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Author Mihu, M.R.; Cabral, V.; Pattabhi, R.; Tar, M.T.; Davies, K.P.; Friedman, A.J.; Martinez, L.R.; Nosanchuk, J.D.
Title Sustained Nitric Oxide-Releasing Nanoparticles Interfere with Methicillin-Resistant Staphylococcus aureus Adhesion and Biofilm Formation in a Rat Central Venous Catheter Model Type Journal Article
Year 2017 Publication Antimicrobial Agents and Chemotherapy Abbreviated Journal Antimicrob Agents Chemother
Volume 61 Issue 1 Pages
Keywords Animals; Anti-Bacterial Agents/chemistry/*pharmacology; Bacterial Adhesion/drug effects; Biofilms/*drug effects/growth & development; Catheter-Related Infections/*drug therapy/microbiology; Central Venous Catheters; Chitosan/chemistry/pharmacology; Delayed-Action Preparations; Disease Models, Animal; Female; Glucose/chemistry; Humans; Methicillin-Resistant Staphylococcus aureus/*drug effects/growth & development/ultrastructure; Nanoparticles/*administration & dosage/chemistry; Nitric Oxide/chemical synthesis/*pharmacology; Oxidation-Reduction; Plankton/drug effects/growth & development; Rats; Rats, Sprague-Dawley; Sodium Nitrite/chemistry; Staphylococcal Infections/*drug therapy/microbiology; Staphylococcus aureus; antimicrobials; biofilms; nanoparticles; nitric oxide
Abstract Staphylococcus aureus is frequently isolated in the setting of infections of indwelling medical devices, which are mediated by the microbe's ability to form biofilms on a variety of surfaces. Biofilm-embedded bacteria are more resistant to antimicrobial agents than their planktonic counterparts and often cause chronic infections and sepsis, particularly in patients with prolonged hospitalizations. In this study, we demonstrate that sustained nitric oxide-releasing nanoparticles (NO-np) interfere with S. aureus adhesion and prevent biofilm formation on a rat central venous catheter (CVC) model of infection. Confocal and scanning electron microscopy showed that NO-np-treated staphylococcal biofilms displayed considerably reduced thicknesses and bacterial numbers compared to those of control biofilms in vitro and in vivo, respectively. Although both phenotypes, planktonic and biofilm-associated staphylococci, of multiple clinical strains were susceptible to NO-np, bacteria within biofilms were more resistant to killing than their planktonic counterparts. Furthermore, chitosan, a biopolymer found in the exoskeleton of crustaceans and structurally integrated into the nanoparticles, seems to add considerable antimicrobial activity to the technology. Our findings suggest promising development and translational potential of NO-np for use as a prophylactic or therapeutic against bacterial biofilms on CVCs and other medical devices.
Address Department of Microbiology and Immunology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York, 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 0066-4804 ISBN Medium
Area Expedition Conference
Notes (up) PMID:27821454 Approved no
Call Number ref @ user @ Serial 100161
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Author Moimaz, S.A.S.; Rocha, N.B.; Garbin, C.A.S.; Rovida, T.A.; Saliba, N.A.
Title Factors affecting intention to breastfeed of a group of Brazilian childbearing women Type Journal Article
Year 2017 Publication Women and Birth : Journal of the Australian College of Midwives Abbreviated Journal Women Birth
Volume 30 Issue 2 Pages e119-e124
Keywords Adult; Age Factors; Brazil; Breast Feeding/*psychology; Female; Humans; Mothers/*psychology; Pregnancy; Retrospective Studies; Socioeconomic Factors; Young Adult; Brazil; Breastfeeding; Breastfeeding difficulties; Breastfeeding initiation; Pregnancy
Abstract BACKGROUND: Knowing the intention of mothers is important to plan actions to improve exclusive breastfeeding rates. AIM: The objective of this retrospective study was to verify the intention to breastfeed and the intended breastfeeding duration of a group of women participating in a public prenatal dental care program in the city of Aracatuba, Brazil. METHODS: The records of 933 childbearing women were analyzed and their intention to breastfeed and intended breastfeeding duration were associated to women's age, ethnicity, marital status, education, employment, number of gestations, previous breastfeeding experience, previous breastfeeding guidance, presence of complications during pregnancy, and systemic diseases. Data were inserted into Epi Info 2000 and analyzed with Biostat, at a 5% level of significance, and confidence interval of 95%. FINDINGS: Participants mean age was 26.1+/-5.9years. The majority of women (96.5%) declared their intention to breastfeed their babies. The main variables to affect the intention to breastfeed were the number of gestations (p=0.001), previous breastfeeding experience (p=0.03), and previous breastfeeding guidance (p=0.01). Intended breastfeeding duration was significantly affected by women's age (p=0.04), employment (0.02), the number of gestations (p=0.001), and previous breastfeeding experience (p=0.04). CONCLUSIONS: Previous positive breastfeeding experience and guidance during prenatal examinations positively affected women's intention to breastfeed; while older, unemployed women in their second or more gestation and previous breastfeeding experience intended to breastfeed their children for longer periods of time.
Address Preventive and Social Dentistry Department, School of Dentistry, Sao Paulo State University (UNESP), Aracatuba, Brazil. Electronic address: nemre@foa.unesp.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 1871-5192 ISBN Medium
Area Expedition Conference
Notes (up) PMID:27840072 Approved no
Call Number ref @ user @ Serial 97339
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Author Clark, P.A.; Gaal, J.T.; Strebe, J.K.; Pasch, C.A.; Deming, D.A.; Kuo, J.S.; Robins, H.I.
Title The effects of tumor treating fields and temozolomide in MGMT expressing and non-expressing patient-derived glioblastoma cells Type Journal Article
Year 2017 Publication Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia Abbreviated Journal J Clin Neurosci
Volume 36 Issue Pages 120-124
Keywords Antineoplastic Agents, Alkylating/*pharmacology; Cell Line, Tumor; Cell Proliferation/drug effects/radiation effects; Cell Survival/drug effects/radiation effects; Cells, Cultured; DNA Modification Methylases/genetics/*metabolism; DNA Repair Enzymes/genetics/*metabolism; Dacarbazine/*analogs & derivatives/pharmacology; *Electromagnetic Fields; Glioblastoma/genetics/*metabolism; Humans; Neoplastic Stem Cells/drug effects/radiation effects; Neurons/drug effects/radiation effects; Tumor Suppressor Proteins/genetics/*metabolism; Cancer stem cells; Glioblastoma; MGMT methylation; Temozolomide; Tumor treating fields
Abstract A recent Phase 3 study of newly diagnosed glioblastoma (GBM) demonstrated the addition of tumor treating fields (TTFields) to temozolomide (TMZ) after combined radiation/TMZ significantly increased survival and progression free survival. Preliminary data suggested benefit with both methylated and unmethylated O-6-methylguanine-DNA methyl-transferase (MGMT) promoter status. To date, however, there have been no studies to address the potential interactions of TTFields and TMZ. Thus, the effects of TTFields and TMZ were studied in vitro using patient-derived GBM stem-like cells (GSCs) including MGMT expressing (TMZ resistant: 12.1 and 22GSC) and non-MGMT expressing (TMZ sensitive: 33 and 114GSC) lines. Dose-response curves were constructed using cell proliferation and sphere-forming assays. Results demonstrated a 10-fold increase in TMZ resistance of MGMT-expressing (12.1GSCs: IC50=160muM; 22GSCs: IC50=44muM) compared to MGMT non-expressing (33GSCs: IC50=1.5muM; 114GSCs: IC50=5.2muM) lines. TTFields inhibited 12.1 GSC proliferation at all tested doses (50-500kHz) with an optimal frequency of 200kHz. At 200kHz, TTFields inhibited proliferation and tumor sphere formation of both MGMT GSC subtypes at comparable levels (12.1GSC: 74+/-2.9% and 38+/-3.2%, respectively; 22GSC: 61+/-11% and 38+/-2.6%, respectively; 33GSC: 56+/-9.5% and 60+/-7.1%, respectively; 114 GSC: 79+/-3.5% and 41+/-4.3%, respectively). In combination, TTFields (200kHz) and TMZ showed an additive anti-neoplastic effect with equal efficacy for TTFields in both cell types (i.e., +/- MGMT expression) with no effect on TMZ resistance. This is the first demonstration of the effects of TTFields on cancer stem cells. The expansion of such studies may have clinical implications.
Address University of Wisconsin Carbone Cancer Center, UWSMPH, United States; Division of Hematology and Oncology, Department of Medicine, UWSMPH, United States; William S Middleton Memorial Veterans Hospital, Madison, WI, United States; Department of Neurology, UWSMPH, United States; Department of Human Oncology, UWSMPH, United States. Electronic address: hirobins@wisc.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 0967-5868 ISBN Medium
Area Expedition Conference
Notes (up) PMID:27865821 Approved no
Call Number ref @ user @ Serial 96622
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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.
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 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 (up) PMID:27893012 Approved no
Call Number ref @ user @ Serial 97649
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Author Sareddy, G.R.; Viswanadhapalli, S.; Surapaneni, P.; Suzuki, T.; Brenner, A.; Vadlamudi, R.K.
Title Novel KDM1A inhibitors induce differentiation and apoptosis of glioma stem cells via unfolded protein response pathway Type Journal Article
Year 2017 Publication Oncogene Abbreviated Journal Oncogene
Volume 36 Issue 17 Pages 2423-2434
Keywords Animals; Apoptosis/*drug effects; Cell Differentiation/*drug effects; Cell Line, Tumor; Cell Survival/drug effects; Cell Transformation, Neoplastic; Disease Progression; Enzyme Inhibitors/*pharmacology; Gene Expression Regulation, Neoplastic/drug effects; Glioma/*pathology; Histone Demethylases/*antagonists & inhibitors; Mice; Neoplastic Stem Cells/*drug effects/metabolism/pathology; Signal Transduction/drug effects; Survival Analysis; Transcription, Genetic/drug effects; Unfolded Protein Response/*drug effects
Abstract Glioma stem cells (GSCs) have a central role in glioblastoma (GBM) development and chemo/radiation resistance, and their elimination is critical for the development of efficient therapeutic strategies. Recently, we showed that lysine demethylase KDM1A is overexpressed in GBM. In the present study, we determined whether KDM1A modulates GSCs stemness and differentiation and tested the utility of two novel KDM1A-specific inhibitors (NCL-1 and NCD-38) to promote differentiation and apoptosis of GSCs. The efficacy of KDM1A targeting drugs was tested on purified GSCs isolated from established and patient-derived GBMs using both in vitro assays and in vivo orthotopic preclinical models. Our results suggested that KDM1A is highly expressed in GSCs and knockdown of KDM1A using shRNA-reduced GSCs stemness and induced the differentiation. Pharmacological inhibition of KDM1A using NCL-1 and NCD-38 significantly reduced the cell viability, neurosphere formation and induced apoptosis of GSCs with little effect on differentiated cells. In preclinical studies using orthotopic models, NCL-1 and NCD-38 significantly reduced GSCs-driven tumor progression and improved mice survival. RNA-sequencing analysis showed that KDM1A inhibitors modulate several pathways related to stemness, differentiation and apoptosis. Mechanistic studies showed that KDM1A inhibitors induce activation of the unfolded protein response (UPR) pathway. These results strongly suggest that selective targeting of KDM1A using NCL-1 and NCD-38 is a promising therapeutic strategy for elimination of GSCs.
Address Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, San Antonio, TX, 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 0950-9232 ISBN Medium
Area Expedition Conference
Notes (up) PMID:27893719 Approved no
Call Number ref @ user @ Serial 96621
Permanent link to this record