Microcirculatory alterations induced by sedation in intensive care patients. Effects of midazolam alone and in association with sufentanil

INTRODUCTION: Sedation is widely used in intensive care unit (ICU) patients to limit the risk of pulmonary barotrauma and to decrease oxygen needs. However, adverse effects of cc5128sedation have not been fully evaluated; in particular, effects of benzodiazepine and opiates on microcirculation have not been extensively studied. The aim of this study was to evaluate the microcirculatory effects of a sedation protocol commonly prescribed in the ICU. METHODS: Ten non-septic patients under controlled ventilation requiring sedation for therapeutic purposes were enrolled in a prospective observational study conducted in an ICU of a university hospital. Sedation was conducted in two successive steps: first, each patient received midazolam (0.1 mg/kg per hour after a bolus of 0.05 mg/kg, then adapted to reach a Ramsay score of between 3 and 5). Second, after one hour, sufentanil was added (0.1 μg/kg per hour after a bolus of 0.1 μg/kg). Arterial pressure, heart rate, cardiac output determined by transthoracic impedance, transcutaneous oxygen (tcPO(2)) and carbon dioxide (tcPCO(2)) pressures, and microcirculatory blood flow determined by laser Doppler flowmetry at rest and during a reactive hyperaemia challenge were measured before sedation (NS period), one hour after midazolam infusion (H period), and one hour after midazolam-sufentanil infusion (HS period). RESULTS: Arterial pressure decreased in both sedation periods, but heart rate, cardiac output, tcPO(2), and tcPCO(2 )remained unchanged. In both sedation periods, microcirculatory changes occurred with an increase in cutaneous blood flow at rest (H period: 207 ± 25 perfusion units [PU] and HS period: 205 ± 25 PU versus NS period: 150 ± 22 PU, p < 0.05), decreased response to ischaemia (variation of blood flow to peak: H period: 97 ± 16 PU and HS period: 73 ± 9 PU versus NS period: 141 ± 14 PU, p < 0.05), and attenuation of vasomotion. CONCLUSION: Sedation with midazolam or a combination of midazolam and sufentanil induces a deterioration of vasomotion and microvascular response to ischaemia, raising the question of whether this effect may further alter tissue perfusion when already compromised, as in septic patients

Monoclonal antibodies against sporangia and spores of Marteilla sp. (Protozoa: Ascetospora)

6 pages, 4 figures.Digestive glands of mussels Mytilus edulis from Brittany, France, infected with Marteilia sp. (Ascetospora) were used to purify the parasite. A modification of a previously used punfication protocol increased purification efficiency, permitting sporangial primordia and sporangia of Marteilia sp. to be obtained. Mouse (Balb/c) monoclonal antibodies were generated against this parasite. From the fusion, 26 monoclonal antibodies against Marteilia sp. were obtained. Antibodies from 6 clones reacted only with Marteilia sp. cells and not with normal host tissues. Four of these antibodies (1/1-3, 3/1-1, 4/1-1 and 6/2-3) reacted with the sporangia wall and two with the spore cytoplasm (9/1-1 and 12/5-1), Antibodies cross-reacted with Marteilia refringens from Mytilus galloprovincialis obtained in the Ría de Vigo, Spain.J.A.F.R. acknowledges Xunta de Galicia, Spain, for his with research fellowship at the IIM-CSIC and Caixa Galicia for his research fellowship at IFREMER - La Tremblade.Peer reviewe

Whole-Genome Sequence of Pseudoalteromonas sp. NC201, a Probiotic Strain for Litopenaeus stylirostris Hatcheries in New Caledonia

Sorieul L, Rückert C, Al-Dilaimi A, et al. Whole-Genome Sequence of Pseudoalteromonas sp. NC201, a Probiotic Strain for Litopenaeus stylirostris Hatcheries in New Caledonia. Microbiology resource announcements. 2019;8(34): e00477-19.The marine bacterium Pseudoalteromonas sp. strain NC201 has shown probiotic potential in Litopenaeus stylirostris rearing. In this study, the complete genome of NC201 was sequenced. This genome consists of a chromosome (4.13Mb) and a chromid (1.24Mb). The genome contains gene clusters coding for antibacterial peptides and secondary metabolites. Copyright © 2019 Sorieul et al

Intensive care unit-acquired Stenotrophomonas maltophilia: incidence, risk factors, and outcome

INTRODUCTION: The aim of this study was to determine incidence, risk factors, and impact on outcome of intensive care unit (ICU)-acquired Stenotrophomonas maltophilia. METHODS: This prospective observational case-control study, which was a part of a cohort study, was conducted in a 30-bed ICU during a three year period. All immunocompetent patients hospitalised >48 hours were eligible. Patients with non-fermenting Gram-negative bacilli (NF-GNB) at ICU admission were excluded. Patients without ICU-acquired S. maltophilia who developed an ICU-acquired NF-GNB other than S. maltophilia were also excluded. Screening (tracheal aspirate and skin, anal, and nasal swabs) for NF-GNB was performed in all patients at ICU admission and weekly. Univariate and multivariate analyses were performed to determine risk factors for ICU-acquired S. maltophilia and for ICU mortality. RESULTS: Thirty-eight (2%) patients developed an S. maltophilia ICU-acquired colonisation and/or infection and were all successfully matched with 76 controls. Chronic obstructive pulmonary disease (COPD) and duration of antibiotic treatment (odds ratio [OR] [95% confidence interval (CI)] = 9.4 [3 to 29], p < 0.001, and 1.4 [1 to 2.3], p = 0.001, respectively) were independently associated with ICU-acquired S. maltophilia. Mortality rate (60% versus 40%, OR [95% CI] = 1.3 [1 to 1.7, p = 0.037]), duration of mechanical ventilation (23 ± 16 versus 7 ± 11 days, p < 0.001), and duration of ICU stay (29 ± 21 versus 15 ± 17 days, p < 0.001) were significantly higher in cases than in controls. In addition, ICU-acquired infection related to S. maltophilia was independently associated with ICU mortality (OR [95% CI] = 2.8 [1 to 7.7], p = 0.044). CONCLUSION: COPD and duration of antibiotic treatment are independent risk factors for ICU-acquired S. maltophilia. ICU-acquired S. maltophilia is associated with increased morbidity and mortality rates. ICU-acquired infection related to S. maltophilia is an independent risk factor for ICU mortality

Body movement strategies to initiate the crossing of a street in front of traditional and self-driving cars in young and older adults

International audienceBACKGROUND AND AIM: The safety of elderlies is a key societal issue, especially when considering that 48% of pedestrian fatalities involve people aged 65 or more (Sécurité Routière 2017-France). Aging affects street crossing behavior, with a decrease of walking speed or more risky decisions because elderly people have difficulties to estimate the approaching speed of vehicles, especially in complex situations. In young adults, recent work focused on body movement performed to initiate the crossing, showing a top down sequence of advancement along the antero-posterior axis: the head initiates the crossing movement, followed by the shoulders, elbows, wrists, hips, knees and ankles. Identifying such motion invariants can be particularly useful in the context of self-driving vehicles which aim at predicting the intent of crossing. In this study, we aim at investigating body movement strategies performed before crossing in older adults in complex mixed traffic. METHODS: 30 young adults (YA, 21-39yo) and 30 older adults (OA, 68-81yo) were asked to cross (or not) a virtual two-way street by walking in a simulator. Participants performed a total of 120 trials where we manipulated: the type of vehicles (Conventional and/or Self driving car, the latest always stopping to let the pedestrian cross the street), their speed (30 or 50km/h), their position on the lane (far/near lane), as well as the temporal gap available to cross the street (1,2,3,4 or 5s). After computing temporal body segment motion and orientations, we analyzed the delays in initiating the crossing movement for the head, shoulders and hips with respect to the feet. We also performed hierarchical clustering to identify specific groups of behavior. RESULTS: Preliminary results show a top-down sequence of forward body motion, starting from the head to the feet, whatever the traffic condition and the group. In OA, the head initiates the motion sooner than YA wrt their feet. Moreover, while the horizontal angle profile of the head, shoulders and hips does not allow to identify invariants due to the large variety of behaviors before crossing, the trunk tilt angle profile appears to be a relevant marker for predicting the intent to cross the street. CONCLUSIONS: While aging was shown to affect street crossing decisions, our results highlight consistent behavior between YA and OA regarding trunk tilt profile when initiating the crossing. In line with previous work on YA, we also show a top down sequence of advancement of body segments. Future work is needed to use our results to predict the intent of crossing on a new database. Beside the choice to cross the street, future work is also needed to understand body segment motion and walking speed profile while crossing

CERTIFICATION REPORT: The certification of Amyloid β1-42 in CSF in ERM®-DA480/IFCC, ERM®-DA481/IFCC and ERM®-DA482/IFCC

This report describes the production of ERM®-DA480/IFCC, ERM®-DA481/IFCC and ERM®-DA482/IFCC, which are human cerebrospinal fluid (CSF) materials certified for the mass concentration of amyloid β1-42 peptide (Aβ1-42). These materials were produced by the European Commission, Joint Research Centre (EC-JRC) in collaboration with the International Federation for Clinical Chemistry and Laboratory Medicine (IFCC) following ISO Guide 34:2009 and are certified in accordance with ISO Guide 35:2006. The starting material used to prepare ERM-DA480/IFCC, ERM-DA481/IFCC and ERM-DA482/IFCC was human CSF collected from normal pressure hydrocephalus patients by continuous lumbar drainage. After collection, the CSF was aliquoted and frozen at -80 °C. For the preparation of each certified reference material (CRM) a selected number of CSF donations were thawed, pooled, mixed, filled in microvials and stored at (-70 ± 10) °C immediately thereafter. Between unit-homogeneity was quantified and stability during dispatch and storage were assessed in accordance with ISO Guide 35:2006 [ ]. The material was characterised by an interlaboratory comparison of laboratories of demonstrated competence and adhering to ISO/IEC 17025 [ ]. Technically invalid results were removed but no outlier was eliminated on statistical grounds only. Uncertainties of the certified values were calculated in accordance with the Guide to the Expression of Uncertainty in Measurement (GUM) [ ] and include uncertainties related to possible inhomogeneity, instability and characterisation. The materials are intended for the calibration of methods, quality control and/or the assessment of method performance. As with any reference material, they can be used for establishing control charts or validation studies. The CRMs are available in microvials containing at least 0.5 mL of frozen liquid. The minimum amount of sample to be used is 15 µL.JRC.F.6-Reference Material

Generation and analysis of a 29,745 unique Expressed Sequence Tags from the Pacific oyster (Crassostrea gigas) assembled into a publicly accessible database: the GigasDatabase

Background: Although bivalves are among the most-studied marine organisms because of their ecological role and economic importance, very little information is available on the genome sequences of oyster species. This report documents three large-scale cDNA sequencing projects for the Pacific oyster Crassostrea gigas initiated to provide a large number of expressed sequence tags that were subsequently compiled in a publicly accessible database. This resource allowed for the identification of a large number of transcripts and provides valuable information for ongoing investigations of tissue-specific and stimulus-dependant gene expression patterns. These data are crucial for constructing comprehensive DNA microarrays, identifying single nucleotide polymorphisms and microsatellites in coding regions, and for identifying genes when the entire genome sequence of C. gigas becomes available. Description: In the present paper, we report the production of 40,845 high-quality ESTs that identify 29,745 unique transcribed sequences consisting of 7,940 contigs and 21,805 singletons. All of these new sequences, together with existing public sequence data, have been compiled into a publicly-available Website http://public-contigbrowser.sigenae.org:9090/Crassostrea_gigas/index.htm l. Approximately 43% of the unique ESTs had significant matches against the SwissProt database and 27% were annotated using Gene Ontology terms. In addition, we identified a total of 208 in silico microsatellites from the ESTs, with 173 having sufficient flanking sequence for primer design. We also identified a total of 7,530 putative in silico, single-nucleotide polymorphisms using existing and newly-generated EST resources for the Pacific oyster. Conclusion: A publicly-available database has been populated with 29,745 unique sequences for the Pacific oyster Crassostrea gigas. The database provides many tools to search cleaned and assembled ESTs. The user may input and submit several filters, such as protein or nucleotide hits, to select and download relevant elements. This database constitutes one of the most developed genomic resources accessible among Lophotrochozoans, an orphan clade of bilateral animals. These data will accelerate the development of both genomics and genetics in a commercially-important species with the highest annual, commercial production of any aquatic organism

Nucleozin Targets Cytoplasmic Trafficking of Viral Ribonucleoprotein-Rab11 Complexes in Influenza A Virus Infection

Novel antivirals are needed to supplement existing control strategies for influenza A virus (IAV). A promising new class of drug, exemplified by the compound nucleozin, has recently been identified that targets the viral nucleoprotein (NP). These inhibitors are thought to act as "molecular staples" that stabilize interactions between NP monomers, promoting the formation of nonfunctional aggregates. Here we detail the inhibitory mechanism of nucleozin, finding that the drug has both early- and late-acting effects on the IAV life cycle. When present at the start of infection, it inhibited viral RNA and protein synthesis. However, when added at later time points, it still potently blocked the production of infectious progeny but without affecting viral macromolecular synthesis. Instead, nucleozin blocked the cytoplasmic trafficking of ribonucleoproteins (RNPs) that had undergone nuclear export, promoting the formation of large perinuclear aggregates of RNPs along with cellular Rab11. This effect led to the production of much reduced amounts of often markedly smaller virus particles. We conclude that the primary target of nucleozin is the viral RNP, not NP, and this work also provides proof of the principle that IAV replication can be effectively inhibited by blocking cytoplasmic trafficking of the viral genome.MRC grant: (G0700815), University of Cambridge/Trinity College grant: (Newton Trust), RGC Hong Kong grant: (GRF 768010 M)

First amyloid β1-42 certified reference material for re-calibrating commercial immunoassays

INTRODUCTION: Reference materials based on human cerebrospinal fluid were certified for the mass concentration of amyloid beta (Aβ)1-42 (Aβ42 ). They are intended to be used to calibrate diagnostic assays for Aβ42 . METHODS: The three certified reference materials (CRMs), ERM-DA480/IFCC, ERM-DA481/IFCC and ERM-DA482/IFCC, were prepared at three concentration levels and characterized using isotope dilution mass spectrometry methods. Roche, EUROIMMUN, and Fujirebio used the three CRMs to re-calibrate their immunoassays. RESULTS: The certified Aβ42 mass concentrations in ERM-DA480/IFCC, ERM-DA481/IFCC, and ERM-DA482/IFCC are 0.45, 0.72, and 1.22 μg/L, respectively, with expanded uncertainties (k = 2) of 0.07, 0.11, and 0.18 μg/L, respectively. Before re-calibration, a good correlation (Pearson's r > 0.97), yet large biases, were observed between results from different commercial assays. After re-calibration the between-assay bias was reduced to < 5%. DISCUSSION: The Aβ42 CRMs can ensure the equivalence of results between methods and across platforms for the measurement of Aβ42