incidence in this rural setting is comparable to that reported from the developed world. Besides age and high blood pressure, severe edentulism is a major factor independently predicting incident strokes. Public awareness of the consequences of poor dental care might reduce stroke incidence in rural settings.  
  Address 4 Department of Neurology, University of Chicago, Chicago, IL, 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 1747-4930 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:27777377 Approved no  
  Call Number ref @ user @ Serial 97187  
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