Bacterial infections are becoming increasingly difficult to treat due to the development and spread of antibiotic resistance. Therefore, identifying novel antibacterial targets and new antibacterial agents capable of treating infections from drug-resistant bacteria is of vital importance. Structurally simple, yet potent fusaricidin or LI-F class of natural products represents a particularly attractive source of candidates for the development of new antibacterial agents. We have synthesized eighteen fusaricidin/LI-F analogs and investigated the effect of their structure modification on conformation, serum stability, antibacterial activity and human cell toxicity. Our findings show that substitution of an ester bond in depsipeptides with an amide bond may afford equally potent analogs with improved stability and greatly decreased cytotoxicity. Lower overall hydrophobicity/amphiphilicity of amide analogs in comparison to their parent depsipeptides, as indicated by the HPLC retention times, may explain dissociation of antibacterial activity and human cell cytotoxicity. These results indicate that amide analogs may have significant advantages over fusaricidin/LI-F natural products and their depsipeptide analogs as lead structures for the development of new antibacterial agents.
ACC of the breast has an indolent course, despite triple negative status. Our study suggests that radiation may not be warranted and confirms the rarity of axillary node metastases, indicating that sentinel node excision may also not be necessary. Ultimately, the hope is that our findings along with the reviewed literature will aid in determining the most appropriate options for management of ACC of the breast.
BackgroundThe initial approach to gastroesophageal reflux disease (GERD) management typically involves lifestyle modification and medical therapy utilizing acid reducing agents such as histamine blockers and proton pump inhibitors. In severe cases refractory to such treatments, surgical therapy may be indicated. The gold standard for surgical treatment of GERD is the laparoscopic Nissen fundoplication. In recent years, a new technique known as magnetic sphincter augmentation (MSA) has been developed using the Linx™ Reflux Management System. This is an implantable ring of magnetic beads that is placed around the esophagus at the gastroesophageal junction to restore lower esophageal integrity. The aim of this review is to discuss the current literature regarding indications, surgical technique, efficacy, and complications of MSA using the Linx device.MethodsA standardized literature search was performed yielding 367 abstracts. After elimination due to duplicates between databases and irrelevance, 96 articles remained. The information found to be significant and non-redundant was included in this review.ConclusionAfter several years of clinical application, the Linx device has been shown to not only be effective for the management of GERD but also be as effective as fundoplication. With respect to safety, the most common complication of MSA is dysphagia. This often resolved without intervention, but esophageal dilation or device explanation are occasionally necessary. Not fully appreciated in earlier reviews, erosion of the device into the esophagus appears to be the most significant complication of the device after extended follow-up. While very rare, the potentially severe consequences of this phenomenon suggest that the device should be used with some restraint and that patients should be made aware of this potential morbidity. Fortunately, in the few cases of device erosion described in the literature reviewed, the Linx device was easily and safely removed.
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