| Records |
| 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. |
| Title |
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 |
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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 |
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English |
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| ISSN |
1742-7061 |
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| Notes |
PMID:28576716 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
96583 |
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| Author |
Fogel, O.; Richard-Miceli, C.; Tost, J. |
| Title |
Epigenetic Changes in Chronic Inflammatory Diseases |
Type |
Journal Article |
| Year |
2017 |
Publication |
Advances in Protein Chemistry and Structural Biology |
Abbreviated Journal |
Adv Protein Chem Struct Biol |
| Volume |
106 |
Issue |
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Pages |
139-189 |
| Keywords |
Behcet's disease; Crohn's disease; DNA methylation; Ewas; Epigenetics; Histone modifications; Inflammatory bowel disease; Psoriasis; Spondyloarthritis; Ulcerative colitis |
| Abstract |
The number of people diagnosed with chronic inflammatory diseases has increased noteworthy in the last 40 years. Spondyloarthritis (SpA), inflammatory bowel diseases (IBD), and psoriasis are the most frequent chronic inflammatory diseases, resulting from a combination of genetic predisposition and environmental factors. Epigenetic modifications include DNA methylation, histone modifications, and small and long noncoding RNAs. They are influenced by environmental exposure, life-style, and aging and have recently been shown to be altered in many complex diseases including inflammatory diseases. While epigenetic modifications have been well characterized in other diseases such as cancer and autoimmune diseases, knowledge on changes in inflammatory diseases is lagging behind with some disease-specific differences. While the DNA methylation profile of different cell types in patients with IBD has been relatively well described, less is known on changes implicated in psoriasis, and no systematic genome-wide studies have so far been performed in SpA. In this chapter, we review in detail the reported changes in patterns of DNA methylation and posttranslational histone modifications in chronic inflammatory diseases highlighting potential connections between disease-associated pathophysiological changes such as the dysbiosis of the microbiome or genetic variations associated with disease susceptibility and the epigenome. We also discuss important parameters of meaningful epigenetic studies such as the use of well defined, disease-relevant cell populations, and elude on the potential future of engineering of the epigenome in inflammatory diseases. |
| Address |
Laboratory for Epigenetics and Environment, Centre National de Genotypage, CEA-Institut de Genomique, Evry, France. Electronic address: tost@cng.fr |
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English |
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1876-1623 |
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| Notes |
PMID:28057210 |
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no |
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ref @ user @ |
Serial |
96374 |
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| Author |
Goetz, L.G.; Valeggia, C. |
| Title |
The ecology of anemia: Anemia prevalence and correlated factors in adult indigenous women in Argentina |
Type |
Journal Article |
| Year |
2017 |
Publication |
American Journal of Human Biology : the Official Journal of the Human Biology Council |
Abbreviated Journal |
Am J Hum Biol |
| Volume |
29 |
Issue |
3 |
Pages |
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| Abstract |
OBJECTIVES: The Toba/Qom of Namqom are an indigenous community native to the Gran Chaco region of northern Argentina. Historically seminomadic foragers, the diet of peri-urban community members has rapidly changed from high-protein, high-fiber to hypercaloric, processed. This study aims to understand the impact of this nutritional transition on aspects of women's health by exploring the relationship between prevalence of anemia and current diet composition, place of birth, and reproductive history. METHODS: We measured the capillary hemoglobin (Hb) levels of 153 adult women. Each participant was also given two interviews characterizing reproductive history and a 24-hour food recall. RESULTS: The average Hb level was 12.6 g/dL (range 5.8-15.7 g/dL). In our sample, 28% of participants were anemic and 31% were borderline anemic. Iron and vitamin C consumption were negatively associated with Hb levels. Body mass index was marginally associated with Hb levels. Being born in a peri-urban setting, a proxy for early Westernized diet was associated with higher risk of anemia, suggesting developmental experience may play a role. Pregnant and lactating women had lower Hb levels than menstruating and menopausal women. Age, height, parity, and age at first pregnancy were not found to be statistically significant predictors of anemia. CONCLUSIONS: Iron deficiency represents a serious health concern for women, particularly pregnant ones. Our results suggest that both past and current nutritional ecology variables may be associated with the risk of anemia. These findings inform public health interventions, since reproductive history may be more difficult to modify than current diet. |
| Address |
Department of Anthropology, Yale University, New Haven, Connecticut, 05611 |
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English |
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Edition |
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| ISSN |
1042-0533 |
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| Notes |
PMID:28101997 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
98030 |
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| Author |
Cole, D.C.; Giordano, C.R.; Vasilopoulos, T.; Fahy, B.G. |
| 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 |
300-307 |
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| 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 |
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English |
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0003-2999 |
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| Notes |
PMID:27918336 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
95061 |
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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 |
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| 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 |
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English |
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Edition |
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0066-4804 |
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| Notes |
PMID:27821454 |
Approved |
no |
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ref @ user @ |
Serial |
99131 |
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