Controversial Issues Concerning Norepinephrine and Intensive Care Following Severe Traumatic Brain Injury

Norepinephrine and corresponding intra- and interorgan pathways are of clinical pathophysiologic and pharmacologic importance as exaggerated activation needs to be reduced and insufficient activation must be supported to prevent further deterioration and therapy-induced organ damage. This is of high relevance in critically ill patients in whom various norepinephrine-influenced organ systems are simultaneousy affected with varying degrees of tolerability and resistance to norepinephrine-induced cell damage and finds its maximal challenge in patients suffering from severe traumatic brain injury (TBI). This comprehensive review describes complex pathophysiologic interactions, including hemodynamic, microcirculatory, hormonal, metabolic, inflammatory, and thrombocytic alterations overshadowed by differential consequences of commonly applied pharmacological interventions following TBI. Overall, investigations published to date suggest that receptor-dependent effects of norepinephrine might predispose to complex evolving deterioration especially during intensive care which is characterized by differentiated complication-driven changes and specific complication-dependent needs. In this context, thrombocytes and leukocytes with their adrenergic receptors and differential norepinephric functional regulation are ideal candidates to influence all organs at once. Despite its secure integration of norepinephrine in clinical routine, future emphasis must be directed at unmasking, monitoring, and controlling possible receptor-mediated detrimental influences which could offset anticipated organ protectio

Treating Intracranial Hypertension in Patients with Severe Traumatic Brain Injury during Neurointensive Care: New Features of Old Problems?

Despite the envisioned breakthrough prophesied for the end of the past century in healing brain injured patients, both clinicians and basic scientists are still struggling with this burden. In the past decades, intensive research has brought forward a plethora of different targets which—in part—have already been integrated in clinical routine directed at detailed monitoring, therapeutic interventions, and prevention of secondary deterioration. While intracellular targets remain obscure alterations on a larger scale as e. g., measured intracranial pressure (ICP), calculated cerebral perfusion pressure (CPP), and various imaging techniques are fundamental components of our present clinical understanding. At bedside, comprehension of pathophysiological loops and circuits of a given value (e. g., ICP) depends on individual knowledge, interpretation, and availability of additional diagnostic steps. As stated in the guidelines brought forward by the American Association of Neurological Surgeons and evaluated in various reports by the Cochrane Library we are still lacking prospective, randomized trials for the majority of the proposed diagnostic and therapeutic interventions. In this context, a recent meta-analysis even questioned the importance of ICP monitoring as we are lacking data from randomized controlled trials clarifying the role of ICP monitoring. The present review is to give an overview of various diagnostic and therapeutic possibilities based on reports published in the past 5 years to strengthen current approaches and nourish future well-designed investigations how to avoid and treat intracranial hypertensio

Switzerland and its relationship to European and global security institutions

Switzerland was a member of the League of Nations, but has never joined the United Nations (UN). Switzerland nonetheless works closely with the UN, and the Swiss are active in the OSCE. The Swiss never tried to join NATO, but there is growing engagement in Partnership for Peace (PfP). Switzerland is an island surrounded by the European Union (EU), and still resists membership. The Swiss Government wants to join the UN and the EU, but the Swiss public, in 1986 and in 1992, said "no" to such entries, because it wants to remain neutral and to keep its political rights. The thesis examines the proposition that the new policy of "Security through Cooperation," as written in sever governmental reports, is compatible with Swiss neutrality. Therefore, the thesis examines Swiss history, the country's system, an its relationship to the UN, the OSCE, NATO, and the EU. In every step, where the Swiss Government followed the Swiss history the Good Offices, the Swiss public said "yes," in all other steps "no." The thesis shows the reasons for this development.http://archive.org/details/switzerlandndits109459329Swiss Army author.Approved for public release; distribution is unlimited

Morphological description and multilocus genotyping of Onchocerca spp. in red deer (Cervus elaphus) in Switzerland

Onchocercosis is a parasitic disease caused by over 30 Onchocerca spp. (Nematoda: Filarioidea) and predominantly affecting ungulates. Four Onchocerca spp. have been described in the European red deer (Cervus elaphus). Onchocerca flexuosa and Onchocerca jakutensis form subcutaneous nodules in the back region. The other two species, Onchocerca skrjabini and the lesser-known Onchocerca garmsi, are found freely in the subcutaneous tissue of carpal and tarsal joints, and the sternal region, respectively. The presence of Onchocerca spp. in eight red deer shot in the hunting season during September 2020 in the Grisons region, Switzerland, was investigated by analysing nodules and free worms in the subcutaneous tissue. The obtained worms were morphologically and genetically identified as O. jakutensis, O. flexuosa and O. skrjabini. The latter two are first reports from Switzerland, and morphological redescriptions of these two species are presented. Onchocerca skrjabini and O. jakutensis are newly described from the sternal region of deer. One female of O. jakutensis was found free in the subcutaneous tissue of the sternal region, an atypical presentation for this species. Phylogenetic analyses were based on four mitochondrial and one nuclear loci, revealing that O. jakutensis belongs to a clade which so far only included non-cervid Onchocerca spp. Analysis of sequences from this study and GenBank entries revealed two distinct subpopulations of O. skrjabini: one from European red deer and another from Japanese serow and sika deer. Morphological identification can be challenging, also because worm location in the host is less strictly determined than previously described. Genetic identification is straightforward for O. flexuosa, O. jakutensis and O. skrjabini for which complete data of five loci are now available whereas genetic data of O. garmsi is still lacking

Continuous records of the atmospheric greenhouse gases CO2, CH4, and N2O and their radiative forcing since the penultimate glacial maximum

Continuous records of the atmospheric greenhouse gases (GHG) CO2, CH4, and N2O are necessary input data for transient climate simulations and their related radiative forcing important components in analyses of climate sensitivity and feedbacks. Since the available data from ice cores are discontinuous and partly ambiguious a well-documented decision process during data compilation followed by some interpolating post- processing are necessary to obtain those desired time series. Here we document our best-guess data compilation of published ice core records and recent measurements on firn air and atmospheric samples covering the period from the penultimate glacial maximum (∼156 kyr BP) to 2016 CE. A smoothing spline method is applied to translate the discrete and irregularly spaced data points in continuous time series. These splines are assumed to represent the evolution of the atmospheric mixing ratios for the three GHGs. Global-mean radiative forcing for each GHG is computed using well-established, simple formulations. Newest published age scales are used for the ice core data. While CO2 is representing an integrated global signal, we compile only a southern hemisphere record of CH4 and identify how much larger a northern hemisphere or global CH4 record might have been due to its interhemispheric gradient. Data resolution and uncertainties are considered in the spline procedure and typical cutoff periods, defining the degree of smoothing, range from 5000 years for the less resolved older parts of the records to 4 years for the densely- sampled recent years. The data sets describe seamlessly the GHG evolution on orbital and millennial time scales for glacial and glacial-interglacial variations and on centennial and decadal time scales for the anthropogenic period

Photodynamic therapy of prostate cancer by means of 5-aminolevulinic acid-induced protoporphyrin IX - In vivo experiments on the dunning rat tumor model

Objective: In order to expand the use of photodynamic therapy (PDT) in the treatment of prostate carcinoma (PCA), the aim of this study was to evaluate PDT by means of 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX ( PPIX) in an in vivo tumor model. Methods: The model used was the Dunning R3327 tumor. First of all, the pharmacokinetics and the localization of PPIX were obtained using fluorescence measurement techniques. Thereafter, PDT using 150 mg 5-ALA/kg b.w.i.v. was performed by homogenous irradiation of the photosensitized tumor (diode laser lambda = 633 nm). The tumors necrosis was determined histopathologically. Results: The kinetics of PPIX fluorescence revealed a maximum intensity in the tumor tissue within 3 and 4.5 h post-application of 5-ALA. At this time, specific PPIX fluorescence could be localized selectively in the tumor cells. The PDT-induced necrosis (n = 18) was determined to be 94 B 12% (range 60-100%), while the necrosis of the controls ( n = 12) differs significantly (p < 0.01), being less than 10%. Conclusion: These first in vivo results demonstrate the effective potential of 5-ALA-mediated PDT on PCA in an animal model. Copyright (C) 2004 S. Karger AG, Basel

Variability in Microbial Community Composition and Function Between Different Niches Within a Coral Reef

To explore how microbial community composition and function varies within a coral reef ecosystem, we performed metagenomic sequencing of seawater from four niches across Heron Island Reef, within the Great Barrier Reef. Metagenomes were sequenced from seawater samples associated with (1) the surface of the coral species Acropora palifera, (2) the surface of the coral species Acropora aspera, (3) the sandy substrate within the reef lagoon and (4) open water, outside of the reef crest. Microbial composition and metabolic function differed substantially between the four niches. The taxonomic profile showed a clear shift from an oligotroph-dominated community (e.g. SAR11, Prochlorococcus, Synechococcus) in the open water and sandy substrate niches, to a community characterised by an increased frequency of copiotrophic bacteria (e.g. Vibrio, Pseudoalteromonas, Alteromonas) in the coral seawater niches. The metabolic potential of the four microbial assemblages also displayed significant differences, with the open water and sandy substrate niches dominated by genes associated with core house-keeping processes such as amino acid, carbohydrate and protein metabolism as well as DNA and RNA synthesis and metabolism. In contrast, the coral surface seawater metagenomes had an enhanced frequency of genes associated with dynamic processes including motility and chemotaxis, regulation and cell signalling. These findings demonstrate that the composition and function of microbial communities are highly variable between niches within coral reef ecosystems and that coral reefs host heterogeneous microbial communities that are likely shaped by habitat structure, presence of animal hosts and local biogeochemical conditions.Human Frontier Science Program (Strasbourg, France) (Grant RGY0089/2011