Flupenthixol in relapse prevention in schizophrenics with comorbid alcoholism: Results from an open clinical study

Substance use, especially alcoholism, has been recognized as a significant problem in schizophrenic patients, though only a few studies on the effects of pharmacotherapy in these patients have been conducted so far. The thioxanthene neuroleptic flupenthixol, which can be given intramuscularly (i.m.) for improving compliance, has been studied as a possible anti-craving drug both in animal models of alcoholism and some clinical studies. Pilot studies suggest that comorbid schizophrenics with substance use may benefit from treatment with flupenthixol. Efficacy of flupenthixol (10-60 mg i.m.) in reducing alcohol consumption of dual diagnosis patients was studied in an open 6-month clinical trial in 27 schizophrenics with comorbid alcoholism. Twenty-one patients entered the intention-to-treat analysis. Fourteen subjects were completers, 13 dropped out. Six patients completely abstained from alcohol during treatment. Alcohol consumption was significantly reduced compared to baseline (4 weeks before treatment as measured by timeline follow-back interview). In general, while patients showed a marked improvement concerning alcohol consumption, only a slight improvement in psychopathology was recorded. Overall tolerability was good. These data indicate a probable beneficial effect of flupenthixol in schizophrenic patients with comorbid alcoholism. Although the efficacy of flupenthixol as an anti-craving drug in dual diagnosis patients has to be explored in further studies, the drug may be considered a promising medication for these patients. Copyright (C) 2003 S. Karger AG, Basel

Inhibition of iodine organification and regulation of follicular size in rat thyroid tissue in vitro

The factors mediating the accumulation of thyroglobulin are of great importance to the understanding of the pathogenesis of human and experimentally induced colloid goiters. To elucidate further the underlying cellular mechanism, thyroid fragments from newborn rats were incorporated into semisolid alginate beads and were cultured as three-dimensional organoids for up to 21 d. In five parallel cultures, the medium contained either no supplements (group A), Nal (group B), thyroid-stimulating hormone (TSH) (group C), Nal plus TSH in the same concentrations as B and C (group D), or Nal and TSH (as in group D) plus methimazole (MMI, group E). The thyroid organoids maintained morphological intergrity, functional activity, and ability to proliferate in vitro. Addition of iodine to the cultures significantly increased mean (±SEM) follicular diameters from 19.5±0.7 μm in controls to 33.9±2.2 μm (p<0.0001) when Nal was added alone (group B), and 30.4±1.7 μm (p<0.0001) when combined with TSH (group D). The effect of Nal on follicular size was abolished by MMI (group E, follicular diameter 23.5±1.3 μm). The results presented support the recent finding, using a rat colloid goiter model, that not only TSH but also iodine organification or its inhibition are important factors in modulating follicular morpholog

Crystallographic order and decomposition of [MnIII6CrIII]3+ single-molecule magnets deposited in submonolayers and monolayers on HOPG studied by means of molecular resolved Atomic Force Microscopy (AFM) and Kelvin Probe Force Microscopy in UHV

Gryzia A, Volkmann T, Brechling A, et al. Crystallographic order and decomposition of [MnIII6CrIII]3+ single-molecule magnets deposited in submonolayers and monolayers on HOPG studied by means of molecular resolved Atomic Force Microscopy (AFM) and Kelvin Probe Force Microscopy in UHV. Nanoscale Research Letters. 2014;9(1): 60.Monolayers and submonolayers of [MnIII6CrIII]3+ single-molecule magnets (SMMs) adsorbed on highly oriented pyrolytic graphite (HOPG) using the droplet technique characterized by non-contact atomic force microscopy (nc-AFM) as well as by Kelvin probe force microscopy (KPFM) show island-like structures with heights resembling the height of the molecule. Furthermore, islands were found which revealed ordered 1D as well as 2D structures with periods close to the width of the SMMs. Along this, islands which show half the heights of intact SMMs were observed which are evidences for a decomposing process of the molecules during the preparation. Finally, models for the structure of the ordered SMM adsorbates are proposed to explain the observations

P2X7 receptor isoform B is a key drug resistance mediator for neuroblastoma

Drug resistance is a major challenge for all oncological treatments that involve the use of cytotoxic agents. Recent therapeutic alternatives cannot circumvent the ability of cancer cells to adapt or alter the natural selection of resistant cells, so the problem persists. In neuroblastoma, recurrence can occur in up to 50% of high-risk patients. Therefore, the identification of novel therapeutic targets capable of modulating survival or death following classical antitumor interventions is crucial to address this problem. In this study, we investigated the role of the P2X7 receptor in chemoresistance. Here, we elucidated the contributions of P2X7 receptor A and B isoforms to neuroblastoma chemoresistance, demonstrating that the B isoform favors resistance through a combination of mechanisms involving drug efflux via MRP-type transporters, resistance to retinoids, retaining cells in a stem-like phenotype, suppression of autophagy, and EMT induction, while the A isoform has opposite and complementary roles

Effect of exposure to natural environment on health inequalities: an observational population study

&lt;b&gt;Background:&lt;/b&gt; Studies have shown that exposure to the natural environment, or so-called green space, has an independent effect on health and health-related behaviours. We postulated that income-related inequality in health would be less pronounced in populations with greater exposure to green space, since access to such areas can modify pathways through which low socio-economic position can lead to disease.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods:&lt;/b&gt; We classified the population of England at younger than retirement age (n=40 813 236) into groups on the basis of income deprivation and exposure to green space. We obtained individual mortality records (n=366 348) to establish whether the association between income deprivation, all-cause mortality, and cause-specific mortality (circulatory disease, lung cancer, and intentional self-harm) in 2001—05, varied by exposure to green space measured in 2001, with control for potential confounding factors. We used stratified models to identify the nature of this variation.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Findings:&lt;/b&gt; The association between income deprivation and mortality differed significantly across the groups of exposure to green space for mortality from all causes (p&lt;0·0001) and circulatory disease (p=0·0212), but not from lung cancer or intentional self-harm. Health inequalities related to income deprivation in all-cause mortality and mortality from circulatory diseases were lower in populations living in the greenest areas. The incidence rate ratio (IRR) for all-cause mortality for the most income deprived quartile compared with the least deprived was 1·93 (95% CI 1·86—2·01) in the least green areas, whereas it was 1·43 (1·34—1·53) in the most green. For circulatory diseases, the IRR was 2·19 (2·04—2·34) in the least green areas and 1·54 (1·38—1·73) in the most green. There was no effect for causes of death unlikely to be affected by green space, such as lung cancer and intentional self-harm.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Interpretation:&lt;/b&gt; Populations that are exposed to the greenest environments also have lowest levels of health inequality related to income deprivation. Physical environments that promote good health might be important to reduce socio-economic health inequalities.&lt;p&gt;&lt;/p&gt

Reconstructing Quaternary vegetation history in the Carpathian Basin, SE-Europe, using n-alkane biomarkers as molecular fossils

Seit einigen Jahren gibt es zunehmend Studien, die, basierend auf der Untersuchung von fossilen Holzkohlen und Schneckenschalen aus Löss-Paläoboden Sequenzen, die traditionelle Vorstellung von weitestgehend baumlosen Steppen im Karpaten-Becken während der letzten Kaltzeit in Frage stellen. Mit unseren Arbeiten versuchen wir anhand von Biomarkern einen Beitrag zu dieser Diskussion zu leisten und herauszufinden, welches Potenzial in der Untersuchung von Alkan Biomarkern für die Rekonstruktion der Vegetationsgeschichte während der letzten glazialen Zyklen steckt. Kürzlich veröffentlichte erste Ergebnisse weisen darauf hin, dass der Degradationsgrad der pflanzenbürtigen organischen Substanz einen starken Einfluss auf das Alkanmuster in Böden hat und dass der in der Literatur häufig verwendete Alkanquotient nC31/nC27 kein reiner Vegetations-Proxy ist, sondern auch maßgeblich die unterschiedliche Degradation widerspiegelt. In der vorliegenden Arbeit führen wir daher erstmals einen End Member Modellierungsansatz ein, bei dem der Degradationsgrad der organischen Bodensubstanz mit berücksichtig wird. Das Modell wird auf die Loess-Paläoboden Sequenz Crvenka auf dem Bačka Loess Plateau (Serbien) zwischen Donau und Theiss angewendet. Die so für den letzten Interglazial-Glazial-Zyklus rekonstruierte Vegetationsgeschichte bestätigt die Holzkohle- und Mollusken-Befunde und deutet auf Gras-Steppen während des letzten Interglazials und -stadials hin (Marine Isotopenstadien (MIS) 5 bzw. 3). Die Ergebnisse machen deutlich, dass Steppen während des gesamten letzten glazialen Zyklus vorgeherrscht haben. Für das letzte Interglazial und das Interstadial der Marinen Isotopen Stufe (MIS) 3 deuten die Biomarker Befunde auf reine Grassteppen hin. Dagegen prägten in den Glazialen vermutlich auch vereinzelte Bäume das Landschaftsbild einer ‚Taiga-Steppe’. Die so rekonstruierte Vegetationsgeschichte steht im Einklang mit den Holzkohle- und Schneckenfunden, wie auch mit Ergebnissen von Klima- und Biom-Modellierungen.researc

Novel Evidence That Extracellular Nucleotides and Purinergic Signaling Induce Innate Immunity-Mediated Mobilization of Hematopoietic Stem/Progenitor Cells

Pharmacological mobilization of hematopoietic stem progenitor cells (HSPCs) from bone marrow (BM) into peripheral blood (PB) is a result of mobilizing agent-induced “sterile inflammation” in the BM microenvironment due to complement cascade (ComC) activation. Here we provide evidence that ATP, as an extracellular nucleotide secreted in a pannexin-1-dependent manner from BM cells, triggers activation of the ComC and initiates the mobilization process. This process is augmented in a P2X7 receptor-dependent manner, and P2X7-KO mice are poor mobilizers. Furthermore, after its release into the extracellular space, ATP is processed by ectonucleotidases: CD39 converts ATP to AMP, and CD73 converts AMP to adenosine. We observed that CD73-deficient mice mobilize more HSPCs than do wild-type mice due to a decrease in adenosine concentration in the extracellular space, indicating a negative role for adenosine in the mobilization process. This finding has been confirmed by injecting mice with adenosine along with pro-mobilizing agents. In sum, we demonstrate for the first time that purinergic signaling involving ATP and its metabolite adenosine regulate the mobilization of HSPCs. Although ATP triggers and promotes this process, adenosine has an inhibitory effect. Thus, administration of ATP together with G-CSF or AMD3100 or inhibition of CD73 by small molecule antagonists may provide the basis for more efficient mobilization strategies

Knowledge practices in design: The role of visual representations as 'epistemic objects'

We use a detailed study of the knowledge work around visual representations to draw attention to the multidimensional nature of `objects'. Objects are variously described in the literatures as relatively stable or in flux; as abstract or concrete; and as used within or across practices. We clarify these dimensions, drawing on and extending the literature on boundary objects, and connecting it with work on epistemic and technical objects. In particular, we highlight the epistemic role of objects, using our observations of knowledge work on an architectural design project to show how, in this setting, visual representations are characterized by a `lack' or incompleteness that precipitates unfolding. The conceptual design of a building involves a wide range of technical, social and aesthetic forms of knowledge that need to be developed and aligned. We explore how visual representations are used, and how these are meaningful to different stakeholders, eliciting their distinct contributions. As the project evolves and the drawings change, new issues and needs for knowledge work arise. These objects have an `unfolding ontology' and are constantly in flux, rather than fully formed. We discuss the implications for wider understandings of objects in organizations and for how knowledge work is achieved in practice

Heptanuclear [FeIII6CrIII]3+ Complexes Experimentally Studied by Means of Magnetometry, X-ray Diffraction, XAS, XMCD and Spin-Polarized Electron Spectroscopy in Cross-Comparison with [MnIII6CrIII]3+ Single-Molecule Magnets

Dohmeier N, Helmstedt A, Müller N, et al. Heptanuclear [FeIII6CrIII]3+ Complexes Experimentally Studied by Means of Magnetometry, X-ray Diffraction, XAS, XMCD and Spin-Polarized Electron Spectroscopy in Cross-Comparison with [MnIII6CrIII]3+ Single-Molecule Magnets. Magnochemistry. 2016;2(1): 5

Beyond words: Aesthetic knowledge and knowing in design

Aesthetic knowledge comes from practitioners understanding the look, feel, smell, taste and sound of things. It is vital to work in many organizational contexts. In this paper, we explore aesthetic knowledge and knowing in organizations through detailed observation of design work in the architectural practice Edward Cullinan Architects. Through our research, we explore aesthetic knowledge in the context of architectural work, we unpack what it is, how it is generated, and how it is applied in design projects, shared between practitioners and developed at the level of the organization. Our analysis suggests that aesthetic knowledge plays an important part in organizational practice, not only as the symbolic context for work, but as an integral part of the work that people do. It suggests that aesthetic reflexivity, which involves an opening up and questioning of what is known, is experienced as part of practice as well as a `time out' from practice