Physiological parameters of mental health predict the emergence of post-traumatic stress symptoms in physicians treating COVID-19 patients.

Lack of established knowledge and treatment strategies, and change in work environment, may altogether critically affect the mental health and functioning of physicians treating COVID-19 patients. Thus, we examined whether treating COVID-19 patients affect the physicians' mental health differently compared with physicians treating non-COVID-19 patients. In this cohort study, an association was blindly computed between physiologically measured anxiety and attention vigilance (collected from 1 May 2014 to 31 May 31 2016) and self-reports of anxiety, mental health aspects, and sleep quality (collected from 20 April to 30 June 2020, and analyzed from 1 July to 1 September 2020), of 91 physicians treating COVID-19 or non-COVID-19 patients. As a priori hypothesized, physicians treating COVID-19 patients showed a relative elevation in both physiological measures of anxiety (95% CI: 2317.69-2453.44 versus 1982.32-2068.46; P < 0.001) and attention vigilance (95% CI: 29.85-34.97 versus 22.84-26.61; P < 0.001), compared with their colleagues treating non-COVID-19 patients. At least 3 months into the pandemic, physicians treating COVID-19 patients reported high anxiety and low quality of sleep. Machine learning showed clustering to the COVID-19 and non-COVID-19 subgroups with a high correlation mainly between physiological and self-reported anxiety, and between physiologically measured anxiety and sleep duration. To conclude, the pattern of attention vigilance, heightened anxiety, and reduced sleep quality findings point the need for mental intervention aimed at those physicians susceptible to develop post-traumatic stress symptoms, owing to the consequences of fighting at the forefront of the COVID-19 pandemic.

H in α-Zr and in zirconium hydrides: solubility, effect on dimensional changes, and the role of defects.

Structural, thermodynamic and elastic properties of the hydrogen-zirconium system including all major hydrides are studied from first principles. Interstitial hydrogen atoms occupy preferentially tetrahedral sites. The calculations show that a single vacancy in α-Zr can trap up to nine hydrogen atoms. Self-interstitial Zr atoms attract hydrogen to a lesser extent. Accumulation of hydrogen atoms near self-interstitials may become a nucleation site for hydrides. By including the temperature-dependent terms of the free energy based on ab initio calculations, hydrogen adsorption isotherms are computed and shown to be in good agreement with experimental data. The solubility of hydrogen decreases in Zr under compressive strain. The volume dependence on hydrogen concentration is similar for hydrogen in solution and in hydrides. The bulk modulus increases with hydrogen concentration from 96 to 132 GPa.

Using clinically approved cyclophosphamide regimens to control the humoral immune response to oncolytic viruses.

Oncolytic viruses can be neutralized in the bloodstream by antiviral antibodies whose titers increase progressively with each exposure, resulting in faster virus inactivation and further reductions in efficacy with each successive dose. A single dose of cyclophosphamide (CPA) at 370 mg m(-2) was not sufficient to control the primary antiviral immune responses in mice, squirrel monkeys and humans. We therefore tested clinically approved multidose CPA regimens, which are known to kill proliferating lymphocytes, to determine if more intensive CPA therapy can more effectively suppress antiviral antibody responses during virotherapy. In virus-susceptible mice, primary antibody responses to intravenously (i.v.) administered oncolytic measles virus (MV) or vesicular stomatitis virus (VSV) were partially or completely suppressed, respectively, by oral (1 mg × 8 days) or systemic (3 mg × 4 days) CPA regimens initiated 1 day before virus. When MV- or VSV-immune mice were re-challenged with the respective viruses and concurrently treated with four daily systemic doses of CPA, their anamnestic antibody responses were completely suppressed and antiviral antibody titers fell significantly below pre-booster levels. We conclude that the CPA regimen of four daily doses at 370 mg m(-2) should be evaluated clinically with i.v. virotherapy to control the antiviral antibody response and facilitate effective repeat dosing.

Ictal onset slow potential shifts recorded with hippocampal depth electrodes.

PURPOSE: Reports of direct current shifts at the onset of scalp-recorded seizures prompted us to inspect depth-recorded seizures for the presence of similar slow potential shifts at the onset of the seizure to determine whether slow potential (SP) shifts actually occur at the onset of depth-recorded seizures and if these shifts can facilitate localization of the seizure focus. METHODS: With the low frequency filter "opened" (LLF=0.1 Hz, HLF=70 Hz, 3 dB/octave), 32 seizures recorded with hippocampal depth and subdural electrodes were visually inspected to identify an SP shift at the onset of the seizure. A seizure was considered as having an SP shift when the slow potential waveform was > 1.5 sec in duration and > 100 microV in amplitude. Seizures were obtained from 5 subjects; 4 underwent epilepsy surgery (3=Engel I, 1=Engel II) and one received VNS. SP shift duration, peak voltage and polarity were measured for each seizure. The ability to identify seizures based on SP shift configuration was also evaluated. RESULTS: In 84% of the seizures, ictal onset was associated with a localized SP shift. Shift duration ranged from 1.5 sec to 11.5 sec (96% > 2 sec, 62% > 5 sec). The maximum shift ranged from 139 microV to 2305 microV (mean = 1123 microV, SD = 660 microV). In all the seizures, polarity was positive at the point of maximum shift. By visually examining the SP shift, seizures could be identified as originating from the same focus or from different foci. CONCLUSIONS: The onset of depth-recorded seizures appears to be commonly associated with a localized positive SP shift. An SP shift at the onset of depth-recorded seizures is likely to be a useful visual aid for localizing electrographic seizure onset.

Postictal EEG suppression and hippocampal atrophy in temporal lobe epilepsy.

Postictal EEG suppression and slowing recorded with scalp electrodes in patients with partial epilepsy is often maximal over the cortical area of ictal onset. The aim of this study was to determine whether a quantitative relationship exists between immediate postictal EEG suppression and hippocampal atrophy. Immediate postictal EEG was analyzed in 31 scalp-recorded seizures obtained from 8 patients who underwent temporal lobectomy with seizure-free outcomes (2 left, 6 right). Quantitative EEG analysis was performed using a temporal power asymmetry index for each frequency band. The hippocampal asymmetry (left-to-right ratio) based on T1- and T2-weighted MR images was determined by hippocampal volumetric analysis. The relationship between the average temporal power asymmetry index and either T1 or T2 hippocampal asymmetry ratio was assessed for each frequency band using Pearson's correlation coefficient. Only correlations of the temporal power asymmetry index with T1 hippocampal asymmetry were significant for the total bands (r = 0.768, P < 0.026) and 8-bands (r = 0.728, P < 0.041). The findings suggest that a quantitative relationship exists between postictal EEG suppression in the 6-frequency band and hippocampal atrophy in temporal lobe epilepsy.

Sustained release of injectable zinc-recombinant hirudin suspensions: development and validation of in vitro release model.

In humans, recombinant hirudin (rHir), an anticoagulant protein, has a relatively short half-life (about 1 h). Therefore, a rHir formulation with sustained biological activity was previously proposed to result from complexing zinc salts and rHir (Zn-rHir). The purpose of this paper is to introduce and validate an in vitro release model for subcutaneous Zn-rHir formulations. In glass vials the formulations were suspended in agarose gel (2%) and coated with an extra layer of protein-free agarose. The agarose layers were covered with receiver solution, either buffered solutions (HEPES or PBS, pH 7.4) or human serum. To validate the release model and to demonstrate its potential to discriminate between different formulations, several commercial insulin and Zn-insulin formulations were also tested. The release profiles were evaluated by statistical moment analysis (mean times). Only in HEPES buffer was good discrimination between the investigated insulin formulations observed. The mean times of in vitro release of the insulin formulations and the proposed duration of their biological activities were in correlation. Low discrimination was found in PBS. For rHir, clear discrimination between the investigated rHir formulations was achieved in HEPES buffer, whereas low discrimination was found in PBS or in serum. The developed release model may be a sensitive in vitro test to assure the quality of subcutaneous insulin and rHir formulations, and may also be applicable to assess other slow-release protein and low molecular weight drug injectables.