Intraoperative Electroencephalography Alpha-Band Power Is a Better Proxy for Preoperative Low MoCA Under Propofol Compared With Sevoflurane.

BACKGROUND: Preoperative abnormal cognitive status is a risk factor for postoperative complications yet remains underdiagnosed. During propofol general anesthesia, intraoperative electroencephalography (EEG) variables, such as alpha band power (α-BP), correlate with cognitive status. This relationship under sevoflurane is unclear. We investigated whether EEG biomarkers of poor cognitive status found under propofol could be extended to sevoflurane. METHODS: In this monocentric prospective observational study, 106 patients with intraoperative EEG monitoring were included (propofol/sevoflurane = 55/51). We administered the Montreal Cognitive Assessment (MoCA) scale to identify abnormal cognition (low MoCA) 1 day before intervention. EEG variables included delta to beta frequency band powers. Results were adjusted to age and drug dosage. We assessed depth of anesthesia (DoA) using the spectral edge frequency (SEF 95 ) and maintained it within (8-13) Hz. RESULTS: The difference in α-BP between low and normal MoCA patients was significantly larger among propofol patients (propofol: 4.3 ± 4.8 dB versus sevoflurane: 1.5 ± 3.4 dB, P = .022). SEF 95 and age were not statistically different between sevoflurane and propofol groups. After adjusting to age and dose, low α-BP was significantly associated with low MoCA under propofol (odds ratio [OR] [confidence interval {CI}] = 0.39 [0.16-0.94], P = .034), but not under sevoflurane, where theta-band power was significantly associated with low MoCA (OR [CI] = 0.31 [0.13-0.73], P = .007). CONCLUSIONS: We suggest that intraoperative EEG biomarkers of abnormal cognition differ between propofol and sevoflurane under general anesthesia.

Towards individualised and optimalised positioning of non-ventilated COVID-19 patients: Putting the affected parts of the lung(s) on top?

The outbreak of COVID-19 led to an unprecedented inflow of hospitalised patients with severe acute respiratory syndrome (SARS), requiring high-flow non-invasive oxygenation, if not invasive mechanical ventilation. While the best option in terms of non-invasive systems of oxygen delivery is still a matter of debate, it also remains unclear as to whether or not the optimal in-bed positioning of patients might also help to improve their oxygen saturation levels. On the basis of three representative cases, it is possible to propose the following hypotheses: (i) how patients are positioned has a strong influence on their oxygen saturation levels; (ii) saturation-optimalised positions are patient-specific; (iii) prone positions require ergonomic devices; and (iv) saturation-optimalised positions should aim to place the most affected part(s) of the lung(s) on top. Considered together, these hypotheses have led us to recommend that COVID-19 patients should undergo a specific assessment at admission to determine their saturation-optimalised in-bed position. However, further studies are still needed to assess the benefits of such a strategy on clinical outcomes.

[How a self-managed team can improve cohesion and communication during the patient's journey in a radiotherapy department: Experience of centre Jean-Bernard (Le Mans, France)]. / Comment une équipe autonome peut améliorer la cohésion et la communication autour de la prise en charge du patient en radiothérapie : expérience du centre Jean-Bernard.

Efficient communication between professionals is of upmost importance in improving treatment safety in a radiotherapy department, and is also necessary to enhance the quality of work life. Taking as example the organizations in industry, a self-managed team centred on patients with head and neck cancers treated with radiation has been implemented in 2018 in centre Jean-Bernard (Le Mans, France). After over a year's experience, a real benefice has been found and validates the plan to extend this model to other departments.

The use of MapPop1.0 for choosing a QTL mapping sample from an advanced backcross population.

QTL detection is a good way to assess the genetic basis of quantitative traits such as the plant response to its environment, but requires large mapping populations. Experimental constraints, however, may require a restriction of the population size, risking a decrease in the quality level of QTL mapping. The purpose of this paper was to test if an advanced backcross population sample chosen by MapPop 1.0 could limit the effect of size restriction and improve the QTL detection when compared to random samples. We used the genotypic and phenotypic data obtained for 280 genotypes, considered as the reference population. The "MapPop sample" of 100 genotypes was first compared to the reference population, and genetic maps, genotypic and phenotypic data and QTL results were analysed. Despite the increase in donor allele frequency in the MapPop sample, this did not lead to an increase of the genetic map length or a biased phenotypic distribution. Three QTL among the 10 QTL found in the reference population were also detected in the MapPop sample. Next, the MapPop sample results were compared to those from 500 random samples of the same size. The main conclusion was that the MapPop software avoided the selection of biased samples and the detection of false QTL and appears particularly interesting to select a sample from an unbalanced population.

Development and transferability of a cost-effective laparoscopic camera navigation simulator.

BACKGROUND: Laparoscopic camera navigation (LCN) is vital for the successful performance of laparoscopic operations, yet little time is spent on training. This study aimed to develop an inexpensive LCN simulator, to design a structured curriculum, and to determine the transferability of skills acquired. METHODS: In this study, 0 degrees and 30 degrees LCN simulators were developed for use on a videotrainer platform. Transferability was tested by enrolling 20 medical students in an institutional review board-approved, randomized, controlled, blinded protocol. Subjects viewed a video tutorial and were pretested in LCN on a porcine Nissen model. Procedures were videotaped and the LCN performance was scored by a blinded rater according to the number of standardized verbal cues required and the percentage of time an optimal surgical view (%OSV) was obtained. Procedure time also was recorded. Subjects were stratified and randomized. The trained group practiced on the LCN simulator until competency was demonstrated. The control group received no training. Both groups were posttested on the porcine Nissen model. RESULTS: The constructed simulators required 35 man hours for development, cost $25 per board for materials, and proved to be durable. The trained group demonstrated significant improvement in verbal cues (p = 0.001), %OSV (p < 0.001), and procedure time (p = 0.001), whereas the control group showed improvement only in verbal cues (p < 0.02). At posttesting, the training group demonstrated significantly better scores for verbal cues (2.1 vs 8.0; p = 0.02) and %OSV (64% vs 45% p = 0.01) than the control group. CONCLUSION: These data suggest that the LCN simulator is cost effective and provides trainees with skills that translate to the operating room.

Genetic diversity associated with variation in silage corn digestibility for three O-methyltransferase genes involved in lignin biosynthesis.

Polymorphisms within three candidate genes for lignin biosynthesis were investigated to identify alleles useful for the improvement of maize digestibility. The allelic diversity of two caffeoyl-CoA 3-O-methyltransferase genes, CCoAOMT2 and CCoAOMT1, as well as that of the aldehyde O-methyltransferase gene, AldOMT, was evaluated for 34 maize lines chosen for their varying degrees of cell wall digestibility. Frequency of nucleotide changes averaged one SNP every 35 bp. Ninety-one indels were identified in non-coding regions and only four in coding regions. Numerous distinct and highly diverse haplotypes were identified at each locus. Numerous sites were in linkage disequilibrium that declined rapidly within a few hundred bases. For F4, an early flint French line with high cell wall digestibility, the CCoAOMT2 first exon presented many non-synonymous polymorphisms. Notably we found an 18-bp indel, which resembled a microsatellite and was associated with cell wall digestibility variation. Additionally, the CCoAOMT2 gene co-localized with a QTL for cell wall digestibility and lignin content. Together, these results suggest that genetic diversity investigated on a broader genetic basis could contribute to the identification of favourable alleles to be used in the molecular breeding of elite maize germplasm.

Mechanism of heme oxygenase-1 gene activation by cadmium in MCF-7 mammary epithelial cells. Role of p38 kinase and Nrf2 transcription factor.

The mouse heme oxygenase-1 (HO-1) gene, ho-1, contains two inducible enhancers, E1 and E2. Of several cell lines tested, induction of an E1/luciferase fusion construct, pE1-luc, by CdCl(2) is most pronounced in MCF-7 cells. In these cells, E1, but not E2, is necessary and sufficient for ho-1 gene activation. Exposure of MCF-7 cells to 10 micrometer CdCl(2) stimulates phosphorylation of ERK, JNK, and p38 mitogen-activated protein kinases, implicating one or more of these signaling pathways in ho-1 gene induction. SB203580, an inhibitor of p38, diminishes cadmium-stimulated pE1-luc expression and HO-1 mRNA levels by up to 70-80%. PD098059, an ERK pathway inhibitor, does not affect HO-1 mRNA induction at the highest concentration (40 micrometer) tested. Similarly, co-expression of a dominant-negative mutant of p38alpha, but not of ERK1, ERK2, JNK1, or JNK2, reduces basal and cadmium-induced pE1-luc activity. E1 contains binding sites for the activator protein-1 (Fos/Jun), Cap'n'Collar/basic leucine zipper (CNC-bZIP), and CCAAT/enhancer-binding protein (C/EBP) families of transcription factors. A dominant-negative mutant of Nrf2 (a CNC-bZIP member), but not of c-Jun or C/EBPbeta, inhibits pE1-luc activation by cadmium. Induction of the endogenous ho-1 gene is also inhibited by the Nrf2 mutant. Mutations of E1 that inhibit cadmium inducibility also suppress the trans-activation and DNA binding activities of Nrf2, and SB203580, but not PD098059, attenuates Nrf2-mediated trans-activation of pE1-luc. Taken together, these results indicate that cadmium induces ho-1 gene expression via sequential activation of the p38 kinase pathway and Nrf2.

Nrf2, a Cap'n'Collar transcription factor, regulates induction of the heme oxygenase-1 gene.

Stress response elements, which mediate induction of the mouse heme oxygenase-1 (HO-1) gene by several agents, resemble the binding site for the activator protein-1 (Jun/Fos), Maf, and Cap'n'Collar/basic leucine zipper (CNC-bZIP) families of proteins. In L929 fibroblasts, significant activation of an HO-1 enhancer-reporter fusion gene was observed only with the CNC-bZIP class of proteins with Nrf2 exhibiting the highest level of trans-activation, between 25- and 30-fold. To further examine the role of this factor in HO-1 gene regulation, a dominant-negative mutant, Nrf2M, was generated and conditionally expressed in L929 cells. The mutant protein was detected in cytoplasmic and nuclear fractions but did not affect cell growth. Under conditions of Nrf2M overexpression, HO-1 mRNA accumulation in response to heme, cadmium, zinc, arsenite, and tert-butylhydroquinone was inhibited by 85-95%. In contrast, overexpression of a dominant-negative mutant of c-Jun decreased L929 cell growth but did not inhibit HO-1 gene activation. Nrf2 does not homodimerize, but CNC-bZIP.small Maf protein heterodimers and Nrf2. Jun protein complexes are proposed to function as trans-activators. Co-expression of Jun proteins or p18, however, had no significant affect or inhibited Nrf2-mediated trans-activation. Taken together, these results implicate Nrf2 in the induction of the HO-1 gene but suggest that the Nrf2 partner in this function is a factor other than p18 or Jun proteins.

Coordinate up-regulation of CYP1A1 and heme oxygenase-1 (HO-1) expression and modulation of delta-aminolevulinic acid synthase and tryptophan pyrrolase activities in pyridine-treated rats.

To determine the changes in heme metabolism associated with induction of cytochrome P450 expression by pyridine, we compared the time course of CYP1A expression with the time course of (i) expression of heme oxygenase-1 (HO-1) (EC 1.14.99.3), (ii) activity of delta-aminolevulinic acid synthetase (ALAS) (EC 2.3.1.37), and (iii) heme saturation of tryptophan pyrrolase (TPO) (EC 1.13.11.11) in tissues of rats administered a single 100 or 150 mg/kg i.p. dose of pyridine. Both mRNA and protein of HO-1 and CYP1A1 were induced in the liver, kidney, and lung, with the induction of HO-1 mRNA preceding and paralleling that of CYP1A1 mRNA in the liver and lung but not kidney. Induction of CYP1A1 mRNA expression peaked within 9-12 hr and returned to control levels by 24 hr in all tissues examined, whereas induction of HO-1 mRNA expression was sustained for 48 hr in the lung and liver. In contrast to the transient up-regulation of CYP1A1 mRNA, increased microsomal CYP1A1 protein was sustained in all three tissues. Similar to the induction of HO-1 expression, lipid peroxidation was stimulated by pyridine treatment in the kidney, lung, and liver, but with the stimulation being more persistent in the liver and lung than in the kidney. Increased hepatic CYP1A1 or CYP1A2 activity was preceded by increased activities of HO-1 and ALAS. Pyridine treatment negatively modulated heme saturation of hepatic TPO. The findings indicate that pyridine stimulates the synthesis, utilization, and degradation of heme in a coordinate manner, and suggest that these alterations in heme metabolism may contribute to CYP1A1 induction by pyridine.

New cell substrates for in vitro evaluation of microcystin hepato-cytotoxicity.

Algal toxins, as Microcystins released in water supplies, may represent a serious health hazard. The behaviour of primary hepatocytes was compared with that of immortalized liver cells, with the intention of providing a new test on Microcystin cellular toxicity. Immortalized liver cells were obtained by transfection with SV40 Large T antigen-bearing plasmids. Primary hepatocytes were used as a reference. Microcystin-LR at 10(-6), 10(-7)and 10(-9)m was added to hepatocytes maintained in suspension or cultured as three-dimensional hepatospheroids for 20 and 90 min at 37 degrees C. Toxic effects were monitored by cytoskeletal disruption ('blebs') using both light and scanning electron microscopy (SEM), lactate dehydrogenase release (LDH) and trypan blue dye exclusion test. Microcystin-LR at all doses induced bleb formation and a loss of microvilli in both primary hepatocytes and immortalized cell suspensions in comparison with controls. A high level of blebbed cells was detected in the absence of increased LDH release. The blebbing phenomenon was readily detectable by light microscopy but its morpho-complexity was unmasked by SEM, with early toxic events being indentified as loss of microvilli prior to bleb formation. Cells of primary hepatospheroids appeared to be less tightly attached to each other and more likely to bleb than immortalized ones. These immortalized cells could limit the use of primary cells and increase the reproducibility of the assay.

Repletion of high energy phosphates in the postischemic neonatal heart.

Milrinone improves function in failing adult hearts, but it has not been examined in the immature myocardium. The purpose of this study was to characterize the effects of milrinone, a phosphodiesterase inhibitor, on immature hearts, and compare these to dobutamine, a commonly used catecholamine inotrope. One hundred isolated working neonatal rabbit hearts were used. Hearts were made ischemic (37 degrees C) for 1 hour and reperfused for 0, 10, 40, or 70 minutes. In separate groups, infusion of milrinone (1.0 microg/mL) or dobutamine (0.1 microg/mL) was begun after reperfusion for 10 or 40 minutes. High energy phosphates, total nondiffusable nucleotides, cyclic adenosine monophosphate (cAMP), and the percent recovery of cardiac output were determined. Cardiac output returned to normal, and adenosine triphosphate (ATP) and total nondiffusable nucleotide levels did not decline when dobutamine or milrinone were begun after 10 minutes of reperfusion. In hearts receiving inotropes after 40 minutes of reperfusion, when high energy phosphates were low, ATP increased, and total nondiffusable nucleotide repletion was observed. Cardiac output did not improve when inotropes were begun after 40 minutes. cAMP was higher in milrinone hearts compared to dobutamine, but there was no simple relation between cAMP and ventricular function. Inotropes may increase purine salvage pathway activity. Deriving maximum benefit from inotropes may depend on beginning infusions early, before the appearance of irreversible changes.

Different ATP effects on natriuretic peptide receptor subtypes in LLC-PK1 and NIH-3T3 cells.

We have observed different ATP interactions in two guanylate cyclase (GC)-coupled natriuretic peptide (NP) receptor subtypes, designated NPR-A and NPR-B. The NPR-A is selectively expressed by LLC-PK1 epithelial cells and the NPR-B by NIH-3T3 fibroblast cells. In LLC-PK1 membranes, ATP-Mg2+ potentiated ANP-stimulated GC activity (ANP-s-GC). In contrast, in NIH-3T3 membranes, ATP-Mg2+ inhibited ANP-s-GC but enhanced CNP-stimulated GC activity (CNP-s GC). ATP in the presence of Mn2+ inhibited LLC-PK1 and NIH-3T3 membrane ANP-s-GC and CNP-s-GC. These are the first data suggesting that the ATP-Mg2+ produces different effects between membrane NPR-A and -B subtypes. We have also demonstrated that GC of NPR-B is sensitive to methylene blue.