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Zapotoczna, M.; Forde, E.; Hogan, S.; Humphreys, H.; O'Gara, J.P.; Fitzgerald-Hughes, D.; Devocelle, M.; O'Neill, E. |
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Title |
Eradication of Staphylococcus aureus Biofilm Infections Using Synthetic Antimicrobial Peptides |
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Journal Article |
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Year |
2017 |
Publication |
The Journal of Infectious Diseases |
Abbreviated Journal |
J Infect Dis |
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Volume |
215 |
Issue  |
6 |
Pages |
975-983 |
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Keywords |
Animals; Anti-Bacterial Agents/*pharmacology; Biofilms/*drug effects; Catheter-Related Infections/*drug therapy; Cytokines/blood; Disease Models, Animal; Humans; Methicillin-Resistant Staphylococcus aureus/*drug effects; Microbial Sensitivity Tests; Peptides/*pharmacology; Peptides, Cyclic/pharmacology; Rats; Rats, Sprague-Dawley; Staphylococcal Infections/*drug therapy; Vancomycin/administration & dosage; *Staphylococcus aureus; *antimicrobial peptides (AMPs); *biofilm; *catheter lock solution (CLS) |
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Abstract |
Here, we demonstrate that antimicrobial peptides (AMPs) are an effective antibiofilm treatment when applied as catheter lock solutions (CLSs) against S. aureus biofilm infections. The activity of synthetic AMPs (Bac8c, HB43, P18, Omiganan, WMR, Ranalexin, and Polyphemusin) was measured against early and mature biofilms produced by methicillin-resistant S. aureus and methicillin-susceptible S. aureus isolates from patients with device-related infections grown under in vivo-relevant biofilm conditions. The cytotoxic and hemolytic activities of the AMPs against human cells and their immunomodulatory potential in human blood were also characterized. The D-Bac8c2,5Leu variant emerged as the most effective AMP during in vitro studies and was also highly effective in eradicating S. aureus biofilm infection when used in a CLS rat central venous catheter infection model. These data support the potential use of D-Bac8c2,5Leu, alone or in combination with other AMPs, in the treatment of S. aureus intravenous catheter infections. |
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Department of Microbiology, School of Natural Sciences, National University of Ireland, Galway, Ireland |
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0022-1899 |
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PMID:28453851 |
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no |
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ref @ user @ |
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100541 |
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Liu, Y.; Shen, Y.; Sun, T.; Yang, W. |
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Title |
Mechanisms regulating radiosensitivity of glioma stem cells |
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Journal Article |
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Year |
2017 |
Publication |
Neoplasma |
Abbreviated Journal |
Neoplasma |
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Volume |
64 |
Issue |
5 |
Pages |
655-665 |
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Keywords |
glioma stem cells; radiosensitivity signaling pathways. |
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Abstract |
Malignant glioblastoma (GBM) has become a very common and difficult brain tumor given its low cure rate and high recurrence rate. GBMs are resistant to treatments because glioma stem cells (GSCs)/glioma-initiating cells (GICs), a specific subpopulation of GBM, possess properties of tumor stem cells, such as unlimited proficiency, self-renewal, differentiation and resistance to chemotherapy and radiotherapy, and exhibit a very strong DNA repair capability. Radiotherapy has become a preponderant treatment, and researchers have found many significant tumor microenvironmental factors and valuable signaling pathways regulating the GSC radioresistance, including NOTCH, Wnt/beta-catenin, Hedgehog, STAT3, and PI3K/AKT/mTOR. Therefore, we seek to boost GSC radiosensitivity through activating or inactivating pathways alone or together to eliminate the likely source of glioma and prolong survival of patients. |
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0028-2685 |
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PMID:28592117 |
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Call Number |
ref @ user @ |
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96582 |
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Shahar, T.; Rozovski, U.; Hess, K.R.; Hossain, A.; Gumin, J.; Gao, F.; Fuller, G.N.; Goodman, L.; Sulman, E.P.; Lang, F.F. |
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Title |
Percentage of mesenchymal stem cells in high-grade glioma tumor samples correlates with patient survival |
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Journal Article |
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Year |
2017 |
Publication |
Neuro-Oncology |
Abbreviated Journal |
Neuro Oncol |
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Volume |
19 |
Issue |
5 |
Pages |
660-668 |
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Keywords |
*glioblastoma; *mesenchymal stem cells; *microenvironment; *prognosis |
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Abstract |
Background: Human mesenchymal stem cells (hMSCs) have been shown to reside as stromal cells in human gliomas as glioma-associated hMSCs (GA-hMSCs), but their biological role remains unclear. Because recent evidence indicates that GA-hMSCs drive tumor cell proliferation and stemness, we hypothesized that a higher percentage of GA-hMSCs in tumors predicts poor patient prognosis. Method: We determined the percentage of cells coexpressing GA-hMSC markers CD105+/CD73+/CD90+ from patients with newly diagnosed high-grade glioma and analyzed the association between this percentage and overall survival (OS) in 3 independent cohorts: fresh surgical glioblastoma specimens (cohort 1, N = 9), cultured tumor specimens at passage 3 (cohort 2, N = 28), and The Cancer Genome Atlas (TCGA) database. Results: In all cohorts, patient OS correlated with the percentages of GA-hMSCs in tumors. For cohort 1, the median OS of patients with tumors with a low percentage of triple-positive cells was 46 months, and for tumors with a high percentage of triple-positive cells, it was 12 months (hazard ratio [HR] = 0.24; 95% CI: 0.02-0.5, P = .02). For cohort 2, the median OS of patients with tumors with a low percentage of GA-hMSCs was 66 months, and for tumors with a high percentage, it was 11 months (HR = 0.38; 95% CI: 0.13-0.9, P = .04). In the database of TCGA, the median OS times in patients with high and low coexpression levels of CD105/CD73/CD90 were 8.4 months and 13.1 months (HR = 0.4; 95% CI: 0.1-0.88; P = .04), respectively. Conclusions: The percentage of GA-MSCs inversely correlates with OS, suggesting a role for GA-MSCs in promoting aggressive behavior of gliomas. |
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Brain Tumor Center, Unit 442, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA |
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1522-8517 |
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PMID:28453745 |
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Call Number |
ref @ user @ |
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96589 |
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Author |
Hudgins, J.D.; Goldberg, V.; Fell, G.L.; Puder, M.; Eisenberg, M.A. |
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Title |
Reducing Time to Antibiotics in Children With Intestinal Failure, Central Venous Line, and Fever |
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Journal Article |
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Year |
2017 |
Publication |
Pediatrics |
Abbreviated Journal |
Pediatrics |
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Volume |
140 |
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5 |
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Keywords |
Anti-Bacterial Agents/*administration & dosage; Bacteremia/diagnosis/drug therapy/epidemiology; Central Venous Catheters/microbiology; Child, Preschool; Cohort Studies; Female; Fever/diagnosis/*drug therapy/*epidemiology; Humans; Intestinal Diseases/diagnosis/drug therapy/epidemiology; Length of Stay/*trends; Male; Short Bowel Syndrome/diagnosis/*drug therapy/*epidemiology; Time-to-Treatment |
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BACKGROUND: Children with intestinal failure (IF) on parenteral nutrition (PN) are at high risk for bacteremia, and delays in antibiotic administration have been associated with increased morbidity and mortality. We designed an emergency department (ED) quality improvement (QI) initiative to reduce time to administration of intravenous antibiotics in febrile children with IF on PN. METHODS: Our aim was to decrease the mean time for febrile children with IF on PN to receive intravenous antibiotics by 50% to <60 minutes over a 12-month period. Secondary outcome measures were ED, hospital, and ICU length of stay (LOS). Our process measure was the rate of ordering recommended antibiotics, and our balancing measure was the rate of hypoglycemia. Interventions included increasing provider knowledge of IF, streamlining order entry, providing individualized feedback, and standardizing the triage process. Results were analyzed by using statistical process control methodology and time series analysis. RESULTS: We identified 149 eligible ED patients, of which 62 (41.6%) had bacteremia. The mean time to antibiotics decreased after the onset of the QI initiative from 112 to 39 minutes, and the ED LOS decreased from 286 to 247 minutes, but the total length of hospital and ICU stays were unchanged. The rate of hypoglycemia was also unchanged. CONCLUSIONS: Our QI intervention for febrile children with IF on PN shortened the time to receive antibiotics. Larger studies are needed to demonstrate the impact on overall LOS and mortality. |
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Division of Emergency Medicine and |
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0031-4005 |
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PMID:29066581 |
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Call Number |
ref @ user @ |
Serial |
98935 |
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Author |
Loza-Correa, M.; Kou, Y.; Taha, M.; Kalab, M.; Ronholm, J.; Schlievert, P.M.; Cahill, M.P.; Skeate, R.; Cserti-Gazdewich, C.; Ramirez-Arcos, S. |
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Septic transfusion case caused by a platelet pool with visible clotting due to contamination with Staphylococcus aureus |
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Journal Article |
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Year |
2017 |
Publication |
Transfusion |
Abbreviated Journal |
Transfusion |
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57 |
Issue |
5 |
Pages |
1299-1303 |
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Keywords |
Aged; Anti-Bacterial Agents/therapeutic use; Central Venous Catheters/microbiology; Erythrocyte Transfusion/adverse effects; Female; Humans; Leukemia, Myeloid, Acute/therapy; Platelet Transfusion/*adverse effects; Sepsis/*etiology; Staphylococcal Infections/*transmission; *Staphylococcus aureus; Transfusion Reaction/*microbiology |
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BACKGROUND: Contamination of platelet concentrates (PCs) with Staphylococcus aureus is one of the most significant ongoing transfusion safety risks in developed countries. CASE REPORT: This report describes a transfusion reaction in an elderly patient diagnosed with acute myeloid leukemia, transfused with a 4-day-old buffy coat PC through a central venous catheter. The transfusion was interrupted when a large fibrous clot in the PC obstructed infusion pump flow. Shortly afterward, a red blood cell (RBC) unit transfusion started. After septic symptoms were developed, the RBC transfusion was also interrupted. While the RBC unit tested negative for bacterial contamination, the PC and the patient samples were found to be contaminated with a S. aureus strain that exhibited the same phenotypic and genome sequencing profiles. The isolated S. aureus forms biofilms and produces the superantigen enterotoxin-like U, which was detected in a sample of the transfused PCs. The patient received posttransfusion antibiotic treatment and had her original central line removed and replaced. DISCUSSION: As the implicated PC had been tested for bacterial contamination during routine screening yielding negative results, this is a false-negative transfusion sepsis case. Using a point-of-care test could have prevented the transfusion reaction. This report highlights the increasing incidence of S. aureus as a major PC contaminant with grave clinical implications. Importantly, S. aureus is able to interact with platelet components resulting in visible changes in PCs. CONCLUSION: Visual inspection of blood components before transfusion is an essential safety practice to interdict the transfusion of bacterially contaminated units. |
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Canadian Blood Services |
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0041-1132 |
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PMID:28205241 |
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ref @ user @ |
Serial |
99087 |
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