In Vitro Postantibiotic Effect Following Repeated Exposure to Imipenem, Temafloxacin, and Tobramycin

The postantibiotic effect (PAE) following three consecutive 2-h exposures to imipenem, temafloxacin, and tobramycin was determined in Pseudomonas aeruginosa. A PAE and a bactericidal effect were consistently observed for imipenem following each cycle of drug exposure and regrowth. In contrast, the PAE increased with repeated exposure with temafloxacin (1.8 to \u3e 5 h), but disappeared with tobramycin by the third exposure (0.9 to 0 h). These data show that the in vitro PAE may change within a strain following multiple cycles of drug exposure and bacterial regrowth

Adenosine receptor expression and function in rat striatal cholinergic interneurons

1. Cholinergic neurons were identified in rat striatal slices by their size, membrane properties, sensitivity to the NK(1) receptor agonist (Sar(9), Met(O(2))(11)) Substance P, and expression of choline acetyltransferase mRNA. A(1) receptor mRNA was detected in 60% of the neurons analysed, and A(2A) receptor mRNA in 67% (n=15). 2. The A(1) receptor agonist R-N(6)-(2-phenylisopropyl)adenosine (R-PIA) hyperpolarized cholinergic neurons in a concentration dependent manner sensitive to the A(1) antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 nM). 3. In dual stimulus experiments, the A(2A) receptor antagonist 8-(3-chlorostyryl)caffeine (CSC, 500 nM) decreased release of [(3)H]-acetylcholine from striatal slices (S2/S1 0.78±0.07 versus 0.95±0.05 in control), as did adenosine deaminase (S2/S1 ratio 0.69±0.05), whereas the A(1) receptor antagonist DPCPX (100 nM) had no effect (S2/S1 1.05±0.14). 4. In the presence of adenosine deaminase the adenosine A(2A) receptor agonist 2-p-((carboxyethyl)phenylethylamino)-5′-N-ethylcarboxamidoadenosine (CGS21680, 10 nM) increased release (S2/S1 ratio 1.03±0.05 versus 0.88±0.05 in control), an effect blocked by the antagonist CSC (500 nM, S2/S1 0.68±0.05, versus 0.73±0.08 with CSC alone). The combined superfusion of bicuculline (10 μM), saclofen (1 μM) and naloxone (10 μM) had no effect on the stimulation by CGS21680 (S2/S1 ratio 0.99±0.04). 5. The A(1) receptor agonist R-PIA (100 nM) inhibited the release of [(3)H]-acetylcholine (S2/S1 ratio 0.70±0.03), an effect blocked by DPCPX (S2/S1 ratio 1.06±0.07). 6. It is concluded that both A(1) and A(2A) receptors are expressed on striatal cholinergic neurons where they are functionally active

Measurements from the RV Ronald H. Brown and related platforms as part of the Atlantic Tradewind Ocean-Atmosphere Mesoscale Interaction Campaign (ATOMIC)

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Quinn, P. K., Thompson, E. J., Coffman, D. J., Baidar, S., Bariteau, L., Bates, T. S., Bigorre, S., Brewer, A., de Boer, G., de Szoeke, S. P., Drushka, K., Foltz, G. R., Intrieri, J., Iyer, S., Fairall, C. W., Gaston, C. J., Jansen, F., Johnson, J. E., Krueger, O. O., Marchbanks, R. D., Moran, K. P., Noone, D., Pezoa, S., Pincus, R., Plueddemann, A. J., Poehlker, M. L., Poeschl, U., Melendez, E. Q., Royer, H. M., Szczodrak, M., Thomson, J., Upchurch, L. M., Zhang, C., Zhang, D., & Zuidema, P. Measurements from the RV Ronald H. Brown and related platforms as part of the Atlantic Tradewind Ocean-Atmosphere Mesoscale Interaction Campaign (ATOMIC). Earth System Science Data, 13(4), (2021): 1759-1790, https://doi.org/10.5194/essd-13-1759-2021.The Atlantic Tradewind Ocean-Atmosphere Mesoscale Interaction Campaign (ATOMIC) took place from 7 January to 11 July 2020 in the tropical North Atlantic between the eastern edge of Barbados and 51∘ W, the longitude of the Northwest Tropical Atlantic Station (NTAS) mooring. Measurements were made to gather information on shallow atmospheric convection, the effects of aerosols and clouds on the ocean surface energy budget, and mesoscale oceanic processes. Multiple platforms were deployed during ATOMIC including the NOAA RV Ronald H. Brown (RHB) (7 January to 13 February) and WP-3D Orion (P-3) aircraft (17 January to 10 February), the University of Colorado's Robust Autonomous Aerial Vehicle-Endurant Nimble (RAAVEN) uncrewed aerial system (UAS) (24 January to 15 February), NOAA- and NASA-sponsored Saildrones (12 January to 11 July), and Surface Velocity Program Salinity (SVPS) surface ocean drifters (23 January to 29 April). The RV Ronald H. Brown conducted in situ and remote sensing measurements of oceanic and atmospheric properties with an emphasis on mesoscale oceanic–atmospheric coupling and aerosol–cloud interactions. In addition, the ship served as a launching pad for Wave Gliders, Surface Wave Instrument Floats with Tracking (SWIFTs), and radiosondes. Details of measurements made from the RV Ronald H. Brown, ship-deployed assets, and other platforms closely coordinated with the ship during ATOMIC are provided here. These platforms include Saildrone 1064 and the RAAVEN UAS as well as the Barbados Cloud Observatory (BCO) and Barbados Atmospheric Chemistry Observatory (BACO). Inter-platform comparisons are presented to assess consistency in the data sets. Data sets from the RV Ronald H. Brown and deployed assets have been quality controlled and are publicly available at NOAA's National Centers for Environmental Information (NCEI) data archive (https://www.ncei.noaa.gov/archive/accession/ATOMIC-2020, last access: 2 April 2021). Point-of-contact information and links to individual data sets with digital object identifiers (DOIs) are provided herein.NOAA's Climate Variability and Predictability Program provided funding under NOAA CVP NA19OAR4310379, GC19-301, and GC19-305. The Joint Institute for the Study of the Atmosphere and Ocean (JISAO) supported this study under NOAA cooperative agreement NA15OAR4320063. Additional support was provided by the NOAA's Uncrewed Aircraft Systems (UAS) Program Office, NOAA's Physical Sciences Laboratory, and NOAA AOML's Physical Oceanography Division. The NTAS project is funded by the NOAA's Global Ocean Monitoring and Observing Program (CPO FundRef number 100007298), through the Cooperative Institute for the North Atlantic Region (CINAR) under cooperative agreement NA14OAR4320158

Probing the competition among different coordination motifs in metal-ciprofloxacin complexes through IRMPD spectroscopy and DFT calculations

The vibrational spectra of ciprofloxacin complexes with monovalent (Li+, Na+, K+, Ag+) and polyvalent (Mg2+, Al3+) metal ions are recorded in the range 1000-1900 cm(-1) by means of infrared multiple-photon dissociation (IRMPD) spectroscopy. The IRMPD spectra are analyzed and interpreted in the light of density functional theory (DFT)-based quantum chemical calculations in order to identify the possible structures present under our experimental conditions. For each metal-ciprofloxacin complex, four isomers are predicted, considering different chelation patterns. A good agreement is found between the measured IRMPD spectrum and the calculated absorption spectrum of the most stable isomer for each complex. Metal ion size and charge are found to drive the competition among the different coordination motifs: small size and high charge density metal ions prefer to coordinate the quinolone between the two carbonyl oxygen atoms, whereas large-size metal ions prefer the carboxylate group as a coordination site. In the latter case, an intramolecular hydrogen bond compensates the weaker interaction established by these cations. The role of the metal cation on the stabilization of ionic and nonionic structures of ciprofloxacin is also investigated. It is found that large-size metal ions preferentially stabilize charge separated motifs and that the increase of metal ion charge has a stabilizing effect on the zwitterionic form of ciprofloxacin

The Potential for Enhancing the Power of Genetic Association Studies in African Americans through the Reuse of Existing Genotype Data

We consider the feasibility of reusing existing control data obtained in genetic association studies in order to reduce costs for new studies. We discuss controlling for the population differences between cases and controls that are implicit in studies utilizing external control data. We give theoretical calculations of the statistical power of a test due to Bourgain et al (Am J Human Genet 2003), applied to the problem of dealing with case-control differences in genetic ancestry related to population isolation or population admixture. Theoretical results show that there may exist bounds for the non-centrality parameter for a test of association that places limits on study power even if sample sizes can grow arbitrarily large. We apply this method to data from a multi-center, geographically-diverse, genome-wide association study of breast cancer in African-American women. Our analysis of these data shows that admixture proportions differ by center with the average fraction of European admixture ranging from approximately 20% for participants from study sites in the Eastern United States to 25% for participants from West Coast sites. However, these differences in average admixture fraction between sites are largely counterbalanced by considerable diversity in individual admixture proportion within each study site. Our results suggest that statistical correction for admixture differences is feasible for future studies of African-Americans, utilizing the existing controls from the African-American Breast Cancer study, even if case ascertainment for the future studies is not balanced over the same centers or regions that supplied the controls for the current study

Overview of the 2010 Carbonaceous Aerosols and Radiative Effects Study (CARES)

Substantial uncertainties still exist in the scientific understanding of the possible interactions between urban and natural (biogenic) emissions in the production and transformation of atmospheric aerosol and the resulting impact on climate change. The US Department of Energy (DOE) Atmospheric Radiation Measurement (ARM) program's Carbonaceous Aerosol and Radiative Effects Study (CARES) carried out in June 2010 in Central Valley, California, was a comprehensive effort designed to improve this understanding. The primary objective of the field study was to investigate the evolution of secondary organic and black carbon aerosols and their climate-related properties in the Sacramento urban plume as it was routinely transported into the forested Sierra Nevada foothills area. Urban aerosols and trace gases experienced significant physical and chemical transformations as they mixed with the reactive biogenic hydrocarbons emitted from the forest. Two heavily-instrumented ground sites – one within the Sacramento urban area and another about 40 km to the northeast in the foothills area – were set up to characterize the evolution of meteorological variables, trace gases, aerosol precursors, aerosol size, composition, and climate-related properties in freshly polluted and "aged" urban air. On selected days, the DOE G-1 aircraft was deployed to make similar measurements upwind and across the evolving Sacramento plume in the morning and again in the afternoon. The NASA B-200 aircraft, carrying remote sensing instruments, was also deployed to characterize the vertical and horizontal distribution of aerosols and aerosol optical properties within and around the plume. This overview provides: (a) the scientific background and motivation for the study, (b) the operational and logistical information pertinent to the execution of the study, (c) an overview of key observations and initial findings from the aircraft and ground-based sampling platforms, and (d) a roadmap of planned data analyses and focused modeling efforts that will facilitate the integration of new knowledge into improved representations of key aerosol processes and properties in climate models.United States. Dept. of Energy. Atmospheric System Research Program (Contract DE-AC06-76RLO 1830)United States. National Oceanic and Atmospheric AdministrationUnited States. National Aeronautics and Space Administration. HQ Science Mission Directorate Radiation Sciences ProgramUnited States. National Aeronautics and Space Administration. CALIPSO ProgramUnited States. Dept. of Energy. Atmospheric Radiation Measurement Program (Interagency Agreement No. DE-AI02-05ER63985

Hormone-related risk factors for breast cancer in women under age 50 years by estrogen and progesterone receptor status: results from a case–control and a case–case comparison

INTRODUCTION: It has been suggested that hormonal risk factors act predominantly on estrogen receptor and progesterone receptor (ER/PR)-positive breast cancers. However, the data have been inconsistent, especially in younger women. METHODS: We evaluated the impact of age at menarche, pregnancy history, duration of breastfeeding, body mass index, combined oral contraceptive use, and alcohol consumption on breast cancer risk by ER/PR status in 1,725 population-based case patients and 440 control subjects aged 20 to 49 years identified within neighborhoods of case patients. We used multivariable unconditional logistic regression methods to conduct case–control comparisons overall as well as by ER/PR status of the cases, and to compare ER(+)PR(+ )with ER(-)PR(- )case patients. RESULTS: The number of full-term pregnancies was inversely associated with the risk of ER(+)PR(+ )breast cancer (p(trend )= 0.005), whereas recent average alcohol consumption was associated with an increased risk of ER(+)PR(+ )breast cancer (p(trend )= 0.03). Neither of these two factors was associated with the risk of ER(- )PR(- )breast cancer. Late age at menarche and a longer duration of breastfeeding were both associated with decreased breast cancer risk, irrespective of receptor status (all p(trend)≤ 0.03). CONCLUSION: Our results suggest that the number of full-term pregnancies and recent alcohol consumption affect breast cancer risk in younger women predominantly through estrogen and progesterone mediated by their respective receptors. Late age at menarche and breastfeeding may act through different hormonal mechanisms

Androgens and the breast

Androgens have important physiological effects in women while at the same time they may be implicated in breast cancer pathologies. However, data on the effects of androgens on mammary epithelial proliferation and/or breast cancer incidence are not in full agreement. We performed a literature review evaluating current clinical, genetic and epidemiological data regarding the role of androgens in mammary growth and neoplasia. Epidemiological studies appear to have significant methodological limitations and thus provide inconclusive results. The study of molecular defects involving androgenic pathways in breast cancer is still in its infancy. Clinical and nonhuman primate studies suggest that androgens inhibit mammary epithelial proliferation and breast growth while conventional estrogen treatment suppresses endogenous androgens. Abundant clinical evidence suggests that androgens normally inhibit mammary epithelial proliferation and breast growth. Suppression of androgens using conventional estrogen treatment may thus enhance estrogenic breast stimulation and possibly breast cancer risk. Addition of testosterone to the usual hormone therapy regimen may diminish the estrogen/progestin increase in breast cancer risk but the impact of this combined use on mammary gland homeostasis still needs evaluation

Teacher led school-based surveillance can allow accurate tracking of emerging infectious diseases - evidence from serial cross-sectional surveys of febrile respiratory illness during the H1N1 2009 influenza pandemic in Singapore

10.1186/1471-2334-12-336BMC Infectious Diseases12-BIDM