Benderwinther3103

Margulies et al. (2016) demonstrated the existence of at least five independent functional connectivity gradients in the human brain. However, it is unclear how these functional gradients might link to anatomy. The dual origin theory proposes that differences in cortical cytoarchitecture originate from two trends of progressive differentiation between the different layers of the cortex, referred to as the hippocampocentric and olfactocentric systems. When conceptualising the functional connectivity gradients within the evolutionary framework of the Dual Origin theory, the first gradient likely represents the hippocampocentric system anatomically. Here we expand on this concept and demonstrate that the fifth gradient likely links to the olfactocentric system. We describe the anatomy of the latter as well as the evidence to support this hypothesis. Together, the first and fifth gradients might help to model the Dual Origin theory of the human brain and inform brain models and pathologies. SM04690 It is generally accepted that antibiotic-resistant mutants are selected in a range of concentrations ranging from the minimum inhibitory concentration (MIC) to the mutant preventive concentration. More recently, it has been found that antibiotic-resistant mutants can also be selected at concentrations below MIC, which expands the conditions where this selection may occur. Using experimental evolution approaches followed by whole-genome sequencing, the current study compares the evolutionary trajectories of Pseudomonas aeruginosa in the presence of tobramycin or tigecycline at lethal and sublethal concentrations. Mutants were selected at sublethal concentrations of tigecycline (1/10 and 1/50 MIC), whereas no mutants were selected in the case of tobramycin, indicating that the width of sub-MIC selective windows is antibiotic-specific. In addition, the patterns of evolution towards tigecycline resistance depend on selection strength. Sublethal concentrations of tigecycline select mutants with lower tigecycline MICs and higher MICs to other antibiotics belonging to different structural families than mutants selected under lethal concentrations. This indicates that the strength of the cross-resistance phenotype associated with tigecycline resistance is decoupled from selection strength. Accurate information on the sublethal selection window for each antibiotic of clinical value, including the phenotypes of cross-resistance of mutants selected at each antibiotic concentration, is needed to understand the role of ecosystems polluted with different antibiotic concentrations in the selection of antibiotic resistance. Integration of this information into clinical and environmental safety controls may help to tackle the problem of antibiotic resistance. The use of ampicillin in the outpatient setting has traditionally been avoided because of the short half-life and instability in solution of this drug. However, recent in vitro data and two case series support the safe and effective administration of ampicillin by continuous infusion in the community. Therapeutic drug monitoring (TDM) of beta-lactam antibiotics can be used to optimise antibiotic exposure and ensure adequate clinical responses. A case series is presented of patients receiving ampicillin via prolonged infusion in the outpatient setting, with TDM to ensure adequate plasma antibiotic levels were achieved. Three patients who received ampicillin by continuous infusion under the Outpatient Parenteral Antimicrobial Therapy (OPAT) program are described, including details of antibiotic dose and steady-state plasma drug concentration as measured by high-performance liquid chromatography. All three patients had an infection with ampicillin-susceptible Enterococcus faecalis; one patient had post-partum endometritis, one had urosepsis and one had a complex polymicrobial bone and joint infection. Adequate plasma drug levels were achieved in all patients. Management of the antibiotic temperature and infusion times, and appropriate timing of drug levels in the community were required. Two patients achieved clinical cure, while the third required further surgical debridement and antibiotic therapy. TDM in this setting enabled the contemporaneous management and dose alteration of ampicillin. Ampicillin may be a safe and effective drug when administered by continuous infusion with appropriate TDM in the community setting. Elizabethkingia genus is an opportunistic life-threatening pathogen with intrinsic multidrug-resistant phenotype. It is the only known microorganism with multi-chromosome-borne metallo-β-lactamase genes. To determine the diversity and distribution of MBLs BlaBlaB and BlaGOB in this genus, we applied comprehensive bioinformatic screening in 109 available Elizabethkingia genomes. A total of 23 and 32 novel BlaBlaB and BlaGOB variants were found in Elizabethkingia spp., 12 and 15 clusters were assigned in these BlaBlaB and BlaGOB based on the amino acid identities and phylogenetic studies. Clustering of some variants did not conform to species-specific clades which suggested potential inter-species dissemination of MBLs genes among Elizabethkingia species. Cloning of representative blaBlaB and blaGOB into E. coli DH5α resulted in increased and diverse MICs to most β-lactams, including cephalosporins, carbapenems, and β-lactams-inhibitors. This study extends the database of class B carbapenemases, emphasizing the diversity of different MBLs genes in the genus Elizabethkingia, which may represent potential reservoirs of acquired MBLs. V.Patients labelled β-lactam allergic are frequently exposed to treatments by broad spectrum antibiotics. However, the risk of extended spectrum β-lactamase (ESBL) carriage in this population has been poorly investigated. Aim of this study was to evaluate characteristics and clinical outcomes of patients admitted in intensive care unit (ICU) with and without declared β-lactam allergy at admission. A retrospective monocentric study was performed including adult patients admitted in ICU between 2007 and 2012. The presence of multidrug resistant bacteria was documented in rectal and nasal swab at admission and discharge. Patients labelled allergic to β-lactams and unlabelled patients were compared. Patients labelled allergic had significantly higher rates of ESBL at admission (13.3 % vs 4.3%, p=0.0220) and at discharge (20% vs 8.9%, p=0.0460) than unlabelled patients but no significant difference in rates of ESBL acquisition was detected. No differences in mortality, duration of hospitalisation and typical risk factors of ESBL acquisition (intubation, CVC and duration of hospitalization) were reported.