Phage ΦPan70, a Putative Temperate Phage,Controls Pseudomonas aeruginosa in Planktonic,Biofilm and Burn Mouse Model Assays

Pseudomonas aeruginosa is one of the Multi-Drug-Resistant organisms most frequently isolated worldwide and, because of a shortage of new antibiotics, bacteriophages are considered an alternative for its treatment. Previously, P. aeruginosa phages were isolated and best candidates were chosen based on their ability to form clear plaques and their host range. This work aimed to characterize one of those phages, ΦPan70, preliminarily identified as a good candidate for phage-therapy. We performed infection curves, biofilm removal assays, transmission-electron-microscopy, pulsed-field-gel-electrophoresis, and studied the in vivo ΦPan70 biological activity in the burned mouse model. ΦPan70 was classified as a member of the Myoviridae family and, in both planktonic cells and biofilms, was responsible for a significant reduction in the bacterial population. The burned mouse model showed an animal survival between 80% and 100%, significantly different from the control animals (0%). However, analysis of the ΦPan70 genome revealed that it was 64% identical to F10, a temperate P. aeruginosa phage. Gene annotation indicated ΦPan70 as a new, but possible temperate phage, therefore not ideal for phage-therapy. Based on this, we recommend genome sequence analysis as an early step to select candidate phages for potential application in phage-therapy, before entering into a more intensive characterization.     

Smoking and chronic pain: a real-but-puzzling relationship

Smoking produces profound changes in physiology beyond those associated with the delivery of nicotine to the bloodstream. It has long been known that these changes put patients at risk for heart disease, cancers, and lung diseases. More recently, it has been discovered that smoking is a risk factor for chronic pain. Robust epidemiological evidence is showing that smokers not only have higher rates of chronic pain but also rate their pain as more intense than nonsmokers. Because the relationship between smoking and pain is of relevance to clinicians in many specialties, researchers at Mayo Clinic are examining this relationship in depth. This article describes some of what they and others have discovered in recent years about the interactions between smoking and chronic pain.     

Treatment of Middle Cerebral Artery Aneurysms with Flow-Diverter Stents: A Systematic Review and Meta-Analysis

BACKGROUND:The safety and efficacy of flow-diversion treatment of MCA aneurysms have not been well-established.PURPOSE:Our aim was to evaluate angiographic and clinical outcomes after flow diversions for MCA aneurysms.DATA SOURCES:A systematic search of PubMed, MEDLINE, and Embase was performed for studies published from 2008 to May 2017.STUDY SELECTION:According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we selected studies with >5 patients describing angiographic and clinical outcomes after flow-diversion treatment of MCA aneurysms.DATA ANALYSIS:Random-effects meta-analysis was used to pool the following outcomes: aneurysm occlusion rate, procedure-related complications, rupture rate of treated aneurysms, and occlusion of the jailed branches.DATA SYNTHESIS:Twelve studies evaluating 244 MCA aneurysms were included in this meta-analysis. Complete/near-complete occlusion was obtained in 78.7% (95% CI, 67.8%–89.7%) of aneurysms. The rupture rate of treated aneurysms during follow-up was 0.4% per aneurysm-year. The rate of treatment-related complications was 20.7% (95% CI, 14%–27.5%), and approximately 10% of complications were permanent. The mortality rate was close to 2%. Nearly 10% (95% CI, 4.7%–15.5%) of jailed arteries were occluded during follow-up, whereas 26% (95% CI, 14.4%–37.6%) had slow flow. Rates of symptoms related to occlusion and slow flow were close to 5%.LIMITATIONS:Small and retrospective series could affect the strength of the reported results.CONCLUSIONS:Given the not negligible rate of treatment-related complications, flow diversion for MCA aneurysms should be considered an alternative treatment when traditional treatment methods are not feasible. However, when performed in this select treatment group, high rates of aneurysm occlusion and protection against re-rupture can be achieved.

Flow-diverter stents have become a feasible and effective treatment for most intracranial aneurysms, and their indications are constantly extended, including distal aneurysm locations.^1–3 Commonly, middle cerebral artery aneurysms present with a particularly complex anatomy because of the frequency of wide-neck configurations with incorporating MCA branches. Endovascular treatment of MCA aneurysms can be technically more challenging, and in many institutions, surgical treatment is considered the first option because of the high rate of long-term occlusion with low surgical morbidity.⁴ However, with the improvement of angiographic images, increased operator experience, and the use of more complex techniques, an increasing number of MCA aneurysms are treated with endovascular techniques.¹ Recently, flow diversion has been used as an alternative technique for complex wide-neck MCA aneurysms, incorporating ≥1 side branch or in cases of previous endovascular or surgical failure.^5–14 However, the role of flow diversion in this location is controversial, and the efficacy and safety of this technique remain unclear. We performed a systematic review and meta-analysis of all published series examining flow diversions for the treatment of MCA aneurysms with the aim of clarifying the following: 1) aneurysm occlusion rate, 2) treatment-related complications and clinical outcome, and 3) the fate of the MCA side branch covered with the device.     

Diaphragm motor unit recruitment in rats

We hypothesized that considerable force reserve exists for the diaphragm muscle (DIAm) to generate transdiaphragmatic pressures (Pdi) necessary to sustain ventilation. In rats, we measured Pdi and DIAm EMG activity during different ventilatory (eupnea and hypoxia (10% O₂)–hypercapnia (5% CO₂)) and non-ventilatory (airway occlusion and sneezing induced by intranasal capsaicin) behaviors. Compared to maximum Pdi (Pdi_max generated by bilateral phrenic nerve stimulation), the Pdi generated during eupnea (21 ± 2%) and hypoxia–hypercapnia (28 ± 4%) were significantly less (p < 0.0001) than that generated during airway occlusion (63 ± 4%) and sneezing (94 ± 5%). The Pdi generated during spontaneous sighs was 62 ± 5% of Pdi_max. Relative DIAm EMG activity (root mean square [RMS] amplitude) paralleled the changes in Pdi during different ventilatory and non-ventilatory behaviors (r² = 0.78; p < 0.0001). These results support our hypothesis of a considerable force reserve for the DIAm to accomplish ventilatory behaviors. A model for DIAm motor unit recruitment predicted that ventilatory behaviors would require activation of only fatigue resistant units.