Design of Triazolium-Grafted Peptidomimetic Macrocycles with Facial Amphipathicity to Target Pathogenic Bacteria.

Access to 1,2,3-triazolium-grafted peptoid macrocycles was developed by macrocyclization and multivalent postmodification of linear peptoid oligomers carrying an alternance of benzylic and propargyl groups as side chains. X-ray analysis and NMR studies revealed a conformational preference for constrained hairpin-shaped structures leading to the facial amphipathic character of these macrocycles. A preliminary evaluation showed the antimicrobial activities of these new cationic amphipathic architectures.

Clinical safety and efficacy of a single-dose gentamicin, posaconazole and mometasone furoate otic suspension for treatment of canine otitis externa.

BACKGROUND: A single-dose, in-clinic, veterinary professional-administered treatment for canine otitis externa was developed to improve compliance and canine welfare. METHODS: This multicentre, controlled, examiner-masked, randomised field trial was conducted in 316 dogs over 42 days. Dogs were treated once, on day 0, with the investigational product containing gentamicin, posaconazole and mometasone furoate (Mometamax Ultra [MU]) or twice (days 0 and 7) with a control product containing florfenicol, terbinafine and betamethasone acetate (CP). The primary endpoint was a composite otitis index score of 4 or less (of 12) on day 14 and 3 or less (of 12) on day 28. RESULTS: On day 28, treatment success was recorded in 128 of 143 MU-treated dogs (89.5%), significantly non-inferior to 116 of 133 (87.2%) CP-treated dogs (Farrington-Manning test, Z = 4.1351, p < 0.0001). For mixed cultures of Staphylococcus pseudintermedius and Malassezia pachydermatis, there was 100% treatment success in MU-treated dogs (n = 33), significantly non-inferior to 90.2% (37 of 41) in CP-treated dogs (Farrington-Manning test, Z = 3.1954, p = 0.0007). LIMITATIONS: Efficacy in chronic otitis externa cases was not investigated. Cytology was not used to aid in diagnosis or for identification of secondary pathogens. CONCLUSION: This unique combination, single-dose product is safe and effective in dogs with otitis externa. It offers enhanced compliance, canine welfare and quality of life by eliminating the owner burden of treating this painful condition.

The petawatt laser of ELI ALPS: reaching the 700 TW level at 10†Hz repetition rate.

Performance of the novel high repetition rate HF-PW laser system of ELI ALPS is presented in its first operation phase at 400 TW and 700 TW levels. Long-term operation was tested at 2.5 and 10 Hz repetition rates, where an exceptional 0.66% and 1.08% shot-to-shot energy stability was demonstrated, respectively. Thorough spatio-spectral and temporal measurements confirmed high quality output pulses with a Strehl ratio of >0.9 after compression at both repetition rates. Amplified pulses with an unprecedentedly high 240 W average power were reached for the first time from a PW-class amplifier chain by using novel pseudo-active mirror disk amplification-based pump lasers.

The Fat-glandular Interface and Breast Tumor Locations: Appearances on Ultrasound Tomography Are Supported by Quantitative Peritumoral Analyses.

OBJECTIVE: To analyze the preferred tissue locations of common breast masses in relation to anatomic quadrants and the fat-glandular interface (FGI) using ultrasound tomography (UST). METHODS: Ultrasound tomography scanning was performed in 206 consecutive women with 298 mammographically and/or sonographically visible, benign and malignant breast masses following written informed consent to participate in an 8-site multicenter, Institutional Review Board-approved cohort study. Mass locations were categorized by their anatomic breast quadrant and the FGI, which was defined by UST as the high-contrast circumferential junction of fat and fibroglandular tissue on coronal sound speed imaging. Quantitative UST mass comparisons were done for each tumor and peritumoral region using mean sound speed and percentage of fibroglandular tissue. Chi-squared and analysis of variance tests were used to assess differences. RESULTS: Cancers were noted at the FGI in 95% (74/78) compared to 51% (98/194) of fibroadenomas and cysts combined (P < 0.001). No intra-quadrant differences between cancer and benign masses were noted for tumor location by anatomic quadrants (P = 0.66). Quantitative peritumoral sound speed properties showed that cancers were surrounded by lower mean sound speeds (1477 m/s) and percent fibroglandular tissue (47%), compared to fibroadenomas (1496 m/s; 65.3%) and cysts (1518 m/s; 84%) (P < 0.001; P < 0.001, respectively). CONCLUSION: Breast cancers form adjacent to fat and UST localized the vast majority to the FGI, while cysts were most often completely surrounded by dense tissue. These observations were supported by quantitative peritumoral analyses of sound speed values for fat and fibroglandular tissue.