Phenotypic screening, transcriptional profiling, and comparative genomic analysis of an invasive and non-invasive strain of Candida albicans

<p>Abstract</p> <p>Background</p> <p>Invasion of host tissue by the human fungal pathogen <it>Candida albicans </it>is an important step during the development of candidosis. However, not all <it>C. albicans </it>strains possess the same invasive and virulence properties. For example, the two clinical isolates SC5314 and ATCC10231 differ in their ability to invade host tissue and cause experimental infections. Strain SC5314 is invasive whereas strain ATCC10231 is non-invasive and strongly attenuated in virulence compared to SC5314. In this study we compare the <it>in vitro </it>phenotypic, transcriptional and genomic profiles of these two widely used laboratory strains in order to determine the principal biological and genetic properties responsible for their differential virulence.</p> <p>Results</p> <p>In all media tested, the two strains showed the same metabolic flexibility, stress resistance, adhesion properties and hydrolytic enzyme secretion <it>in vitro</it>. However, differences were observed in response to cell-surface disturbing agents and alkaline pH. Furthermore, reduced hyphal formation in strain ATCC10231 under certain conditions correlated with reduced invasive properties in an <it>in vitro </it>invasion assay and a reduced ability to invade epithelial tissue. Despite these diverse phenotypic properties, no substantial genomic differences were detected by comparative genome hybridisation within the open reading frames. However, <it>in vitro </it>transcriptional profiling displayed major differences in the gene expression of these two strains, even under normal <it>in vitro </it>growth conditions.</p> <p>Conclusion</p> <p>Our data suggest that the reason for differential virulence of <it>C. albicans </it>strains is not due to the absence of specific genes, but rather due to differences in the expression, function or activity of common genes.</p

Molecular imaging of potential bone metastasis from differentiated thyroid cancer: a case report

<p>Abstract</p> <p>Introduction</p> <p>Molecular imaging of the spine is a rarely used diagnostic method for which only a few case reports exist in the literature. Here, to the best of our knowledge we present the first case of a combination of molecular imaging by single photon emission computer tomography and positron emission tomography used in post-operative spinal diagnostic assessment.</p> <p>Case presentation</p> <p>We present the case of a 50-year-old Caucasian woman experiencing progressive spinal cord compression caused by a vertebral metastasis of a less well differentiated thyroid cancer. Following tumor resection and vertebral stabilization, total thyroidectomy was performed revealing follicular thyroid carcinoma pT2 pNxM1 (lung, bone). During follow-up our patient underwent five radioiodine therapy procedures (5.3 to 5.7 GBq each) over a two-year period. Post-therapeutic I-131 scans showed decreasing uptake in multiple Pulmonary metastases. However, following an initial decrease, stimulated thyroglobulin remained at pathologically increased levels, indicating further neoplastic activity. F18 Fludeoxyglucose positron emission tomography, which was performed in parallel, showed remaining hypermetabolism in the lungs but no hypermetabolism of the spinal lesions correlating with the stable neurological examinations. While on single photon emission computer tomography images Pulmonary hyperfixation of I-131 disappeared (most likely indicating dedifferentiation), there was persistent spinal hyperfixation at the operated level and even higher fixation at the spinal process of L3. Based on the negative results of the spinal F18 fludeoxyglucose positron emission tomography, a decision was made not to operate again on the spine since our patient was completely asymptomatic and the neurological risk seemed to be too high. During further follow-up our patient remained neurologically stable.</p> <p>Conclusions</p> <p>Molecular imaging by F18 fludeoxyglucose positron emission tomography helps to exclude metabolically active spinal metastases and to spare further risky surgery.</p

Assessment of mobilization capacity in 10 different ICU scenarios by different professions

Background: Mobilization of intensive care patients is a multi-professional task. Aim of this study was to explore how different professions working at Intensive Care Units (ICU) estimate the mobility capacity using the ICU Mobility Score in 10 different scenarios. Methods: Ten fictitious patient-scenarios and guideline-related knowledge were assessed using an online survey. Critical care team members in German-speaking countries were invited to participate. All datasets including professional data and at least one scenario were analyzed. Kruskal Wallis test was used for the individual scenarios, while a linear mixed-model was used over all responses. Results: In total, 515 of 788 (65%) participants could be evaluated. Physicians (p = 0.001) and nurses (p = 0.002) selected a lower ICU Mobility Score (-0.7 95% CI -1.1 to -0.3 and -0.4 95% CI -0.7 to -0.2, respectively) than physical therapists, while other specialists did not (p = 0.81). Participants who classified themselves as experts or could define early mobilization in accordance to the "S2e guideline: positioning and early mobilisation in prophylaxis or therapy of pulmonary disorders" correctly selected higher mobilization levels (0.2 95% CI 0.0 to 0.4, p = 0.049 and 0.3 95% CI 0.1 to 0.5, p = 0.002, respectively). Conclusion: Different professions scored the mobilization capacity of patients differently, with nurses and physicians estimating significantly lower capacity than physical therapists. The exact knowledge of guidelines and recommendations, such as the definition of early mobilization, independently lead to a higher score. Interprofessional education, interprofessional rounds and mobilization activities could further enhance knowledge and practice of mobilization in the critical care team

The Functional Trajectory in Frail Compared With Non-frail Critically Ill Patients During the Hospital Stay

Background: Long-term outcome is determined not only by the acute critical illness but increasingly by the reduced functional reserve of pre-existing frailty. The patients with frailty currently account for one-third of the critically ill, resulting in higher mortality. There is evidence of how frailty affects the intrahospital functional trajectory of critically ill patients since prehospital status is often missing. Methods: In this prospective single-center cohort study at two interdisciplinary intensive care units (ICUs) at a university hospital in Germany, the frailty was assessed using the Clinical Frailty Scale (CFS) in the adult patients with critical illness with an ICU stay >24 h. The functional status was assessed using the sum of the subdomains "Mobility" and "Transfer" of the Barthel Index (MTB) at three time points (pre-hospital, ICU discharge, and hospital discharge). Results: We included 1,172 patients with a median age of 75 years, of which 290 patients (25%) were frail. In a propensity score-matched cohort, the probability of MTB deterioration till hospital discharge did not differ in the patients with frailty (odds ratio (OR) 1.3 [95% CI 0.8-1.9], p = 0.301), confirmed in several sensitivity analyses in all the patients and survivors only. Conclusion: The patients with frailty have a reduced functional status. Their intrahospital functional trajectory, however, was not worse than those in non-frail patients, suggesting a rehabilitation potential of function in critically ill patients with frailty

Standalone vertex finding in the ATLAS muon spectrometer

A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011

Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC

Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H →γ γ, H → Z Z∗ →4l and H →W W∗ →lνlν. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV, corresponding to an integrated luminosity of about 25 fb−1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined fits probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson

Measurement of the top quark-pair production cross section with ATLAS in pp collisions at \sqrt{s}=7\TeV

A measurement of the production cross-section for top quark pairs(\ttbar) in $pp$ collisions at \sqrt{s}=7 \TeV is presented using data recorded with the ATLAS detector at the Large Hadron Collider. Events are selected in two different topologies: single lepton (electron $e$ or muon $\mu$) with large missing transverse energy and at least four jets, and dilepton ($ee$, $\mu\mu$ or $e\mu$) with large missing transverse energy and at least two jets. In a data sample of 2.9 pb-1, 37 candidate events are observed in the single-lepton topology and 9 events in the dilepton topology. The corresponding expected backgrounds from non-\ttbar Standard Model processes are estimated using data-driven methods and determined to be $12.2 \pm 3.9$ events and $2.5 \pm 0.6$ events, respectively. The kinematic properties of the selected events are consistent with SM \ttbar production. The inclusive top quark pair production cross-section is measured to be \sigmattbar=145 \pm 31 ^{+42}_{-27} pb where the first uncertainty is statistical and the second systematic. The measurement agrees with perturbative QCD calculations.Comment: 30 pages plus author list (50 pages total), 9 figures, 11 tables, CERN-PH number and final journal adde