Motorcycling performance and sleepiness during an extended ride on a dynamic simulator: relationship with stress biomarkers.

OBJECTIVE: Powered two-wheelers (PTW) make up a large proportion of fatal accidents. The aim of this study was to investigate the effects of time-of-day and total sleep deprivation (SD) on simulated motorcycling performance during extended riding sessions (60 min), while evaluating stress mechanisms. APPROACH: A total of 16 healthy males participated in four simulated motorcycling sessions at 07:00, 11:00, 15:00 and 19:00, including city (8 min), country (2 min) and highway pathways (40 min), after a normal night of sleep and after total SD (30 h), in a randomized counterbalanced order. The recorded motorcycle parameters included: variation of lateral position, number of inappropriate line crossings (ILC), falls, riding errors, speed and speed limit violations. Subject parameters included the number of microsleeps in each pathway, the number of lapses during the 3-min psychomotor vigilance task (PVT-Brief version), and the Karolinska sleepiness scale (KSS) score. Saliva samples were used to assess cortisol (sC), α-amylase (sAA), and chromogranin-A (sCgA). ANOVAs and Pearson's correlation analysis were performed between these variables. MAIN RESULTS: Most parameters were influenced by an interaction effect between 'Motorcycling pathways' × 'SD' (speed (p < 0.05), legal speed violations (p < 0.01), variation of lateral position (p < 0.001), falls (p < 0.001), EEG-microsleeps (p < 005)). An interaction effect between 'SD' × 'Time-of-day' influenced the number of ILCs (p < 0.01), sC (p < 0.05) and sCgA (p < 0.05) levels. SD affected KSS scores (p < 0.001) and PVT lapses (p < 0.05). The highest disturbances were associated with highway motorcycling simulation. SIGNIFICANCE: Sleepiness due to circadian or SD and fatigue effects significantly affect riding and increase the risks involved with PTWs. The activation of both stress systems seems not sufficient to alleviate these deleterious effects.

The effectiveness of influenza vaccination in pregnancy in relation to child health outcomes: Systematic review and meta-analysis.

OBJECTIVES: To determine the effectiveness of influenza vaccination during pregnancy on child health outcomes. DESIGN: Systematic review/meta-analysis. DATA SOURCES: Clinical Trials.gov, Cochrane Library, EMBASE, Medline, Medline in process, PubMed and Web of Science, from 1st January 1996 to 29th June 2018. An updated Medline search was performed 30th June 2018 to 31st October 2019. METHODS: Randomised controlled trials (RCTs) and observational studies reporting health outcomes of infants and children born to women who received inactivated influenza vaccine during pregnancy. The primary outcome was infant laboratory confirmed influenza (LCI). Secondary outcomes included influenza-like illness (ILI), other respiratory illnesses, primary care, clinic visit or hospitalisations due to influenza illness and long-term respiratory childhood outcomes. RESULTS: 19 studies were included; 15 observational studies and 4 primary RCTs with an additional 3 papers reporting secondary outcomes of these RCTs. In a random effects meta-analysis of 2 RCTs including 5742 participants, maternal influenza vaccination was associated with an overall reduction of LCI in infants of 34% (95% confidence interval 15-50%). However, there was no effect of maternal influenza vaccination on ILI in infants ≤6 months old. Two RCTs were excluded from the meta-analysis for the outcome of LCI in infants (different controls used). Both of these studies showed a protective effect for infants from LCI, with a vaccine efficacy of up to 70%. Overall observational studies showed an inverse (protective) association between maternal influenza vaccination and infant LCI, hospitalisation and clinic visits due to LCI or ILI in infants and other respiratory illness in infants ≤6 months old. CONCLUSIONS: This systematic review supports maternal influenza vaccination as a strategy to reduce LCI and influenza-related hospitalisations in young infants. Communicating these benefits to pregnant women may support their decision to accept influenza vaccination in pregnancy and increase vaccine coverage in pregnant women. REGISTRATION: PROSPERO CRD42018102776.

Investigation of the mechanism for current induced network failure for spray deposited silver nanowires.

Silver nanowires are one of the prominent candidates for the replacement of the incumbent indium tin oxide in thin and flexible electronics applications. Their main drawback is their inferior electrical robustness. Here, the mechanism of the short duration direct current induced failure in large networks is investigated by current stress tests and by examining the morphology of failures. It is found that the failures are due to the heating of the film and they initiate at the nanowire junctions, indicating that the main failure mechanism is based on the Joule heating of the junctions. This failure mechanism is different than what has been seen in literature for single nanowires and sparse networks. In addition, finite element heating simulations are performed to support the findings. Finally, we suggest ways of improving these films, in order to make them more suitable for device applications.

Different implications of the dorsal and ventral hippocampus on contextual memory retrieval after stress.

This study assessed the relative contributions of dorsal (dHPC) and ventral (vHPC) hippocampus regions in mediating the rapid effects of an acute stress on contextual memory retrieval. Indeed, we previously showed that an acute stress (3 electric footschocks; 0.9 mA each) delivered 15 min before the 24 h-test inversed the memory retrieval pattern in a contextual discrimination task. Specifically, mice learned in a four-hole board two successive discriminations (D1 and D2) varying by the color and texture of the floor. Twenty-four hours later, nonstressed animals remembered accurately D1 but not D2 whereas stressed mice showed an opposite memory retrieval pattern, D2 being more accurately remembered than D1. We showed here that, at the time of memory testing in that task, stressed animals exhibited no significant changes neither in pCREB activity nor in the time-course evolution of corticosterone into the vHPC; in contrast, a significant decrease in pCREB activity and a significant increase in corticosterone were observed in the dHPC as compared to nonstressed mice. Moreover, local infusion of the anesthetic lidocaine into the vHPC 15 min before the onset of the stressor did not modify the memory retrieval pattern in nonstress and stress conditions whereas lidocaine infusion into the dHPC induced in nonstressed mice an memory retrieval pattern similar to that observed in stressed animals. The overall set of data shows that memory retrieval in nonstress condition involved primarily the dHPC and that the inversion of memory retrieval pattern after stress is linked to a dHPC but not vHPC dysfunction.

Instrumental improvements and sample preparations that enable reproducible, reliable acquisition of mass spectra from whole bacterial cells.

RATIONALE: Rapid sub-species characterization of pathogens is required for timely responses in outbreak situations. Pyrolysis mass spectrometry (PyMS) has the potential to be used for this purpose. METHODS: However, in order to make PyMS practical for traceback applications, certain improvements related to spectrum reproducibility and data acquisition speed were required. The main objectives of this study were to facilitate fast detection (<30 min to analyze 6 samples, including preparation) and sub-species-level bacterial characterization based on pattern recognition of mass spectral fingerprints acquired from whole cells volatilized and ionized at atmospheric pressure. An AccuTOF DART mass spectrometer was re-engineered to permit ionization of low-volatility bacteria by means of Plasma Jet Ionization (PJI), in which an electric discharge, and, by extension, a plasma beam, impinges on sample cells. RESULTS: Instrumental improvements and spectral acquisition methodology are described. Performance of the re-engineered system was assessed using a small challenge set comprised of assorted bacterial isolates differing in identity by varying amounts. In general, the spectral patterns obtained allowed differentiation of all samples tested, including those of the same genus and species but different serotypes. CONCLUSIONS: Fluctuations of ±15% in bacterial cell concentrations did not substantially compromise replicate spectra reproducibility.

Role of corticosteroid binding globulin in the fast actions of glucocorticoids on the brain.

Corticosteroid binding globulin (CBG) is a glycoprotein synthesized in liver and secreted in the blood where it binds with a high affinity but low capacity glucocorticoid hormones, cortisol in humans and corticosterone in laboratory rodents. In mammals, 95% of circulating glucocorticoids are bound to either CBG (80%) or albumin (15%) and only the 5% free fraction is able to enter the brain. During stress, the concentration of glucocorticoids rises significantly and the free fraction increases even more because CBG becomes saturated. However, glucocorticoids unbound to CBG are cleared from the blood more quickly. Our studies on mice totally devoid of CBG (Cbg k.o.) showed that during stress these mutant mice display a lower rise of glucocorticoids than the wild-type controls associated with altered emotional reactivity. These data suggested that CBG played a role in the fast actions of glucocorticoids on behavior. Further analyses demonstrated that stress-induced memory retrieval impairment, an example of the fast action of glucocorticoids on the brain is abolished in the Cbg k.o. mice. This effect of stress on memory retrieval could be restored in the Cbg k.o. mice by infusing corticosterone directly in the hippocampus. The mechanisms explaining these effects involved an increased clearance but no difference in corticosterone production. Thus, CBG seems to have an important role in maintaining in blood a glucocorticoid pool that will be able to access the brain for the fast effects of glucocorticoids.

Stress-induced memory retrieval impairments: different time-course involvement of corticosterone and glucocorticoid receptors in dorsal and ventral hippocampus.

The present study was aimed at determining the relative contribution of the dorsal (DH) and ventral (VH) hippocampus in stress-induced memory retrieval impairments. Thus, we studied the temporal involvement of corticosterone and its receptors, i.e. mineralocorticoid (MR) and glucocorticoid (GR) in the DH and VH, in relation with the time-course evolution of stress-induced memory retrieval impairments. In a first experiment, double microdialysis allowed showing on the same animal that an acute stress (electric footshocks) induced an earlier corticosterone rise in the DH (15-60 min post-stress) and then in the VH (90-105 min post-stress). The return to baseline was faster in the DH (105 min) than in the VH (120 min). Memory deficits assessed by delayed alternation occurred at 15-, 60-, and 105-min delays after stress and were closely related to the kinetic of corticosterone rises within the DH and VH. In a second experiment, the GR antagonist RU-38486 and the MR antagonist RU-28318 were administered in the DH or VH 15 min before stress. RU-38486 restored memory at 60 but not at 105 min post-stress delays in the DH, whereas the opposite pattern was observed in the VH. By contrast, RU-28318 had no effect on memory impairments at both the 60- and 105-min post-stress delays, showing that MR receptors are not involved at these delays. However, RU-28318 administered in the DH restored memory when administered at a shorter post-stress delay (15 min). Overall, our data are first to evidence that stress induces a functional switch from the DH to VH via different corticosterone time-course evolutions in these areas and the sequential GR receptors involvement in the DH and then in the VH, as regards the persistence of stress-induced memory retrieval deficits over time.

Electrohydrodynamic deposition of nanostructured lead zirconate titanate.

The deposition of a propanol-based lead zirconate titanate (PZT) sol using electrohydrodynamic atomization (EHDA) in the stable cone-jet mode was investigated. The droplets generated were deposited onto a copper substrate as a film, which was investigated using X-ray diffraction and scanning electron microscopy. The PZT film was shown to contain uniform nano-particles of PZT, which maintained their shape on sintering (650 degrees C, 1 hour) while forming the perovskite phase of PZT.

Results compared for tricyclic antidepressants as assayed by liquid chromatography and enzyme immunoassay.

The tricyclic antidepressants amitriptyline, nortriptyline, imipramine, and desipramine in serum of patients taking one of the drugs were quantified in two laboratories by high-performance liquid chromatography (HPLC) and enzyme-multiplied immunoassay (EMIT; Syva). Results for split samples were highly correlated, but EMIT gave higher results in most cases, and the slopes of the correlation lines for each analyte were greater than 1. Detection limits for the two procedures were such that 18% of the EMIT results for the drug(s) were considered negative, as compared with 4% of the HPLC results. Additional assay of desmethyl or hydroxy antidepressant metabolites by HPLC did not explain the higher EMIT results. The relatively high detection limit for EMIT greatly limits its use in therapeutic drug monitoring, where low concentrations of tricyclic antidepressants are as important as high ones for dose adjustment or determination of compliance. Other problems with EMIT measurement of tricyclic antidepressants are discussed.

Therapeutic drug monitoring of tricyclic antidepressants.

The traditional dose-response method of medication adjustment depends on several assumptions that are not met in the case of tricyclic antidepressants (TCAs), which makes therapeutic drug monitoring (TDM) particularly useful with these drugs. TDM can facilitate treatment by providing objective guidelines for dose adjustment. It provides a means of assessing compliance, ensuring an effective concentration, and avoiding toxicity. The latter is an often-overlooked benefit of therapeutic monitoring of TCAs and yet is just as important as improving response. The cardiac and central nervous system toxicity of TCAs is concentration-dependent and potentially life-threatening. Such toxicity will predictably occur in up to 5% of patients on standard antidepressant doses of TCAs when TDM is not used to rationally adjust the dose. Without TDM, such toxicity is difficult to detect early. A cost/benefit analysis supports the cost effectiveness of TDM as a standard part of TCA chemotherapy when doses in the 100-300 ng/day range are used.

Inhibitory effect of disulfiram (Antabuse) on alcohol dehydrogenase activity.

We investigated the effect of disulfiram (Antabuse) on the activity of alcohol dehydrogenase (EC 1.1.1.1) in vitro. We observed a time-dependent inhibition of this dehydrogenase by disulfiram and diethyldithiocarbamate similar to that obtained for aldehyde dehydrogenase (EC 1.2.1.3). These results suggest a possible explanation for various side effects observed in the clinical use of Antabuse.