Evaluation of the Use of Ketamine in Prehospital Seizure Management: A Retrospective Review of the ESO Database.

Objectives: Benzodiazepines are the primary antiseizure medication used by Emergency Medical Services (EMS) for seizures. Available literature in the United States and internationally shows 30% to 40% of seizures do not terminate with benzodiazepines called benzodiazepine refractory status epilepticus (BRSE). Ketamine is a potential treatment for BRSE due to its unique pharmacology. However, its application in the prehospital setting is mostly documented in case reports. Little is known about its use by EMS professionals for seizure management, whether as initial treatment or for BRSE, creating an opportunity to describe its current use and inform future research.Methods: We performed a retrospective review of 9-1-1 EMS encounters with a primary or secondary impression of seizure using the ESO Data Collaborative from 2018-2021. We isolated encounters during which ketamine was administered. We excluded medication administrations prior to EMS arrival and encounters without medication administration. Subgroup analysis was performed to control for airway procedure as an indication for ketamine administration. We also evaluated for co-administration with other antiseizure medications, dose and route of administration, and response to treatment.Results: We identified 99,576 encounters that met inclusion. There were 2,531/99,576 (2.54%) encounters with ketamine administration and 50.7% (1,283/2,531) received ketamine without an airway procedure. There were 616 cases (48%, 616/1,283) where ketamine was given without another antiseizure medication (ASM) and without any airway procedure. The remaining 667 (52%) cases received ketamine with at least one other ASM, most commonly midazolam (89%, 593/667). Adjusted for the growth in the ESO dataset, ketamine use by EMS professionals during encounters for seizures without an airway procedure increased from 0.90% (139/15,375) to 1.45% (416/28,651) an increase of 62% over the study period.Conclusions: In this retrospective review of the ESO Data Collaborative, ketamine administration for seizure encounters without an airway procedure increased over the study period, both as a single agent and with another ASM. Most ketamine administrations were for adult patients in the south and in urban areas. The frequency of BRSE, the need for effective treatment, and the growth in ketamine use warrant prospective prehospital research to evaluate the value of ketamine in prehospital seizure management.

TRopical Oil Pollution Investigations in Coastal Systems [TROPICS]: A synopsis of impacts and recovery.

The TRopical Oil Pollution Investigations in Coastal Systems (TROPICS) experiment, conducted on the Caribbean coast of Panama, has become one of the most comprehensive field experiments examining the long-term impacts of oil and dispersed oil exposures in nearshore tropical marine environments. From the initial experiment through more than three decades of study and data collection visits, the intertidal and subtidal communities have exhibited significantly different impact and recovery regimes, depending on whether the sites were exposed to crude oil only or crude oil treated with a chemical dispersant. This review provides a synopsis of the original experiment and a cumulative summary of the results and observations, illustrating the environmental and ecosystem trade-offs of chemical dispersant use in mangrove, seagrass, and coral reef environments.

Counter-historical study of alternative dispersant use in the Deepwater Horizon oil spill response.

Recent completion of oil fate modeling and a mass budget of the Deepwater Horizon (DWH) oil spill allows for a counter-historical study using quantitative Comparative Risk Assessment (CRA) methodology. Novel application of subsea dispersant injection (SSDI) during the response reduced surfacing oil, volatile organic carbon emissions, and oil on shorelines. The effectiveness of that application, and potential alternatives had dispersant not been used or been used more aggressively, were evaluated by modifying and comparing the validated oil fate model under different SSDI strategies. A comparison of mass balance results, exposure metrics, and CRA scoring for Valued Ecological Components (VECs) shows the value of SSDI in achieving risk reduction and tradeoffs that were made. Actual SSDI applied during the DWH oil spill reduced exposures to varying degrees for different VECs. Exposures and relative risks across the ecosystem would have been substantially reduced with more effective SSDI.

Acute and subacute toxicity of the polycyclic aromatic hydrocarbon 1-methylnaphthalene to the shallow-water coral Porites divaricata: Application of a novel exposure protocol.

Previous research evaluating hydrocarbon toxicity to corals and coral reefs has generally focused on community-level effects, and results often are not comparable between studies because of variability in hydrocarbon exposure characterization and evaluation of coral health and mortality during exposure. Toxicity of the polycyclic aromatic hydrocarbon 1-methylnaphthalene to the coral Porites divaricata was assessed in a constant exposure toxicity test utilizing a novel toxicity testing protocol uniquely applicable to shallow-water corals, which considered multiple assessment metrics and evaluated the potential for post-exposure mortality and/or recovery. Acute and subacute effects (gross morphological changes, photosynthetic efficiency, mortality, and histologic cellular changes) were evaluated during pre-exposure (4 wk), exposure (48 h), and post-exposure recovery (4 wk) periods. Coral condition scores were used to determine a 48-h median effective concentration of 7442 µg/L. Significant physical and histological changes resulted from exposure to 640 µg/L and 5427 µg/L 1-methylnaphthalene, with a 1-d to 3-d delay in photosynthetic efficiency effects (ΔF/Fm). Pigmented granular amoebocyte area was found to be a potentially useful sublethal endpoint for this species. Coral mortality was used to estimate a 48-h median lethal concentration of 12 123 µg/L. Environ Toxicol Chem 2017;36:212-219. © 2016 SETAC.

Structure-function relationships in Macadamia integrifolia seed coats--fundamentals of the hierarchical microstructure.

The shells/coats of nuts and seeds are often very hard to crack. This is particularly the case with Macadamia seed coats, known to exhibit astoundingly high strength and toughness. We performed an extensive materials science characterization of the complex hierarchical structure of these coats, using light and scanning electron microscopy in 2D as well as microCT for 3D characterization. We differentiate nine hierarchical levels that characterize the structure ranging from the whole fruit on the macroscopic scale down to the molecular scale. From a biological viewpoint, understanding the hierarchical structure may elucidate why it is advantageous for these seed coats to be so difficult to break. From an engineering viewpoint, microstructure characterization is important for identifying features that contribute to the high strength and cracking resistance of these objects. This is essential for revealing the underlying structure-function-relationships. Such information will help us develop engineering materials and lightweight-structures with improved fracture and puncture resistance.

The ROS-induced cytotoxicity of ascorbate is attenuated by hypoxia and HIF-1alpha in the NCI60 cancer cell lines.

Intravenous application of high-dose ascorbate is used in complementary palliative medicine to treat cancer patients. Pharmacological doses of ascorbate in the mM range induce cytotoxicity in cancer cells mediated by reactive oxygen species (ROS), namely hydrogen peroxide and ascorbyl radicals. However, little is known about intrinsic or extrinsic factors modulating this ascorbate-mediated cytotoxicity. Under normoxia and hypoxia, ascorbate IC50 values were determined on the NCI60 cancer cells. The cell cycle, the influence of cobalt chloride-induced hypoxia-inducible factor-1α (HIF-1α) and the glucose transporter 1 (GLUT-1) expression (a pro-survival HIF-1α-downstream-target) were analysed after ascorbate exposure under normoxic and hypoxic conditions. The amount of ascorbyl radicals increased with rising serum concentrations. Hypoxia (0.1% O2 ) globally increased the IC50 of ascorbate in the 60 cancer cell lines from 4.5 ± 3.6 mM to 10.1 ± 5.9 mM (2.2-fold increase, P < 0.001, Mann-Whitney t-test), thus inducing cellular resistance towards ascorbate. This ascorbate resistance depended on HIF-1α-signalling, but did not correlate with cell line-specific expression of the ascorbate transporter GLUT-1. However, under normoxic and hypoxic conditions, ascorbate treatment at the individual IC50 reduced the expression of GLUT-1 in the cancer cells. Our data show a ROS-induced, HIF-1α- and O2 -dependent cytotoxicity of ascorbate on 60 different cancer cells. This suggests that for clinical application, cancer patients should additionally be oxygenized to increase the cytotoxic efficacy of ascorbate.

[6,6]-Open and [6,6]-closed isomers of C70(CF2): synthesis, electrochemical and quantum chemical investigation.

Novel difluoromethylenated [70]fullerene derivatives, C70(CF2 )n (n=1-3), were obtained by the reaction of C70 with sodium difluorochloroacetate. Two major products, isomeric C70(CF2 ) mono-adducts with [6,6]-open and [6,6]-closed configurations, were isolated and their homofullerene and methanofullerene structures were reliably determined by a variety of methods that included X-ray analysis and high-level spectroscopic techniques. The [6,6]-open isomer of C70(CF2 ) constitutes the first homofullerene example of a non-hetero [70]fullerene derivative in which functionalisation involves the most reactive bond in the polar region of the cage. Voltammetric estimation of the electron affinity of the C70(CF2 ) isomers showed that it is substantially higher for the [6,6]-open isomer (the 70-electron π-conjugated system is retained) than the [6,6]-closed form, the latter being similar to the electron affinity of pristine C70. In situ ESR spectroelectrochemical investigation of the C70(CF2 ) radical anions and DFT calculations of the hyperfine coupling constants provide evidence for the first example of an inter-conversion between the [6,6]-closed and [6,6]-open forms of a cage-modified fullerene driven by an electrochemical one-electron transfer. Thus, [6,6]-closed C70(CF2 ) constitutes an interesting example of a redox-switchable fullerene derivative.

Online coupling of enantioselective capillary gas chromatography with proton nuclear magnetic resonance spectroscopy.

The hyphenation of enantioselective capillary gas chromatography and mass spectrometry is not always sufficient to distinguish between structural isomers, thus requiring peak identification by NMR spectroscopy. Here the first online coupling of enantioselective capillary gas chromatography with proton nuclear resonance spectroscopy is described for the unfunctionalized chiral alkane 2,4-dimethylhexane resolved on octakis(6-O-methyl-2,3-di-O-pentyl)-gamma-cyclodextrin at 60 degrees C. NMR allows constitutional and configurational isomers (diastereomers and enantiomers) to be distinguished. Enantiomers display identical spectra at different retention times, which enable an indirect identification of these unfunctionalized alkanes. The presented method is still at an early development stage, and will require instrumental optimization in the future.

Determination of astaxanthin and astaxanthin esters in the microalgae Haematococcus pluvialis by LC-(APCI)MS and characterization of predominant carotenoid isomers by NMR spectroscopy.

The oily product ZANTHIN consists of natural astaxanthin, which is manufactured from the microalgae Haematococcus pluvialis by supercritical CO(2) extraction. An HPLC method was developed to separate all of the components of the complex astaxanthin extract using a C(30) column. The separation resulted in different isomers of astaxanthin accompanied by two other carotenoids. The main component consisted of astaxanthin singly esterified with several different fatty acids. C18:3, C18:2, C18:1 and C16:0 were identified as the most commonly occurring fatty acids. Doubly esterified astaxanthin was also found, although in lower concentrations compared to singly esterified astaxanthin. After performing a detailed fatty acid analysis by GC-MS, the peaks from the extract were assigned via HPLC-MS. A trans to cis transmutation of the all-trans compound was performed by thermal treatment in order to obtain an enrichment of cis isomers as the basis for unambiguous identification via NMR experiments. The all-trans as well as the 9- and 13-cis isomers of astaxanthin were characterized in detail by UV/Vis, (1)H, and (1)H,(1)H COSY NMR spectroscopy.

Online coupling of gas chromatography to nuclear magnetic resonance spectroscopy: method for the analysis of volatile stereoisomers.

The identification of volatile cis/trans-stereoisomers was accomplished by employing a hyphenated GC-NMR system. The chromatographic and spectroscopic conditions were optimized with respect to the (1)H NMR detection. A special processing technique was developed to handle the recorded NMR spectra in the gas phase with very low sample amounts. The processed stopped-flow (1)H NMR spectra of the investigated chromatographic peaks unequivocally revealed the structure of the corresponding compounds.

Characterization of bixin by LC-MS and LC-NMR.

An overview upon modern analytical techniques for the isolation, separation, and structural identification of the essential bioactive carotenoid bixin is given. Isolation from biological matrices is performed by matrix solid phase dispersion (MSPD). The extract is separated with shape-selective C(30 )columns. Structural assignment of the separated compounds is done by online LC-MS and capillary HPLC-NMR.

Hyphenation of gas chromatography to microcoil 1H nuclear magnetic resonance spectroscopy.

Whereas the hyphenation of gas chromatography (GC) with mass spectrometry is of great importance, little is known about the coupling to nuclear magnetic resonance spectroscopy (NMR). The investigation of this technique is an attractive proposition because of the valuable information given by NMR on molecular structure. The experiments shown here are to our knowledge the first hyphenating capillary GC to microcoil NMR. In contrast to liquids, gases have rarely been investigated by NMR, mainly due to the experimental difficulties in handling gases and the low signal-to-noise-ratio (SNR) of the NMR signal obtained at atmospheric pressure. With advances in NMR sensitivity (higher magnetic fields and solenoidal microprobes), this limitation can be largely overcome. In this paper, we describe the use of a custom-built solenoidal NMR microprobe with an active volume of 2 microL for the NMR detection of several compounds at 400 MHz, first in a mixture, and then with full coupling to capillary GC to identify them separately. The injected amounts of each analyte in the hyphenated experiments are in the range of 15-50 micromol, resulting in reasonable SNR for sample masses of 1-2 microg.

Hyphenation of capillary HPLC to microcoil (1)H NMR spectroscopy for the determination of tocopherol homologues.

Highly selective reversed phases (C(30) phases) are self-packed in 250 microm inner diameter fused-silica capillaries and employed for capillary HPLC separation of shape-constrained natural compounds (tocopherol homologues, vitamin E). Miniaturized hyphenated systems such as capillary HPLC-ESI-MS (positive ionization mode) and, with special emphasis, continuous-flow capillary HPLC- NMR are used for structural determination of the separated compounds. Despite the small amount of sample available (1.33 microg of each tocopherol), the authors have been able to monitor the capillary HPLC separation under continuous-flow (1)H NMR conditions, thus allowing an immediate peak identification. Further structural assignment was carried out in the stopped-flow NMR mode as shown, for example, by a 2D (1)H,(1)H COSY NMR spectrum of alpha-tocopherol. We demonstrate in this paper the considerable potential of hyphenated capillary separations coupled to MS and NMR for the investigation of restricted amounts of sample.

Activation of stress-activated protein kinases (SAPK) in tendon cells following cyclic strain: the effects of strain frequency, strain magnitude, and cytosolic calcium.

Cyclic strain has been shown to benefit tendon health. However, repetitive loading has also been implicated in the etiology of tendon overuse injuries. Recent studies demonstrated that in several cell lines cyclic strain was associated with an activation of stress-activated protein kinases (SAPKs). These SAPKs, in turn, were shown to be important upstream regulators of a variety of cell processes including apoptosis. To examine the effect of repetitive loading on SAPK activation in tendon cells in vitro, canine patellar tendon cells were cyclically strained, and the cellular stress response evaluated by measuring c-Jun N-terminal kinase (JNK) activation. The effects of strain frequency and strain magnitude as well as the role of calcium signaling in this mechanotransduction mechanism were also examined. Cyclic strain resulted in an immediate activation of JNK, which peaked at 30 min and returned to resting levels by 2 h. This activation was regulated by a magnitude-dependent but not frequency-dependent response and appeared to be mediated through a calcium-dependent mechanotransduction pathway. While transient JNK activation is associated with normal cell processes. persistent JNK activation has been linked to the initiation of the apoptotic cascade. A similar mechanism could be responsible for initiating the pathological events (localized cell death) seen in tendon overuse injury.

EPR and ENDOR study of chiral nitroxides.

Racemic and achiral alkyl aryl nitroxides were examined at various temperatures. The restricted rotation of the aminoxyl substituents was indicated both by the ß-proton coupling constants and by the inequivalence of the aromatic ortho protons. These results are interpreted by the presence of two different rotamers which may lead to two splitting constants for the ß-proton. The capability for inter- and intra-molecular hydrogen bond formation in the nitroxides investigated was demonstrated. However, complexes consisting of chiral radicals and chiral auxiliaries do not show hyperfine structures which unambiguously indicate diastereomeric species. Therefore, hydrogen bonding between chiral molecules is not sufficient for chiral recognition if an alteration of the hyperconjugation angle does not occur. Simple steric interactions can result in the doubling of the ß-proton coupling constant, independently of diastereomeric complex formation.