[Electrical Accidents]. / Stromunfälle.

Electrical Accidents Abstract: When persons seek medical help after an electrical injury, physicians have to inquire on the type (AC/DC) and strength of current (>1000V is considered "high voltage") as well as the exact circumstances (loss of consciousness, falls) of the accident. In the advent of high-voltage accidents, loss of consciousness, arrhythmias, abnormal ECG or elevated troponin levels, in-hospital rhythm monitoring is warranted. In all other cases, the type of extra cardiac injury primarily directs the management. Superficial skin marks may disguise more extensive thermal injuries of inner organs.

Effect of mild α-chymotrypsin treatment of highly viscous semen samples on fertilization rates.

BACKGROUND: Highly viscous semen reduces sperm motility significantly and can contribute to infertility. When processing semen samples, few techniques exist to induce liquefaction in case of seminal hyperviscosity such as different washing steps and mechanical treatment. The use of α-chymotrypsin seems controversial due to possible negative effects on fertilisation rates after in vitro fertilization (IVF). The main objective of this study was to examine the influence of mild α-chymotrypsin treatment of semen samples on the fertilisation rate after artificial reproductive treatment (ART). METHODS: The fertilization rate of 52 ART cycles was examined following IVF using a low dose of α-chymotrypsin to induce liquefaction of highly viscous semen and was compared to a control group of 88 ART cycles. RESULTS: There was no significant difference in the fertilization rates of α-chymotrypsin treated semen samples compared to the control group; pregnancy rates were unaffected. CONCLUSIONS: The use of mild α-chymotrypsin treatment of semen samples in case of hyperviscosity does not appear to impact negatively on the fertilization rates after ART and could be regarded as an additional method to induce liquefaction of highly viscous semen samples in IVF.

Infrared Excitation Induces Heating and Calcium Microdomain Hyperactivity in Cortical Astrocytes.

Unraveling how neural networks process and represent sensory information and how these cellular signals instruct behavioral output is a main goal in neuroscience. Two-photon activation of optogenetic actuators and calcium (Ca2+) imaging with genetically encoded indicators allow, respectively, the all-optical stimulation and readout of activity from genetically identified cell populations. However, these techniques locally expose the brain to high near-infrared light doses, raising the concern of light-induced adverse effects on the biology under study. Combining 2P imaging of Ca2+ transients in GCaMP6f-expressing cortical astrocytes and unbiased machine-based event detection, we demonstrate the subtle build-up of aberrant microdomain Ca2+ transients in the fine astroglial processes that depended on the average rather than peak laser power. Illumination conditions routinely being used in biological 2P microscopy (920-nm excitation, ∼100-fs, and ∼10 mW average power) increased the frequency of microdomain Ca2+ events but left their amplitude, area, and duration largely unchanged. Ca2+ transients in the otherwise silent soma were secondary to this peripheral hyperactivity that occurred without overt morphological damage. Continuous-wave (nonpulsed) 920-nm illumination at the same average power was as damaging as femtosecond pulses, unraveling the dominance of a heating-mediated damage mechanism. In an astrocyte-specific inositol 3-phosphate receptor type-2 knockout mouse, near-infrared light-induced Ca2+ microdomains persisted in the small processes, underpinning their resemblance to physiological inositol 3-phosphate receptor type-2-independent Ca2+ signals, whereas somatic hyperactivity was abolished. We conclude that, contrary to what has generally been believed in the field, shorter pulses and lower average power can help to alleviate damage and allow for longer recording windows at 920 nm.

Quantitative analysis of the sHLA-G protein in seminal plasma.

BACKGROUND: Recent studies revealed that maternal and embryonic contributions impact on HLA-G protein expression and might contribute to pregnancy success or failure. The main objective of this study was to examine the paternal levels of the immunoregulatory soluble human leukocyte antigen-G (sHLA-G) protein in seminal plasma and testicular biopsy samples during artificial reproductive technique (ART) treatment and to investigate possible correlations with other semen parameters, age, and pregnancy outcome of the female partner. METHODS: Soluble HLA-G levels of 106 seminal plasma samples and eight testicular biopsy samples were determined using a commercial sHLA-G Enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: We observed a significant negative correlation of male age with total sHLA-G amount (P 0.023, R -0.221) and semen volume (P = 0.047, R -0.193). Testicular biopsy samples were analyzed and tested positively with sHLA-G ELISA. Levels of sHLA-G in seminal plasma samples from men with normozoospermia did not deviate significantly from those with reduced semen quality. No significant difference of sHLA-G levels in seminal plasma and pregnancy outcome of the female partner was detected. Our data showed that age of men with normozoospermia was significantly lower when the female partner conceived after ART treatment (P = 0.016, Mann-Whitney U test). CONCLUSION: High sHLA-G levels in seminal plasma of the male partner appear not to be required for pregnancy but might contribute among other factors to the success of establishing and maintaining pregnancy through long-term priming of the female uterine milieu.

Are Lovers Ever One? Reconstructing the Union Theory of Love.

Current analytical philosophies of romantic love tend to identify the essence of such love with one specific element, such as concern for the beloved person, valuing the beloved person or the union between the lovers. This paper will deal with different forms of the union theory of love which takes love to be the physical, psychic or ontological union of two persons. Prima facie, this theory might appear to be implausible because it has several contra-intuitive implications, and yet, I submit, it is more coherent and attractive than it seems to be. I shall distinguish three specific models and thereby offer a differentiated account of the union theory which has not previously been provided in the literature (1). I will claim that two of these models (the strong ontological model and the striving model) should be rejected (2). I shall then defend the third model (the moderate ontological model) against certain possible objections (3); but nevertheless, I shall conclude by showing how this model, too, faces further significant objections which ultimately expose the limits of the union theory of love (4). In conclusion, I will sketch the outlines of a non-reductive cluster theory of love.

Local energy on demand: Are 'spontaneous' astrocytic Ca2+-microdomains the regulatory unit for astrocyte-neuron metabolic cooperation?

Astrocytes are a neural cell type critically involved in maintaining brain energy homeostasis as well as signaling. Like neurons, astrocytes are a heterogeneous cell population. Cortical astrocytes show a complex morphology with a highly branched aborization and numerous fine processes ensheathing the synapses of neighboring neurons, and typically extend one process connecting to blood vessels. Recent studies employing genetically encoded fluorescent calcium (Ca2+) indicators have described 'spontaneous' localized Ca2+-transients in the astrocyte periphery that occur asynchronously, independently of signals in other parts of the cells, and that do not involve somatic Ca2+ transients; however, neither it is known whether these Ca2+-microdomains occur at or near neuronal synapses nor have their molecular basis nor downstream effector(s) been identified. In addition to Ca2+ microdomains, sodium (Na+) transients occur in astrocyte subdomains, too, most likely as a consequence of Na+ co-transport with the neurotransmitter glutamate, which also regulates mitochondrial movements locally - as do cytoplasmic Ca2+ levels. In this review, we cover various aspects of these local signaling events and discuss how structural and biophysical properties of astrocytes might foster such compartmentation. Astrocytes metabolically interact with neurons by providing energy substrates to active neurons. As a single astrocyte branch covers hundreds to thousands of synapses, it is tempting to speculate that these metabolic interactions could occur localized to specific subdomains of astrocytes, perhaps even at the level of small groups of synapses. We discuss how astrocytic metabolism might be regulated at this scale and which signals might contribute to its regulation. We speculate that the astrocytic structures that light up transiently as Ca2+-microdomains might be the functional units of astrocytes linking signaling and metabolic processes to adapt astrocytic function to local energy demands. The understanding of these local regulatory and metabolic interactions will be fundamental to fully appreciate the complexity of brain energy homeostasis as well as its failure in disease and may shed new light on the controversy about neuron-glia bi-directional signaling at the tripartite synapse.

Higher transport and metabolism of glucose in astrocytes compared with neurons: a multiphoton study of hippocampal and cerebellar tissue slices.

Glucose is the most important energy substrate for the brain, and its cellular distribution is a subject of great current interest. We have employed fluorescent glucose probes, the 2-deoxy-D-glucose derivates 6- and 2-([N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose) (2-NBDG), to measure transport and metabolism of glucose in acute slices of mouse hippocampus and cerebellum. In the hippocampus, 6-NBDG, which is not metabolized and hence indicates glucose transport, was taken up faster in astrocyte-rich layers (Stratum radiatum [S.r.], Stratum oriens [S.o.]) than in pyramidal cells. Metabolizable 2-NBDG showed larger signals in S.r. and S.o. than in Stratum pyramidale, suggesting faster glucose utilization rate in the astrocyte versus the neuronal compartment. Similarly, we found higher uptake and temperature-sensitive metabolism of 2-NBDG in Bergmann glia when compared with adjacent Purkinje neurons of cerebellar slices. A comparison between 6-NBDG transport and glucose transport in cultured cells using a fluorescence resonance energy transfer nanosensor showed that relative to glucose, 6-NBDG is transported better by neurons than by astrocytes. These results indicate that the preferential transport and metabolism of glucose by glial cells versus neurons proposed for the hippocampus and cerebellum by ourselves (in vitro) and for the barrel cortex by Chuquet et al. (in vivo) is more pronounced than anticipated.

New tools for investigating astrocyte-to-neuron communication.

Gray matter protoplasmic astrocytes extend very thin processes and establish close contacts with synapses. It has been suggested that the release of neuroactive gliotransmitters at the tripartite synapse contributes to information processing. However, the concept of calcium (Ca(2+))-dependent gliotransmitter release from astrocytes, and the release mechanisms are being debated. Studying astrocytes in their natural environment is challenging because: (i) astrocytes are electrically silent; (ii) astrocytes and neurons express an overlapping repertoire of transmembrane receptors; (iii) the size of astrocyte processes in contact with synapses are below the resolution of confocal and two-photon microscopes (iv) bulk-loading techniques using fluorescent Ca(2+) indicators lack cellular specificity. In this review, we will discuss some limitations of conventional methodologies and highlight the interest of novel tools and approaches for studying gliotransmission. Genetically encoded Ca(2+) indicators (GECIs), light-gated channels, and exogenous receptors are being developed to selectively read out and stimulate astrocyte activity. Our review discusses emerging perspectives on: (i) the complexity of astrocyte Ca(2+) signaling revealed by GECIs; (ii) new pharmacogenetic and optogenetic approaches to activate specific Ca(2+) signaling pathways in astrocytes; (iii) classical and new techniques to monitor vesicle fusion in cultured astrocytes; (iv) possible strategies to express specifically reporter genes in astrocytes.

Improved pharmaceutical stability of a boronphenylalanine mannitol formulation for boron neutron capture therapy.

Boron neutron capture therapy (BNCT) is a radiotherapy based cancer treatment requiring the availability of a low energy thermal neutron beam and a boron containing drug. These requirements limit BNCT availability with the latter pharmaceutical issue related to the extremely short shelf-life and clinical acceptability of the current fructose based L-boronphenylalanine (BPA) formulation. Resolution of the formulation issues would remove this factor and therefore the stability of an alternative mannitol BPA formulation has been investigated. A mannitol BPA solution formulation was prepared and either lyophilised or stored as a solution at varying temperatures. After suitable periods the formulation was analysed by HPLC for BPA and degradation products. Lyophilised and solution mannitol BPA formulations exhibited a temperature and time dependent loss of BPA with concomitant increases in degradation products. Autoclaving the solution induced and accelerated degradation. A solution or lyophilised mannitol BPA formulation has a shelf-life of between 1 and 4 years respectively, a marked improvement over the current fructose formulation. Due to temperature dependent degradation the formulation cannot be terminally sterilised by autoclaving. The enhanced stability of the mannitol formulation removes the requirement for extemporaneous aseptic preparation of BPA just prior to treatment and eliminates one of the issues complicating the delivery of BNCT.

Synthesis, full chemical characterisation and development of validated methods for the quantification of the components found in the evolved "legal high" NRG-2.

The recent global increase in the abuse of 4'-methylmethcathinone (mephedrone) and related compounds has developed a requirement for full chemical characterisation of these products. This work presents full synthetic and chemical characterisation data for the hydrobromide salts of two mephedrone derivatives: 4'-methyl-N-ethylcathinone (4-MEC) and 4'-methyl-N-benzylcathinone (4-MBC) which have been identified in samples of the "legal high" NRG-2. The first fully validated chromatographic methods for the detection and quantitative analysis of these substances both in their pure form and in the presence of a number of common adulterants used in illicit drug manufacture is also reported.

Physicochemical investigation of the influence of saccharide-based parenteral formulation excipients on L-p-boronphenylalanine solubilisation for boron neutron capture therapy.

This paper investigates the physicochemical properties of possible pharmaceutical alternatives to L-p-boronphenylalanine (BPA)-fructose intravenous formulation currently employed in boron neutron capture therapy. The physicochemical properties of BPA in the absence and presence of fructose, mannitol, trehalose and hydroxypropyl-ß-cyclodextrin (HPCD) was investigated by determination of pKa values, solubility, precipitation and dissolution using a Sirius T3 instrument. Complex formation was also assessed using (10) B-Nuclear magnetic resonance (NMR). The results indicate that fructose and mannitol form a complex with BPA through a reversible interaction with the boronic acid group, determined by changes in the pKa of the boronic acid group, the ultraviolet and NMR spectra, and increase in kinetic solubility. Trehalose and HPCD did not undergo this reaction and, consequently, did not affect boronphenylalanaine physicochemical properties. Although mannitol is complexed with BPA in an identical manner to fructose, it is superior because it provides increased kinetic solubility. Replacement of fructose by mannitol in the current clinical BPA formulation is, therefore, feasible with advantages of increased dosing and removal of issues related to fructose intolerance and calorific load. Results also indicated that important pharmaceutical parameters are the complex's solubility and dissociation behaviours rather than, as originally assumed, the complex formation reaction.

Efficient large core fiber-based detection for multi-channel two-photon fluorescence microscopy and spectral unmixing.

Low-magnification high-numerical aperture objectives maximize the collection efficiency for scattered two-photon excited fluorescence (2PEF), but non-descanned detection schemes for such objectives demand optical components much bigger than standard microscope optics. Fiber coupling offers the possibility of removing bulky multi-channel detectors from the collection site, but coupling and transmission losses are generally believed to outweigh the benefits of optical fibers. We present here two new developments based on large-core fiber-optic fluorescence detection that illustrate clear advantages over conventional air-coupled 2PEF detection schemes. First, with minimal modifications of a commercial microscope, we efficiently couple the output of a 20×/NA0.95 objective to a large-core liquid light guide and we obtain a 7-fold collection gain when imaging astrocytes at 100 µm depth in acute brain slices of adult ALDH1L1-GFP mice. Second, combining 2PEF microscopy and 4-color detection on a custom microscope, mode scrambling inside a 2-mm plastic optical fiber is shown to cancel out the spatially non-uniform spectral sensitivity observed with air-coupled detectors. Spectral unmixing of images of brainbow mice taken with a fiber-coupled detector revealed a uniform color distribution of hippocampal neurons across a large field of view. Thus, fiber coupling improves both the efficiency and the homogeneity of 2PEF collection.

Conciencia de enfermedad y abstnencia absoluta en un grupo de alcohólicos en rehabilitación / Conscience of disease and absolute abstinence in an alcoholic group in rehabilitation

Se describe la evolución de la Conciencia de Enfermedad y la permanencia en abstinencia absoluta de un grupo de 12 alcohólicos hombres en rehabilitación. Se describe también las vivencias de las cónyuges. Se efectuó un seguimiento de 2 años