Biofilms are slimy aggregates of microbes that are likely responsible for many chronic infections as well as for contamination of clinical and industrial environments. Pseudomonas aeruginosa is a prevalent hospital pathogen that is well known for its ability to form biofilms that are recalcitrant to many different antimicrobial treatments. We have devised a high-throughput method for testing combinations of antimicrobials for synergistic activity against biofilms, including those formed by P. aeruginosa. This approach was used to look for changes in biofilm susceptibility to various biocides when these agents were combined with metal ions. This process identified that Cu 2؉ works synergistically with quaternary ammonium compounds (QACs; specifically benzalkonium chloride, cetalkonium chloride, cetylpyridinium chloride, myristalkonium chloride, and Polycide) to kill P. aeruginosa biofilms. In some cases, adding Cu 2؉ to QACs resulted in a 128-fold decrease in the biofilm minimum bactericidal concentration compared to that for single-agent treatments. In combination, these agents retained broad-spectrum antimicrobial activity that also eradicated biofilms of Escherichia coli, Staphylococcus aureus, Salmonella enterica serovar Cholerasuis, and Pseudomonas fluorescens. To investigate the mechanism of action, isothermal titration calorimetry was used to show that Cu 2؉ and QACs do not interact in aqueous solutions, suggesting that each agent exerts microbiological toxicity through independent biochemical routes. Additionally, Cu 2؉ and QACs, both alone and in combination, reduced the activity of nitrate reductases, which are enzymes that are important for normal biofilm growth. Collectively, the results of this study indicate that Cu 2؉ and QACs are effective combinations of antimicrobials that may be used to kill bacterial biofilms.

Objectives: The objective was to examine the feasibility, effectiveness, and adverse effect profile of intranasal ketamine for analgesia in emergency department (ED) patients.Methods: This was a prospective observational study examining a convenience sample of patients aged older than 6 years experiencing moderate or severe pain, defined as a visual analog scale (VAS) score of 50 mm or greater. Patients received 0.5 to 0.75 mg/kg intranasal ketamine. Pain scores were recorded on a standard 100-mm VAS by trained investigators at baseline, then every 5 minutes for 30 minutes, and then every 10 minutes for an additional 30 minutes. The primary outcome was the number and proportion of patients experiencing clinically significant reductions in VAS pain scores, defined as VAS reductions of 13 mm or more, within 30 minutes. Secondary outcomes included the median reduction in VAS, the median time required to achieve a 13 mm reduction in VAS, vital sign changes, and adverse events. Continuous data are reported with medians and interquartile ranges (IQRs). The Wilcoxon signed-ranks test was used to assess changes in VAS scores. Adverse effects are reported with proportions and 95% confidence intervals (CIs).Results: Forty patients were enrolled with a median age of 47 years (IQR = 36 to 57 years; range = 11 to 79 years) for primarily orthopedic injuries. A reduction in VAS of 13 mm or more within 30 minutes was achieved in 35 patients (88%). The median change in VAS at 30 minutes was 34 mm (44%). Median time required to achieve a 13 mm VAS reduction was 9.5 minutes (IQR = 5 to 13 minutes; range = 5 to 25 minutes). No serious adverse effects occurred. Minor adverse effects included dizziness (21 patients, 53%; 95% CI = 38% to 67%), feeling of unreality (14 patients, 35%; 95% CI = 22% to 50%), nausea (four patients, 10%; 95% CI = 4% to 23%), mood change (three patients, 8%; 95% CI = 3% to 20%), and changes in hearing (one patient, 3%; 95% CI = 0% to 13%). All adverse effects were transient and none required intervention. There were no changes in vital signs requiring clinical intervention.Conclusions: Intranasal ketamine reduced VAS pain scores to a clinically significant degree in 88% of ED patients in this series. Adverse effects were minor and transient. Intranasal ketamine may have a role in the provision of effective, expeditious analgesia to ED patients. ACADEMIC EMERGENCY MEDICINE 2013; 20:1050-1054 © 2013 by the Society for Academic Emergency Medicine T he provision of analgesia is a frequent and integral component of care in the emergency department (ED) setting, yet adequate and timely analgesia is often challenging due to scarcity of available health care providers, stretcher space, and monitoring availability in overcrowded EDs. This study

Summary To efficiently generate cardiomyocytes from embryonic stem (ES) cells in culture it is essential to identify key regulators of the cardiac lineage and to develop methods to control them. Using a tet-inducible ES cell line to enforce expression of a constitutively activated form of the Notch 4 receptor, we show that signaling through the Notch pathway can efficiently respecify hemangioblasts to a cardiac fate resulting in the generation of populations consisting of more than 60% cardiomyocytes. Microarray analyses revealed that this respecification is mediated, in part, through the coordinated regulation of the BMP and Wnt pathways by Notch signaling. Together, these findings have uncovered a potential novel role for the Notch pathway in cardiac development and in doing so provide a new approach for generating large numbers of cardiac progenitors from ES cells.

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Objectives: Current documentation methods for patients with skin and soft tissue infections receiving outpatient parenteral anti-infective therapy (OPAT) include written descriptions and drawings of the infection that may inadequately communicate clinical status. We undertook a study to determine whether photodocumentation (PD) improves the duration of outpatient treatment of skin and soft tissue infections. Methods: A single-blinded, prospective, randomized trial was conducted in the emergency departments of a community hospital and an academic tertiary centre. Participants included consecutive patients age $ 14 years presenting with noninvasive skin and soft tissue infections requiring OPAT. Patients in the intervention arm were treated with standard of care plus PD at each emergency physician assessment. Control subjects received care provided at the discretion of the treating physician and non-photographic documentation. The primary outcome was duration of therapy measured in half-days. The required sample size to detect a difference of one half-day was 253 patients per group (a 5 0.05). Secondary outcomes included (1) completion and therapeutic failure rates, (2) patient satisfaction, and (3) physician and nurse satisfaction. Results: Enrolment was slower and follow-up rates lower than anticipated, and the trial was terminated when funds were exhausted. A total of 468 subjects with similar age and gender characteristics were enrolled, with 244 receiving the intervention and 224 in the control arm. The mean OPAT duration was similar in the two groups (3.6 days v. 3.5 days, p 5 0.73). No differences in the rate for completion and therapeutic failure were observed (71% v. 68% and , 1% for both, respectively). Survey response rates varied significantly: patients, 65%; nurses, 17%; and physicians, 87%. Physicians endorsed more comfort with their assessment and OPAT judgment with PD (65% and 64%, respectively).Physicians cited too much time lost with technological challenges, which would affect implementation in a busy ED. Conclusions: PD as an intervention is acceptable to patients and has reasonable endorsement by the majority of physicians. This trial had significant limitations that threatened the integrity of the study, so the results are inconclusive. RÉ SUMÉObjectif: Les moyens actuels de documentation des infections de la peau et des tissus mous chez les patients soumis à un traitement anti-infectieux parenté ral ambulatoire (TAIPA) comprennent les descriptions é crites et les croquis des tissus infecté s, mais ces moyens peuvent ne pas rendre pleinement l'é tat clinique. Aussi avons-nous mené une é tude visant à dé terminer si la photodocumentation (PD) pouvait amé liorer la duré e du traitement des infections de la peau et des tissus mous chez les patients externes. Mé thode: Un essai prospectif, à ré partition alé atoire, et à simple insu a é té mené au service des urgences d'un hô pital communautaire et d'un centre hospitalier universitaire de soins tertiaires. Ont participé à l'essai des pati...

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