The effects of hypertonic fluid administration on the gene expression of inflammatory mediators in circulating leucocytes in patients with septic shock: a preliminary study

Contains fulltext : 98426.pdf (publisher's version ) (Open Access)ABSTRACT: OBJECTIVE: This study was designed to investigate the effect of hypertonic fluid administration on inflammatory mediator gene expression in patients with septic shock. DESIGN AND SETTING: Prospective, randomized, controlled, double-blind clinical study in a 15-bed mixed intensive care unit in a tertiary referral teaching hospital. INTERVENTIONS: Twenty-four patients, who met standard criteria for septic shock, were randomized to receive a bolus of hypertonic fluid (HT, 250 ml 6% HES/7.2% NaCl) or isotonic fluid (IT, 500 ml 6% HES/0.9% NaCl) administered over 15 minutes. Randomization and study fluid administration was within 24 hours of ICU admission for all patients. This trial is registered with ANZCTR.org.au as ACTRN12607000259448. RESULTS: Blood samples were taken immediately before and 4, 8, 12, and 24 hours after fluid administration. Real-time reverse transcriptase polymerase chain reaction (RT rtPCR) was used to quantify mRNA expression of different inflammatory mediators in peripheral leukocytes. In the HT group, compared with the IT group, levels of gene expression of MMP9 and L-selectin were significantly suppressed (p = 0.0002 and p = 0.007, respectively), and CD11b gene expression tended to be elevated (p = NS). No differences were found in the other mediators examined. CONCLUSIONS: In septic shock patients, hypertonic fluid administration compared with isotonic fluid may modulate expression of genes that are implicated in leukocyte-endothelial interaction and capillary leakage.The study was performed at the Intensive Care Department, Waikato Hospital, and at the Molecular Genetics Laboratory, University of Waikato, Hamilton, New Zealand. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12607000259448

The Alcohol Dehydrogenase System in the Xylose-Fermenting Yeast Candida maltosa

The alcohol dehydrogenase (ADH) system plays a critical role in sugar metabolism involving in not only ethanol formation and consumption but also the general "cofactor balance" mechanism. Candida maltosa is able to ferment glucose as well as xylose to produce a significant amount of ethanol. Here we report the ADH system in C. maltosa composed of three microbial group I ADH genes (CmADH1, CmADH2A and CmADH2B), mainly focusing on its metabolic regulation and physiological function.Genetic analysis indicated that CmADH2A and CmADH2B tandemly located on the chromosome could be derived from tandem gene duplication. In vitro characterization of enzymatic properties revealed that all the three CmADHs had broad substrate specificities. Homo- and heterotetramers of CmADH1 and CmADH2A were demonstrated by zymogram analysis, and their expression profiles and physiological functions were different with respect to carbon sources and growth phases. Fermentation studies of ADH2A-deficient mutant showed that CmADH2A was directly related to NAD regeneration during xylose metabolism since CmADH2A deficiency resulted in a significant accumulation of glycerol.Our results revealed that CmADH1 was responsible for ethanol formation during glucose metabolism, whereas CmADH2A was glucose-repressed and functioned to convert the accumulated ethanol to acetaldehyde. To our knowledge, this is the first demonstration of function separation and glucose repression of ADH genes in xylose-fermenting yeasts. On the other hand, CmADH1 and CmADH2A were both involved in ethanol formation with NAD regeneration to maintain NADH/NAD ratio in favor of producing xylitol from xylose. In contrast, CmADH2B was expressed at a much lower level than the other two CmADH genes, and its function is to be further confirmed

The Impact of Augmented Information on Visuo-Motor Adaptation in Younger and Older Adults

BACKGROUND: Adjustment to a visuo-motor rotation is known to be affected by ageing. According to previous studies, the age-related differences primarily pertain to the use of strategic corrections and the generation of explicit knowledge on which strategic corrections are based, whereas the acquisition of an (implicit) internal model of the novel visuo-motor transformation is unaffected. The present study aimed to assess the impact of augmented information on the age-related variation of visuo-motor adjustments. METHODOLOGY/PRINCIPAL FINDINGS: Participants performed aiming movements controlling a cursor on a computer screen. Visual feedback of direction of cursor motion was rotated 75 degrees relative to the direction of hand motion. Participants had to adjust to this rotation in the presence and absence of an additional hand-movement target that explicitly depicted the input-output relations of the visuo-motor transformation. An extensive set of tests was employed in order to disentangle the contributions of different processes to visuo-motor adjustment. Results show that the augmented information failed to affect the age-related variations of explicit knowledge, adaptive shifts, and aftereffects in a substantial way, whereas it clearly affected initial direction errors during practice and proprioceptive realignment. CONCLUSIONS: Contrary to expectations, older participants apparently made no use of the augmented information, whereas younger participants used the additional movement target to reduce initial direction errors early during practice. However, after a first block of trials errors increased, indicating a neglect of the augmented information, and only slowly declined thereafter. A hypothetical dual-task account of these findings is discussed. The use of the augmented information also led to a selective impairment of proprioceptive realignment in the younger group. The mere finding of proprioceptive realignment in adaptation to a visuo-motor rotation in a computer-controlled setup is noteworthy since visual and proprioceptive information pertain to different objects

Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur

Search for rare quark-annihilation decays, B --> Ds(*) Phi

We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context of the Standard Model, these decays are expected to be highly suppressed since they proceed through annihilation of the b and u-bar quarks in the B- meson. Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected with the BABAR detector at SLAC. We find no evidence for these decays, and we set Bayesian 90% confidence level upper limits on the branching fractions BF(B- --> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid Communications

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Gene expression of bacterial collagenolytic proteases in root caries

Objective: It is unknown whether bacteria play a role in the collagen matrix degradation that occurs during caries progression. Our aim was to characterize the expression level of genes involved in bacterial collagenolytic proteases in root biofilms with and without caries. Method: we collected samples from active cavitated root caries lesions (RC, n = 30) and from sound root surfaces (SRS, n = 10). Total microbial RNA was isolated and cDNA sequenced on the Illumina Hi-Seq2500. Reads were mapped to 162 oral bacterial reference genomes. Genes encoding putative bacterial collagenolytic proteases were identified. Normalization and differential expression analysis was performed on all metatranscriptomes (FDR8) but none in SRS were Pseudoramibacter alactolyticus [HMPREF0721_RS02020; HMPREF0721_RS04640], Scardovia inopinata [SCIP_RS02440] and Olsenella uli DSM7084 [OLSU_RS02990]. Conclusion: Our findings suggest that the U32 proteases may be related to carious dentine. The contribution of a small number of species to dentine degradation should be further investigated. These proteases may have potential in future biotechnological and medical applications, serving as targets for the development of therapeutic agents

Motor Adaptation Scaled by the Difficulty of a Secondary Cognitive Task

Background: Motor learning requires evaluating performance in previous movements and modifying future movements. The executive system, generally involved in planning and decision-making, could monitor and modify behavior in response to changes in task difficulty or performance. Here we aim to identify the quantitative cognitive contribution to responsive and adaptive control to identify possible overlap between cognitive and motor processes. Methodology/Principal Findings: We developed a dual-task experiment that varied the trial-by-trial difficulty of a secondary cognitive task while participants performed a motor adaptation task. Subjects performed a difficulty-graded semantic categorization task while making reaching movements that were occasionally subjected to force perturbations. We find that motor adaptation was specifically impaired on the most difficult to categorize trials. Conclusions/Significance: We suggest that the degree of decision-level difficulty of a particular categorization differentially burdens the executive system and subsequently results in a proportional degradation of adaptation. Our results suggest

Cooperation between Apoptotic and Viable Metacyclics Enhances the Pathogenesis of Leishmaniasis

Mimicking mammalian apoptotic cells by exposing phosphatidylserine (PS) is a strategy used by virus and parasitic protozoa to escape host protective inflammatory responses. With Leishmania amazonensis (La), apoptotic mimicry is a prerogative of the intramacrophagic amastigote form of the parasite and is modulated by the host. Now we show that differently from what happens with amastigotes, promastigotes exposing PS are non-viable, non-infective cells, undergoing apoptotic death. As part of the normal metacyclogenic process occurring in axenic cultures and in the gut of sand fly vectors, a sub-population of metacyclic promastigotes exposes PS. Apoptotic death of the purified PS-positive (PSPOS) sub-population was confirmed by TUNEL staining and DNA laddering. Transmission electron microscopy revealed morphological alterations in PSPOS metacyclics such as DNA condensation, cytoplasm degradation and mitochondrion and kinetoplast destruction, both in in vitro cultures and in sand fly guts. TUNELPOS promastigotes were detected only in the anterior midgut to foregut boundary of infected sand flies. Interestingly, caspase inhibitors modulated parasite death and PS exposure, when added to parasite cultures in a specific time window. Efficient in vitro macrophage infections and in vivo lesions only occur when PSPOS and PS-negative (PSNEG) parasites were simultaneously added to the cell culture or inoculated in the mammalian host. The viable PSNEG promastigote was the infective form, as shown by following the fate of fluorescently labeled parasites, while the PSPOS apoptotic sub-population inhibited host macrophage inflammatory response. PS exposure and macrophage inhibition by a subpopulation of promastigotes is a different mechanism than the one previously described with amastigotes, where the entire population exposes PS. Both mechanisms co-exist and play a role in the transmission and development of the disease in case of infection by La. Since both processes confer selective advantages to the infective microorganism they justify the occurrence of apoptotic features in a unicellular pathogen