Identification of Bithionol, Dichlorophen, and Miconazole as Antibacterial Agents against Acinetobacter calcoaceticus.

The rising prevalence of multidrug-resistant hospital-acquired infections has increased the need for new antibacterial agents. In this study, a library of 1586 FDA-approved drugs was screened against A. calcoaceticus, a representative of the Acinetobacter calcoaceticus-baumannii complex. Three compounds were found to have previously undiscovered antibacterial properties against A. calcoaceticus: antifungal Miconazole, anthelminthic Dichlorophen, and Bithionol. These three drugs were tested against a wide range of Gram-positive and Gram-negative bacteria and confirmed to have broad-spectrum antibacterial properties. Combinations of these three drugs were also tested against the same bacteria, and two novel combination therapies with synergistic effects were discovered. In the future, antibacterial properties of these three drugs and two combination therapies will be evaluated against pathogenic bacteria using an animal model.

Assessing the effects of body weight on subchondral bone formation with quantitative 18F-sodium fluoride PET.

OBJECTIVES: The aim of this study was to quantify subchondral bone remodeling in the elbows, hands, knees, and feet using volumetric and metabolic parameters derived from 18F-sodium fluoride positron emission tomography (NaF-PET) and to assess the convergent validity of these parameters as an index of joint degeneration and preclinical osteoarthritis. METHODS: A retrospective analysis was conducted in 34 subjects (32 males, 2 females) with metastatic bone disease who underwent full-body NaF-PET/CT scans. An adaptive contrast-oriented thresholding algorithm was applied to segment NaF-avid regions in the bilateral elbows, hands, knees, and feet of each subject, and metabolically active volume (MAV), maximum standardized uptake value (SUVmax), mean metabolic volumetric product (MVPmean), and partial volume-corrected MVPmean (cMVPmean) of the segmented regions were calculated. Global parameters for MAV, SUVmax, MVPmean, and cMVPmean were defined as the sum of the corresponding values in all the joints of a subject. Inter-rater reliability was determined with Lin's concordance correlation, and associations of global values with subject body weight and age were assessed with Pearson correlation and Spearman correlation analyses. RESULTS: Inter-rater reliability was observed to be the highest in SUVmax (ρc = 0.99), followed by MVPmean (ρc = 0.96), cMVPmean (ρc = 0.93), and MAV (ρc = 0.93). MAV, MVPmean, and cMVPmean were observed to significantly increase with weight (all p < 0.0001) determined by Pearson correlation. In addition, Spearman rank-order analysis demonstrated a significant correlation between SUVmax and weight in addition to MAV, MVPmean, and cMVPmean and weight (all p < 0.01). No significant association between age and any PET parameter was observed. CONCLUSIONS: These preliminary data demonstrate the feasibility and reliability of assessing bone turnover at the joints using quantitative NaF-PET. Our findings corroborate the fact that biomechanical factors including mechanical loading and weight-bearing are contributors to osteoarthritis disease progression.

The Caenorhabditis elegans Female-Like State: Decoupling the Transcriptomic Effects of Aging and Sperm Status.

Understanding genome and gene function in a whole organism requires us to fully comprehend the life cycle and the physiology of the organism in question. Caenorhabditis elegans XX animals are hermaphrodites that exhaust their sperm after 3 d of egg-laying. Even though C. elegans can live for many days after cessation of egg-laying, the molecular physiology of this state has not been as intensely studied as other parts of the life cycle, despite documented changes in behavior and metabolism. To study the effects of sperm depletion and aging of C. elegans during the first 6 d of adulthood, we measured the transcriptomes of first-day adult hermaphrodites and sixth-day sperm-depleted adults, and, at the same time points, mutant fog-2(lf) worms that have a feminized germline phenotype. We found that we could separate the effects of biological aging from sperm depletion. For a large subset of genes, young adult fog-2(lf) animals had the same gene expression changes as sperm-depleted sixth-day wild-type hermaphrodites, and these genes did not change expression when fog-2(lf) females reached the sixth day of adulthood. Taken together, this indicates that changing sperm status causes a change in the internal state of the worm, which we call the female-like state. Our data provide a high-quality picture of the changes that happen in global gene expression throughout the period of early aging in the worm.