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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. |
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Title |
Sustained Nitric Oxide-Releasing Nanoparticles Interfere with Methicillin-Resistant Staphylococcus aureus Adhesion and Biofilm Formation in a Rat Central Venous Catheter Model |
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Journal Article |
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Year |
2017 |
Publication |
Antimicrobial Agents and Chemotherapy |
Abbreviated Journal |
Antimicrob Agents Chemother |
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61 |
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1 |
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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 |
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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. |
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Department of Microbiology and Immunology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York, USA |
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0066-4804 |
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PMID:27821454 |
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Call Number |
ref @ user @ |
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100161 |
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Author |
Rogers, A.E.J.; Eisenman, K.M.; Dolan, S.A.; Belderson, K.M.; Zauche, J.R.; Tong, S.; Gralla, J.; Hilden, J.M.; Wang, M.; Maloney, K.W.; Dominguez, S.R. |
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Title |
Risk factors for bacteremia and central line-associated blood stream infections in children with acute myelogenous leukemia: A single-institution report |
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Journal Article |
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Year |
2017 |
Publication |
Pediatric Blood & Cancer |
Abbreviated Journal |
Pediatr Blood Cancer |
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64 |
Issue |
3 |
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Keywords |
Adolescent; Bacteremia/*etiology; Bacteria/isolation & purification; Case-Control Studies; Catheter-Related Infections/*etiology; Catheterization, Central Venous/*adverse effects; Child; Child, Preschool; Cross Infection/*etiology; Female; Follow-Up Studies; Humans; Infant; Intensive Care Units, Pediatric; Leukemia, Myeloid, Acute/*complications/microbiology; Male; Prognosis; Retrospective Studies; Risk Factors; Clabsi; acute myelogenous leukemia; bacteremia; pediatric oncology |
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BACKGROUND: Central line-associated blood stream infections (CLABSIs) are a source of high morbidity and mortality in children with acute myelogenous leukemia (AML). PROCEDURE: To understand the epidemiology and risk factors associated with the development of CLABSI in children with AML. METHODS: We retrospectively reviewed all patients with AML over a 5-year period between 2007 and 2011 at the Children's Hospital Colorado. Cases and controls were classified on the basis of the presence of a CLABSI as defined by the National Healthcare Safety Network. RESULTS: Of 40 patients in the study, 25 (62.5%) developed at least one CLABSI during therapy. The majority of CLABSIs were due to oral or gastrointestinal organisms (83.0%). Skin organisms accounted for 8.5%. In a multivariable analysis, the strongest risk factors associated with CLABSI were diarrhea (odds ratio [OR] 6.7, 95% confidence interval [CI] 1.6-28.7), receipt of blood products in the preceding 4-7 days (OR 10.0, 95%CI 3.2-31.0), not receiving antibiotics (OR 8.3, 95%CI 2.8-25.0), and chemotherapy cycle (OR 3.5, 95%CI 1.4-8.9). CLABSIs led to increased morbidity, with 13 cases (32.5%) versus two controls (1.9%) requiring transfer to the pediatric intensive care unit (P < 0.001). Three (7.5%) of 40 CLABSI events resulted in or contributed to death. CONCLUSIONS: Intensified line care efforts cannot eliminate all CLABSIs in the patients with AML. Exploring the role of mucosal barrier breakdown and/or the use of antibiotic prophylaxis may be effective strategies for further prevention of CLABSIs, supporting ongoing trials in this patient population. |
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Department of Infectious Disease, University of Colorado Denver School of Medicine and Children's Hospital Colorado, Aurora, Colorado |
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1545-5009 |
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PMID:27616655 |
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Call Number |
ref @ user @ |
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100321 |
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Bijangi-Vishehsaraei, K.; Reza Saadatzadeh, M.; Wang, H.; Nguyen, A.; Kamocka, M.M.; Cai, W.; Cohen-Gadol, A.A.; Halum, S.L.; Sarkaria, J.N.; Pollok, K.E.; Safa, A.R. |
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Sulforaphane suppresses the growth of glioblastoma cells, glioblastoma stem cell-like spheroids, and tumor xenografts through multiple cell signaling pathways |
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Journal Article |
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Year |
2017 |
Publication |
Journal of Neurosurgery |
Abbreviated Journal |
J Neurosurg |
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1-12 |
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CCCP = carbonyl cyanide m-chlorophenylhydrazone; DMSO = dimethyl sulfoxide; DSB = double-strand break; EGF = epidermal growth factor; FACS = fluorescence-activated cell sorting; FGF = fibroblast growth factor; GBM = glioblastoma; GSC = glioblastoma stem cell; IC50 = 50% inhibition of cell survival; MRC = mitochondrial respiratory chain; MSC = mesenchymal stromal cell; NAC = N-acetylcysteine; NSG = nonobese diabetic scid gamma; PE = phycoerythrin; ROS = reactive oxygen species; SFN = sulforaphane; SSB = single-strand break; apoptosis; cancer stem cells; glioblastoma; oncology; sulforaphane |
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OBJECTIVE Defects in the apoptotic machinery and augmented survival signals contribute to drug resistance in glioblastoma (GBM). Moreover, another complexity related to GBM treatment is the concept that GBM development and recurrence may arise from the expression of GBM stem cells (GSCs). Therefore, the use of a multifaceted approach or multitargeted agents that affect specific tumor cell characteristics will likely be necessary to successfully eradicate GBM. The objective of this study was to investigate the usefulness of sulforaphane (SFN)-a constituent of cruciferous vegetables with a multitargeted effect-as a therapeutic agent for GBM. METHODS The inhibitory effects of SFN on established cell lines, early primary cultures, CD133-positive GSCs, GSC-derived spheroids, and GBM xenografts were evaluated using various methods, including GSC isolation and the sphere-forming assay, analysis of reactive oxygen species (ROS) and apoptosis, cell growth inhibition assay, comet assays for assessing SFN-triggered DNA damage, confocal microscopy, Western blot analysis, and the determination of in vivo efficacy as assessed in human GBM xenograft models. RESULTS SFN triggered the significant inhibition of cell survival and induced apoptotic cell death, which was associated with caspase 3 and caspase 7 activation. Moreover, SFN triggered the formation of mitochondrial ROS, and SFN-triggered cell death was ROS dependent. Comet assays revealed that SFN increased single- and double-strand DNA breaks in GBM. Compared with the vehicle control cells, a significantly higher amount of gamma-H2AX foci correlated with an increase in DNA double-strand breaks in the SFN-treated samples. Furthermore, SFN robustly inhibited the growth of GBM cell-induced cell death in established cell cultures and early-passage primary cultures and, most importantly, was effective in eliminating GSCs, which play a major role in drug resistance and disease recurrence. In vivo studies revealed that SFN administration at 100 mg/kg for 5-day cycles repeated for 3 weeks significantly decreased the growth of ectopic xenografts that were established from the early passage of primary cultures of GBM10. CONCLUSIONS These results suggest that SFN is a potent anti-GBM agent that targets several apoptosis and cell survival pathways and further preclinical and clinical studies may prove that SFN alone or in combination with other therapies may be potentially useful for GBM therapy. |
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Departments of 2 Pharmacology and Toxicology and |
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0022-3085 |
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PMID:28059653 |
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ref @ user @ |
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96613 |
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Barros, J.; Morales, S.; Echavarri, O.; Garcia, A.; Ortega, J.; Asahi, T.; Moya, C.; Fischman, R.; Maino, M.P.; Nunez, C. |
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Suicide detection in Chile: proposing a predictive model for suicide risk in a clinical sample of patients with mood disorders |
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Journal Article |
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Year |
2017 |
Publication |
Revista Brasileira de Psiquiatria (Sao Paulo, Brazil : 1999) |
Abbreviated Journal |
Rev Bras Psiquiatr |
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39 |
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1-11 |
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Adolescent; Adult; Chile; Female; Humans; Male; Mental Disorders/complications/*psychology; Middle Aged; Models, Theoretical; Risk Factors; Sensitivity and Specificity; Socioeconomic Factors; Suicide/*prevention & control; Surveys and Questionnaires; Young Adult |
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Objective:: To analyze suicidal behavior and build a predictive model for suicide risk using data mining (DM) analysis. Methods:: A study of 707 Chilean mental health patients (with and without suicide risk) was carried out across three healthcare centers in the Metropolitan Region of Santiago, Chile. Three hundred forty-three variables were studied using five questionnaires. DM and machine-learning tools were used via the support vector machine technique. Results:: The model selected 22 variables that, depending on the circumstances in which they all occur, define whether a person belongs in a suicide risk zone (accuracy = 0.78, sensitivity = 0.77, and specificity = 0.79). Being in a suicide risk zone means patients are more vulnerable to suicide attempts or are thinking about suicide. The interrelationship between these variables is highly nonlinear, and it is interesting to note the particular ways in which they are configured for each case. The model shows that the variables of a suicide risk zone are related to individual unrest, personal satisfaction, and reasons for living, particularly those related to beliefs in one's own capacities and coping abilities. Conclusion:: These variables can be used to create an assessment tool and enables us to identify individual risk and protective factors. This may also contribute to therapeutic intervention by strengthening feelings of personal well-being and reasons for staying alive. Our results prompted the design of a new clinical tool, which is fast and easy to use and aids in evaluating the trajectory of suicide risk at a given moment. |
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Private practice |
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1516-4446 |
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PMID:27783715 |
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ref @ user @ |
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97654 |
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Author |
Leite, F.H.M.; de Carvalho Cremm, E.; de Abreu, D.S.C.; Oliveira, M.A. de; Budd, N.; Martins, P.A. |
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Association of neighbourhood food availability with the consumption of processed and ultra-processed food products by children in a city of Brazil: a multilevel analysis |
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Journal Article |
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2017 |
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Public Health Nutrition |
Abbreviated Journal |
Public Health Nutr |
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1-12 |
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Children; Food consumption; Food environment; Neighbourhood; Ultra-processed food products |
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OBJECTIVE: To investigate the association between neighbourhood food availability and the consumption of ready-to-consume products (RCP), either processed or ultra-processed, and unprocessed/minimally processed foods (UF-MPF) by children. DESIGN: Cross-sectional. 24 h Dietary recalls were collected from children from January 2010 to June 2011. Neighbourhood food availability data were collected from 672 food stores located within 500 m of participants' homes, using an adapted and validated instrument. Neighbourhood-level socio-economic status (SES) was obtained by calculating the mean years of household head's education level in each census tract covered by 500 m buffers. Foods that were consumed by children and/or available in the food stores were classified based on their degree of industrial processing. Multilevel random-effect models examined the association between neighbourhood food availability and children's diets. SETTING: Santos, Brazil. SUBJECTS: Children (n 513) under 10 years old (292 aged <6 years, 221 aged >/=6 years). RESULTS: The availability of RCP in food stores was associated with increased RCP consumption (P<0.001) and decreased UF-MPF consumption (P<0.001). The consumption of UF-MPF was positively associated with neighbourhood-level SES (P<0.01), but not with the availability of UF-MPF in the neighbourhood. CONCLUSIONS: Results suggest that food policies and interventions that aim to reduce RCP consumption in Santos and similar settings should focus on reducing the availability in food stores. The results also suggest that interventions should not only increase the availability of UF-MPF in lower-SES neighbourhoods, but should strive to make UF-MPF accessible within these environments. |
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1Department of Human Movement Science,Nutritional Epidemiology Laboratory,Federal University of Sao Paulo,95 Ana Costa Avenue,Santos,Sao Paulo 11060001,Brazil |
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1368-9800 |
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PMID:28095942 |
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ref @ user @ |
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98031 |
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