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Polymyxin is used as a last resort antibiotics for infections caused by multi-drug resistant (MDR) Gram-negative bacteria and is often combined with other antibiotics to improve clinical effectiveness. However, the synergism of colistin and other antibiotics remains obscure. Here, we revealed a notable synergy between colistin and flavomycin, which was traditionally used as an animal growth promoter and has limited activity against Gram-negative bacteria, using checkerboard assay and time-kill curve analyses. The importance of membrane penetration induced by colistin was assessed by examining the intracellular accumulation of flavomycin and its antimicrobial impact on Escherichia coli ( E. coli ) strains with truncated lipopolysaccharides. Besides, a mutation in the flavomycin binding site was created to confirm its role in the observed synergy. This synergy is manifested as an augmented penetration of the E. coli outer membrane by colistin, leading to increased intracellular accumulation of flavomycin and enhanced cell killing thereafter. The observed synergy was dependent on the antimicrobial activity of flavomycin, as mutation of its binding site abolished the synergy. In vivo studies confirmed the efficacy of colistin combined with flavomycin against MDR E. coli infections. This study is the first to demonstrate the synergistic effect between colistin and flavomycin, shedding light on their respective roles in this synergism. Therefore, we propose flavomycin as an adjuvant to enhance the potency of colistin against MDR Gram-negative bacteria., Importance: Colistin is a critical antibiotic in combating multi-drug resistant Gram-negative bacteria, but the emergence of mobilized colistin resistance (mcr) undermines its effectiveness. Previous studies have found that colistin can synergy with various drugs; however, its exact mechanisms with hydrophobic drugs are still unrevealed. Generally, the membrane destruction of colistin is thought to be the essential trigger for its interactions with its partner drugs. Here, we use clustered regularly interspaced palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) for specifically mutating the binding site of one hydrophobic drug (flavomycin) and show that antimicrobial activity of flavomycin is critical for the synergy. Our results first give the evidence that the synergy is set off by colistin's membrane destruction and operated the final antimicrobial function by its partner drugs., Competing Interests: The authors declare no conflict of interest.

The plants of genus Clinopodium are perennial herbs of Labiatae, which are widely distributed in the world and have a promising medicinal value. Modern researches have shown flavonoids, triterpenoid saponins, terpene glycosides, terpenoids, volatile oils and phenylpropanoids are the main compounds in the plants, presenting various pharmacological effects such as hemostasis, anti-bacteria, anti-inflammation, immunoregulation, reducing blood glucose, antioxidation, and anti-tumor effects. The preparations made of those plants are mainly used for treatment of various bleeding diseases in clinical application. In this review, we systematically summarized the research progress on taxonomy, resource distribution, chemical compositions, pharmacological activities, and clinical application of the medicinal plants of genus Clinopodium. This review provides references and scientific basis for further research and development of genus Clinopodium.

Background: Eight infections occurred after modified radical mastectomies in a tertiary-care hospital. Group A streptococci (GAS) were isolated from three of the eight patients., Methods: To control the outbreak, an epidemiologic investigation was conducted, and healthcare workers were screened for pathogens. Strains isolated from healthcare workers were compared with patient strains by emm typing., Results: One surgeon attended one of the eight operations and observed the other seven. Streptococcus strains from the hands of this surgeon were identical to the patient strains. After the surgeon was suspended from duty and underwent eradication treatment, the outbreak was controlled., Conclusions: This outbreak of GAS infection is believed to have occurred by airborne transmission. Suspending patient care by healthcare workers who carry the causative GAS in a site(s) other than the respiratory tract for only the first 24 h they are receiving chemoprophylaxis may not be long enough. Sampling of the hands of healthcare workers during an investigation of nosocomial GAS infection is valuable.

One of the goal of the Nephron-Sparing Surgery properative planning is to delineate as exactly as possible the renal carcinoma and to specify its relations to the renal arterial, venous and collecting system anatomies. The classical preoperative imaging system is the Spiral CT Urography, which gives sucessive 3D acquisitions of complementary information The integration of this information within the a patient spacific anatomical referential can be achieved by intra-patient registration techniques. A local MI maximization registration method is proposed in this paper. The kidneys are extracted from the abdomen volumes and then the registration between the extracted kidneys is implemented by maximizing the MI between them. The experimental results demonstrates that this method is effective.

This paper describes an exonuclease-mediated enzyme-linked immunosorbent assay (ELISA)-like assay (EMEA) for detecting the DNA binding activity of nuclear factor kappaB (NF-kappaB). For EMEA, a special double-stranded DNA (dsDNA)-coupled plate was first prepared by immobilizing a DNA probe on an N-oxysuccinimide ester-coated plate. The immobilized DNA probe, which was internally labeled with digoxigenin (DIG)-dT contained a NF-kappaB binding consensus sequence for capturing activated NF- kappaB in analyzed samples. For measurement, the plate was first incubated with a protein sample and then treated with exonuclease III to eliminate the probes not bound by NF-kappaB. Finally, the probes protected by NF-kappaB were colorimetrically detected by an alkaline phosphatase (AP)-conjugated anti-DIG antibody. The major advantage of EMEA is that it detects NF-kappaB without the need for NF-kappaB antibodies. EMEA may provide a general approach for assays of DNA sequence-specific transcription factors for which specific antibodies are unavailable, expensive, or of insufficient quality.

Three isoforms of nitric oxide synthase (NOS) have been identified: endothelial NOS, neuronal NOS, and inducible NOS (iNOS). The enhanced expression of iNOS at the protein level using immunohistochemical technique has been reported previously in chemically induced oral carcinomas in hamster buccal-pouch mucosa. However, the corresponding expression of iNOS at the mRNA level has not yet been demonstrated using in situ reverse transcription-polymerase chain reaction (IS RT-PCR). The purpose of the present study is to assess the iNOS mRNA expression level in 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal-pouch carcinomas using IS RT-PCR. Thirty outbred, young (6-weeks old), male, Syrian golden hamsters (Mesocricatus auratus) were randomly divided into one experimental group (10 animals), and two control groups (10 animals each). The pouches of a group of 10 animals of the experimental group were painted bilaterally with a 0.5% DMBA solution three times a week for 15 weeks. Each animal of one of the control groups was similarly treated with only mineral oil. Another control group of 10 animals remained untreated throughout the experiment. Invasive squamous-cell carcinomas with a 100% tumour incidence developed in all of the DMBA-treated buccal pouches. The mineral oil-treated and untreated pouches revealed no obvious changes. Inducible NOS mRNA was demonstrated amongst all the 15-week DMBA-treated hamster buccal-pouch mucosa animals, but not in the untreated animals and not in the animals for which the buccal-pouch was treated with mineral oil. Further study is necessary to evaluate the mechanism(s) which contribute to the increased iNOS mRNA expression for experimentally induced oral carcinogenesis.

Introduction: Epileptic manifestations of Neurocysticercosis (NC) appear to depend on number and localization of the cysts. The objective of this study was to investigate the relationship between CT findings, number of parasites and the evolutive stage of the cysts, and the prognosis of epilepsy in children with NC., Method: We studied 28 patients with the parenchymal form of NC, considering: epilepsy duration; seizure frequency before and after AED treatment; seizure control; number of AED and recurrence after AED withdrawal. Clinical information was crossed with the number of lesions and disease activity in univariate comparison., Results: The analysis of the clinical data in relation to the number of lesions and disease activity showed no statistical difference among the variables (p>0.05)., Conclusion: We conclude that the course of epilepsy due to NC in childhood cannot be based exclusively on the number or stage of the parasites.