Antibacterial mode of fibrauretine and synergistic effect with kanamycin against multi-drug resistant Escherichia coli.

OBJECTIVE: The present study evaluated the antibacterial activity and mode of action of fibrauretine on Escherichia coli (E. coli) and Staphylococcus aureus, and synergistic effect with kanamycin against multi-drug resistant E. coli. RESULTS: The fibrauretine exhibited inhibitory effect on the growth of the tested bacteria with minimum inhibitory concentration (MIC) and minimum bactericidal concentration of 2.5-5 and 5-10 mg/ml, respectively. Morphological changes of cell microstructure were observed after adding fibrauretine at MIC. The mode of action was further confirmed by measuring release of 260-nm absorbing materials and extracellular potassium ions. Checkerboard dilution test suggested that fibrauretine exhibited synergistic activity when combined with kanamycin (FICI ranging from 0.5625 to 0.625). CONCLUSIONS: Our results indicated that fibrauretine exerted synergistic effect with kanamycin and its antibacterial mode of action mainly attributed to disruption of cell membrane integrity.

Novel and shared neoantigen derived from histone 3 variant H3.3K27M mutation for glioma T cell therapy.

The median overall survival for children with diffuse intrinsic pontine glioma (DIPG) is less than one year. The majority of diffuse midline gliomas, including more than 70% of DIPGs, harbor an amino acid substitution from lysine (K) to methionine (M) at position 27 of histone 3 variant 3 (H3.3). From a CD8+ T cell clone established by stimulation of HLA-A2+ CD8+ T cells with synthetic peptide encompassing the H3.3K27M mutation, complementary DNA for T cell receptor (TCR) α- and ß-chains were cloned into a retroviral vector. TCR-transduced HLA-A2+ T cells efficiently killed HLA-A2+H3.3K27M+ glioma cells in an antigen- and HLA-specific manner. Adoptive transfer of TCR-transduced T cells significantly suppressed the progression of glioma xenografts in mice. Alanine-scanning assays suggested the absence of known human proteins sharing the key amino acid residues required for recognition by the TCR, suggesting that the TCR could be safely used in patients. These data provide us with a strong basis for developing T cell-based therapy targeting this shared neoepitope.

Aminoglycoside susceptibility of Pasteurella multocida isolates from bovine respiratory infections in China and mutations in ribosomal protein S5 associated with high-level induced spectinomycin resistance.

Twenty-three isolates of Pasteurella multocida were tested for susceptibility to six aminoglycoside agents and screened by polymerase chain reaction for the presence of aminoglycoside resistance genes. In addition, mutations in the resistance-determining region of strains showing a high level of induced resistance to spectinomycin strains were examined. Susceptibility testing showed that all of the isolates were resistant to at least two types of aminoglycosides, and that the most effective antimicrobial was spectinomycin. The resistance genes aphA1, strB and aacA4 were present in all 23 isolates. In the three induced spectinomycin-resistant strains, a 9-bp deletion in rpsE that encodes ribosomal protein S5 was detected.

Postoperative [¹²5I] seed brachytherapy in the treatment of acinic cell carcinoma of the parotid gland: with associated risk factors.

BACKGROUND: This retrospective study was undertaken to analyze data from patients receiving iodine-125 ([(125)I]) seed brachytherapy postoperatively for the treatment of acinic cell carcinoma (ACC) of the parotid gland along with the following risk factors: residual tumor, recurrent tumor, facial nerve invasion, positive resection margins, advanced tumor stage, or tumor spillage. PATIENTS AND METHODS: Twenty-nine patients with ACC (17 females, 12 males; age range, 13-73 years; median age, 37.3 years) were included. Median follow-up was 58.2 months (range, 14-122 months). Patients received [(125)I] seed brachytherapy (median actuarial D90, 177 Gy) 3-41 days (median, 14 days) following surgery. Radioactivity was 18.5-33.3 MBq per seed, and the prescription dose was 80-120 Gy. RESULTS: The 3-, 5-, and 10-year rates of local control were 93.1, 88.7, and 88.7 %, respectively; overall survival was 96.6, 92, and 92 %; disease-free survival was 93.1, 88.4, and 88.4 %; and freedom from distant metastasis was 96.6, 91.2, and 91.2 %. Lymph node metastases were absent in all patients, although two patients died with distant metastases. Facial nerve recovery was quick, and no severe radiotherapy-related complications were noted. Recurrence history, local recurrence, and distant metastasis significantly affected overall survival. CONCLUSION: Postoperative [(125)I] seed brachytherapy is effective in treating ACC and has minor complications. Patients with a history of recurrence showed poor prognosis and were more likely to experience disease recurrence and develop metastases.

Using genetic algorithms to calibrate a water quality model.

With the increasing concern over the impact of diffuse pollution on water bodies, many diffuse pollution models have been developed in the last two decades. A common obstacle in using such models is how to determine the values of the model parameters. This is especially true when a model has a large number of parameters, which makes a full range of calibration expensive in terms of computing time. Compared with conventional optimisation approaches, soft computing techniques often have a faster convergence speed and are more efficient for global optimum searches. This paper presents an attempt to calibrate a diffuse pollution model using a genetic algorithm (GA). Designed to simulate the export of phosphorus from diffuse sources (agricultural land) and point sources (human), the Phosphorus Indicators Tool (PIT) version 1.1, on which this paper is based, consisted of 78 parameters. Previous studies have indicated the difficulty of full range model calibration due to the number of parameters involved. In this paper, a GA was employed to carry out the model calibration in which all parameters were involved. A sensitivity analysis was also performed to investigate the impact of operators in the GA on its effectiveness in optimum searching. The calibration yielded satisfactory results and required reasonable computing time. The application of the PIT model to the Windrush catchment with optimum parameter values was demonstrated. The annual P loss was predicted as 4.4 kg P/ha/yr, which showed a good fitness to the observed value.

An investigation into the inputs controlling predictions from a diffuse phosphorus loss model for the UK; the Phosphorus Indicators Tool (PIT).

A simple catchment scale model simulating diffuse phosphorus (P) loss from agricultural land to water, the Phosphorus Indicators Tool (PIT), has been developed. Previous research has shown that this model worked well in simulating the average annual P lost from two catchments: Windermere and Windrush, but it was not known which drivers in the model had the greatest control on predicted P delivery to water from agricultural land. In order to simulate the P export from each catchment source via each hydrological pathway specified individually, 108 coefficients are used in the model code. A univariate sensitivity analysis was conducted to evaluate which coefficient exerted the greatest control on the model output. Results from the univariate analysis suggest that the model is sensitive to a number of coefficients, but importantly, not all of the coefficients that were varied in the sensitivity analysis, altered the model output. The PIT model has been calibrated by optimizing results from the univariate analysis against observed data in the Windermere catchment. The simulated results from model calibration fit the observed data well, at the 95% level. This paper describes the methodology developed for the univariate analysis and evaluates the model calibration procedure against observed data from the Windermere catchment.