Is Charge Scaling Really Mandatory when Developing Fixed-Charge Atomistic Force Fields for Deep Eutectic Solvents?

In recent years, molecular dynamic simulations on choline chloride based deep eutectic solvents (DES) have flourished. Most of these studies point to the fact that in order to accurately reproduce dynamical properties of the latter using a fixed-charge atomistic force field (FF) one has to resort to charge scaling. In this work, we propose an alternative to charge scaling and show that the sole refinement of the Lennard-Jones parameters of the oxygen and hydrogen of the hydroxyl function in the GAFF v2.11 FF enables an accurate description of static, dynamical, and structural properties of two commonly used DES, namely, ethaline (1:2 mixture of choline chloride and ethylene glycol) and glyceline (1:2 mixture of choline chloride and glycerol). Various computed physicochemical properties for both mixtures with our modified version of the GAFF v2.11 FF are found in good agreement with experimental data. Most importantly, however, is the fact that self-diffusion coefficients for the various components of both ethaline and glyceline are found within a maximum deviation of 33% from experimental values, which is at least as good if not better than current scaled-charge FF. Finally, computed radial distribution functions match with those reported in the literature.

[Epidemiology of urinary stones in the French military during the operation Serval]. / Épidémiologie de la lithiase urinaire chez les militaires français au cours de l'opération Serval.

OBJECTIVES: The renal colic crisis is a pathology frequently encountered in foreign operations recently conducted by the French army and often requires a medical repatriation in mainland France. Soldiers deployed in arid areas are at increased risk of developing urolithiasis. The purpose of our study is to analyze the risk factors, the frequency and the methods of management of symptomatic urinary stone disease for French military returnees for renal colic during Serval operation. METHODS: Our study focused on French soldiers repatriated from Mali for a renal colic care between January 11th and November 30th, 2013. For each patient, we recorded: age, sex, deployment date, crisis date, personal and family histories of urolithiasis, initial medical treatment, diagnosis and treatment to return to France. RESULTS: Three hundred and forty-eight soldiers were evacuated during Serval operation, among which 41 were due to the occurrence of renal colic crisis (11.7%). Twenty-nine percent of patients had a personal history of kidney stone disease symptomatically. The average residence time when the crisis appears is 60 days (10-120 days). Ninety-five percent of patients were asymptomatic at their arrival in France and 39% of patients had no stone found in CT scan. The average size of the stones found on the imaging was 2.71 mm (1-8mm). One patient required drainage by JJ ureteral endoprothese in order to have a quick ureteroscopy for recovery of its capacity. CONCLUSION: The French military sent to Serval operation are exposed to multiple contributing factors of urolithiasis as the dehydration and the strong temperature. The analysis of our series reveals that the history of renal stone disease is the main factor favoring and the medical treatment is effective in almost all renal colic cases. The operational impact associated with this common condition in the Sahel region deserves an awareness of field practitioners to the screening and management of this disease in a precarious situation and a reflection of the staffs concerning the access onto the operating theater to appropriate diagnostic and therapeutic means that could facilitate the return to the combat unit.

Potential of an in vitro toolbox combined with exposure data as a first step for the risk assessment of dietary chemical contaminants.

In vitro risk assessment of dietary contaminants has become a priority in human food safety. This paper proposes an in vitro approach associating different complementary tools in an original toolbox and aims to improve the assessment of the toxicological impact of dietary contaminants at realistic human exposure levels, with a special focus on the intestinal compartment. The system is based on the use of four complementary cellular tools, namely stress gene induction in transgenic strains of Escherichia coli, modulation of the activity of key biotransformation enzymes (cytochrome P-450 (CYP) 1A1 and 3A4) in a human intestinal cell line, and activation of aryl hydrocarbon receptor (AhR) and oestrogenic receptor (ER)-dependent genes in agonistic and antagonistic assays with luciferase reporter cells. It was applied to four chosen model molecules: ochratoxin A (OTA) and deoxynivalenol (DON), two common food-borne mycotoxins, and imazalil (IMA) and benomyl (BEN), two fungicides widely occurring in foodstuffs. All these assays were performed at or around a realistic intestinal concentration, determined through a deterministic approach based on the calculation of a theoretical maximum daily intake (TMDI). Using the four model molecules, it is clearly highlighted that induction of CYP1A1 activity and inhibition of CYP3A4 activity occurred in Caco-2 cells at a realistic intestinal concentration of IMA. Furthermore, some bacterial stress genes were induced in a range of realistic concentrations, following exposure to DON and IMA. In addition, BEN clearly provoked an ER agonistic activity in a human oestrogen sensitive reporter cell line. All these results are in accordance with the literature, suggesting that the in vitro toolbox constitutes an interesting approach in order to obtain a first 'fingerprint' of dietary contaminants at realistic human exposure for further risk assessment.

Strontium nitrate extraction to ionic liquids by a crown ether: a molecular dynamics study of aqueous interfaces with C4mim+- vs C8mim+-based ionic liquids.

In order to gain microscopic insights into the extraction mechanism of strontium cations by 18-crown-6 (18C6) to room temperature ionic liquids (ILs), we simulated by molecular dynamics (MD) strontium complexes in neat ionic liquids and at their interfaces with water. We compared two ILs, based on the PF(6)(-) anion and either 1-butyl-3-methylimidazolium (C(4)mim(+)) or 1-octyl-3-methylimidazolium (C(8)mim(+)) cations. Regarding the complexes, two states were considered: charged [Sr⊂18C6](2+) vs neutral [Sr⊂18C6,(NO(3))(2)], where the nitrates are either fully dissociated or coordinated to Sr. In "dry" or "humid" [C(4)mim][PF(6)] and in "dry" [C(8)mim][PF(6)] IL, the neutral complex is found to be the most stable one. In the binary IL/water solutions, the charged complexes mostly partition to the aqueous phase, whereas the neutral [Sr⊂18C6,(NO(3))(2)] complexes are more concentrated in the interfacial domain. The aqueous solutions in contact with the ionic liquids contain C(4)mim(+), but almost no C(8)mim(+) ions, supporting a classical extraction mechanism to [C(8)mim][PF(6)] and an ion exchange mechanism to [C(4)mim][PF(6)]. Furthermore, remarkable events occurred during the dynamics, where complexes were extracted to the IL phases. When compared to the interfacial landscapes obtained with the same solutes at a classical organic liquid (chloroform)/water interface, those with ILs allow us to better understand specific features of liquid-liquid extraction to ILs.

Competitive complexation of nitrates and chlorides to uranyl in a room temperature ionic liquid.

By coupling EXAFS, UV-vis spectroscopy, and molecular dynamics and quantum mechanical calculations, we studied the competitive complexation of uranyl cations with nitrate and chloride ions in a water immiscible ionic liquid (IL), C(4)mimTf(2)N (C(4)mim(+): 1-butyl-3-methyl-imidazolium; Tf(2)N(-) = (CF(3)SO(2))(2)N)(-): bis(trifluoromethylsulfonyl)imide). Both nitrate and chloride are stronger ligands for uranyl than the IL Tf(2)N(-) or triflate anions and when those anions are simultaneously present, neither the limiting complex UO(2)(NO(3))(3)(-) nor UO(2)Cl(4)(2-) alone could be observed. At a U/NO(3)/Cl ratio of 1/2/2, the dominant species is likely UO(2)Cl(NO(3))(2)(-). When chloride is in excess over uranyl with different nitrate concentrations (U/NO(3)/Cl ratio of 1/2/6, 1/4/4, and 1/12/4) the solution contains a mixture of UO(2)Cl(4)(2-) and UO(2)Cl(3)(NO(3))(2-) species. Furthermore, it is shown that the experimental protocol for introducing these anions to the solution (either as uranyl counterion, as added salt, or as IL component) influences the UV-vis spectra, pointing to the formation of different kinetically equilibrated complexes in the IL.

Solvation of Ln((III)) lanthanide cations in the [BMI][SCN], [MeBu(3)N][SCN], and [BMI](5)[Ln(NCS)(8)] ionic liquids: a molecular dynamics study.

We report a molecular dynamics study on the solvation of trivalent lanthanide cations Ln((III)) (Ln = La, Eu and Yb) in the [BMI][SCN] and [MeBu(3)N][SCN] ionic liquids (ILs), based respectively on 1-methyl-3-butylimidazolium (BMI(+)) and tributylmethylammonium (MeBu(3)N(+)) cations, and on thiocyanate (SCN(-)) anions. For this purpose we first derive a force field representation of SCN(-) that simultaneously describes the [BMI][SCN] liquid and SCN(-) as a ligand for Ln((III)) ions and, in particular, for the energy difference between N- vs S-coordination, as compared to QM calculated values. In liquid simulations, we compare different initial states where the solute is either the "naked" Ln((III)) ion or its anionic Ln(NCS)(8)(5-) complex. In all cases, the first solvation shell of Ln((III)) is found to be purely anionic, with 6 to 8 N-coordinated ligands, depending on the nature of Ln((III)) and the immersed solute. This first shell is surrounded by 13 - 14 BMI(+) or 8 - 9 MeBu(3)N(+) cations, leading to an "onion type" solvation of Ln((III)). The comparison of gas phase optimized structures (that are all unstable from n = 5 NCS(-) ligands) to those observed in ILs points to the importance of solvation forces on the nature of the Ln((III)) complex, with a marked contribution of the IL cation. A given Ln(NCS)(n)(3-n) complex is found to be better stabilized by the imidazolium than by the ammonium based IL. Furthermore, according to free energy PMF (potential of mean force) calculations, the imidazolium based liquid favors somewhat higher coordination numbers (CNs), compared to the ammonium based IL. For instance, the coordination of an eight SCN(-) ligand to Eu(NCS)(7)(4-) is favored in the [BMI][SCN] liquid, but not in [MeBu(3)N][SCN]. For the La((III)) and Yb((III)) cations, the CNs are the same in both liquids (8 and 7, respectively), but the free energy differences between the two types of complexes differ markedly. The final part of the paper is devoted to the [BMI](5)[Ln(NCS)(8)] pure ILs, based on BMI(+) as cation and on the Ln(NCS)(8)(5-) complex (Ln = La((III)) and Yb((III))) as anionic component. In these liquids, Ln((III)) CNs are found to be similar to those found in the [BMI][SCN] solutions, and the dynamics is characterized by a fluid behavior of the BMI(+) ions diffusing around a quasi frozen network of anionic complexes.

Uranyl coordination in ionic liquids: the competition between ionic liquid anions, uranyl counterions, and Cl- anions investigated by extended X-ray absorption fine structure and UV-visible spectroscopies and molecular dynamics simulations.

The first coordination sphere of the uranyl cation in room-temperature ionic liquids (ILs) results from the competition between its initially bound counterions, the IL anions, and other anions (e.g., present as impurities or added to the solution). We present a joined spectroscopic (UV-visible and extended X-ray absorption fine structure)-simulation study of the coordination of uranyl initially introduced either as UO2X2 salts (X-=nitrate NO3-, triflate TfO-, perchlorate ClO4-) or as UO2(SO4) in a series of imidazolium-based ILs (C4mimA, A-=PF6-, Tf2N-, BF4- and C4mim=1-methyl-3-butyl-imidazolium) as well as in the Me3NBuTf2N IL. The solubility and dissociation of the uranyl salts are found to depend on the nature of X- and A-. The addition of Cl- anions promotes the solubilization of the nitrate and triflate salts in the C4mimPF6 and the C4mimBF4 ILs via the formation of chloro complexes, also formed with other salts. The first coordination sphere of uranyl is further investigated by molecular dynamics (MD) simulations on associated versus dissociated forms of UO2X2 salts in C4mimA ILs as a function of A- and X- anions. Furthermore, the comparison of UO2Cl(4)2-, 2 X- complexes with dissociated X- anions, to the UO2X2, 4 Cl- complexes with dissociated chlorides, shows that the former is more stable. The case of fluoro complexes is also considered, as a possible result of fluorinated IL anion's degradation, showing that UO2F42- should be most stable in solution. In all cases, uranyl is found to be solvated as formally anionic UO2XnAmClp2-n-m-p complexes, embedded in a cage of stabilizing IL imidazolium or ammonium cations.

Aqueous interfaces with hydrophobic room-temperature ionic liquids: a molecular dynamics study.

We report a molecular dynamics study of the interface between water and (macroscopically) water-immiscible room-temperature ionic liquids "ILs", composed of PF6(-) anions and butyl- versus octyl-substituted methylimidazolium+ cations (noted BMI+ and OMI+). Because the parameters used to simulate the pure ILs were found to exaggerate the water/IL mixing, they have been modified by scaling down the atomic charges, leading to better agreement with the experiment. The comparison of [OMI][PF6] versus [BMI][PF6] ILs demonstrates the importance of the N-alkyl substituent on the extent of solvent mixing and on the nature of the interface. With the most hydrophobic [OMI][PF6] liquid, the "bulk" IL phase is dryer than with the [BMI][PF6] liquid. At the interface, the OMI+ cations retain direct contacts with the bulk IL, whereas the more hydrophilic PF6(-) anions gradually dilute in the local water micro-environment and are thus isolated from the "bulk" IL. The interfacial OMI+ cations are ordered with their imidazolium moiety pointing toward the aqueous side and their octyl chains toward the IL side of the interface. With the [BMI][PF6] liquid, the system gradually evolves from an IL-rich to a water-rich medium, leading to an ill-defined interfacial domain with high intersolvent mixing. As a result, the BMI+ cations are isotropically oriented "at the interface". Because the imidazolium cations are more hydrophobic than the PF6(-) anions, the charge distribution at the interface is heterogeneous, leading to a positive electrostatic potential at the interface with the two studied ILs. Mixing-demixing simulations on [BMI][PF6]/water mixtures are also reported, comparing Ewald versus reaction field treatments of electrostatics. Phase separation is very slow (at least 30 ns), in marked contrast with mixtures involving classical organic liquids, which separate in less than 0.5 ns at the microscopic level. The results allow us to better understand the specificity of the aqueous interfaces with hydrophobic ionic liquids, compared with classical organic solvents, which has important implications as far as the mechanism of liquid-liquid ion extraction is concerned.

Solvation of fluoro and mixed fluoro/chloro complexes of Eu(III) in the [BMI][PF6] room temperature ionic liquid. A theoretical study.

We report a molecular dynamics study on the solvation of EuFn(3-n) complexes in the [BMI][PF6] ionic liquid, composed of 1-butyl-3-methyl-imidazolium+ cations and PF6- anions. It is found that the most fluorinated complex in the liquid should be the EuF6(3-) species. In solution the EUF10(7-) and EuF7(4-) complexes indeed loose, respectively, 4 and 1 F anion to form the EuF6(3-) complex, while the first solvation shell of the less fluorinated complexes (n=1 to 5) is completed with 5 to 1 PF6- anions to form an octahedral first shell around Eu3+. There is one case (simulations with a "small" F model) where the EuF7(4-) complex remains stable, and cannot therefore be fully precluded. The anionic complexes are embedded in a cage formed by 6-9 BMI+ cations at ca. 8 A, hydrogen-bonded by imidazolium-CH..F- interactions. Simulations on the mixed EuF(n)Cl(6-n)3- complexes in solution and in gas phase also reveal the highest stability of EuF6(3-) compared to the mixed or the EuCl6(3-) complexes. This is confirmed by free energy perturbation calculations and results from the stronger coordination of F-, compared to Cl- ligands, as well as from better solvation of the fluoro complexes by the ionic liquid. In the gas phase, however, QM and MM calculations indicate that EuF6(3-) is unstable towards the dissociation of 1 to 2 F- ions, which points to the importance of environment and solvation forces on the stability of this octahedrally coordinated lanthanide complex.

Comparative hemodynamic depression of sevoflurane versus halothane in infants: an echocardiographic study.

BACKGROUND: The cardiovascular side effects of volatile anesthetics are one of the chief causes of postoperative complications in children, and infants seem to be at the greatest risk for this. This study compared cardiovascular changes at equipotent concentrations of sevoflurane and halothane in infants. METHODS: Thirty infants classified as American Society of Anesthesiologists physical status I or II who required elective surgery were randomized to receive either halothane or sevoflurane for inhalation induction. Cardiovascular and echocardiographic data were recorded in both groups at baseline and at end-tidal concentrations of 1 and 1.5 minimum alveolar concentration (MAC). RESULTS: Sevoflurane did not alter heart rate or cardiac index at all concentrations compared with awake values. Sevoflurane significantly decreased blood pressure and systemic vascular resistance compared with awake values at all concentrations. Shortening fraction and rate-corrected velocity of circumferential fiber shortening decreased at 1.5 but not at 1 MAC. Myocardial contractility assessed by stress-velocity index and stress-shortening index decreased significantly at all concentrations, but did not fall into the abnormal range at any concentration. Halothane caused a greater decrease in heart rate, shortening fraction, stress-shortening index, velocity of circumferential fiber shortening, stress-velocity index, and cardiac index at all concentrations than did sevoflurane. CONCLUSION: Sevoflurane causes a lesser decrease in cardiac output than does halothane in infants.

[Analgesia controlled by the patient in pediatrics]. / L'analgésie contrôlée par le patient en pédiatrie.

The development of patient controlled analgesia (PCA) in children is the result of a search for an analgesia being both maximally efficient and secure, in the management of severe pain. The technique is based on self infusions of an analgesic, mainly morphine, by the child, through a special pump. The quality of the pump is essential in order to exclude any risk of overdosage. In order to prevent potential secondary effects and complications, a careful supervision is mandatory (clinical, by pulse oximetry, regular checking of pump parameters). PCA is applicable to children older than 5 years. The main indications are post-operative and oncological pains.

[Pain conduction tracts. From physiology to practice]. / Les voies de la douleur de la physiologie à la pratique.

Some new theories concerning pain physiology have recently been suggested. Experimental facts show that despite its complexity, neuroplasticity is an established fact. The concept of preemptive analgesia is about to receive clinical applications. Nevertheless, the role of many opioid ligands which are involved in the pain physiology can explain the efficacy of some analgesia techniques. The authors review the physiological process of pain from its periphery to its centre and the ensuing practical applications. They point out the difficulty to apprehend peripheral analgesia, and the necessity of further researches concerning especially NMDA spinal receptors and other specific receptors.

[Complementing loco-regional anesthesia in children]. / Complément et anesthésie loco-régionale chez l'enfant.

An accomplishment to loco-regional anesthesia. Yes! but dependent on the age of the child; rather mild general anesthesia than progressive sedation. This should not lead to the neglect of certain basic principles: a faultless technique including the highest security standards without neglecting the psychological aspect. Use of these technique as means of outpatient treatment will be the future outlook.

Parentage determination on aborted fetal material through deoxyribonucleic acid (DNA) profiling.

After a rape, women who are pregnant often elect to abort the fetus. The authors describe ten cases in which deoxyribonucleic acid (DNA) typing was performed on the aborted fetal material to provide evidence of the genetic constitution of the suspect. The problems encountered with this new technique are discussed.

PIP: The feasibility of using DNA typing to identify the probable biological father of the fetus is rape cases was assessed in 10 abortuses, 4 abortions by vacuum aspiration and 6 by prostaglandin. In 2 cases chorionic villus material, and in 6 cases fetal material such as lung, blood, muscle or ribs was used, but in 2 mixed maternal and fetal tissue had to be used. DNA typing was performed by standard techniques using purchased DNA probes (Lifecodes Corp, Valhalla, New York). After visual inspection of matching alleles, results were verified by computer-assisted image analysis. A randomly selected French population of 300 constituted the reference database. In Case 1, maternal and fetal tissue was mixed, but a definite paternal band was evident. In 8 other cases there was strong evidence of paternal DNA bands. In the last case, a paternal band was apparent, but no suspect was available at the time.

Determination of dextromoramide by capillary gas chromatography and electron impact mass spectrometry.

A sensitive and specific quantitative assay for the determination of dextromoramide in human fluids and tissues is described. Dextromoramide and an internal standard, SKF 525 A, are isolated by a basic extraction and back-extraction process. The final extract is separated on a 25-m capillary column B.P. 1 and drugs are detected by selected ion monitoring at m/z 100 and m/z 86 for dextromoramide and the internal standard, respectively. The minimum detectable quantities are 0.5 and 0.3 ng/mL, for dextromoramide in plasma and urine, respectively. Coefficients of variation for within-run data were less than 6%.