Politische Entwicklung im nachsowjetischen Mittelasien: Demokratisierung in Kirgistan

''Im Vergleich zu seinen mittelasiatischen Nachbarrepubliken ist Kirgistan durch eine weitgehende Reformbereitschaft, politische Öffnung und Respektierung der Menschenrechte gekennzeichnet. Dies hat dazu geführt, daß das kleine Land als 'Insel der Demokratie im Herzen Zentralasiens' gilt. Voliegender Bericht beschreibt den Verlauf der kirgisischen Demokratisierung und den gegenwärtigen Konsolidierungsstand. Er sucht nach Gründen für die recht weitgehende Demokratiserung, zeigt aber auch deren Grenzen auf. Die Vorgehensweise orientiert sich am Konzept der strategischen und konfliktfähigen Gruppen. Die Analyse beruht auf einem dreimonatigem Feldforschungsaufenthalt sowie auf russischsprachigen und westlichen Quellen.' (Autorenreferat)'By comparison with its Central-Asian neighbours, Kyrgyzstan is characterized by a high degree of willingness to reform, political opening, and respect for human rights. This has earned this little country its reputation as an 'island of democratization in Kyrgyzstan and the current status of its consolidation. It looks for the reasons why democratization has progressed so far but also points out the limits to the democratiziation process. The report's approach is orientated towards the concept of strategic and conflict-capable groups. The analysis is based on information gained by the author during a three-mounth period of field research and also draws upon Russian-language and Western sources.' (author's abstract

Novel set-up for low-disturbance sampling of volatile and non-volatile compounds from plant roots

Eilers E, Pauls G, Rillig MC, Hansson BS, Hilker M, Reinecke A. Novel set-up for low-disturbance sampling of volatile and non-volatile compounds from plant roots. Journal of Chemical Ecology. 2016;41(3):253-266.Most studies on rhizosphere chemicals are carried out in substrate-free set-ups or in artificial substrates using sampling methods that require an air flow and may thus cause disturbance to the rhizosphere. Our study aimed to develop a simplified and inexpensive system that allows analysis of rhizosphere chemicals at experimentally less disturbed conditions. We designed a mesocosm in which volatile rhizosphere chemicals were sampled passively (by diffusion) without air- and water flow on polydimethylsiloxane-(PDMS) tubes. Dandelion (Taraxacum sect. ruderalia) was used as model plant; roots were left undamaged. Fifteen volatiles were retrieved from the sorptive material by thermal desorption for analysis by gas chromatography/mass spectrometry (GC/MS). Furthermore, three sugars were collected from the rhizosphere substrate by aqueous extraction and derivatized prior to GC/MS analysis. In order to study how the quantity of detected rhizosphere compounds depends on the type of soil or substrate, we determined the matrix-dependent recovery of synthetic rhizosphere chemicals. Furthermore, we compared sorption of volatiles on PDMS tubes with and without direct contact to the substrate. The results show that the newly designed mesocosm is suitable for low-invasive extraction of volatile and non-volatile compounds from rhizospheres. We further highlight how strongly the type of substrate and contact of PDMS tubes to the substrate affect the detectability of compounds from rhizospheres

PRE-INTERVENTIONAL LEFT VENTRICULAR 2D STRAIN PREDICTS THE RECOVERY OF MYOCARDIAL DYSFUNCTION AND IMPROVEMENT IN FUNCTIONAL CAPACITY AFTER TRANSCATHETER AORTIC VALVE IMPLANTATION

International audienceAn extended literature analyzes the accumulation foreign exchange holding observed in many developing and emerging countries since the 2000s. Empirical studies on the self-insurance motive suggest that high-reserves economies are more resilient to financial crises and to international capital inflows volatility. They show also that pre-crisis foreign reserve accumulation explains post-crisis growth. However, some papers suggest that the relationship between international reserves holding and reduced vulnerability is nonlinear, meaning that reserve holding is subject to diminishing returns. This paper devotes more attention to the potential nonlinear relationship between the foreign reserves holding and macroeconomic resilience to shocks. For a sample of 9 emerging economies, we assess to what extent the accumulation of international reserves allows to mitigate negative impacts of external shocks on the output gap. While a major part of the literature focuses on the global financial crisis, we investigate this question by considering two sub-periods: 1995-2003 and 2004-2013. We implement threshold VAR (TVAR) model in which the structure is allow to change if the threshold variable crosses a certain estimated threshold. We find that the effectiveness of reserve holding to improve the resilience of domestic economies to shocks has increased over time. Hence, the diminishing returns of foreign reserve holding stressed in the previous literature must be qualified

Qualitative serum organic acid profiles of HIV-infected individuals not on antiretroviral treatment

The first application of gas chromatography mass spectrometry (GC–MS) metabolomics to the analysis of organic acid profiles in sera of asymptomatic human immunodeficiency virus (HIV)-infected individuals (n = 18) compared to uninfected controls (n = 21), is reported here. Several organic acids are well-established diagnostic biomarkers of mitochondrial dysfunction, making the analysis of the organic acid metabolome well suited to monitoring the progressive disruption of mitochondrial structure and function during HIV infection. Using a multifaceted analytical-bioinformatics procedure, at least 10 of these metabolites could be linked to (1) disrupted mitochondrial metabolism, (2) changes in lipid metabolism and (3) oxidative stress, all of which are aberrations caused by HIV infection. Because of the role of the mitochondria in apoptosis, higher levels of this type of cell death in infected (compared to uninfected) individuals was used to support GC–MS data. This study demonstrates that mass spectrometry metabolomics detects biomarkers of mitochondrial dysfunction which could potentially be developed into indicators of HIV infection, perhaps also to monitor disease progression and the response to antiretroviral treatment.The National Research Foundationhttp://www.springerlink.com/content/1573-3882/nf201

Therapeutic Reference Range for Aripiprazole in Schizophrenia Revised: a Systematic Review and Metaanalysis

Rationale: While one of the basic axioms of pharmacology postulates that there is a relationship between the concentration and effects of a drug, the value of measuring blood levels is questioned by many clinicians. This is due to the often-missing validation of therapeutic reference ranges. Objectives: Here, we present a prototypical meta-analysis of the relationships between blood levels of aripiprazole, its target engagement in the human brain, and clinical effects and side effects in patients with schizophrenia and related disorders. Methods: The relevant literature was systematically searched and reviewed for aripiprazole oral and injectable formulations. Population-based concentration ranges were computed (N = 3,373) and pharmacokinetic influences investigated. Results: Fifty-three study cohorts met the eligibility criteria. Twenty-nine studies report blood level after oral, 15 after injectable formulations, and nine were positron emission tomography studies. Conflicting evidence for a relationship between concentration, efficacy, and side effects exists (assigned level of evidence low, C; and absent, D). Population-based reference ranges are well in-line with findings from neuroimaging data and individual efficacy studies. We suggest a therapeutic reference range of 120-270 ng/ml and 180-380 ng/ml, respectively, for aripiprazole and its active moiety for the treatment of schizophrenia and related disorders. Conclusions: High interindividual variability and the influence of CYP2D6 genotypes gives a special indication for Therapeutic Drug Monitoring of oral and long-acting aripiprazole. A starting dose of 10 mg will in most patients result in effective concentrations in blood and brain. 5 mg will be sufficient for known poor metabolizers

Metabolomics of urinary organic acids in respiratory chain deficiencies in children

Metabolomic analysis of the urinary organic acids from 39 selected children with defined respiratory chain deficiencies (RCDs) was performed using untargeted gas chromatography–mass spectrometry, revealing the presence of 255 endogenous and 46 exogenous substances. Variable reduction identified 92 variables from the endogenous substances, which could be analysed by univariate and multivariate statistical methods. Using these methods, no characteristic organic acid biomarker profile could be defined of practical value for diagnostic purposes for complex I (CI), complex III (CIII) and multiple complex (CM) deficiencies. The statistical procedures used did, however, disclose 24 metabolites that were practical highly (d > 0.75) and statistically (p < 0.05) significant for the combined and clinically closely related group of RCDs. Several of these metabolites occur in single enzyme inherited metabolic diseases, but most were not previously reported to be linked to the metabolic perturbations that are due to RCDs. Ultimately, we constructed a global metabolic profile of carbohydrate, amino acid and fatty acid catabolism, illuminating the diverse and complex biochemical consequences of these disorders. This metabolomics investigation disclosed a metabolite profile that has the potential to define an extended and characteristic biosignature for RCDs and the development of a non-invasive screening procedure for these disorders.This study formed part of BioPAD Project BPP007.The South African Department of Science and Technology and North-West University.http://link.springer.com/journal/11306hb2017Paediatrics and Child Healt

Systematic review and meta-analysis on the therapeutic reference range for escitalopram: Blood concentrations, clinical effects and serotonin transporter occupancy

IntroductionA titration within a certain therapeutic reference range presupposes a relationship between the blood concentration and the therapeutic effect of a drug. However, this has not been systematically investigated for escitalopram. Furthermore, the recommended reference range disagrees with mean steady state concentrations (11–21 ng/ml) that are expected under the approved dose range (10–20 mg/day). This work systematically investigated the relationships between escitalopram dose, blood levels, clinical effects, and serotonin transporter occupancy.MethodsFollowing our previously published methodology, relevant articles were systematically searched and reviewed for escitalopram.ResultsOf 1,032 articles screened, a total of 30 studies met the eligibility criteria. The included studies investigated escitalopram blood levels in relationship to clinical effects (9 studies) or moderating factors on escitalopram metabolism (12 studies) or serotonin transporter occupancy (9 studies). Overall, the evidence for an escitalopram concentration/effect relationship is low (level C).ConclusionBased on our findings, we propose a target range of 20–40 ng/ml for antidepressant efficacy of escitalopram. In maintenance treatment, therapeutic response is expected, when titrating patients above the lower limit. The lower concentration threshold is strongly supported by findings from neuroimaging studies. The upper limit for escitalopram’s reference range rather reflects a therapeutic maximum than a tolerability threshold, since the incidence of side effects in general is low. Concentrations above 40 ng/ml should not necessarily result in dose reductions in case of good clinical efficacy and tolerability. Dose-related escitalopram concentrations in different trials were more than twice the expected concentrations from guideline reports.Systematic review registration[https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=215873], identifier [CRD42020215873]

Haemodynamic Balance in Acute and Advanced Heart Failure: An Expert Perspective on the Role of Levosimendan

Acute and advanced heart failure are associated with substantial adverse short- and longer-term prognosis. Both conditions necessitate complex treatment choices to restore haemodynamic stability and organ perfusion, relieve congestion, improve symptoms and allow the patient to leave the hospital and achieve an adequate quality of life. Among the available intravenous vasoactive therapies, inotropes constitute an option when an increase in cardiac contractility is needed to reverse a low output state. Within the inotrope category, levosimendan is well suited to the needs of both sets of patients since, in contrast to conventional adrenergic inotropes, it has not been linked in clinical trials or wider clinical usage with increased mortality risk and retains its efficacy in the presence of beta-adrenergic receptor blockade; it is further believed to possess beneficial renal effects. The overall haemodynamic profile and clinical tolerability of levosimendan, combined with its extended duration of action, have encouraged its intermittent use in patients with advanced heart failure. This paper summarises the key messages derived from a series of 12 tutorials held at the Heart Failure 2019 congress organised in Athens, Greece, by the Heart Failure Association of the European Society of Cardiology

Genome sequence of the bioplastic-producing ‘‘Knallgas’’ bacterium Ralstonia eutropha H16

The H2-oxidizing lithoautotrophic bacterium Ralstonia eutropha H16 is a metabolically versatile organism capable of subsisting, in the absence of organic growth substrates, on H2 and CO2 as its sole sources of energy and carbon. R. eutropha H16 first attracted biotechnological interest nearly 50 years ago with the realization that the organism’s ability to produce and store large amounts of poly[R-(–)-3-hydroxybutyrate] and other polyesters could be harnessed to make biodegradable plastics. Here we report the complete genome sequence of the two chromosomes of R. eutropha H16. Together, chromosome 1 (4,052,032 base pairs (bp)) and chromosome 2 (2,912,490 bp) encode 6,116 putative genes. Analysis of the genome sequence offers the genetic basis for exploiting the biotechnological potential of this organism and provides insights into its remarkable metabolic versatility