Microbial Enzymatic Synthesis of Amikacin Analogs With Antibacterial Activity Against Multidrug-Resistant Pathogens.

With the constant emergence of multidrug-resistant gram-negative bacteria, interest in the development of new aminoglycoside (AG) antibiotics for clinical use has increased. The regioselective modification of AG scaffolds could be an efficient approach for the development of new antibiotics with improved therapeutic potency. We enzymatically synthesized three amikacin analogs containing structural modifications in the amino groups and evaluated their antibacterial activity and cytotoxicity. Among them, 6'-N-acyl-3″-N-methylated analogs showed improved antibacterial activity against the multidrug-resistant gram-negative bacteria tested, while exhibiting reduced in vitro nephrotoxicity compared to amikacin. This study demonstrated that the modifications of the 6'-amino group as well as the 3″-amino group have noteworthy advantages for circumventing the AG-resistance mechanism. The regiospecific enzymatic modification could be exploited to develop novel antibacterial agents with improved pharmacological potential.

Radiation dose and image conspicuity comparison between conventional 120 kVp and 150 kVp with spectral beam shaping for temporal bone CT.

OBJECTIVE: The purpose of this article is to compare radiation doses and conspicuity of anatomic landmarks of the temporal bone between the CT technique using spectral beam shaping at 150 kVp with a dedicated tin filter (150 kVp-Sn) and the conventional protocol at 120 kVp. METHODS: 25 patients (mean age, 46.8 ±â€¯21.2 years) were examined using the 150-kVp Sn protocol (200 reference mAs using automated tube current modulation, 64 × 0.6 mm collimation, 0.6 mm slice thickness, pitch 0.8), whereas 30 patients (mean age, 54.5 ±â€¯17.8 years) underwent the 120-kVp protocol (180 mAs, 128 × 0.6 mm collimation, 0.6 mm slice thickness, pitch 0.8). Radiation doses were compared between the two acquisition techniques, and dosimetric data from the literature were reviewed for comparison of radiation dose reduction. Subjective conspicuity of 23 anatomic landmarks of the temporal bone, expressed by 5-point rating scale and objective conspicuity by signal-to-noise ratio (SNR) which measured in 4 different regions of interest (ROI), were compared between 150-kVp Sn and 120-kVp acquisitions. RESULTS: The mean dose-length-product (DLP) and effective dose were significantly lower for the 150-kVp Sn scans (0.26 ±â€¯0.26 mSv) compared with the 120-kVp scans (0.92 ±â€¯0.10 mSv, p < 0.001). The lowest effective dose from the literature-based protocols was 0.31 ±â€¯0.12 mSv, which proposed as a low-dose protocol in the setting of spiral multislice temporal bone CT. SNR was slightly superior for 120-kVp images, however analyzability of the 23 anatomic structures did not differ significantly between 150-kVp Sn and 120-kVp scans. CONCLUSION: Temporal bone CT performed at 150 kVp with an additional tin filter for spectral shaping markedly reduced radiation exposure when compared with conventional temporal bone CT at 120 kVp while maintaining anatomic conspicuity. The decreased radiation dose of the 150-kVp Sn was also lower in comparison to the previous literature-based low-dose temporal bone CT protocol.

Histologic subtypes are not associated with the presence of sarcopenia in lung cancer.

BACKGROUND: Sarcopenia is prevalent and a known adverse prognostic effector in lung cancer (LCA). However, the relationship between sarcopenia and histology remains uncertain in LCA. METHODS: Consecutive patients with newly diagnosed LCA (n = 778) between June 2012 and February 2015 were retrospectively reviewed to identify factors associated with sarcopenia. Sarcopenia was defined as CT-determined L3 muscle index (muscle area at L3/height2) of < 55 cm2/m2 for men and < 39 cm2/m2 for women. RESULTS: Mean patient age was 67.7 ± 10.8 years, and most (73.1%) were male. The most prevalent histology was adenocarcinoma (44.0%) and 71.6% of patients had stage III or IV disease. The overall prevalence of sarcopenia was 48.2% (60.3% in men, and 15.3% in women). Univariable analysis showed sarcopenia was significantly associated with male gender, age (≥ 65 years), smoking status, lower BMI (< 23 kg/m2), advanced stage (III and IV), and high comorbidity score (Charlson index ≥ 3). Furthermore, the prevalence of sarcopenia was higher in squamous cell carcinoma (54.9%) and small cell LCA (56.4%) than in adenocarcinoma (39.8%). Multivariable analyses showed sarcopenia was independently associated with a male gender (odds ratio [OR], 11.13), elderly (OR, 2.02) and low BMI (OR, 6.28), stage IV (OR, 1.98), and high comorbidity (OR, 1.93). However, no significant association was found between histologic subtypes and sarcopenia. CONCLUSIONS: Sarcopenia was found to be significantly associated with old age, male gender, an advanced stage, comorbidities, and low BMI in LCA. However, histology subtype was not an independent factor for the presence of sarcopenia.