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Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Bacterial genomes encode various multidrug efflux pumps (MDR) whose specific conditions for fitness advantage are unknown. We show that the efflux pump MdtEF-TolC, in Escherichia coli, confers a fitness advantage during exposure to extreme acid (pH 2). Our flow cytometry method revealed pH-dependent fitness trade-offs between bile acids (a major pump substrate) and salicylic acid, a membrane-permeant aromatic acid that induces a drug resistance regulon but depletes proton motive force (PMF). The PMF drives MdtEF-TolC and related pumps such as AcrAB-TolC. Deletion of mdtE (with loss of the pump MdtEF-TolC) increased the strain's relative fitness during growth with or without salicylate or bile acids. However, when the growth cycle included a 2-h incubation at pH 2 (below the pH growth range), MdtEF-TolC conferred a fitness advantage. The fitness advantage required bile salts but was decreased by the presence of salicylate, whose uptake is amplified by acid. For comparison, AcrAB-TolC, the primary efflux pump for bile acids, conferred a PMF-dependent fitness advantage with or without acid exposure in the growth cycle. A different MDR pump, EmrAB-TolC, conferred no selective benefit during growth in the presence of bile acids. Without bile acids, all three MDR pumps incurred a large fitness cost with salicylate when exposed at pH 2. These results are consistent with the increased uptake of salicylate at low pH. Overall, we showed that MdtEF-TolC is an MDR pump adapted for transient extreme-acid exposure and that low pH amplifies the salicylate-dependent fitness cost for drug pumps. IMPORTANCE Antibiotics and other drugs that reach the gut must pass through stomach acid. However, little is known of how extreme acid modulates the effect of drugs on gut bacteria. We find that extreme-acid exposure leads to a fitness advantage for a multidrug pump that otherwise incurs a fitness cost. At the same time, extreme acid amplifies the effect of salicylate selection against multidrug pumps. Thus, organic acids and stomach acid could play important roles in regulating multidrug resistance in the gut microbiome. Our flow cytometry assay provides a way to measure the fitness effects of extreme-acid exposure to various membrane-soluble organic acids, including plant-derived nutrients and pharmaceutical agents. Therapeutic acids might be devised to control the prevalence of multidrug pumps in environmental and host-associated habitats.
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Proteínas de Transporte/metabolismo , Escherichia coli K12/metabolismo , Proteínas de Escherichia coli/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Ácidos/metabolismo , Proteínas de Transporte/genética , Escherichia coli K12/genética , Escherichia coli K12/crescimento & desenvolvimento , Proteínas de Escherichia coli/genética , Regulação Bacteriana da Expressão Gênica , Proteínas de Membrana/genética , Proteínas de Membrana Transportadoras/genéticaAssuntos
Pesquisa Biomédica , Procedimentos de Cirurgia Plástica , Cirurgia Plástica , Humanos , RedaçãoRESUMO
Targeted muscle reinnervation offers an approach to regain use of the affected extremity through electronic prosthesis while limiting phantom pain and neuroma limb production or pain. In this case report, we present the first reported case of leveraging the rectus flap for targeted muscle reinnervation. The case herein is of a 28-year-old woman who sustained a severe right upper extremity crush injury while being involved in a vehicular roll-over collision requiring right transhumeral amputation. Plastic surgery, orthopedic surgery, and vascular surgery were consulted to manage the right upper extremity injury.
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Background: OpenAI's ChatGPT can generate novel ideas for a number of applications. The aim of this study was to prompt the chatbot to generate possible innovations in aesthetic surgery relating to rhinoplasty. Methods: ChatGPT was prompted to develop rhinoplasty patents. The resulting outputs were tabulated and categorized based on technology domain and anatomic location. A Google Patents search was conducted to find uses of the term "rhinoplasty" between 2021 and 2023. Patents not pertaining to rhinoplasty were excluded. Filed patents were compared with those generated by ChatGPT to determine predictive power. Results: A total of 40 patents resulted from ChatGPT and 42 Google Patents from 2021 to 2023 were included. Patents generated without a detailed description command were related to preoperative planning (35%), intraoperative tools (30%), functional evaluation (15%), and 3D printing and implants (10%). Patents with a detailed description command resulted in the majority being postoperative tools (40%), followed by intraoperative tools (30%), 3D printing and implants (10%), and nonsurgical (10%) categories. The anatomic locations included the airway, dorsum, septum, and nasal tip. ChatGPT's predictive power yielded 45% for the detailed prompting, which was higher than the prompt without the detail command. Conclusions: ChatGPT has reasonable potential to generate ideas for innovations in plastic surgery with the assistance of an experienced surgeon-innovator. With new artificial intelligence generations and updates, chatbots will continue to improve. Determining whether these technologies can assist in the later portions of the patent process beyond idea generation will be crucial.
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TMR (targeted muscle reinnervation) or RPNI (regenerative peripheral nerve interface) have been the standard after nerve injuries. In this case report, we explain our approach in combining these two techniques (TMRpni) for a patient undergoing left above-the-knee amputation. Using this method, both phantom and nerve pain were reduced in our patient's case. As this technique becomes more well understood and widely adopted, amputee patients may achieve a greater quality of life post operation.