CT analysis of skull contents in naturally mummified human corpses, a multicentric study.

INTRODUCTION: This study aimed to assess skull contents, brain appearance, and density on postmortem computed tomography in naturally mummified corpses. MATERIAL AND METHODS: For this purpose, a retrospective multicentric study, including mummified corpses from two French centers (Brest and Nantes) and from the New Mexico Decedent Image Database (USA), was performed by analyzing postmortem computed tomography (PMCT) focused on the head and neck of partially or fully mummified corpses discovered between 2011 and 2022. The PMCT analysis provided data on the CT appearance of brains, allowing them to be classified into four different categories (desiccation, liquefaction, dura mater only (DMO), and absence), and to measure densities (HU) of the brain remains. In addition, data on postmortem intervals (PMI) from Nantes and Brest centers were collected and analyzed to test the link between brain densities and PMIs. RESULTS: 54 cases of naturally mummified corpses were included. The brains were classified as liquefied (56%), desiccated (17 %), DMO (20 %), and absent (7 %) based on their CT appearance. Dehydrated brains were significantly (p < 0.004) denser (median 102 HU, interquartile range (IQR) 41) than either liquefied brains (median 39.5 HU, IQR 9) or brains with DMO (median -25 HU, IQR 57). However, the density of brain remains was not significantly affected by where the bodies were found (p = 0,41). Analysis of PMI and brain densities was performed on 22 cases. The results showed that brain remains were significantly (p = 0.039) denser when they were found after a PMI of more than six months. CONCLUSION: Brain desiccation was the aspect with the highest densities on PMCT, and for which we were able to highlight great preservation of anatomical structures observable in living organisms.

Carotid and Femoral Arterial Wall Distensibility During Long-Duration Spaceflight.

INTRODUCTION: This study aimed to assess changes in common carotid (CA) and superficial femoral (FA) arterial stiffness during long-duration spaceflight. METHODS: Ultrasound imaging was used to investigate the CA and FA of 10 astronauts preflight (PRE), on flight day 15 (FD15), after 4-5 mo (FD4-5m), and 4 d after return to Earth (R+4). Arterial wall properties were assessed through the calculation of strain, stiffness (ß), pressure-strain elastic modulus (Ep), and distensibility (DI). Stiffness indices were assessed for potential correlations to measurements of intima-media thickness (IMT). RESULTS: Significant effects of spaceflight were found for all CA stiffness indices, indicating an increase in arterial stiffness. CA strain was reduced by 34 ± 31% on FD15 and 50 ± 16% on FD4-5m and remained reduced by 42 ± 14% on R+4 with respect to PRE values. On FD4-5m, with respect to PRE values, DI was reduced by 46 ± 25% and ß and Ep were increased by 124 ± 95% and 118 ± 92%, respectively. FA arterial stiffness indices appeared to show similar changes; however, a main effect of spaceflight was only found for strain. Correlation analysis showed weak but significant relationships between measurements of CA IMT and arterial stiffness indices, but no relationships were found for FA measurements. DISCUSSION: The observed change in CA and FA stiffness indices suggest that spaceflight results in an increase in arterial stiffness. That these changes were not strongly related to measurements of IMT suggests the possibility of different mechanisms contributing to the observed results.Arbeille P, Provost R, Zuj K. Carotid and femoral arterial wall distensibility during long-duration spaceflight. Aerosp Med Hum Perform. 2017; 88(10):924-930.

Carotid and Femoral Artery Intima-Media Thickness During 6 Months of Spaceflight.

INTRODUCTION: The objective was to determine the effects of 6 mo of microgravity exposure on conduit artery diameter and wall thickness. METHODS: Diagnostic images of the common carotid artery (CC) and superficial femoral artery (FA) were obtained using echography which astronauts performed on themselves after receiving minimal training in the use of ultrasound imaging. Echographic video was recorded using a volume capture method directed by a trained sonographer on the ground through videoconferencing. Vessel properties were later assessed by processing the downlinked video. Data were collected from 10 astronauts who performed the echographic video capture at the beginning of the spaceflight (day 15) and near the end of the spaceflight (day 115 to 165). In-flight and postflight measurements were compared to preflight assessments. RESULTS: No significant changes with spaceflight were found for CC and FA diameter. Intima-media thickness (IMT) of the CC was found to be significantly increased (12% ± 4) in all astronauts during the spaceflight (early and late flight) and remained elevated 4 d after returning to Earth. Similarly, FA IMT was increased during the flight but returned to preflight levels 4 d postflight. CONCLUSION: The experiment demonstrated that, using the volume capture method of echography, untrained astronauts were able to capture enough echographic data to display vessel images of good quality for analysis. The increase in both CC and FA IMT during the flight suggest an adaptation to microgravity and to the confined environment of spaceflight which deserves further investigation.

5-Day Bed Rest: Portal and Lower Limb Veins With and Without Artificial Gravity Countermeasures.

PURPOSE: The objective of the study was to evaluate the effect of short-term, head-down bed rest (HDBR), with and without artificial gravity countermeasures, on splanchnic and lower limb vein properties. METHODS: Data were collected from 12 men before and after 5 d of continuous -6° HDBR without countermeasures (CON) and with two artificial gravity countermeasure protocols: 30-min continuous centrifugation (AG1), and 30-min intermittent centrifugation (AG2). Portal (PV), tibial (TibV), and gastrocnemius (GastV) veins were investigated by echography supine and after 30 min of head-up tilt. RESULTS: After HDBR, there was no change in PV, TibV, or GastV cross-sectional area at rest in any of the three conditions. In response to tilt, GastV and TibV area increased (168±141% and 192±124%, respectively) with no change in this response post-HDBR in any of the experimental conditions (P>0.05). PV area decreased with tilt (-33±13%) and was not different pre- to post-HDBR in the CON or AG1 conditions. However, there was a greater reduction in PV area in the AG2 group post-HDBR (-32±10% pre, -49±9% post-HDBR, P=0.003). CONCLUSIONS: Calf veins were not significantly affected by 5 d of HDBR and did not appear to be negatively impacted by the artificial gravity countermeasures over this time period. In addition, the intermittent protocol resulted in better splanchnic vasoconstriction in response to head-up tilt, which may have contributed to a better maintenance of orthostatic tolerance post-HDBR.

Teles-operated echocardiography using a robotic arm and an internet connection.

The objective was to design and validate a method of tele-operated echocardiography. The method was tested in a hospital facility with an expert sonographer located in a room 10 m away from the patient. An ultrasound probe, fixed to a motorized probe holder, was located on the patient by a non-sonographer and was remotely controlled by the expert sonographer via an Internet connection. Scans were performed on 41 cardiac patients. The quality of the cardiac views obtained using tele-echocardiography was lower than that of reference echocardiography, but generated similar measurements in 93%-100% of the cases. Bland-Altman plots and statistical comparison of tele- and reference echocardiography measures revealed no differences (p > 0.05). Of the 71 valve leaks or aortic stenoses present, 61 (86%) were detected using tele-echocardiography. These results indicate that tele-echocardiography provided reliable diagnoses and acceptable measurements in 86% and 93% of cases, respectively, with no false-positive diagnoses being reported.

Adaptation of the main peripheral artery and vein to long term confinement (Mars 500).

PURPOSE: The objective was to check if 520 days in confinement (MARS 500), may affect the main peripheral arterial diameter and wall thickness and the main vein size. METHOD: Common carotid (CC) femoral artery (FA) portal vein (PV), jugular (JG), femoral vein (FV) and tibial vein were assessed during MARS 500 by echography, performed by the subjects. A hand free volumic echographic capture method and a delayed 3D reconstruction software developed by our lab were used for collecting and measuring the vascular parameters. RESULTS: During the MARS 500 experiment the subjects performed 6 sessions among which 80% of the echographic data were of sufficient quality to be processed. No significant change was found for the Common carotid, Jugular vein, femoral artery, femoral vein, portal vein, and tibial vein diameter. CC and FA IMT (intima media thickness) were found significantly increased (14% to 28% P<0.05) in all the 6 subjects, during the confinement period and also at +2 days after the confinement period, but there was no significant difference 6 month later compare to pre MARS 500. CONCLUSION: The experiment confirmed that even untrained to performing echography the subjects were able to capture enough echographic data to reconstruct the vessel image from which the parameters were measured. The increase in both CC and FA IMT should be in relation with the stress generated by the confined environment or absence of solar radiation, as there was no change in gravity, temperature and air in the MARS 500 module, and minor changes in physical exercise and nutrition.

New modified ß-cyclodextrin derivatives as detoxifying agents of chemical warfare agents (II). In vitro detoxification of cyclosarin (GF): general screening and toxicokinetic aspects of OP scavengers.

As standard therapy of intoxication with organophosphorus (OP) compounds is still insufficient, developing new treatment strategies is urgently required. For evaluating potential of OP detoxification of several compounds correctly, different toxicodynamic impact of OP enantiomers has to be considered thoroughly. It has already been demonstrated that ß-cyclodextrin (ß-CD) derivatives with attached nucleophilic substituent iodosobenzoic acid (IBA) can be regarded as potent OP scavengers due to an accelerating effect on decay of different OP. Herein, six CD derivatives permethylated or not on CD torus as well as differently attached nucleophilic substituent IBA derivative were investigated regarding detoxification of GF as an OP model substance. Acceleration of GF detoxification could be detected for all compounds with highest rate constants for propylene chain linked nucleophilic substituents on CD derivative. In addition, fast initial binding of GF on CD could be observed and is ascribed to formation of CD complexes. Furthermore, terminal plateau phase was detected of about 1% of each enantiomer reflecting the necessity of a quantitative determination at low concentrations. Moreover, this molecular depot formation may represent an additional detoxification pathway for OP.

New modified ß-cyclodextrin derivatives as detoxifying agents of chemical warfare agents (I). Synthesis and preliminary screening: evaluation of the detoxification using a half-quantitative enzymatic assay.

Current treatments of organophosphorus nerve agents poisoning are imperfect, and more efficient medical countermeasures need to be developed. Chemical scavengers based on ß-cyclodextrin displayed promising results, but further investigations have to be performed to evaluate the possibility of application of substituted cyclodextrins as potential detoxification agents. Herein, five new cyclodextrins scavengers were synthesized. New optimal conditions for regioselectively monosubstitution of ß-cyclodextrin at O-2 position were then studied to access to key intermediates. After these optimizations, a new series of three permethylated derivatives was developed, and two compounds bearing an α-nucleophilic group via a three carbon atoms linker were prepared. The ability of these five scavengers to detoxify nerve agents (cyclosarin, soman, tabun and VX) was evaluated by a semi-quantitative biological assay. All the modified cyclodextrins significantly decreased the inhibitory effect of chemical warfare G agents on acetylcholinesterase activity. For this purpose, we showed that the specific interactions between the organophosphorus compound and the oligosaccharidic moiety of the scavenger played a pivotal role in the detoxification process.

Optimized strategies to synthesize ß-cyclodextrin-oxime conjugates as a new generation of organophosphate scavengers.

A new generation of organophosphate (OP) scavengers was obtained by synthesis of ß-cyclodextrin-oxime derivatives 8-12. Selective monosubstitution of ß-cyclodextrin was the main difficulty in order to access these compounds, because reaction onto the oligosaccharide was closely related to the nature of the incoming group. For this purpose, non-conventional activation conditions were also evaluated. Intermediates 5 and 7 were then obtained with the better yields under ultrasounds irradiation. Finally, the desired compounds 8-10 were obtained from 5-7 in high purity by desilylation using potassium fluoride. Quaternarisation of compounds 8 and 9 was carried out. OP hydrolytic activity of compounds 8-12 was evaluated against cyclosarin (GF) and VX. None of the tested compounds was active against VX, but these five cyclodextrin derivatives detoxified GF, and the most active scavengers 10 and 11 allowed an almost complete hydrolysis of GF within 10 min. Even more fascinating is the fact that compounds 9 and 10 were able to hydrolyze enantioselectively GF.

In vitro detoxification of cyclosarin (GF) by modified cyclodextrins.

Developing potent detoxification strategies for prophylaxis and therapy against organophosphate (OP) intoxication still represents a challenging task. Clinical application of numerous investigated substances including enzymes and low molecular scavengers like metal ions or nucleophiles could not yet be realised due to profound disadvantages. Presenting a promising attempt, cyclodextrins (CDs) efficiently enhance the degradation of some organophosphorus compounds. The present study examined the in vitro GF degradation mediated by three CDs and a nucleophilic precursor performed by mass spectrometric detection with ammonia chemical ionisation. All four compounds caused a notable enhancement of GF detoxification that was synergistically accelerated in the case of 2-O-(3-carboxy-4-iodosobenzyl)-ß-cyclodextrin (IBA-ß-CD) with the alpha-nucleophile 2-iodosobenzoic acid (IBA) grafted on the secondary face of ß-cyclodextrin (ß-CD). In vitro toxicokinetic investigations of CD derivatives are needed to evaluate the effect of slow terminal elimination phase of the more toxic (-)-GF shown for two CD-derivatives underlining the necessity of detecting the complete kinetic course of inactivation. The observed effect of fast high affinity binding (20-30%) represents an additional therapeutic option of an extremely rapid reduction of GF concentration in vivo. Distinctive differences in the course of reaction are detected depending on ß-CD-derivatives, allowing a first inference of possible mechanisms and relevance of attached substituents. However, further profound investigation needs to be done to evaluate the basis of a clinical application of substituted CDs as potential detoxification agents.

Regioselective access to 3I-O-substituted-beta-cyclodextrin derivatives.

Formation of a copper(ii)-beta-cyclodextrin (beta-CD) complex in an aqueous medium allowed the regioselective introduction into the oligosaccharide of a benzyl or a bromo-allyl substituent at O-3.