Sample records for factor gef ect2

  1. The Role of Ect2 Nuclear RhoGEF Activity in Ovarian Cancer Cell Transformation

    PubMed Central

    Huff, Lauren P.; DeCristo, Molly J.; Trembath, Dimitri; Kuan, Pei Fen; Yim, Margaret; Liu, Jinsong; Cook, Danielle R.; Miller, C. Ryan; Der, Channing J.

    2013-01-01

    Ect2, a Rho guanine nucleotide exchange factor (RhoGEF), is atypical among RhoGEFs in its predominantly nuclear localization in interphase cells. One current model suggests that Ect2 mislocalization drives cellular transformation by promoting aberrant activation of cytoplasmic Rho family GTPase substrates. However, in ovarian cancers, where Ect2 is both amplified and overexpressed at the mRNA level, we observed that the protein is highly expressed and predominantly nuclear and that nuclear but not cytoplasmic Ect2 increases with advanced disease. Knockdown of Ect2 in ovarian cancer cell lines impaired their anchorage-independent growth without affecting their growth on plastic. Restoration of Ect2 expression rescued the anchorage-independent growth defect, but not if either the DH catalytic domain or the nuclear localization sequences of Ect2 were mutated. These results suggested a novel mechanism whereby Ect2 could drive transformation in ovarian cancer cells by acting as a RhoGEF specifically within the nucleus. Interestingly, Ect2 had an intrinsically distinct GTPase specificity profile in the nucleus versus the cytoplasm. Nuclear Ect2 bound preferentially to Rac1, while cytoplasmic Ect2 bound to RhoA but not Rac. Consistent with nuclear activation of endogenous Rac, Ect2 overexpression was sufficient to recruit Rac effectors to the nucleus, a process that required a functional Ect2 catalytic domain. Furthermore, expression of active nuclearly targeted Rac1 rescued the defect in transformed growth caused by Ect2 knockdown. Our work suggests a novel mechanism of Ect2-driven transformation, identifies subcellular localization as a regulator of GEF specificity, and implicates activation of nuclear Rac1 in cellular transformation. PMID:24386507

  2. Cdc42 and the Guanine Nucleotide Exchange Factors Ect2 and Trio Mediate Fn14-Induced Migration and Invasion of Glioblastoma Cells

    PubMed Central

    Fortin, Shannon P.; Ennis, Matthew J.; Schumacher, Cassie A.; Zylstra-Diegel, Cassandra R.; Williams, Bart O.; Ross, Julianna T.D.; Winkles, Jeffrey A.; Loftus, Joseph C.; Symons, Marc H.; Tran, Nhan L.

    2012-01-01

    Malignant glioblastomas are characterized by their ability to infiltrate into normal brain. We previously reported that binding of the multifunctional cytokine TNF-like weak inducer of apoptosis (TWEAK) to its receptor fibroblast growth factor–inducible 14 (Fn14) induces glioblastoma cell invasion via Rac1 activation. Here, we show that Cdc42 plays an essential role in Fn14-mediated activation of Rac1. TWEAK-treated glioma cells display an increased activation of Cdc42, and depletion of Cdc42 using siRNA abolishes TWEAK-induced Rac1 activation and abrogates glioma cell migration and invasion. In contrast, Rac1 depletion does not affect Cdc42 activation by Fn14, showing that Cdc42 mediates TWEAK-stimulated Rac1 activation. Furthermore, we identified two guanine nucleotide exchange factors (GEF), Ect2 and Trio, involved in TWEAK-induced activation of Cdc42 and Rac1, respectively. Depletion of Ect2 abrogates both TWEAK-induced Cdc42 and Rac1 activation, as well as subsequent TWEAK-Fn14–directed glioma cell migration and invasion. In contrast, Trio depletion inhibits TWEAK-induced Rac1 activation but not TWEAK-induced Cdc42 activation. Finally, inappropriate expression of Fn14 or Ect2 in mouse astrocytes in vivo using an RCAS vector system for glial-specific gene transfer in G-tva transgenic mice induces astrocyte migration within the brain, corroborating the in vitro importance of the TWEAK-Fn14 signaling cascade in glioblastoma invasion. Our results suggest that the TWEAK-Fn14 signaling axis stimulates glioma cell migration and invasion through two GEF-GTPase signaling units, Ect2-Cdc42 and Trio-Rac1. Components of the Fn14-Rho GEF-Rho GTPase signaling pathway present innovative drug targets for glioma therapy. PMID:22571869

  3. Changes in Ect2 Localization Couple Actomyosin-Dependent Cell Shape Changes to Mitotic Progression

    PubMed Central

    Matthews, Helen K.; Delabre, Ulysse; Rohn, Jennifer L.; Guck, Jochen; Kunda, Patricia; Baum, Buzz

    2012-01-01

    Summary As they enter mitosis, animal cells undergo profound actin-dependent changes in shape to become round. Here we identify the Cdk1 substrate, Ect2, as a central regulator of mitotic rounding, thus uncovering a link between the cell-cycle machinery that drives mitotic entry and its accompanying actin remodeling. Ect2 is a RhoGEF that plays a well-established role in formation of the actomyosin contractile ring at mitotic exit, through the local activation of RhoA. We find that Ect2 first becomes active in prophase, when it is exported from the nucleus into the cytoplasm, activating RhoA to induce the formation of a mechanically stiff and rounded metaphase cortex. Then, at anaphase, binding to RacGAP1 at the spindle midzone repositions Ect2 to induce local actomyosin ring formation. Ect2 localization therefore defines the stage-specific changes in actin cortex organization critical for accurate cell division. PMID:22898780

  4. Quantitative Analysis of Guanine Nucleotide Exchange Factors (GEFs) as Enzymes

    PubMed Central

    Randazzo, Paul A; Jian, Xiaoying; Chen, Pei-Wen; Zhai, Peng; Soubias, Olivier; Northup, John K

    2014-01-01

    The proteins that possess guanine nucleotide exchange factor (GEF) activity, which include about ~800 G protein coupled receptors (GPCRs),1 15 Arf GEFs,2 81 Rho GEFs,3 8 Ras GEFs,4 and others for other families of GTPases,5 catalyze the exchange of GTP for GDP on all regulatory guanine nucleotide binding proteins. Despite their importance as catalysts, relatively few exchange factors (we are aware of only eight for ras superfamily members) have been rigorously characterized kinetically.5–13 In some cases, kinetic analysis has been simplistic leading to erroneous conclusions about mechanism (as discussed in a recent review14). In this paper, we compare two approaches for determining the kinetic properties of exchange factors: (i) examining individual equilibria, and; (ii) analyzing the exchange factors as enzymes. Each approach, when thoughtfully used,14,15 provides important mechanistic information about the exchange factors. The analysis as enzymes is described in further detail. With the focus on the production of the biologically relevant guanine nucleotide binding protein complexed with GTP (G•GTP), we believe it is conceptually simpler to connect the kinetic properties to cellular effects. Further, the experiments are often more tractable than those used to analyze the equilibrium system and, therefore, more widely accessible to scientists interested in the function of exchange factors. PMID:25332840

  5. Expression of a Rho guanine nucleotide exchange factor, Ect2, in the developing mouse pituitary.

    PubMed

    Islam, M S; Tsuji, T; Higashida, C; Takahashi, M; Higashida, H; Koizumi, K

    2010-05-01

    The pituitary gland is a highly mitotically active tissue after birth. Various cell types are known to undergo proliferation in the anterior pituitary. However, little is known about the mechanisms regulating mitotic activity in this tissue. When searching for genes specifically expressed in the pituitary gland among those that we previously screened in Drosophila, we found epithelial cell-transforming gene 2 (Ect2). Ect2 is a guanine nucleotide exchange factor for Rho GTPases, which is known to play an essential role in cytokinesis. Although there have been many cellular studies regarding the function of Ect2, the temporal and spatial expression patterns of Ect2 in vivo have not been determined. In the present study, we examined the postnatal developmental expression of Ect2 in the mouse pituitary. Enhanced Ect2 expression was detected in the mouse pituitary gland during the first 3 weeks after birth, which coincided well with the period of rapid pituitary expansion associated with increased growth rate. Immunostaining analysis showed that Ect2-expressing cells were distributed in the anterior and intermediate lobes, but not the posterior lobe, of the pituitary. These Ect2-expressing cells frequently incorporated the thymidine analogue, EdU (5-ethynyl-2'-deoxyuridine), indicating that these cells were mitotically active. Taken together, the results demonstrate the functional role of Ect2 in postnatal proliferating cells in the two lobes of the pituitary, thereby suggesting roles in developmental growth of the mammalian pituitary.

  6. DRhoGEF2 and Diaphanous Regulate Contractile Force during Segmental Groove Morphogenesis in the Drosophila Embryo

    PubMed Central

    Mulinari, Shai; Barmchi, Mojgan Padash

    2008-01-01

    Morphogenesis of the Drosophila embryo is associated with dynamic rearrangement of the actin cytoskeleton mediated by small GTPases of the Rho family. These GTPases act as molecular switches that are activated by guanine nucleotide exchange factors. One of these factors, DRhoGEF2, plays an important role in the constriction of actin filaments during pole cell formation, blastoderm cellularization, and invagination of the germ layers. Here, we show that DRhoGEF2 is equally important during morphogenesis of segmental grooves, which become apparent as tissue infoldings during mid-embryogenesis. Examination of DRhoGEF2-mutant embryos indicates a role for DRhoGEF2 in the control of cell shape changes during segmental groove morphogenesis. Overexpression of DRhoGEF2 in the ectoderm recruits myosin II to the cell cortex and induces cell contraction. At groove regression, DRhoGEF2 is enriched in cells posterior to the groove that undergo apical constriction, indicating that groove regression is an active process. We further show that the Formin Diaphanous is required for groove formation and strengthens cell junctions in the epidermis. Morphological analysis suggests that Dia regulates cell shape in a way distinct from DRhoGEF2. We propose that DRhoGEF2 acts through Rho1 to regulate acto-myosin constriction but not Diaphanous-mediated F-actin nucleation during segmental groove morphogenesis. PMID:18287521

  7. ECT2 and RASAL2 mediate mesenchymal-amoeboid transition in human astrocytoma cells.

    PubMed

    Weeks, Adrienne; Okolowsky, Nadia; Golbourn, Brian; Ivanchuk, Stacey; Smith, Christian; Rutka, James T

    2012-08-01

    Malignant astrocytomas are highly invasive brain tumors. The Rho family of cytoskeletal GTPases are key regulators of astrocytoma migration and invasion; expression of the guanine nucleotide exchange factor ECT2 is elevated in primary astrocytomas and predicts both survival and malignancy. Mice bearing orthotopically implanted astrocytoma cells with diminished ECT2 levels following ECT2 knockdown exhibit longer survival. Although ECT2 is normally expressed in the nucleus, we show that ECT2 is aberrantly localized to the cytoplasm in both astrocytoma cell lines and primary human astrocytomas, and colocalizes with RAC1 and CDC42 at the leading edge of migrating astrocytoma cells. Inhibition of ECT2 expression by RNA interference resulted in decreased RAC1 and CDC42 activity, but no change in RHO activity, suggesting that ECT2 is capable of activating these pro-migratory Rho family members. ECT2 overexpression in astrocytoma cells resulted in a transition to an amoeboid phenotype that was abolished with the ROCK inhibitor, Y-27632. Cytoplasmic fractionation of astrocytoma cells followed by ECT2 immunoprecipitation and mass spectrometry were used to identify protein-binding partners that modulate the activity of ECT2 toward RAC1 and RHO/ROCK. We identified RASAL2 as an ECT2-interacting protein that regulates RHO activity in astrocytoma cells. RASAL2 knockdown leads to a conversion to an amoeboid phenotype. Our studies reveal that ECT2 has a novel role in mesenchymal-amoeboid transition in human astrocytoma cells. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  8. Poly(ADP-ribosyl)ation is recognized by ECT2 during mitosis.

    PubMed

    Li, Mo; Bian, Chunjing; Yu, Xiaochun

    2014-01-01

    Poly(ADP-ribosyl)ation is an unique posttranslational modification and required for spindle assembly and function during mitosis. However, the molecular mechanism of poly(ADP-ribose) (PAR) in mitosis remains elusive. Here, we show the evidence that PAR is recognized by ECT2, a key guanine nucleotide exchange factor in mitosis. The BRCT domain of ECT2 directly binds to PAR both in vitro and in vivo. We further found that α-tubulin is PARylated during mitosis. PARylation of α-tubulin is recognized by ECT2 and recruits ECT2 to mitotic spindle for completing mitosis. Taken together, our study reveals a novel mechanism by which PAR regulates mitosis.

  9. Release of GTP Exchange Factor Mediated Down-Regulation of Abscisic Acid Signal Transduction through ABA-Induced Rapid Degradation of RopGEFs

    PubMed Central

    Waadt, Rainer; Schroeder, Julian I.

    2016-01-01

    The phytohormone abscisic acid (ABA) is critical to plant development and stress responses. Abiotic stress triggers an ABA signal transduction cascade, which is comprised of the core components PYL/RCAR ABA receptors, PP2C-type protein phosphatases, and protein kinases. Small GTPases of the ROP/RAC family act as negative regulators of ABA signal transduction. However, the mechanisms by which ABA controls the behavior of ROP/RACs have remained unclear. Here, we show that an Arabidopsis guanine nucleotide exchange factor protein RopGEF1 is rapidly sequestered to intracellular particles in response to ABA. GFP-RopGEF1 is sequestered via the endosome-prevacuolar compartment pathway and is degraded. RopGEF1 directly interacts with several clade A PP2C protein phosphatases, including ABI1. Interestingly, RopGEF1 undergoes constitutive degradation in pp2c quadruple abi1/abi2/hab1/pp2ca mutant plants, revealing that active PP2C protein phosphatases protect and stabilize RopGEF1 from ABA-mediated degradation. Interestingly, ABA-mediated degradation of RopGEF1 also plays an important role in ABA-mediated inhibition of lateral root growth. The presented findings point to a PP2C-RopGEF-ROP/RAC control loop model that is proposed to aid in shutting off ABA signal transduction, to counteract leaky ABA signal transduction caused by “monomeric” PYL/RCAR ABA receptors in the absence of stress, and facilitate signaling in response to ABA. PMID:27192441

  10. The Putative Exchange Factor Gef3p Interacts with Rho3p GTPase and the Septin Ring during Cytokinesis in Fission Yeast*

    PubMed Central

    Muñoz, Sofía; Manjón, Elvira; Sánchez, Yolanda

    2014-01-01

    The small GTP-binding proteins of the Rho family and its regulatory proteins play a central role in cytokinetic actomyosin ring assembly and cytokinesis. Here we show that the fission yeast guanine nucleotide exchange factor Gef3p interacts with Rho3p at the division site. Gef3p contains a putative DH homology domain and a BAR/IMD-like domain. The protein localized to the division site late in mitosis, where it formed a ring that did not constrict with actomyosin ring (cytokinetic actomyosin ring) invagination; instead, it split into a double ring that resembled the septin ring. Gef3p co-localized with septins and Mid2p and required septins and Mid2p for its localization. Gef3p interacts physically with the GTP-bound form of Rho3p. Although Gef3p is not essential for cell separation, the simultaneous disruption of gef3+ and Rho3p-interacting proteins, such as Sec8p, an exocyst component, Apm1p, a subunit of the clathrin adaptor complex or For3p, an actin-polymerizing protein, yielded cells with strong defects in septation and polarity respectively. Our results suggest that interactions between septins and Rho-GEFs provide a new targeting mechanism for GTPases in cytokinesis, in this case probably contributing to Rho3p function in vesicle tethering and vesicle trafficking in the later steps of cell separation. PMID:24947517

  11. Regulated Localization Is Sufficient for Hormonal Control of Regulator of G Protein Signaling Homology Rho Guanine Nucleotide Exchange Factors (RH-RhoGEFs)*

    PubMed Central

    Carter, Angela M.; Gutowski, Stephen; Sternweis, Paul C.

    2014-01-01

    The regulator of G protein signaling homology (RH) Rho guanine nucleotide exchange factors (RhoGEFs) (p115RhoGEF, leukemia-associated RhoGEF, and PDZ-RhoGEF) contain an RH domain and are specific GEFs for the monomeric GTPase RhoA. The RH domains interact specifically with the α subunits of G12 heterotrimeric GTPases. Activated Gα13 modestly stimulates the exchange activity of both p115RhoGEF and leukemia-associated RhoGEF but not PDZ-RhoGEF. Because all three RH-RhoGEFs can localize to the plasma membrane upon expression of activated Gα13, cellular localization of these RhoGEFs has been proposed as a mechanism for controlling their activity. We use a small molecule-regulated heterodimerization system to rapidly control the localization of RH-RhoGEFs. Acute localization of the proteins to the plasma membrane activates RhoA within minutes and to levels that are comparable with activation of RhoA by hormonal stimulation of G protein-coupled receptors. The catalytic activity of membrane-localized RhoGEFs is not dependent on activated Gα13. We further show that the conserved RH domains can rewire two different RacGEFs to activate Rac1 in response to a traditional activator of RhoA. Thus, RH domains act as independent detectors for activated Gα13 and are sufficient to modulate the activity of RhoGEFs by hormones via mediating their localization to substrate, membrane-associated RhoA. PMID:24855647

  12. Vav1 GEF activity is required for T cell mediated allograft rejection.

    PubMed

    Haubert, Dirk; Li, Jianping; Saveliev, Alexander; Calzascia, Thomas; Sutter, Esther; Metzler, Barbara; Kaiser, Daniel; Tybulewicz, Victor L J; Weckbecker, Gisbert

    2012-06-01

    The GDP exchange factor (GEF) Vav1 is a central signal transducer downstream of the T cell receptor and has been identified as a key factor for T cell activation in the context of allograft rejection. Vav1 has been shown to transduce signals both dependent and independent of its GEF function. The most promising approach to disrupt Vav1 activity by pharmacological inhibition would be to target its GEF function. However, the contribution of Vav1 GEF activity for allogeneic T cell activation has not been clarified yet. To address this question, we used knock-in mice bearing a mutated Vav1 with disrupted GEF activity but intact GEF-independent functions. T cells from these mice showed strongly reduced proliferation and activation in response to allogeneic stimulation. Furthermore, lack of Vav1 GEF activity strongly abrogated the in vivo expansion of T cells in a systemic graft-versus-host model. In a cardiac transplantation model, mice with disrupted Vav1 GEF activity show prolonged allograft survival. These findings demonstrate a strong requirement for Vav1 GEF activity for allogeneic T cell activation and graft rejection suggesting that disruption of Vav1 GEF activity alone is sufficient to induce significant immunosuppression. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Vav1 GEF activity is required for T cell mediated allograft rejection

    PubMed Central

    Haubert, Dirk; Li, Jianping; Saveliev, Alexander; Calzascia, Thomas; Sutter, Esther; Metzler, Barbara; Kaiser, Daniel; Tybulewicz, Victor L.J.; Weckbecker, Gisbert

    2012-01-01

    The GDP exchange factor (GEF) Vav1 is a central signal transducer downstream of the T cell receptor and has been identified as a key factor for T cell activation in the context of allograft rejection. Vav1 has been shown to transduce signals both dependent and independent of its GEF function. The most promising approach to disrupt Vav1 activity by pharmacological inhibition would be to target its GEF function. However, the contribution of Vav1 GEF activity for allogeneic T cell activation has not been clarified yet. To address this question, we used knock-in mice bearing a mutated Vav1 with disrupted GEF activity but intact GEF-independent functions. T cells from these mice showed strongly reduced proliferation and activation in response to allogeneic stimulation. Furthermore, lack of Vav1 GEF activity strongly abrogated the in vivo expansion of T cells in a systemic graft-versus-host model. In a cardiac transplantation model, mice with disrupted Vav1 GEF activity show prolonged allograft survival. These findings demonstrate a strong requirement for Vav1 GEF activity for allogeneic T cell activation and graft rejection suggesting that disruption of Vav1 GEF activity alone is sufficient to induce significant immunosuppression. PMID:22456277

  14. Structural Basis of Membrane Targeting by the Dock180 Family of Rho Family Guanine Exchange Factors (Rho-GEFs)*

    PubMed Central

    Premkumar, Lakshmanane; Bobkov, Andrey A.; Patel, Manishha; Jaroszewski, Lukasz; Bankston, Laurie A.; Stec, Boguslaw; Vuori, Kristiina; Côté, Jean-Francois; Liddington, Robert C.

    2010-01-01

    The Dock180 family of atypical Rho family guanine nucleotide exchange factors (Rho-GEFs) regulate a variety of processes involving cellular or subcellular polarization, including cell migration and phagocytosis. Each contains a Dock homology region-1 (DHR-1) domain that is required to localize its GEF activity to a specific membrane compartment where levels of phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3) are up-regulated by the local activity of PtdIns 3-kinase. Here we define the structural and energetic bases of phosphoinositide specificity by the DHR-1 domain of Dock1 (a GEF for Rac1), and show that DHR-1 utilizes a C2 domain scaffold and surface loops to create a basic pocket on its upper surface for recognition of the PtdIns(3,4,5)P3 head group. The pocket has many of the characteristics of those observed in pleckstrin homology domains. We show that point mutations in the pocket that abolish phospholipid binding in vitro ablate the ability of Dock1 to induce cell polarization, and propose a model that brings together recent mechanistic and structural studies to rationalize the central role of DHR-1 in dynamic membrane targeting of the Rho-GEF activity of Dock180. PMID:20167601

  15. Emerging Communication Technologies (ECT) Phase 2 Report. Volume 2; Appendices

    NASA Technical Reports Server (NTRS)

    Bastin, Gary L.; Harris, William G.; Chiodini, Robert; Nelson, Richard A.; Huang, PoTien; Kruhm, David A.

    2003-01-01

    The Emerging Communication Technology (ECT) project investigated three First Mile communication technologies in support of NASA s Second Generation Reusable Launch Vehicle (2nd Gen RLV), Orbital Space Plane, Advanced Range Technology Working Group (ARTWG) and the Advanced Spaceport Technology Working Group (ASTWG). These First Mile technologies have the purpose of interconnecting mobile users with existing Range Communication infrastructures. ECT was a continuation of the Range Information System Management (RISM) task started in 2002. RISM identified the three advance communication technologies investigated under ECT. These were Wireless Ethernet (Wi-Fi), Free Space Optics (FSO), and Ultra Wideband (UWB). Due to the report s size, it has been broken into three volumes: 1) Main Report 2) Appendices 3) UWB

  16. Students’ Factors Affecting Undergraduates’ Perceptions of their Teaching and Learning Process within ECTS Experience

    PubMed Central

    la Fuente, Jesús De; Cardelle-Elawar, María; Peralta, F. Javier; Sánchez, M. Dolores; Martínez-Vicente, José Manuel; Zapata, Lucía

    2010-01-01

    Introduction: In the present study, we investigated the potential factors that influenced the level of students satisfaction with the teaching–learning process (TLP), from the perspective of students participating in the European Credit Transfer System (ECTS) experience. Method: A total of 1490 students from the Universities of Almería and Granada (Spain) participated in an evaluation of their class discipline area. They completed the new revised protocol for evaluating the ECTS experience. Analyses of variance were carried out, taking the following factors as independent variables: student's grade average, year in school, study discipline, credit load in terms of ECTS credits assigned to a subject, the e-learning approach. Perception of the TLP was used as the dependent variable. Results: The data analyses showed variability of the degree of statistically significance among the factors that influenced students’ perceptions of the TLP. These factors included: Student's grade average (in favor of high performers), year in school (in favor of earlier years), ECTS load (in favor of subjects with a medium load of credits), and e-learning (in favor of its use). These research findings provided evidence to explore the delineation of a potential profile of factors that trigger a favorable perception of the TLP. Discussion and Conclusion: The present findings certainly have implications to deepen our understanding of the core beliefs, commitment, and the experience in shaping the implementation of the European Higher Education Area through the ECTS. PMID:21713171

  17. The RhoGAP activity of CYK-4/MgcRacGAP functions non-canonically by promoting RhoA activation during cytokinesis

    PubMed Central

    Zhang, Donglei; Glotzer, Michael

    2015-01-01

    Cytokinesis requires activation of the GTPase RhoA. ECT-2, the exchange factor responsible for RhoA activation, is regulated to ensure spatiotemporal control of contractile ring assembly. Centralspindlin, composed of the Rho family GTPase-activating protein (RhoGAP) MgcRacGAP/CYK-4 and the kinesin MKLP1/ZEN-4, is known to activate ECT-2, but the underlying mechanism is not understood. We report that ECT-2-mediated RhoA activation depends on the ability of CYK-4 to localize to the plasma membrane, bind RhoA, and promote GTP hydrolysis by RhoA. Defects resulting from loss of CYK-4 RhoGAP activity can be rescued by activating mutations in ECT-2 or depletion of RGA-3/4, which functions as a conventional RhoGAP for RhoA. Consistent with CYK-4 RhoGAP activity contributing to GEF activation, the catalytic domains of CYK-4 and ECT-2 directly interact. Thus, counterintuitively, CYK-4 RhoGAP activity promotes RhoA activation. We propose that the most active form of the cytokinetic RhoGEF involves complex formation between ECT-2, centralspindlin and RhoA. DOI: http://dx.doi.org/10.7554/eLife.08898.001 PMID:26252513

  18. MADRS symptom subtypes in ECT-treated depressed patients: relationship to response and subsequent ECT.

    PubMed

    Spashett, Renee; Fernie, Gordon; Reid, Ian C; Cameron, Isobel M

    2014-09-01

    This study aimed to explore the relationship of Montgomery-Åsberg Depression Rating Scale (MADRS) symptom subtypes with response to electroconvulsive therapy (ECT) and subsequent ECT treatment within 12 months. A consecutive sample of 414 patients with depression receiving ECT in the North East of Scotland was assessed by retrospective chart review. Response rate was defined as greater than or equal to 50% decrease in pretreatment total MADRS score or a posttreatment total MADRS less than or equal to 10. Principal component analyses were conducted on a sample with psychotic features (n = 124) and a sample without psychotic features (n = 290). Scores on extracted factor subscales, clinical and demographic characteristics were assessed for association with response and subsequent ECT treatment within 12 months. Where more than 1 variable was associated with response or subsequent ECT, logistic regression analysis was applied. MADRS symptom subtypes formed 3 separate factors in both samples. Logistic regression revealed older age and high "Despondency" subscale score predicted response in the nonpsychotic group. Older age alone predicted response in the group with psychotic features. Nonpsychotic patients subsequently re-treated with ECT were older than those not prescribed subsequent ECT. No association of variables emerged with subsequent ECT treatment in the group with psychotic features. Being of older age and the presence of psychotic features predicted response. Presence of psychotic features alone predicted subsequent retreatment. Subscale scores of the MADRS are of limited use in predicting which patients with depression will respond to ECT, with the exception of "Despondency" subscale scores in patients without psychotic features.

  19. Ictal EEG fractal dimension in ECT predicts outcome at 2 weeks in schizophrenia.

    PubMed

    Abhishekh, Hulegar A; Thirthalli, Jagadisha; Manjegowda, Anusha; Phutane, Vivek H; Muralidharan, Kesavan; Gangadhar, Bangalore N

    2013-09-30

    Studies of electroconvulsive therapy (ECT) have found an association between ictal electroencephalographic (EEG) measures and clinical outcome in depression. Such studies are lacking in schizophrenia. Consenting schizophrenia patients receiving ECT were assessed using the Brief Psychiatric Rating Scale (BPRS) before and 2 weeks after the start of ECT. The patients' seizure was monitored using EEG. In 26 patients, completely artifact-free EEG derived from the left frontal-pole (FP1) channel and electrocardiography (ECG) were available. The fractal dimension (FD) was computed to assess 4-s EEG epochs, and the maximal value from the earliest ECT session (2nd, 3rd or 4th) was used for analysis. There was a significant inverse correlation between the maximum FD and the total score following 6th ECT. An inverse Inverse correlation was also observed between the maximum FD and the total number of ECTs administered as well as the maximum heart rate (HR) and BPRS scores following 6th ECT. In patients with schizophrenia greater intensity of seizures (higher FD) during initial sessions of ECT is associated with better response at the end of 2 weeks. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  20. Mechanisms of CDC-42 activation during contact-induced cell polarization

    PubMed Central

    Chan, Emily; Nance, Jeremy

    2013-01-01

    Summary Polarization of early embryos provides a foundation to execute essential patterning and morphogenetic events. In Caenorhabditis elegans, cell contacts polarize early embryos along their radial axis by excluding the cortical polarity protein PAR-6 from sites of cell contact, thereby restricting PAR-6 to contact-free cell surfaces. Radial polarization requires the cortically enriched Rho GTPase CDC-42, which in its active form recruits PAR-6 through direct binding. The Rho GTPase activating protein (RhoGAP) PAC-1, which localizes specifically to cell contacts, triggers radial polarization by inactivating CDC-42 at these sites. The mechanisms responsible for activating CDC-42 at contact-free surfaces are unknown. Here, in an overexpression screen of Rho guanine nucleotide exchange factors (RhoGEFs), which can activate Rho GTPases, we identify CGEF-1 and ECT-2 as RhoGEFs that act through CDC-42 to recruit PAR-6 to the cortex. We show that ECT-2 and CGEF-1 localize to the cell surface and that removing their activity causes a reduction in levels of cortical PAR-6. Through a structure–function analysis, we show that the tandem DH-PH domains of CGEF-1 and ECT-2 are sufficient for GEF activity, but that regions outside of these domains target each protein to the cell surface. Finally, we provide evidence suggesting that the N-terminal region of ECT-2 may direct its in vivo preference for CDC-42 over another known target, the Rho GTPase RHO-1. We propose that radial polarization results from a competition between RhoGEFs, which activate CDC-42 throughout the cortex, and the RhoGAP PAC-1, which inactivates CDC-42 at cell contacts. PMID:23424200

  1. Mechanisms of CDC-42 activation during contact-induced cell polarization.

    PubMed

    Chan, Emily; Nance, Jeremy

    2013-04-01

    Polarization of early embryos provides a foundation to execute essential patterning and morphogenetic events. In Caenorhabditis elegans, cell contacts polarize early embryos along their radial axis by excluding the cortical polarity protein PAR-6 from sites of cell contact, thereby restricting PAR-6 to contact-free cell surfaces. Radial polarization requires the cortically enriched Rho GTPase CDC-42, which in its active form recruits PAR-6 through direct binding. The Rho GTPase activating protein (RhoGAP) PAC-1, which localizes specifically to cell contacts, triggers radial polarization by inactivating CDC-42 at these sites. The mechanisms responsible for activating CDC-42 at contact-free surfaces are unknown. Here, in an overexpression screen of Rho guanine nucleotide exchange factors (RhoGEFs), which can activate Rho GTPases, we identify CGEF-1 and ECT-2 as RhoGEFs that act through CDC-42 to recruit PAR-6 to the cortex. We show that ECT-2 and CGEF-1 localize to the cell surface and that removing their activity causes a reduction in levels of cortical PAR-6. Through a structure-function analysis, we show that the tandem DH-PH domains of CGEF-1 and ECT-2 are sufficient for GEF activity, but that regions outside of these domains target each protein to the cell surface. Finally, we provide evidence suggesting that the N-terminal region of ECT-2 may direct its in vivo preference for CDC-42 over another known target, the Rho GTPase RHO-1. We propose that radial polarization results from a competition between RhoGEFs, which activate CDC-42 throughout the cortex, and the RhoGAP PAC-1, which inactivates CDC-42 at cell contacts.

  2. Synthesis and properties of Rb2GeF6:Mn4+ red-emitting phosphors

    NASA Astrophysics Data System (ADS)

    Sakurai, Shono; Nakamura, Toshihiro; Adachi, Sadao

    2018-02-01

    Rb2GeF6:Mn4+ red-emitting phosphors were synthesized by coprecipitation and their structural and optical properties were investigated by laser microscopy observation, X-ray diffraction (XRD) analysis, photoluminescence (PL) analysis, PL excitation (PLE) spectroscopy, and PL decay measurement. Single-crystalline ingots in the form of a hexagonal pyramid were prepared with a basal plane diameter of ˜2 mm. The XRD analysis suggested that Rb2GeF6 crystallizes in the hexagonal structure (C6v4 = P63mc) with a = 0.5955 nm and c = 0.9672 nm. The phosphor exhibited the strong Mn4+-related zero-phonon line (ZPL) emission peak typically observed in host crystals with piezoelectrically active lattices such as a hexagonal lattice. The quantum efficiencies of the bulk ingot and powdered samples were 87 and 74%, respectively, with nearly the same luminescence decay time of ˜6 ms. The exact ZPL energies and related crystal-field and Racah parameters were obtained from the PL and PLE spectra by Franck-Condon analysis. Temperature-dependent PL intensities were analyzed from T = 20 to 500 K using a thermal quenching model by considering Bose-Einstein phonon statistics. A comparative discussion on the phosphor properties of Rb2GeF6:Mn4+ and Rb2MF6:Mn4+ with M = Si and Ti was also given.

  3. DIS[subscript 2]ECT: A Framework for Effective Inclusive Science Instruction

    ERIC Educational Resources Information Center

    Spaulding, Lucinda S.; Flannagan, Jenny Sue

    2012-01-01

    The purpose of this article is to provide special education and general education teachers a framework (DIS[subscript 2]ECT) for teaching science in inclusive settings. DIS2ECT stands for Design (Backwards); Individualization; Scaffolding and Strategies; Experiential learning; Cooperative Learning; and Teamwork. This framework was derived from our…

  4. High-sensitivity Cardiac Troponin Elevation after Electroconvulsive Therapy (ECT)

    PubMed Central

    Duma, Andreas; Pal, Swatilika; Johnston, Joshua; Helwani, Mohammad A.; Bhat, Adithya; Gill, Bali; Rosenkvist, Jessica; Cartmill, Christopher; Brown, Frank; Miller, J. Philip; Scott, Mitchell G; Sanchez-Conde, Francisco; Jarvis, Michael; Farber, Nuri B.; Zorumski, Charles F.; Conway, Charles; Nagele, Peter

    2017-01-01

    Background While electroconvulsive therapy (ECT) is widely regarded as a life-saving and safe procedure, evidence regarding its effects on myocardial cell injury are sparse. The objective of this investigation was to determine incidence and magnitude of new cardiac troponin elevation after ECT using a novel high-sensitivity cardiac troponin I (hscTnI) assay. Methods This was a prospective cohort study in adult patients undergoing ECT in a single academic center (up to three ECT treatments per patient). The primary outcome was new hscTnI elevation after ECT, defined as an increase of hscTnI >100% after ECT compared to baseline with at least one value above the limit of quantification (10 ng/L). 12-lead ECG and hscTnI values were obtained prior to and 15–30 minutes after ECT; in a subset of patients an additional 2-hour hscTnI value was obtained. Results The final study population was 100 patients and a total of 245 ECT treatment sessions. Eight patients (8/100, 8%) experienced new hscTnI elevation after ECT with a cumulative incidence of 3.7% (9/245 treatments; one patient had two hscTnI elevations), two of whom had a non-ST-elevation myocardial infarction (incidence 2/245, 0.8%). Median hscTnI concentrations did not increase significantly after ECT. Tachycardia and/or elevated systolic blood pressure developed after approximately two thirds of ECT treatments. Conclusions ECT appears safe from a cardiac standpoint in a large majority of patients. A small subset of patients with pre-existing cardiovascular risk factors, however, may develop new cardiac troponin elevation after ECT, the clinical relevance of which is unclear in the absence of signs of myocardial ischemia. PMID:28166110

  5. Relief of Expressed Suicidal Intent by ECT: A Consortium for Research in ECT Study

    PubMed Central

    Kellner, Charles H.; Fink, Max; Knapp, Rebecca; Petrides, Georgios; Husain, Mustafa; Rummans, Teresa; Mueller, Martina; Bernstein, Hilary; Rasmussen, Keith; O'Connor, Kevin; Smith, Glenn; Rush, A. John; Biggs, Melanie; McClintock, Shawn; Bailine, Samuel; Malur, Chitra

    2013-01-01

    Objective This study assessed the incidence, severity, and course of expressed suicidal intent in depressed patients who were treated with ECT. The data are from the first phase of an ongoing, collaborative multicenter study, the overall aim of which was to compare continuation ECT with pharmacotherapy in the prevention of relapse after a successful course of ECT. Method Suicidal intent, as expressed by patients during an interview, was scored at baseline and before each ECT session with item 3 on the 24-item Hamilton Depression Rating Scale in 444 patients with unipolar depression. Results One hundred thirty-one patients (29.5%) reported suicidal thoughts and acts (score of 3 or 4) at baseline. Scores decreased to 0 after 1 week (three ECT sessions) in 38.2% of the patients, after 2 weeks (six ECT sessions) in 61.1%, and in 80.9% at the end of the course of treatment. Conclusions Expressed suicidal intent in depressed patients was rapidly relieved with ECT. Evidence-based treatment algorithms for major depressive mood disorders should include dichotomization according to suicide risk, as assessed by interview. For patients at risk, ECT should be considered earlier than at its conventional “last resort” position. PMID:15863801

  6. ECT practices in Iraq: a national audit.

    PubMed

    Alhemiary, Nesif; Ali, Zainab; Abbas, Mohammed J

    2015-12-01

    Aims and method This national audit examined practice of electroconvulsive therapy (ECT) in Iraq against local standards. Data were collected by a questionnaire sent to heads of departments or medical directors in the 10 Iraqi hospitals which provide ECT and by examining case notes of all patients who had ECT in the first 6 months of 2013. Results Of the 26 psychiatric hospitals in Iraq, 10 provide ECT. There were some resource shortcomings in the ECT clinics (e.g. only 2 had a minimum of 2 rooms and all had no EEG monitoring). During the audit period, 251 patients had ECT. The mean age was 36.2 years and 51.8% were males. Bilateral ECT was used in all cases, general anaesthesia in 77.15%. The main indication for ECT was schizophrenia, followed by severe depression, resistant mania, catatonia and others. Clinical implications More work is needed to ensure all patients receive modified ECT. ECT is still used widely for schizophrenia. This needs further exploration and training.

  7. A Novel GABRG2 Mutation, p.R136*, in a family with GEFS+ and extended phenotypes

    PubMed Central

    Shen, Wangzhen; Pickrell, William O.; Cushion, Thomas D.; Davies, Jeffrey S.; Baer, Kristin; Mullins, Jonathan G.L.; Hammond, Carrie L.; Chung, Seo-Kyung; Thomas, Rhys H.; White, Cathy; Smith, Phil E.M.

    2014-01-01

    Genetic mutations in voltage-gated and ligand-gated ion channel genes have been identified in a small number of Mendelian families with genetic generalised epilepsies (GGEs). They are commonly associated with febrile seizures (FS), childhood absence epilepsy (CAE) and particularly with generalised or genetic epilepsy with febrile seizures plus (GEFS+). In clinical practice, despite efforts to categorise epilepsy and epilepsy families into syndromic diagnoses, many generalised epilepsies remain unclassified with a presumed genetic basis. During the systematic collection of epilepsy families, we assembled a cohort of families with evidence of GEFS+ and screened for variations in the γ2 subunit of the γ-aminobutyric acid (GABA) type A receptor gene (GABRG2). We detected a novel GABRG2(p.R136*) premature translation termination codon in one index-case from a two-generation nuclear family, presenting with an unclassified GGE, a borderline GEFS+ phenotype with learning difficulties and autism spectrum disorder (ASD). The GABRG2(p.R136*) mutation segregates with the febrile seizure component of this family's GGE and is absent in 190 healthy control samples. In vitro expression assays demonstrated that γ2(p.R136*) subunits were produced, but had reduced cell-surface and total expression. When γ2(p.R136*) subunits were co-expressed with α1 and β2 subunits in HEK 293T cells, GABA–evoked currents were reduced. Furthermore, γ2(p.R136*) subunits were highly-expressed in intracellular aggregations surrounding the nucleus and endoplasmic reticulum (ER), suggesting compromised receptor trafficking. A novel GABRG2(p.R136*) mutation extends the spectrum of GABRG2 mutations identified in GEFS+ and GGE phenotypes, causes GABAA receptor dysfunction, and represents a putative epilepsy mechanism. PMID:24407264

  8. The Rap GTPase Activator Drosophila PDZ-GEF Regulates Cell Shape in Epithelial Migration and Morphogenesis▿

    PubMed Central

    Boettner, Benjamin; Van Aelst, Linda

    2007-01-01

    Epithelial morphogenesis is characterized by an exquisite control of cell shape and position. Progression through dorsal closure in Drosophila gastrulation depends on the ability of Rap1 GTPase to signal through the adherens junctional multidomain protein Canoe. Here, we provide genetic evidence that epithelial Rap activation and Canoe effector usage are conferred by the Drosophila PDZ-GEF (dPDZ-GEF) exchange factor. We demonstrate that dPDZ-GEF/Rap/Canoe signaling modulates cell shape and apicolateral cell constriction in embryonic and wing disc epithelia. In dPDZ-GEF mutant embryos with strong dorsal closure defects, cells in the lateral ectoderm fail to properly elongate. Postembryonic dPDZ-GEF mutant cells generated in mosaic tissue display a striking extension of lateral cell perimeters in the proximity of junctional complexes, suggesting a loss of normal cell contractility. Furthermore, our data indicate that dPDZ-GEF signaling is linked to myosin II function. Both dPDZ-GEF and cno show strong genetic interactions with the myosin II-encoding gene, and myosin II distribution is severely perturbed in epithelia of both mutants. These findings provide the first insight into the molecular machinery targeted by Rap signaling to modulate epithelial plasticity. We propose that dPDZ-GEF-dependent signaling functions as a rheostat linking Rap activity to the regulation of cell shape in epithelial morphogenesis at different developmental stages. PMID:17846121

  9. The RhoA Activator GEF-H1/Lfc Is a Transforming Growth Factor-β Target Gene and Effector That Regulates α-Smooth Muscle Actin Expression and Cell Migration

    PubMed Central

    Tsapara, Anna; Luthert, Phillip; Greenwood, John; Hill, Caroline S.

    2010-01-01

    Maintenance of the epithelial phenotype is crucial for tissue homeostasis. In the retina, dedifferentiation and loss of integrity of the retinal pigment epithelium (RPE) leads to retinal dysfunction and fibrosis. Transforming growth factor (TGF)-β critically contributes to RPE dedifferentiation and induces various responses, including increased Rho signaling, up-regulation of α-smooth muscle actin (SMA), and cell migration and dedifferentiation. Cellular TGF-β responses are stimulated by different signal transduction pathways: some are Smad dependent and others Smad independent. Alterations in Rho signaling are crucial to both types of TGF-β signaling, but how TGF-β-stimulates Rho signaling is poorly understood. Here, we show that primary RPE cells up-regulated GEF-H1 in response to TGF-β. GEF-H1 was the only detectable Rho exchange factor increased by TGF-β1 in a genome-wide expression analysis. GEF-H1 induction was Smad4-dependant and led to Rho activation. GEF-H1 inhibition counteracted α-SMA up-regulation and cell migration. In patients with retinal detachments and fibrosis, migratory RPE cells exhibited increased GEF-H1 expression, indicating that induction occurs in diseased RPE in vivo. Our data indicate that GEF-H1 is a target and functional effector of TGF-β by orchestrating Rho signaling to regulate gene expression and cell migration, suggesting that it represents a new marker and possible therapeutic target for degenerative and fibrotic diseases. PMID:20089843

  10. A New Type of ECT Stimuli: Burst Stimulus ECT.

    PubMed

    Aksay, S S; Bumb, J M; Janke, C; Kranaster, L; Sartorius, A

    2015-11-01

    Pulse width in electroconvulsive therapy has significant influence on effectiveness and side effects. While shorter pulses are beneficial for cognitive performance, there is still a debate about a negative impact on ECT efficacy at least for ultra-brief pulse durations. We report a first patient treated with burst stimulus ECT, i. e., with 4 consecutive 250-µs pulses, separated by another 250 µs. Within the same patient we compared 6 classical vs. 6 burst stimulus ECT sessions. In all cases a typical tonic-clonic seizure was observed. Seizure parameters like concordance, coherence and mid-ictal amplitude increased numerically, but not significantly with burst ECT. The time needed to show a reorientation was significantly shortened with burst stimuli (30 min vs. 14 min, p=0.007). In conclusion we present the first case of ECT in a single patient comparing "classical" single stimulus pulses vs. burst stimulus ECT. The new burst stimulus was better tolerated regarding reorientation time after the treatment, while parameters of seizure quality remained basically unchanged. Whether burst stimulus ECT has the potential to improve ECT quality by reducing side effects without losing efficacy has to be investigated in clinical trials. © Georg Thieme Verlag KG Stuttgart · New York.

  11. The Impact of STTP on the GEFS Forecast of Week-2 and Beyond in the Presence of Stochastic Physics

    NASA Astrophysics Data System (ADS)

    Hou, D.

    2015-12-01

    The Stochastic Total Tendency Perturbation (STTP) scheme was designed to represent the model related uncertainties not considered in the numerical model itself and the physics based stochastic schemes. It has been applied in NCEP's Global Ensemble Forecast System (GEFS) since 2010, showing significant positive impacts on the forecast with improved spread-error ratio and probabilistic forecast skills. The scheme is robust and it went well with the resolution increases and model improvements in 2012 and 2015 with minimum changes. Recently, a set of stochastic physics schemes are coded in the Global Forecast System model and tested in the GEFS package. With these schemes turned on and STTP off, the forecast performance is comparable or even superior to the operational GEFS, in which STTP is the only contributor to the model related uncertainties. This is true especially in week one. However, over the second week and beyond, both the experimental and the operational GEFS has insufficient spread, especially over the warmer seasons. This is a major challenge when the GEFS is extended to sub-seasonal (week 4-6) time scales. The impact of STTP on the GEFS forecast in the presence of stochastic physics is investigated by turning both the stochastic physics schemes and STTP on and carefully tuning their amplitudes. Analysis will be focused on the forecast of extended range, especially week 2. Its impacts on week 3-4 will also be addressed.

  12. Emerging Communication Technologies (ECT) Phase 2 Report. Volume 1; Main Report

    NASA Technical Reports Server (NTRS)

    Bastin, Gary L.; Harris, William G.; Chiodini, Robert; Nelson, Richard A.; Huang, PoTien; Kruhm, David A.

    2003-01-01

    The Emerging Communication Technology (ECT) project investigated three First Mile communication technologies in support of NASA s Second Generation Reusable Launch Vehicle (2nd Gen RLV), Orbital Space Plane, Advanced Range Technology Working Group (ARTWG) and the Advanced Spaceport Technology Working Group (ASTWG). These First Mile technologies have the purpose of interconnecting mobile users with existing Range Communication infrastructures. ECT was a continuation of the Range Information System Management (RISM) task started in 2002. RISM identified the three advance communication technologies investigated under ECT. These were Wireless Ethernet (Wi-Fi), Free Space Optics (FSO), and Ultra Wideband (UWB). Due to the report s size, it has been broken into three volumes: 1) Main Report 2) Appendices 3) UWB.

  13. Clinical and biological predictors of response to electroconvulsive therapy (ECT): a review.

    PubMed

    Pinna, Martina; Manchia, Mirko; Oppo, Rossana; Scano, Filomena; Pillai, Gianluca; Loche, Anna Paola; Salis, Piergiorgio; Minnai, Gian Paolo

    2018-03-16

    Electroconvulsive therapy (ECT), developed in the 30's by Bini and Cerletti, remains a key element of the therapeutic armamentarium in psychiatry, particularly for severe and life-threatening psychiatric symptoms. However, despite its well-established clinical efficacy, the prescription of ECT has declined constantly over the years due to concerns over its safety (cognitive side effects) and an increasingly negative public perception. As for other treatments in the field of psychiatry, ECT is well suited to a personalized approach that would increment its efficacy, as well as reducing the impact of side effects. This should be based on the priori identification of sub-populations of patients sharing common clinical and biological features that predict a good response to ECT. In this review we have selectively reviewed the evidence on clinical and biological predictors of ECT response. Clinical features such as an older age, presence of psychotic and melancholic depression, a high severity of suicide behavior, and speed of response, appear to be shared by ECT good responders with depressive symptoms. In mania, a greater severity of the index episode, and a reduction of whole brain cortical blood flow are associated with ECT good response. Biological determinants of ECT response in depressive patients are the presence of pre-treatment hyperconnectivity between key areas of brain circuitry of depression, as well as of reduced glutamine/glutamate levels, particularly in the anterior cingulated cortex (ACC). Furthermore, pre ECT high plasma homovanillic acid (HVA) levels, as well as of tumor necrosis factor (TNF)-α, and low pre-ECT levels of S-100B protein, appear to predict ECT response. Finally, polymorphisms within the genes encoding for the brain-derived neurotrophic factor (BDNF), the dopamine 2 receptor gene (DRD2), the dopamine receptor 3 gene (DRD3), the cathechol-o-methyltransferase (COMT), the serotonin-transporter (5-HTT), the 5-hydroxytryptamine 2A receptor

  14. Continuation of ECT after recovery from transient, ECT-induced, postictal cortical blindness.

    PubMed

    Sonavane, Sushma; Bambole, Vivek; Bang, Abha; Shah, Nilesh; Andrade, Chittaranjan

    2012-03-01

    Transient, postictal cortical blindness is a rare adverse effect of electroconvulsive therapy (ECT). There is no information on the safety of continuation of ECT in patients who recover from ECT-induced cortical blindness. An 18-year-old woman with paranoid schizophrenia experienced cortical blindness immediately after her first bifrontotemporal ECT treatment. There was complete, spontaneous recovery of vision after 6 hours. Neurological examination, computed tomography of the brain, and electroencephalographic study revealed no abnormality. A combination of circumstances suggested that continuation of ECT was desirable. After clearances from neurological and ophthalmological teams, she received 6 more ECT treatments, starting 9 days after the first. After resumption of ECT, there was marked improvement in psychopathology across the ECT course. There was no recurrence of visual symptoms. Patients who experience transient, ECT-induced, postictal cortical blindness may not necessarily experience the same adverse effect on rechallenge with ECT.

  15. A Novel Strategy for Continuation ECT in Geriatric Depression: Phase 2 of the PRIDE Study.

    PubMed

    Kellner, Charles H; Husain, Mustafa M; Knapp, Rebecca G; McCall, W Vaughn; Petrides, Georgios; Rudorfer, Matthew V; Young, Robert C; Sampson, Shirlene; McClintock, Shawn M; Mueller, Martina; Prudic, Joan; Greenberg, Robert M; Weiner, Richard D; Bailine, Samuel H; Rosenquist, Peter B; Raza, Ahmad; Kaliora, Styliani; Latoussakis, Vassilios; Tobias, Kristen G; Briggs, Mimi C; Liebman, Lauren S; Geduldig, Emma T; Teklehaimanot, Abeba A; Dooley, Mary; Lisanby, Sarah H

    2016-11-01

    The randomized phase (phase 2) of the Prolonging Remission in Depressed Elderly (PRIDE) study evaluated the efficacy and tolerability of continuation ECT plus medication compared with medication alone in depressed geriatric patients after a successful course of ECT (phase 1). PRIDE was a two-phase multisite study. Phase 1 was an acute course of right unilateral ultrabrief pulse ECT, augmented with venlafaxine. Phase 2 compared two randomized treatment arms: a medication only arm (venlafaxine plus lithium, over 24 weeks) and an ECT plus medication arm (four continuation ECT treatments over 1 month, plus additional ECT as needed, using the Symptom-Titrated, Algorithm-Based Longitudinal ECT [STABLE] algorithm, while continuing venlafaxine plus lithium). The intent-to-treat sample comprised 120 remitters from phase 1. The primary efficacy outcome measure was score on the 24-item Hamilton Depression Rating Scale (HAM-D), and the secondary efficacy outcome was score on the Clinical Global Impressions severity scale (CGI-S). Tolerability as measured by neurocognitive performance (reported elsewhere) was assessed using an extensive test battery; global cognitive functioning as assessed by the Mini-Mental State Examination (MMSE) is reported here. Longitudinal mixed-effects repeated-measures modeling was used to compare ECT plus medication and medication alone for efficacy and global cognitive function outcomes. At 24 weeks, the ECT plus medication group had statistically significantly lower HAM-D scores than the medication only group. The difference in adjusted mean HAM-D scores at study end was 4.2 (95% CI=1.6, 6.9). Significantly more patients in the ECT plus medication group were rated "not ill at all" on the CGI-S compared with the medication only group. There was no statistically significant difference between groups in MMSE score. Additional ECT after remission (here operationalized as four continuation ECT treatments followed by further ECT only as needed) was

  16. Global Environment Facility (GEF): An Overview

    DTIC Science & Technology

    2010-05-17

    e.g., choosing solar energy technology over coal technology meets the same national development goal of power generation but is more costly. GEF grants...mechanism for a specific convention. Through an association with regional agreements, it targets trans-boundary water systems, such as river basins with...Caribbean corridor in Costa Rica. Prevention and Management of Marine Pollution in the East Asian Seas in and around Indonesia GEF Grant: $8,025,000

  17. Annexin V-induced rat Leydig cell proliferation involves Ect2 via RhoA/ROCK signaling pathway.

    PubMed

    Jing, Jun; Chen, Li; Fu, Hai-Yan; Fan, Kai; Yao, Qi; Ge, Yi-Feng; Lu, Jin-Chun; Yao, Bing

    2015-03-24

    This study investigated the effect of annexin V on the proliferation of primary rat Leydig cells and the potential mechanism. Our results showed that annexin V promoted rat Leydig cell proliferation and cell cycle progression in a dose- and time-dependent manner. Increased level of annexin V also enhanced Ect2 protein expression. However, siRNA knockdown of Ect2 attenuated annexin V-induced proliferation of rat Leydig cells. Taken together, these data suggest that increased level of annexin V induced rat Leydig cell proliferation and cell cycle progression via Ect2. Since RhoA activity was increased following Ect2 activation, we further investigated whether Ect2 was involved in annexin V-induced proliferation via the RhoA/ROCK pathway, and the results showed that annexin V increased RhoA activity too, and this effect was abolished by the knockdown of Ect2. Moreover, inhibition of the RhoA/ROCK pathway by a ROCK inhibitor, Y27632, also attenuated annexin V-induced proliferation and cell cycle progression. We thus conclude that Ect2 is involved in annexin V-induced rat Leydig cell proliferation through the RhoA/ROCK pathway.

  18. Electroconvulsive Therapy (ECT) and Race: A Report of ECT Use and Sociodemographic Trends in Texas.

    PubMed

    Williams, Julie; Chiu, Lawrence; Livingston, Robin

    2017-06-01

    Minimal research on race and other sociodemographic disparities in patients receiving electroconvulsive therapy (ECT) exists. One previously noted national trend reveals whites receiving ECT disproportionately more than other races. The aim of this study is to determine whether a county ECT program demonstrates similar disparities observed at the state and national levels. This study examined 21 years of ECT data, between 1993 and 2014, provided by the Texas Department of State Health Services, focusing on race, sex, age, and payer source and 2.5 years of the same variables from a Harris County hospital ECT program. In addition, population demographic data for Harris County and the state of Texas during the same period were obtained from the Department of State Health Services Web site. Despite an overall decrease in the population of whites countywide and statewide, whites continue to use more ECT than African Americans, Latinos, and Asians in both Harris County and Texas. However, the rates of ECT use in minorities increased overall. Both countywide and statewide, ECT was used more than twice as often in women than men. Statewide, elderly patients (>65 years old) saw decreases in ECT use, and there was an increase in private third-party payer source. Electroconvulsive therapy remains underused among African Americans, Latinos, and Asians. Hypotheses and areas for future study include cultural beliefs, stigma, patient and provider knowledge of ECT, and access to care. Despite this, the general use of ECT in Texas has increased overall, and minority use is slowly on the rise.

  19. Remission of depression following electroconvulsive therapy (ECT) is associated with higher levels of brain-derived neurotrophic factor (BDNF).

    PubMed

    Freire, Thiago Fernando Vasconcelos; Fleck, Marcelo Pio de Almeida; da Rocha, Neusa Sica

    2016-03-01

    Research on the association between electroconvulsive therapy (ECT) and increased brain derived neurotrophic factor (BDNF) levels has produced conflicting result. There have been few studies which have evaluated BDNF levels in clinical contexts where there was remission following treatment. The objective of this study was to investigate whether remission of depression following ECT is associated with changes in BDNF levels. Adult inpatients in a psychiatric unit were invited to participate in this naturalistic study. Diagnoses were made using the Mini-International Neuropsychiatric Interview (MINI) and symptoms were evaluated at admission and discharge using the Hamilton Rating Scale for Depression (HDRS-17). Thirty-one patients who received a diagnosis of depression and were subjected to ECT were included retrospectively. Clinical remission was defined as a score of less than eight on the HDRS-17 at discharge. Serum BDNF levels were measured in blood samples collected at admission and discharge with a commercial kit used in accordance with the manufacturer's instructions. Subjects HDRS-17 scores improved following ECT (t = 13.29; p = 0.00). A generalized estimating equation (GEE) model revealed a remission × time interaction with BDNF levels as a dependent variable in a Wald chi-square test [Wald χ(2) = 5.98; p = 0.01]. A post hoc Bonferroni test revealed that non-remitters had lower BDNF levels at admission than remitters (p = 0.03), but there was no difference at discharge (p = 0.16). ECT remitters had higher serum BDNF levels at admission and the level did not vary during treatment. ECT non-remitters had lower serum BDNF levels at admission, but levels increased during treatment and were similar to those of ECT remitters at discharge. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Cognitive Performance Under Electroconvulsive Therapy (ECT) in ECT-Naive Treatment-Resistant Patients With Major Depressive Disorder.

    PubMed

    Ziegelmayer, Christoph; Hajak, Göran; Bauer, Anne; Held, Marion; Rupprecht, Rainer; Trapp, Wolfgang

    2017-06-01

    Although electroconvulsive therapy (ECT) is considered a safe and highly effective treatment option for major depressive disorder, there are still some reservations with regard to possible adverse cognitive adverse effects. This is the case despite a large body of evidence showing that these deficits are transient and that there even seems to be a long-term improvement of cognitive functioning level. However, most data concerning cognitive adverse effects stem from studies using mixed samples of treatment-resistant and non-treatment-resistant as well as ECT-naive and non-ECT-naive subjects. Furthermore, neurocognitive measures might partly be sensitive to practice effects and improvements in depressive symptom level. We examined neurocognitive performance in a sample of 20 treatment-resistant and ECT-naive subjects using repeatable neurocognitive tests, whereas changes in depressive symptom level were controlled. Cognitive functioning level was assessed before (baseline), 1 week, and 6 months (follow-up 1 and 2) after (12 to) 15 sessions of unilateral ECT treatment. No adverse cognitive effects were observed in any of the cognitive domains examined. Instead, a significant improvement in verbal working memory performance was found from baseline to follow-up 2. When changes in depressive symptom levels were controlled statistically, this improvement was no longer seen. Although findings that ECT does not lead to longer lasting cognitive deficits caused by ECT were confirmed, our study adds evidence that previous results of a beneficial effect of ECT on cognition might be questioned.

  1. Which Way In? The RalF Arf-GEF Orchestrates Rickettsia Host Cell Invasion

    PubMed Central

    Rennoll-Bankert, Kristen E.; Rahman, M. Sayeedur; Gillespie, Joseph J.; Guillotte, Mark L.; Kaur, Simran J.; Lehman, Stephanie S.; Beier-Sexton, Magda; Azad, Abdu F.

    2015-01-01

    Bacterial Sec7-domain-containing proteins (RalF) are known only from species of Legionella and Rickettsia, which have facultative and obligate intracellular lifestyles, respectively. L. pneumophila RalF, a type IV secretion system (T4SS) effector, is a guanine nucleotide exchange factor (GEF) of ADP-ribosylation factors (Arfs), activating and recruiting host Arf1 to the Legionella-containing vacuole. In contrast, previous in vitro studies showed R. prowazekii (Typhus Group) RalF is a functional Arf-GEF that localizes to the host plasma membrane and interacts with the actin cytoskeleton via a unique C-terminal domain. As RalF is differentially encoded across Rickettsia species (e.g., pseudogenized in all Spotted Fever Group species), it may function in lineage-specific biology and pathogenicity. Herein, we demonstrate RalF of R. typhi (Typhus Group) interacts with the Rickettsia T4SS coupling protein (RvhD4) via its proximal C-terminal sequence. RalF is expressed early during infection, with its inactivation via antibody blocking significantly reducing R. typhi host cell invasion. For R. typhi and R. felis (Transitional Group), RalF ectopic expression revealed subcellular localization with the host plasma membrane and actin cytoskeleton. Remarkably, R. bellii (Ancestral Group) RalF showed perinuclear localization reminiscent of ectopically expressed Legionella RalF, for which it shares several structural features. For R. typhi, RalF co-localization with Arf6 and PI(4,5)P2 at entry foci on the host plasma membrane was determined to be critical for invasion. Thus, we propose recruitment of PI(4,5)P2 at entry foci, mediated by RalF activation of Arf6, initiates actin remodeling and ultimately facilitates bacterial invasion. Collectively, our characterization of RalF as an invasin suggests that, despite carrying a similar Arf-GEF unknown from other bacteria, different intracellular lifestyles across Rickettsia and Legionella species have driven divergent roles for Ral

  2. RHGF-2 Is an Essential Rho-1 Specific RhoGEF that binds to the Multi-PDZ Domain Scaffold Protein MPZ-1 in Caenorhabditis elegans

    PubMed Central

    Lin, Li; Tran, Thuy; Hu, Shuang; Cramer, Todd; Komuniecki, Richard; Steven, Robert M.

    2012-01-01

    RhoGEF proteins activate the Rho family of small GTPases and thus play a key role in regulating fundamental cellular processes such as cell morphology and polarity, cell cycle progression and gene transcription. We identified a Caenorhabditis elegans RhoGEF protein, RHGF-2, as a binding partner of the C. elegans multi-PDZ domain scaffold protein MPZ-1 (MUPP1 in mammals). RHGF-2 exhibits significant identity to the mammalian RhoGEFs PLEKHG5/Tech/Syx and contains a class I C-terminal PDZ binding motif (SDV) that interacts most strongly to MPZ-1 PDZ domain eight. RHGF-2 RhoGEF activity is specific to the C. elegans RhoA homolog RHO-1 as determined by direct binding, GDP/GTP exchange and serum response element-driven reporter activity. rhgf-2 is an essential gene since rhgf-2 deletion mutants do not elongate during embryogenesis and hatch as short immobile animals that arrest development. Interestingly, the expression of a functional rhgf-2::gfp transgene appears to be exclusively neuronal and rhgf-2 overexpression results in loopy movement with exaggerated body bends. Transient expression of RHGF-2 in N1E-115 neuroblastoma cells prevents neurite outgrowth similar to constitutive RhoA activation in these cells. Together, these observations indicate neuronally expressed RHGF-2 is an essential RHO-1 specific RhoGEF that binds most strongly to MPZ-1 PDZ domain eight and is required for wild-type C. elegans morphology and growth. PMID:22363657

  3. Characterization of the activation of small GTPases by their GEFs on membranes using artificial membrane tethering.

    PubMed

    Peurois, François; Veyron, Simon; Ferrandez, Yann; Ladid, Ilham; Benabdi, Sarah; Zeghouf, Mahel; Peyroche, Gérald; Cherfils, Jacqueline

    2017-03-23

    Active, GTP-bound small GTPases need to be attached to membranes by post-translational lipid modifications in order to process and propagate information in cells. However, generating and manipulating lipidated GTPases has remained difficult, which has limited our quantitative understanding of their activation by guanine nucleotide exchange factors (GEFs) and their termination by GTPase-activating proteins. Here, we replaced the lipid modification by a histidine tag in 11 full-length, human small GTPases belonging to the Arf, Rho and Rab families, which allowed to tether them to nickel-lipid-containing membranes and characterize the kinetics of their activation by GEFs. Remarkably, this strategy uncovered large effects of membranes on the efficiency and/or specificity in all systems studied. Notably, it recapitulated the release of autoinhibition of Arf1, Arf3, Arf4, Arf5 and Arf6 GTPases by membranes and revealed that all isoforms are efficiently activated by two GEFs with different regulatory regimes, ARNO and Brag2. It demonstrated that membranes stimulate the GEF activity of Trio toward RhoG by ∼30 fold and Rac1 by ∼10 fold, and uncovered a previously unknown broader specificity toward RhoA and Cdc42 that was undetectable in solution. Finally, it demonstrated that the exceptional affinity of the bacterial RabGEF DrrA for the phosphoinositide PI(4)P delimits the activation of Rab1 to the immediate vicinity of the membrane-bound GEF. Our study thus validates the histidine-tag strategy as a potent and simple means to mimic small GTPase lipidation, which opens a variety of applications to uncover regulations brought about by membranes. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  4. Emerging Communication Technologies (ECT) Phase 2 Report. Volume 3; Ultra Wideband (UWB) Technology

    NASA Technical Reports Server (NTRS)

    Bastin, Gary L.; Harris, William G.; Chiodini, Robert; Nelson, Richard A.; Huang, PoTien; Kruhm, David A.

    2003-01-01

    The Emerging Communication Technology (ECT) project investigated three First Mile communication technologies in support of NASA s Second Generation Reusable Launch Vehicle (2nd Gen RLV), Orbital Space Plane, Advanced Range Technology Working Group (ARTWG) and the Advanced Spaceport Technology Working Group (ASTWG). These First Mile technologies have the purpose of interconnecting mobile users with existing Range Communication infrastructures. ECT was a continuation of the Range Information System Management (RISM) task started in 2002. RISM identified the three advance communication technologies investigated under ECT. These were Wireless Ethernet (Wi-Fi), Free Space Optics (FSO), and Ultra Wideband (UWB). Due to the report s size, it has been broken into three volumes: 1) Main Report 2) Appendices 3) UWB

  5. Benefits of Returning to Work After ECT.

    PubMed

    Berg, John Erik

    2013-03-01

    Severe unipolar or bipolar depression is often not helped by pharmacotherapy and/or psychotherapeutic treatment alone, whereas more than 80% of these patients remit after sessions of electroconvulsive treatment (ECT). Getting patients back to work after a severe depression may be important for maintaining the effect of ECT. Twenty consecutive patients remitted to an acute psychiatric hospital for depression underwent ECT. None of the patients had been working before the inpatient stay. Four patients were living on a permanent sickness allowance from the State (invalidity pension) before ECT, and thus were not expected to start work thereafter. Ten of the patients returned to work. Hospital treatment in Norway (including ECT) is provided free of charge with no copayments from the patient. The mean length of sick leave before ECT was 14.7 months. The 10 patients who returned to work had accrued public costs before their inpatient stays totalling NOK (Norwegian krone) 2,994,635 or a mean of NOK 299,463 per patient (&OV0556;1 = 9 NOK or $1 = 6 NOK ). The total public cost of their inpatient stays was NOK 1,680,000. During the first year after ECT, these 10 patients received NOK 2,680,000 in wages (NOK 3,238,300 during the mean number of months they were observed). Most of the patients (10 of 16) receiving ECT returned to work and within 2 years had earned more than the total cost both of their sick leave before admittance to hospital and the public cost of their 4 weeks' inpatient treatment. It is a pity that many countries, including Norway, only allow ECT as a treatment of last resort after failed psychotherapy or pharmacotherapy. Higher public spending is an inadvertent result of such a policy toward ECT.

  6. Specific retention of the protostome-specific PsGEF may parallel with the evolution of mushroom bodies in insect and lophotrochozoan brains.

    PubMed

    Higuchi, Nozomu; Kohno, Keigo; Kadowaki, Tatsuhiko

    2009-05-07

    Gene gain and subsequent retention or loss during evolution may be one of the underlying mechanisms involved in generating the diversity of metazoan nervous systems. However, the causal relationships acting therein have not been studied extensively. We identified the gene PsGEF (protostome-specific GEF), which is present in all the sequenced genomes of insects and limpet but absent in those of sea anemones, deuterostomes, and nematodes. In Drosophila melanogaster, PsGEF encodes a short version of a protein with the C2 and PDZ domains, as well as a long version with the C2, PDZ, and RhoGEF domains through alternative splicing. Intriguingly, the exons encoding the RhoGEF domain are specifically deleted in the Daphnia pulex genome, suggesting that Daphnia PsGEF contains only the C2 and PDZ domains. Thus, the distribution of PsGEF containing the C2, PDZ, and RhoGEF domains among metazoans appears to coincide with the presence of mushroom bodies. Mushroom bodies are prominent neuropils involved in the processing of multiple sensory inputs as well as associative learning in the insect, platyhelminth, and annelid brains. In the adult Drosophila brain, PsGEF is expressed in mushroom bodies, antennal lobe, and optic lobe, where it is necessary for the correct axon branch formation of alpha/beta neurons in mushroom bodies. PsGEF genetically interacts with Rac1 but not other Rho family members, and the RhoGEF domain of PsGEF induces actin polymerization in the membrane, thus resulting in the membrane ruffling that is observed in cultured cells with activated forms of Rac. The specific acquisition of PsGEF by the last common ancestor of protostomes followed by its retention or loss in specific animal species during evolution demonstrates that there are some structural and/or functional features common between insect and lophotrochozoan nervous systems (for example, mushroom bodies), which are absent in all deuterostomes and cnidarians. PsGEF is therefore one of genes

  7. The Anaesthetic-ECT Time Interval in Electroconvulsive Therapy Practice--Is It Time to Time?

    PubMed

    Gálvez, Verònica; Hadzi-Pavlovic, Dusan; Wark, Harry; Harper, Simon; Leyden, John; Loo, Colleen K

    2016-01-01

    Because most common intravenous anaesthetics used in ECT have anticonvulsant properties, their plasma-brain concentration at the time of seizure induction might affect seizure expression. The quality of ECT seizure expression has been repeatedly associated with efficacy outcomes. The time interval between the anaesthetic bolus injection and the ECT stimulus (anaesthetic-ECT time interval) will determine the anaesthetic plasma-brain concentration when the ECT stimulus is administered. The aim of this study was to examine the effect of the anaesthetic-ECT time interval on ECT seizure quality and duration. The anaesthetic-ECT time interval was recorded in 771 ECT sessions (84 patients). Right unilateral brief pulse ECT was applied. Anaesthesia given was propofol (1-2 mg/kg) and succinylcholine (0.5-1.0 mg/kg). Seizure quality indices (slow wave onset, amplitude, regularity, stereotypy and post-ictal suppression) and duration were rated through a structured rating scale by a single blinded trained rater. Linear Mixed Effects Models analysed the effect of the anaesthetic-ECT time interval on seizure quality indices, controlling for propofol dose (mg), ECT charge (mC), ECT session number, days between ECT, age (years), initial seizure threshold (mC) and concurrent medication. Longer anaesthetic-ECT time intervals lead to significantly higher quality seizures (p < 0.001 for amplitude, regularity, stereotypy and post-ictal suppression). These results suggest that the anaesthetic-ECT time interval is an important factor to consider in ECT practice. This time interval should be extended to as long as practically possible to facilitate the production of better quality seizures. Close collaboration between the anaesthetist and the psychiatrist is essential. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Battery for ECT Related Cognitive Deficits (B4ECT-ReCoDe): development and validation.

    PubMed

    Viswanath, Biju; Harihara, Shashidhara N; Nahar, Abhinav; Phutane, Vivek Haridas; Taksal, Aarati; Thirthalli, Jagadisha; Gangadhar, Bangalore N

    2013-06-01

    The use of electroconvulsive therapy (ECT) in treatment of psychiatric disorders is associated with adverse cognitive effects. There is a need to develop a short assessment tool of cognitive functions during the course of ECT. This study aimed at developing and validating a short, sensitive battery to assess cognitive deficits associated with ECT in India. Battery for ECT Related Cognitive Deficits (B4ECT-ReCoDe), a brief cognitive battery (20-30 min) to assess verbal, visual, working and autobiographic memory, sustained attention, psychomotor speed and subjective memory impairment, was administered to 30 in-patients receiving bilateral ECT, one day after the 1st, 3rd and 6th ECT. Data was analysed using repeated measures analysis of variance and Pearson's correlation. Significant deficits were found in verbal, visual and autobiographic memory, psychomotor speed. Subjective experience of memory loss correlated positively with verbal memory impairment. B4ECT-ReCoDe, a brief, sensitive measure of cognitive impairments associated with ECT can be used in routine clinical practice. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Trio’s Rho-specific GEF domain is the missing Gαq effector in C. elegans

    PubMed Central

    Williams, Stacey L.; Lutz, Susanne; Charlie, Nicole K.; Vettel, Christiane; Ailion, Michael; Coco, Cassandra; Tesmer, John J.G.; Jorgensen, Erik M.; Wieland, Thomas; Miller, Kenneth G.

    2007-01-01

    The Gαq pathway is essential for animal life and is a central pathway for driving locomotion, egg laying, and growth in Caenorhabditis elegans, where it exerts its effects through EGL-8 (phospholipase Cβ [PLCβ]) and at least one other effector. To find the missing effector, we performed forward genetic screens to suppress the slow growth and hyperactive behaviors of mutants with an overactive Gαq pathway. Four suppressor mutations disrupted the Rho-specific guanine-nucleotide exchange factor (GEF) domain of UNC-73 (Trio). The mutations produce defects in neuronal function, but not neuronal development, that cause sluggish locomotion similar to animals lacking EGL-8 (PLCβ). Strains containing null mutations in both EGL-8 (PLCβ) and UNC-73 (Trio RhoGEF) have strong synthetic phenotypes that phenocopy the arrested growth and near-complete paralysis of Gαq-null mutants. Using cell-based and biochemical assays, we show that activated C. elegans Gαq synergizes with Trio RhoGEF to activate RhoA. Activated Gαq and Trio RhoGEF appear to be part of a signaling complex, because they coimmunoprecipitate when expressed together in cells. Our results show that Trio’s Rho-specific GEF domain is a major Gαq effector that, together with PLCβ, mediates the Gαq signaling that drives the locomotion, egg laying, and growth of the animal. PMID:17942708

  10. A comparison of RUL ultrabrief pulse (0.3 ms) ECT and standard RUL ECT.

    PubMed

    Loo, Colleen K; Sainsbury, Kirby; Sheehan, Patrick; Lyndon, Bill

    2008-11-01

    An important goal in electroconvulsive therapy (ECT) research is to minimize associated cognitive side-effects while maintaining its high efficacy. This study explored the use of a novel approach, right unilateral (RUL) ECT with an ultrabrief pulsewidth (0.3 ms) (RUL-UB), in comparison with standard RUL ECT. Seventy-four depressed in-patients received RUL-UB ECT at six times seizure threshold, and 22 patients received standard RUL ECT (1.0 ms pulsewidth) at five times seizure threshold. Formal, prospective evaluations of mood and cognitive functioning over the treatment course were done by a rater blinded to treatment condition. Efficacy was maintained using the ultrabrief pulsewidth, with equivalent numbers of responders and remitters to the standard RUL ECT group, although the speed of response was slower. Cognitive outcomes were superior in the RUL-UB ECT group, particularly in the retention of verbal and visual information, as well as in retrograde autobiographical memory.

  11. Signaling efficiency of Gαq through its effectors p63RhoGEF and GEFT depends on their subcellular location.

    PubMed

    Goedhart, Joachim; van Unen, Jakobus; Adjobo-Hermans, Merel J W; Gadella, Theodorus W J

    2013-01-01

    The p63RhoGEF and GEFT proteins are encoded by the same gene and both members of the Dbl family of guanine nucleotide exchange factors. These proteins can be activated by the heterotrimeric G-protein subunit Gαq. We show that p63RhoGEF is located at the plasma membrane, whereas GEFT is confined to the cytoplasm. Live-cell imaging studies yielded quantitative information on diffusion coefficients, association rates and encounter times of GEFT and p63RhoGEF. Calcium signaling was examined as a measure of the signal transmission, revealing more efficient signaling through the membrane-associated p63RhoGEF. A rapamycin dependent recruitment system was used to dynamically alter the subcellular location and concentration of GEFT, showing efficient signaling through GEFT only upon membrane recruitment. Together, our results show efficient signal transmission through membrane located effectors, and highlight a role for increased concentration rather than increased encounter times due to membrane localization in the Gαq mediated pathways to p63RhoGEF and PLCβ.

  12. Audit of thrice- versus twice-weekly ECT.

    PubMed

    Roche, Eric; Lope, Jasmin; Hughes, Helen; McCullagh, Niamh; Larkin, Terence; Feeney, Larkin

    2012-09-01

    There is a lack of knowledge regarding some basic differences between different electroconvulsive therapy (ECT) treatment schedules. To examine differences, including ECT technical parameters and length of stay, between thrice- and twice-weekly ECT treatment schedules. Prospective audit of the changeover period of administering thrice- to twice-weekly ECT in a Dublin psychiatric hospital. Twice-weekly ECT was associated with significantly lower total electricity dosage administered, a tendency toward shorter overall hospital stay and fewer ECT treatments compared to thrice-weekly ECT. Our results support the current international trend toward giving ECT twice weekly.

  13. Does remifentanil improve ECT seizure quality?

    PubMed

    Gálvez, Verònica; Tor, Phern-Chern; Bassa, Adriana; Hadzi-Pavlovic, Dusan; MacPherson, Ross; Marroquin-Harris, Mincho; Loo, Colleen K

    2016-12-01

    Studies have reported that co-adjuvant remifentanil can enhance electroconvulsive therapy (ECT) seizure quality, putatively by allowing a reduction in the dosage of the main anaesthetic agents, as the latter have anticonvulsant properties. However, whether remifentanil also has direct effects on ECT seizure quality, and by implication, treatment efficacy, is unknown. This is the first study examining the effect of adjuvant remifentanil on ECT seizure quality when the dose of conventional anaesthesia remained unchanged. A total of 96 ECT sessions (from 36 patients) were retrospectively analysed. Subjects received ECT with and without remifentanil (1 µg/kg), while the dose of thiopentone (3-5 mg/kg) or propofol (1-2 mg/kg) was unchanged. Seizure quality indices (time to slow wave activity or TSLOW, amplitude, regularity, stereotypy, post-ictal suppression) and duration were assessed through a structured rating scale by a single trained blinded rater. Linear mixed-effects models with random subject effects analysed the effect of remifentanil on seizure parameters, controlling for other variables that can affect seizure quality or duration. Remifentanil was given in 47.9 % of the ECT sessions. Co-adjuvant remifentanil had no effects on any of the seizure quality parameters analysed [TSLOW (E = -0.21, p > 0.1), amplitude (E = 0.08, p > 0.5), regularity (E = -0.05, p > 0.5), stereotypy (E = -0.02, p > 0.5), suppression (E = -0.3, p > 0.05)] or on seizure duration (E = -0.25, p > 0.1). While adjuvant remifentanil may be a useful strategy for reducing anaesthetic dosage in ECT, present evidence suggests that remifentanil does not have intrinsic properties that enhance ECT seizures.

  14. Environmental control technology (ECT) for geothermal processes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Katz, G.

    1982-01-01

    The objectives of the environmental control technology (ECT) program are to develop research priorities, research new and alternative technologies and to improve economics and performance of ECT systems. The Interagency Geothermal Coordinating Council, Environmental Control Panel developed priorities and obtained industry input during 1980. H/sub 2/S controls, injection monitoring, solid waste characterization and control and subsidence were reviewed as high priority while noise controls were considered low priority. Since geothermal technology is still developing there is a need to continue researching new and alternative ECT. Often ECT systems must be designed for site specific applications and need modification for usemore » of other sites. Most of the US geothermal experience is found at the Geysers, California where H/sub 2/S abatement is required. Various systems have been tested with mixed results. The bottom line is that the economics and performance of H/sub 2/S abatement systems are less than desirable.« less

  15. GSK-3Beta-Dependent Activation of GEF-H1/ROCK Signaling Promotes LPS-Induced Lung Vascular Endothelial Barrier Dysfunction and Acute Lung Injury.

    PubMed

    Yi, Lei; Huang, Xiaoqin; Guo, Feng; Zhou, Zengding; Chang, Mengling; Huan, Jingning

    2017-01-01

    The bacterial endotoxin or lipopolysaccharide (LPS) leads to the extensive vascular endothelial cells (EC) injury under septic conditions. Guanine nucleotide exchange factor-H1 (GEF-H1)/ROCK signaling not only involved in LPS-induced overexpression of pro-inflammatory mediator in ECs but also implicated in LPS-induced endothelial hyper-permeability. However, the mechanisms behind LPS-induced GEF-H1/ROCK signaling activation in the progress of EC injury remain incompletely understood. GEF-H1 localized on microtubules (MT) and is suppressed in its MT-bound state. MT disassembly promotes GEF-H1 release from MT and stimulates downstream ROCK-specific GEF activity. Since glycogen synthase kinase (GSK-3beta) participates in regulating MT dynamics under pathologic conditions, we examined the pivotal roles for GSK-3beta in modulating LPS-induced activation of GEF-H1/ROCK, increase of vascular endothelial permeability and severity of acute lung injury (ALI). In this study, we found that LPS induced human pulmonary endothelial cell (HPMEC) monolayers disruption accompanied by increase in GSK-3beta activity, activation of GEF-H1/ROCK signaling and decrease in beta-catenin and ZO-1 expression. Inhibition of GSK-3beta reduced HPMEC monolayers hyper-permeability and GEF-H1/ROCK activity in response to LPS. GSK-3beta/GEF-H1/ROCK signaling is implicated in regulating the expression of beta-catenin and ZO-1. In vivo , GSK-3beta inhibition attenuated LPS-induced activation of GEF-H1/ROCK pathway, lung edema and subsequent ALI. These findings present a new mechanism of GSK-3beta-dependent exacerbation of lung micro-vascular hyper-permeability and escalation of ALI via activation of GEF-H1/ROCK signaling and disruption of intracellular junctional proteins under septic condition.

  16. The Amino-Terminus of Vav1 Regulates TCR-Induced SLP-76 Microclusters via the Calponin Homology Domain and Non-Catalytic Surfaces within the GEF Module

    PubMed Central

    Sylvain, Nicholas R.; Nguyen, Ken; Bunnell, Stephen C.

    2013-01-01

    The guanine nucleotide exchange factor (GEF) Vav1 synergizes with the adapter SLP-76 to support T cell development and activation. Here, we demonstrate that Vav1 controls the stability and movement T cell receptor-induced SLP-76 microclusters. The SH2 domain enables the recruitment of Vav1 into SLP-76 microclusters, whereas the SH3 domains of Vav1 cooperate to enhance microcluster stability and function. Although the amino-terminus of Vav1 is essential for downstream signaling, it possesses novel scaffolding functions that are unaffected by the inactivation of the Vav1 GEF or by the constitutive GEF activation that accompanies the mutation of the regulatory tyrosine residues 142, 160, and 174. In contrast, GEF-inactivating point mutations predicted to perturb the structural integrity of the Vav1 GEF abolish these scaffolding functions. Paradoxically, the excision of catalytic Dbl-homology (DH) / pleckstrin homology (PH) cassette produces a relatively mild scaffolding defect, indicating that the L213A and L278Q point mutations antagonize scaffolding functions mediated by adjacent domains. A deletion mutant lacking the CH domain potently inhibits calcium responses, but also exhibits mild scaffolding defects. We conclude multiple GEF-independent scaffolding functions contained within the amino-terminus of Vav1 contribute to T cell activation by acting synergistically to increase the stability and functionality of SLP-76 microclusters. PMID:21386095

  17. The amino acid motif L/IIxxFE defines a novel actin-binding sequence in PDZ-RhoGEF

    PubMed Central

    Banerjee, Jayashree; Fischer, Christopher C.; Wedegaertner, Philip B.

    2009-01-01

    PDZ-RhoGEF is a member of the regulator of G protein signaling (RGS) domain-containing RhoGEFs (RGS-RhoGEFs) that link activated heterotrimeric G protein α subunits of the G12 family to activation of the small GTPase RhoA. Unique among the RGS-RhoGEFs, PDZ-RhoGEF contains a short sequence that localizes the protein to the actin cytoskeleton. In this report, we demonstrate that the actin-binding domain, located between amino acids 561–585, directly binds to F-actin in vitro. Extensive mutagenesis identifies isoleucine 568, isoleucine 569, phenylalanine 572, and glutamic acid 573 as necessary for binding to actin and for co-localization with the actin cytoskeleton in cells. These results define a novel actin-binding sequence in PDZ-RhoGEF with a critical amino acid motif of IIxxFE. Moreover, sequence analysis identifies a similar actin-binding motif in the N-terminus of the RhoGEF frabin, and, as with PDZ-RhoGEF, mutagenesis and actin interaction experiments demonstrate a motif of LIxxFE, consisting of the key amino acids leucine 23, isoleucine 24, phenylalanine 27, and glutamic acid 28. Taken together, results with PDZ-RhoGEF and frabin identify a novel actin binding sequence. Lastly, inducible dimerization of the actin-binding region of PDZ-RhoGEF revealed a dimerization-dependent actin bundling activity in vitro. PDZ-RhoGEF exists in cells as a dimer, raising the possibility that PDZ-RhoGEF could influence actin structure independent of its ability to activate RhoA. PMID:19618964

  18. ECT-Related Anxiety: A Systematic Review.

    PubMed

    Obbels, Jasmien; Verwijk, Esmée; Bouckaert, Filip; Sienaert, Pascal

    2017-12-01

    A significant proportion of electroconvulsive therapy (ECT)-treated patients experience anxiety anticipating the treatment, often to such an extent that they refuse or discontinue a much-needed treatment. Despite its great impact on treatment adherence, anxiety in patients receiving ECT is underexposed in the scientific literature. We aimed to review the prevalence and specific subjects of ECT-related anxiety and therapeutic interventions to reduce it. We performed a computerized search (EMBASE, MEDLINE, and PsycINFO) for articles meeting the following inclusion criteria: (1) qualitative (interview) studies, quantitative (questionnaire) studies, or experimental (interventional) studies that (2) report on anxiety that is related to a planned, ongoing, or past ECT treatment. Of 1160 search results, 31 articles were included. Electroconvulsive therapy-related anxiety is estimated to be present in 14% to 75% of patients and is most often linked to worries about memory impairment or brain damage. Only a few interventions (chlorpromazine, meprobamate, propofol, a talking-through technique, an information leaflet, and animal-assisted therapy) have been proposed to reduce patients' ECT-related anxiety. Electroconvulsive therapy-related anxiety is a highly prevalent phenomenon, and the literature provides little guidance for its clinical management. Most studies are of a low methodological quality and suffer from significant limitations, thereby hampering generalized conclusions. Given the clinical importance of ECT-related anxiety, further study on its nature and evolution through the course of treatment and on anxiety-reducing interventions is warranted.

  19. The Impact of A "Brief ECT Orientation Module" on The Knowledge and Attitudes of Medical Students Towards ECT in India.

    PubMed

    Balhara, Yps; Yadav, T; Mathur, S; Kataria, Dk

    2012-07-01

    Electroconvulsive therapy (ECT) continues to be an intervention that attracts controversy in spite of its proven efficacy. There is limited literature on attitude and knowledge of medical students towards ECT from Asian and African countries. The current study assesses the impact of a "Brief ECT Orientation Module" on the knowledge of and attitudes of Indian medical students towards modified ECT. The study was conducted at a tertiary care multi-specialty hospital associated with a government medical college. The students were administered the study questionnaire on Day 1 of Psychiatry clerkship. Following this, they were administered the Brief ECT Orientation Module. Assessment was made using a questionnaire with items related to knowledge and attitude towards ECT before and after "Brief ECT Orientation Module." Fifty-nine students completed the study. There was a significant improvement in knowledge of medical students on all the three domains of the questionnaire for assessment of knowledge about ECT-related facts. A change in attitudes towards ECT was also observed following Brief ECT Orientation Module, especially among those who witnessed ECT administration. The findings of the current study suggest that the Brief ECT Orientation Module is effective in improving the knowledge and attitude of medical students towards ECT.

  20. The Tea4-PP1 landmark promotes local growth by dual Cdc42 GEF recruitment and GAP exclusion.

    PubMed

    Kokkoris, Kyriakos; Gallo Castro, Daniela; Martin, Sophie G

    2014-05-01

    Cell polarization relies on small GTPases, such as Cdc42, which can break symmetry through self-organizing principles, and landmarks that define the axis of polarity. In fission yeast, microtubules deliver the Tea1-Tea4 complex to mark cell poles for growth, but how this complex activates Cdc42 is unknown. Here, we show that ectopic targeting of Tea4 to cell sides promotes the local activation of Cdc42 and cell growth. This activity requires that Tea4 binds the type I phosphatase (PP1) catalytic subunit Dis2 or Sds21, and ectopic targeting of either catalytic subunit is similarly instructive for growth. The Cdc42 guanine-nucleotide-exchange factor Gef1 and the GTPase-activating protein Rga4 are required for Tea4-PP1-dependent ectopic growth. Gef1 is recruited to ectopic Tea4 and Dis2 locations to promote Cdc42 activation. By contrast, Rga4 is locally excluded by Tea4, and its forced colocalization with Tea4 blocks ectopic growth, indicating that Rga4 must be present, but at sites distinct from Tea4. Thus, a Tea4-PP1 landmark promotes local Cdc42 activation and growth both through Cdc42 GEF recruitment and by creating a local trough in a Cdc42 GAP.

  1. Poor health-related quality of life prior to ECT in depressed patients normalizes with sustained remission after ECT.

    PubMed

    McCall, W Vaughn; Reboussin, David; Prudic, Joan; Haskett, Roger F; Isenberg, Keith; Olfson, Mark; Rosenquist, Peter B; Sackeim, Harold A

    2013-05-01

    Health-related quality of life (HRQOL) is diminished in depressed adult outpatients and especially impaired among depressed patients referred for ECT. We compare pretreatment HRQOL in ECT and non-ECT depressed patients from two large samples, and examined whether sustained remission in depressive symptoms after ECT is associated with normalization of HRQOL. HRQOL was measured with the Medical Outcomes Study Short Form 36 (SF36) before ECT and 6 months after ECT in an effectiveness (n=286) and an efficacy (n=243) clinical trial. ECT patients had very low baseline SF36 scores. With one exception, SF36 subscale scores in both trials were significantly lower than those of depressed outpatients. A minority of patients in both trials entered and sustained remission over the 24 week timeframe. Among sustained remitters, average SF36 scores were no different from normative scores of the general adult population, except that in the effectiveness study ECT patients reported less Bodily Pain (p<0.05) and better Mental Health (p<0.05), while in the efficacy study ECT patients reported more difficulty with Role-Emotional (p<0.01). Only a modest number of patients were observed in sustained remission. HRQOL is very poor in patients referred for ECT. Depressed patients who experience sustained remission after ECT, however, can expect improvement in their quality of life that leaves many in a position indistinguishable from the general adult population. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Poor health-related quality of life prior to ECT in depressed patients normalizes with sustained remission after ECT

    PubMed Central

    McCall, W. Vaughn; Reboussin, David; Prudic, Joan; Haskett, Roger F.; Isenberg, Keith; Olfson, Mark; Rosenquist, Peter B.; Sackeim, Harold A

    2012-01-01

    Background Health-related quality of life (HRQOL) is diminished in depressed adult outpatients and especially impaired among depressed patients referred for ECT. We compare pretreatment HRQOL in ECT and non-ECT depressed patients from two large samples, and examined whether sustained remission in depressive symptoms after ECT is associated with normalization of HRQOL. Methods HRQOL was measured with the Medical Outcomes Study Short Form 36 (SF36) before ECT and 6 months after ECT in an effectiveness (n=286) and an efficacy (n=243) clinical trial. Results ECT patients had very low baseline SF36 scores. With one exception, SF36 subscale scores in both trials were significantly lower than those of depressed outpatients. A minority of patients in both trials entered and sustained remission over the 24 week timeframe. Among sustained remitters, average SF36 scores were no different from normative scores of the general adult population, except that in the effectiveness study ECT patients reported less Bodily Pain (p<0.05) and better Mental Health (p<0.05), while in the efficacy study ECT patients reported more difficulty with Role-Emotional. (p<0.01) Limitations Only a modest number of patients were observed in sustained remission. Conclusions HRQOL is very poor in patients referred for ECT. Depressed patients who experience sustained remission after ECT, however, can expect improvement in their quality of life that leaves many in a position indistinguishable from the general adult population. PMID:23158959

  3. Study protocol for the randomised controlled trial: Ketamine augmentation of ECT to improve outcomes in depression (Ketamine-ECT study).

    PubMed

    Trevithick, Liam; McAllister-Williams, R Hamish; Blamire, Andrew; Branton, Tim; Clark, Ross; Downey, Darragh; Dunn, Graham; Easton, Andrew; Elliott, Rebecca; Ellwell, Clare; Hayden, Katherine; Holland, Fiona; Karim, Salman; Lowe, Jo; Loo, Colleen; Nair, Rajesh; Oakley, Timothy; Prakash, Antony; Sharma, Parveen K; Williams, Stephen R; Anderson, Ian M

    2015-10-21

    There is a robust empirical evidence base supporting the acute efficacy of electroconvulsive therapy (ECT) for severe and treatment resistant depression. However, a major limitation, probably contributing to its declining use, is that ECT is associated with impairment in cognition, notably in anterograde and retrograde memory and executive function. Preclinical and preliminary human data suggests that ketamine, used either as the sole anaesthetic agent or in addition to other anaesthetics, may reduce or prevent cognitive impairment following ECT. A putative hypothesis is that ketamine, through antagonising glutamate receptors, protects from excess excitatory neurotransmitter stimulation during ECT. The primary aim of the ketamine-ECT study is to investigate whether adjunctive ketamine can attenuate the cognitive impairment caused by ECT. Its secondary aim is to examine if ketamine increases the speed of clinical improvement with ECT. The ketamine ECT study is a multi-site randomised, placebo-controlled, double blind trial. It was originally planned to recruit 160 moderately to severely depressed patients who had been clinically prescribed ECT. This recruitment target was subsequently revised to 100 patients due to recruitment difficulties. Patients will be randomly allocated on a 1:1 basis to receive either adjunctive ketamine or saline in addition to standard anaesthesia for ECT. The primary neuropsychological outcome measure is anterograde verbal memory (Hopkins Verbal Learning Test-Revised delayed recall task) after 4 ECT treatments. Secondary cognitive outcomes include verbal fluency, autobiographical memory, visuospatial memory and digit span. Efficacy is assessed using observer and self-report efficacy measures of depressive symptomatology. The effects of ECT and ketamine on cortical activity during cognitive tasks will be studied in a sub-sample using functional near-infrared spectroscopy (fNIRS). The ketamine-ECT study aims to establish whether or not

  4. Bilateral ECT induces bilateral increases in regional cortical thickness.

    PubMed

    van Eijndhoven, P; Mulders, P; Kwekkeboom, L; van Oostrom, I; van Beek, M; Janzing, J; Schene, A; Tendolkar, I

    2016-08-23

    Electroconvulsive therapy (ECT) is the most effective treatment for patients suffering from severe or treatment-resistant major depressive disorder (MDD). Unfortunately its underlying neurobiological mechanisms are still unclear. One line of evidence indicates that the seizures produced by ECT induce or stimulate neuroplasticity effects. Although these seizures also affect the cortex, the effect of ECT on cortical thickness is not investigated until now. We acquired structural magnetic resonance imaging data in 19 treatment-resistant MDD patients before and after a bilateral ECT course, and 16 healthy controls at 2 time points, and compared changes in cortical thickness between the groups. Our results reveal that ECT induces significant, bilateral increases in cortical thickness, including the temporal pole, inferior and middle temporal cortex and the insula. The pattern of increased cortical thickness was predominant in regions that are associated with seizure onset in ECT. Post hoc analyses showed that the increase in thickness of the insular cortex was larger in responders than in non-responders, which may point to a specific relationship of this region with treatment effects of ECT.

  5. Practical considerations in the use of ultrabrief ECT in clinical practice.

    PubMed

    Galletly, Cherrie; Clarke, Patrick; Paterson, Tom; Rigby, Ashlee; Gill, Shane

    2014-03-01

    Electroconvulsive therapy (ECT) is the most effective treatment for major depression. Brief pulse width (BPW; pulse width, 1.0 m/s) ECT is often associated with cognitive impairment. Ultrabrief (UB; pulse width, 0.3 m/s) ECT is better tolerated and causes less cognitive impairment so has been introduced as an alternative. Previous research has shown that more treatments are needed with UB ECT; however, there has not been any previous research into the impact of prescribing UB ECT on length of stay. This study reports naturalistic data collected from 258 inpatients in a private psychiatric hospital for 2 years since the introduction of UB ECT. Clinician and self-rated scales of depression severity and hospital service data were used to evaluate the number of ECT treatments, length of stay, and efficacy. Patients prescribed UB ECT had, on average, 10.9 treatments compared to 8.8 for BPW ECT. They also spent more time in hospital; 30.3 days from the first ECT treatment to discharge compared to 24.7 days for patients prescribed BPW ECT. Excluding patients who switched treatments, 54% of patients prescribed UB ECT responded compared to 66.7% of patients prescribed BPW ECT. More patients (n = 42) switched from UB to BPW than from BPW to UB (n = 3). In the 4 years since the introduction of UB ECT, the number of patients prescribed ECT has increased, and the mean number of treatments per patient (for all patients receiving ECT) has increased from 7.7 to 11.6. Ultrabrief ECT has significant advantages, reflected in the increased use of ECT since UB ECT became available. However, the greater number of treatments and the increased length of stay have important implications for service delivery, costs, and bed accessibility.

  6. Medical student knowledge and attitudes regarding ECT prior to and after viewing ECT scenes from movies.

    PubMed

    Walter, Garry; McDonald, Andrew; Rey, Joseph M; Rosen, Alan

    2002-03-01

    We surveyed samples of medical students in the United Kingdom (U.K.) and Australia, prior to their psychiatry placement, to ascertain views about electroconvulsive therapy (ECT) and the effect on those views of watching ECT scenes in movies. A 26-item questionnaire was constructed by the authors and administered to the students. At set times during the questionnaire, students were asked to view five movie clips showing, or making reference to, ECT. The clips were from Return to Oz, The Hudsucker Proxy, Ordinary People, One Flew Over the Cuckoo's Nest, and Beverly Hillbillies. Ninety-four students participated in the study. Levels of knowledge about the indications, side effects, and mode of administration were poor, and attitudes were generally negative. Viewing the ECT scenes influenced attitudes toward the treatment; after viewing, one-third of the students decreased their support for ECT, and the proportion of students who would dissuade a family member or friend from having ECT rose from less than 10% to almost 25%.

  7. Activation of p115-RhoGEF Requires Direct Association of G[alpha subscript 13] and the Dbl Homology Domain

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chen, Zhe; Guo, Liang; Hadas, Jana

    2012-09-05

    RGS-containing RhoGEFs (RGS-RhoGEFs) represent a direct link between the G{sub 12} class of heterotrimeric G proteins and the monomeric GTPases. In addition to the canonical Dbl homology (DH) and pleckstrin homology domains that carry out the guanine nucleotide exchange factor (GEF) activity toward RhoA, these RhoGEFs also possess RGS homology (RH) domains that interact with activated {alpha} subunits of G{sub 12} and G{sub 13}. Although the GEF activity of p115-RhoGEF (p115), an RGS-RhoGEF, can be stimulated by G{alpha}{sub 13}, the exact mechanism of the stimulation has remained unclear. Using combined studies with small angle x-ray scattering, biochemistry, and mutagenesis, wemore » identify an additional binding site for activated G{alpha}{sub 13} in the DH domain of p115. Small angle x-ray scattering reveals that the helical domain of G{alpha}{sub 13} docks onto the DH domain, opposite to the surface of DH that binds RhoA. Mutation of a single tryptophan residue in the {alpha}3b helix of DH reduces binding to activated G{alpha}{sub 13} and ablates the stimulation of p115 by G{alpha}{sub 13}. Complementary mutations at the predicted DH-binding site in the {alpha}B-{alpha}C loop of the helical domain of G{alpha}{sub 13} also affect stimulation of p115 by G{alpha}{sub 13}. Although the GAP activity of p115 is not required for stimulation by G{alpha}{sub 13}, two hydrophobic motifs in RH outside of the consensus RGS box are critical for this process. Therefore, the binding of G{alpha}{sub 13} to the RH domain facilitates direct association of G{alpha}{sub 13} to the DH domain to regulate its exchange activity. This study provides new insight into the mechanism of regulation of the RGS-RhoGEF and broadens our understanding of G protein signaling.« less

  8. The Impact of A “Brief ECT Orientation Module” on The Knowledge and Attitudes of Medical Students Towards ECT in India

    PubMed Central

    Balhara, YPS; Yadav, T; Mathur, S; Kataria, DK

    2012-01-01

    Background: Electroconvulsive therapy (ECT) continues to be an intervention that attracts controversy in spite of its proven efficacy. There is limited literature on attitude and knowledge of medical students towards ECT from Asian and African countries. Aim: The current study assesses the impact of a “Brief ECT Orientation Module” on the knowledge of and attitudes of Indian medical students towards modified ECT. Subjects and Methods: The study was conducted at a tertiary care multi-specialty hospital associated with a government medical college. The students were administered the study questionnaire on Day 1 of Psychiatry clerkship. Following this, they were administered the Brief ECT Orientation Module. Assessment was made using a questionnaire with items related to knowledge and attitude towards ECT before and after “Brief ECT Orientation Module.” Results: Fifty-nine students completed the study. There was a significant improvement in knowledge of medical students on all the three domains of the questionnaire for assessment of knowledge about ECT-related facts. A change in attitudes towards ECT was also observed following Brief ECT Orientation Module, especially among those who witnessed ECT administration. Conclusion: The findings of the current study suggest that the Brief ECT Orientation Module is effective in improving the knowledge and attitude of medical students towards ECT. PMID:23440565

  9. A Steric-inhibition model for regulation of nucleotide exchange via the Dock180 family of GEFs.

    PubMed

    Lu, Mingjian; Kinchen, Jason M; Rossman, Kent L; Grimsley, Cynthia; Hall, Matthew; Sondek, John; Hengartner, Michael O; Yajnik, Vijay; Ravichandran, Kodi S

    2005-02-22

    CDM (CED-5, Dock180, Myoblast city) family members have been recently identified as novel, evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases . They regulate multiple processes, including embryonic development, cell migration, apoptotic-cell engulfment, tumor invasion, and HIV-1 infection, in diverse model systems . However, the mechanism(s) of regulation of CDM proteins has not been well understood. Here, our studies on the prototype member Dock180 reveal a steric-inhibition model for regulating the Dock180 family of GEFs. At basal state, the N-terminal SH3 domain of Dock180 binds to the distant catalytic Docker domain and negatively regulates the function of Dock180. Further studies revealed that the SH3:Docker interaction sterically blocks Rac access to the Docker domain. Interestingly, ELMO binding to the SH3 domain of Dock180 disrupted the SH3:Docker interaction, facilitated Rac access to the Docker domain, and contributed to the GEF activity of the Dock180/ELMO complex. Additional genetic rescue studies in C. elegans suggested that the regulation of the Docker-domain-mediated GEF activity by the SH3 domain and its adjoining region is evolutionarily conserved. This steric-inhibition model may be a general mechanism for regulating multiple SH3-domain-containing Dock180 family members and may have implications for a variety of biological processes.

  10. ECT treatment outcomes following performance improvement changes.

    PubMed

    Pulia, Kathy; Vaidya, Punit; Jayaram, Geetha; Hayat, Matthew J; Reti, Irving M

    2013-11-01

    Differences in electroconvulsive therapy (ECT) outcomes were explored following changes in ECT administration at our institution. Two changes were introduced: (a) switching the anesthetic agent from propofol to methohexital, and (b) using a more aggressive ECT charge dosing regimen for right unilateral (RUL) electrode placement. Length of stay (LOS) and number of treatments administered per patient were monitored. A retrospective analysis was performed of two inpatient groups treated on our Mood Disorders Unit: those who underwent ECT in the 12 months prior to the changes (n = 40) and those who underwent treatment in the 12 months after the changes (n = 38). Compared with patients receiving ECT with RUL placement prior to the changes, patients who received RUL ECT after the changes had a significantly shorter inpatient LOS (27.4 versus 18 days, p = 0.028). Treatment efficacy monitored by the Montgomery Asberg Depression Rating Scale was not impacted. The change in anesthetic agent and charge dosing each accounted for 11% of the variance in LOS among patients receiving RUL ECT. The implemented changes in ECT administration positively impacted outcome for patients receiving treatment with RUL electrode placement. Copyright 2013, SLACK Incorporated.

  11. Emerging Communication Technologies (ECT) Phase 3 Final Report

    NASA Technical Reports Server (NTRS)

    Bastin, Gary L.; Harris, William G.; Bates, Lakesha D.; Nelson, Richard A.

    2004-01-01

    The Emerging Communication Technology (ECT) project investigated three First Mile communication technologies in support of NASA s Second Generation Reusable Launch Vehicle (2nd Gen RLV), Orbital Space Plane, Advanced Range Technology Working Group (ARTWG) and the Advanced Spaceport Technology Working Group (ASTWG). These First Mile technologies have the purpose of interconnecting mobile users with existing Range Communication infrastructures. ECT was a continuation of the Range Information System Management (RISM) task started in 2002. RISM identified the three advance communication technologies investigated under ECT. These were Wireless Ethernet (Wi-Fi), Free Space Optics (FSO), and Ultra Wideband (UWB). Due to the report s size, it has been broken into three volumes: 1) Main Report 2) Appendices 3) UWB.

  12. Short-term effect of ECT in middle-aged and elderly patients with intractable catatonic schizophrenia.

    PubMed

    Suzuki, Kazumasa; Awata, Shuichi; Matsuoka, Hiroo

    2003-06-01

    The management of middle-aged and elderly patients with catatonic schizophrenia has long been a major problem in clinical geriatric psychiatry. Most cases are intractable because of medication resistance, medication intolerance, or severe medical conditions. Electroconvulsive therapy (ECT) is recognized as one of the most efficacious therapies for catatonic schizophrenia. Thus, we conducted a prospective study of the short-term effect of acute ECT on middle-aged and elderly patients with intractable catatonic schizophrenia. Subjects were nine consecutive patients older than 45 years who had fulfilled the DSM-IV criteria for catatonic-type schizophrenia and had been referred for first-time acute ECT after other treatments had failed. The patients were treated at Tohoku University Hospital between January 1998 and March 2002. We evaluated the clinical response of these patients to acute ECT by means of the brief psychiatric rating scale (BPRS). We also evaluated adverse effects of acute ECT. The response rate was 100%. The total BPRS score was improved in all nine subjects at the end of the ECT course and 1 week after the final session in comparison with the total pre-ECT BPRS score (11.9 +/- 7.5 and 9.3 +/- 9.2 versus 57.1 +/- 13.1, respectively, p = 0.008, p = 0.008). The total Global Assessment of Functioning score was also improved significantly (from 10.8 +/- 9.4 just before ECT to 61.6 +/- 18.9 1 week after ECT, p = 0.008). Guy's five factors (thought disturbance, activation, anxiety-depression, hostility-suspiciousness, and anergia) improved significantly (p = 0.008, p = 0.008, p = 0.018, p = 0.012, p = 0.008, respectively). One patient showed supraventricular premature contractions (SVPCs) during an ECT seizure. After some ECT sessions, three patients exhibited mild to moderate delirium that disappeared within 3 days. However, no patient experienced a severe cognitive or physical adverse effect during the course of ECT. Acute ECT has a good short-term effect

  13. Maintenance ECT in schizophrenia: A systematic review.

    PubMed

    Ward, Heather Burrell; Szabo, Steven T; Rakesh, Gopalkumar

    2018-03-20

    Relapse after discontinuation of ECT is significant in patients with schizophrenia. The purpose of this systematic review was to examine use of M-ECT in schizophrenia to guide clinical decision making for relapse prevention in schizophrenia. We reviewed studies examining the role of continuation (C-ECT) and maintenance electroconvulsive therapy (M-ECT) in schizophrenia. Following PRISMA guidelines, we included randomized controlled trials, open label trials, retrospective chart reviews, case reports, and case series in this review. We evaluated adjunctive pharmacological regimens; ECT treatment parameters, including frequency, duration of continued treatment, electrode placement; clinical outcomes including cognitive side effects and relapse rates from included studies. Our findings suggest M-ECT could provide an effective form of relapse prevention in these patients and persistent cognitive side effects are minimal. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Effectiveness of Electroconvulsive Therapy (ECT) in Parkinsonian Symptoms

    PubMed Central

    Somani, Aditya; Sahni, Neeru; Mehta, Sahil; Choudhary, Swati; Chakravarty, Rahul Kumar; Rabha, Anju Moni

    2018-01-01

    Depression is a common comorbidity in patients suffering from Parkinson’s disease (PD). Available evidence suggests that electroconvulsive therapy (ECT) is an effective treatment for depression and also improves symptoms of PD. However, literature on usefulness of ECT in parkinsonian symptoms is limited. A review of records of all patients receiving ECT from 2010 to April 2017 in the authors’ clinic yielded six cases (0.63% of all patients who received ECT at the authors’ center over last 7 years) of depression with PD who were treated with ECT. All six patients had improvement in both depression and symptoms of PD following ECT treatment. The improvement achieved with ECT was sustained in four patients. Worsening of PD symptoms 3 to 4 months post-treatment was seen in two patients. ECT appears to be an effective treatment option for management of motoric symptoms in patients with PD, especially those with comorbid psychiatric disorders. PMID:29497576

  15. Acute bilateral ECT in a depressed patient with a hip-aztreonam-spacer and subsequent maintenance ECT after prosthesis collocation.

    PubMed

    Gálvez, Verònica; de Arriba Arnau, Aida; Martínez-Amorós, Erika; Ribes, Carmina; Urretavizcaya, Mikel; Cardoner, Narcís

    2014-11-10

    ABSTRACT Electroconvulsive Therapy (ECT) has been demonstrated to be a safe and effective treatment for geriatric depression, although its application might be challenging when medical comorbidities exist. The present case reports a 78-year-old man diagnosed with recurrent unipolar major depressive disorder (MDD), who presented with a severe depressive episode with psychotic features (DSM IV). He successfully received a course of bitemporal (BT) ECT with a hip-aztreonam-spacer due to a hip fracture that occurred during hospitalization. This was followed by maintenance ECT (M-ECT) with a recent prosthesis collocation. This particular case illustrates the importance of a multidisciplinary approach in geriatric patients with somatic complications receiving ECT.

  16. Depression severity in electroconvulsive therapy (ECT) versus pharmacotherapy trials.

    PubMed

    Kellner, Charles H; Kaicher, David C; Banerjee, Hiya; Knapp, Rebecca G; Shapiro, Rachael J; Briggs, Mimi C; Pasculli, Rosa M; Popeo, Dennis M; Ahle, Gabriella M; Liebman, Lauren S

    2015-03-01

    We sought to compare the level of severity of depressive symptoms on entry into electroconvulsive therapy (ECT) clinical trials versus pharmacotherapy clinical trials. English-language MEDLINE/PubMed publication databases were searched for ECT literature (search terms: ECT, electroconvulsive therapy, depression, and Hamilton) for clinical trials in which depressed patients had baseline Hamilton Rating Scale for Depression (HRSD) scores. For comparison, we used a convenience sample of 7 large pharmacotherapy trials in major depression (N = 3677). The search included articles from 1960 to 2011. We included 100 studies that met the following criteria: ECT trial for depression, patients adequately characterized by diagnosis at baseline, and patients rated at baseline by 15-item HRSD (HRSD15), HRSD17, HRSD21, HRSD24, or HRSD28, with mean (SD) and sample size (n) reported. For the comparator pharmacotherapy trials, we chose to use a subset of the studies (excluding one study of minor depression) in the widely publicized meta-analysis of Fournier et al, as well as the STAR*D study and one additional study by Shelton et al. This provided 7 studies of major depression using HRSD17 (total N = 3677). Data extracted included number of subjects and baseline and final HRSD scores, with mean (SD) values. Of 100 ECT studies, 56 studies (N = 2243) used the HRSD17 version. The mean baseline HRSD17 score in the ECT trials was 27.6, the mean in the pharmacotherapy trials was 21.94, a statistically, and clinically, significant difference. In a subanalysis of the 16 ECT studies that used the HRSD24 version, the mean baseline score was 32.2. This selective literature review confirms that patients who entered ECT clinical trials were more severely ill than those who entered the selected comparator pharmacotherapy trials. Such data highlight the critical role of ECT in the treatment of severe and treatment-resistant mood disorders.

  17. Naloxone fails to prolong seizure length in ECT.

    PubMed

    Rasmussen, K G; Pandurangi, A K

    1999-12-01

    Electroconvulsive shock (ECS) in animals has been shown to enhance endogenous opiate systems. The anticonvulsant effects of ECS are also partially blocked by the opiate receptor antagonist naloxone, leading some investigators to postulate that the anticonvulsant effects of ECS are mediated by activation of endogenous opiates. If such a phenomenon occurs in humans, then naloxone might prolong seizure length in electroconvulsive therapy (ECT). In the present study, nine patients were given 2.0 mg intravenous (i.v.) naloxone 2 minutes prior to one-half of their ECT treatments. Motor seizure length was measured via the cuff technique. EEG tracings were read by an investigator blind to naloxone status. There was no difference between the two groups in either EEG or nonblindly evaluated motor seizure length. It is concluded that a dose of 2 mg naloxone does not effectively increase seizure length in ECT.

  18. Kin5 Knockdown in Tetrahymena thermophila Using RNAi Blocks Cargo Transport of Gef1

    PubMed Central

    Awan, Aashir; Bell, Aaron J.; Satir, Peter

    2009-01-01

    A critical process that builds and maintains the eukaryotic cilium is intraflagellar transport (IFT). This process utilizes members of the kinesin-2 superfamily to transport cargo into the cilium (anterograde transport) and a dynein motor for the retrograde traffic. Using a novel RNAi knockdown method, we have analyzed the function of the homodimeric IFT kinesin-2, Kin5, in Tetrahymena ciliary transport. In RNAi transformants, Kin5 was severely downregulated and disappeared from the cilia, but cilia did not resorb, although tip structure was affected. After deciliation of the knockdown cell, cilia regrew and cells swam, which suggested that Kin5 is not responsible for the trafficking of axonemal precursors to build the cilium, but could be transporting molecules that act in ciliary signal transduction, such as guanine nucleotide exchange proteins (GEFs). Gef1 is a Tetrahymena ciliary protein, and current coimmunoprecipitation and immunofluorescence studies showed that it is absent in regrowing cilia of the knockdown cells lacking ciliary Kin5. We suggest that one important cargo of Kin5 is Gef1 and knockdown of Kin5 results in cell lethality. PMID:19290045

  19. Relationship between somatization and remission with ECT.

    PubMed

    Rasmussen, Keith G; Snyder, Karen A; Knapp, Rebecca G; Mueller, Martina; Yim, Eunsil; Husain, Mustafa M; Rummans, Teresa A; Sampson, Shirlene M; O'Connor, M Kevin; Bernstein, Hilary J; Kellner, Charles H

    2004-12-30

    Patients treated with electroconvulsive therapy (ECT) were divided into those with less severe depression and those with more severe depression. In the less severely depressed group, high somatic anxiety and hypochondriasis predicted a low likelihood of sustained remission with ECT. In the more severely depressed group, these traits were not predictive of ECT outcome.

  20. Voices of people who have received ECT.

    PubMed

    Rajkumar, A P; Saravanan, B; Jacob, K S

    2007-01-01

    Electroconvulsive therapy (ECT) is controversial but widely practised in India. We elicited perspectives, using qualitative interviews, from patients who received ECT and their relatives. Ethical issues related to personal autonomy, right to information, competence, informed consent and consent by proxy are discussed. We suggest strategies to ensure a basic minimum standard for obtaining informed consent for ECT in India.

  1. Reduced cell number in the hindgut epithelium disrupts hindgut left-right asymmetry in a mutant of pebble, encoding a RhoGEF, in Drosophila embryos.

    PubMed

    Nakamura, Mitsutoshi; Matsumoto, Kenjiroo; Iwamoto, Yuta; Muguruma, Takeshi; Nakazawa, Naotaka; Hatori, Ryo; Taniguchi, Kiichiro; Maeda, Reo; Matsuno, Kenji

    2013-02-01

    Animals often show left-right (LR) asymmetry in their body structures. In some vertebrates, the mechanisms underlying LR symmetry breaking and the subsequent signals responsible for LR asymmetric development are well understood. However, in invertebrates, the molecular bases of these processes are largely unknown. Therefore, we have been studying the genetic pathway of LR asymmetric development in Drosophila. The embryonic gut is the first organ that shows directional LR asymmetry during Drosophila development. We performed a genetic screen to identify mutations affecting LR asymmetric development of the embryonic gut. From this screen, we isolated pebble (pbl), which encodes a homolog of a mammalian RhoGEF, Ect2. The laterality of the hindgut was randomized in embryos homozygous for a null mutant of pbl. Pbl is a multi-functional protein required for cytokinesis and the epithelial-to-mesenchymal transition in Drosophila. Consistent with Pbl's role in cytokinesis, we found reduced numbers of cells in the hindgut epithelium in pbl homozygous embryos. The specific expression of pbl in the hindgut epithelium, but not in other tissues, rescued the LR defects and reduced cell number in embryonic pbl homozygotes. Embryos homozygous for string (stg), a mutant that reduces cell number through a different mechanism, also showed LR defects of the hindgut. However, the reduction in cell number in the pbl mutants was not accompanied by defects in the specification of hindgut epithelial tissues or their integrity. Based on these results, we speculate that the reduction in cell number may be one reason for the LR asymmetry defect of the pbl hindgut, although we cannot exclude contributions from other functions of Pbl, including regulation of the actin cytoskeleton through its RhoGEF activity. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  2. Improving GEFS Weather Forecasts for Indian Monsoon with Statistical Downscaling

    NASA Astrophysics Data System (ADS)

    Agrawal, Ankita; Salvi, Kaustubh; Ghosh, Subimal

    2014-05-01

    Weather forecast has always been a challenging research problem, yet of a paramount importance as it serves the role of 'key input' in formulating modus operandi for immediate future. Short range rainfall forecasts influence a wide range of entities, right from agricultural industry to a common man. Accurate forecasts actually help in minimizing the possible damage by implementing pre-decided plan of action and hence it is necessary to gauge the quality of forecasts which might vary with the complexity of weather state and regional parameters. Indian Summer Monsoon Rainfall (ISMR) is one such perfect arena to check the quality of weather forecast not only because of the level of intricacy in spatial and temporal patterns associated with it, but also the amount of damage it can cause (because of poor forecasts) to the Indian economy by affecting agriculture Industry. The present study is undertaken with the rationales of assessing, the ability of Global Ensemble Forecast System (GEFS) in predicting ISMR over central India and the skill of statistical downscaling technique in adding value to the predictions by taking them closer to evidentiary target dataset. GEFS is a global numerical weather prediction system providing the forecast results of different climate variables at a fine resolution (0.5 degree and 1 degree). GEFS shows good skills in predicting different climatic variables but fails miserably over rainfall predictions for Indian summer monsoon rainfall, which is evident from a very low to negative correlation values between predicted and observed rainfall. Towards the fulfilment of second rationale, the statistical relationship is established between the reasonably well predicted climate variables (GEFS) and observed rainfall. The GEFS predictors are treated with multicollinearity and dimensionality reduction techniques, such as principal component analysis (PCA) and least absolute shrinkage and selection operator (LASSO). Statistical relationship is

  3. Electroconvulsive therapy (ECT) in schizophrenia: a review of recent literature.

    PubMed

    Sanghani, Sohag N; Petrides, Georgios; Kellner, Charles H

    2018-05-01

    ECT remains an important, yet underutilized, treatment for schizophrenia. Recent research shows that medication-resistant patients with schizophrenia, including those resistant to clozapine, respond well to ECT augmentation. The purpose of this article is to review recent studies of the use of ECT in the treatment of schizophrenia. We performed an electronic database search for articles on ECT and schizophrenia, published in 2017. The main themes of these articles are: epidemiological data on ECT use from various countries; retrospective studies, prospective studies and meta-analyses focusing on efficacy and cognitive side-effects of ECT in schizophrenia; ECT technical parameters and potential biomarkers. There is growing evidence to support the use of ECT for augmentation of antipsychotic response in the treatment of schizophrenia. Cognitive side-effects are generally mild and transient. In fact, many studies show improvement in cognition, possibly related to the improvement in symptoms. There is wide variation among countries in the use of ECT for the treatment of schizophrenia. There are also variations in the choice of ECT electrode placement, parameters and schedules. These technical differences are likely minor and should not interfere with the treatment being offered to patients. Further, long-term studies are needed to optimize ECT treatment parameters, to examine the effect of maintenance ECT and to investigate neuroimaging/biomarkers to understand the mechanism of action and identify potential response predictors to ECT.

  4. Informed consent and ECT: how much information should be provided?

    PubMed

    Torrance, Robert

    2015-05-01

    Obtaining informed consent before providing treatment is a routine part of modern clinical practice. For some treatments, however, there may be disagreement over the requirements for 'informed' consent. Electroconvulsive therapy (ECT) is one such example. Blease argues that patients 'should surely be privy to the matters of fact that: (1) there is continued controversy over the effectiveness of ECT; (2) there is orthodox scientific consensus that there is currently no acknowledged explanation for ECT and (3) there is a serious (mainstream) debate over whether the response to ECT may be a placebo response.' Before embracing these suggestions, two key questions must be asked. Are these claims a reasonable representation of current ECT research? And if so, will this information be of benefit to patients? The evidence-based support for ECT from both National Institute for Health and Care Excellence and the Royal College of Psychiatrists appears to undermine the validity of claims (1) and (3), and therefore the rationale for providing this information. Concerning assertion (2), it is true that the mechanism by which ECT has its therapeutic effect is not yet established, although the importance of conveying this fact to the patient is questionable. Of greater certainty is that the same irresolution surrounds the mechanism of action of pharmaceutical antidepressants, and so a double standard in patient care should be mindfully avoided if provision of this information is deemed a prerequisite for proper 'informed' consent. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  5. Stimulation of Cortical Myosin Phosphorylation by p114RhoGEF Drives Cell Migration and Tumor Cell Invasion

    PubMed Central

    Zihni, Ceniz; Harris, Andrew R.; Bailly, Maryse; Charras, Guillaume T.; Balda, Maria S.; Matter, Karl

    2012-01-01

    Actinomyosin activity is an important driver of cell locomotion and has been shown to promote collective cell migration of epithelial sheets as well as single cell migration and tumor cell invasion. However, the molecular mechanisms underlying activation of cortical myosin to stimulate single cell movement, and the relationship between the mechanisms that drive single cell locomotion and those that mediate collective cell migration of epithelial sheets are incompletely understood. Here, we demonstrate that p114RhoGEF, an activator of RhoA that associates with non-muscle myosin IIA, regulates collective cell migration of epithelial sheets and tumor cell invasion. Depletion of p114RhoGEF resulted in specific spatial inhibition of myosin activation at cell-cell contacts in migrating epithelial sheets and the cortex of migrating single cells, but only affected double and not single phosphorylation of myosin light chain. In agreement, overall elasticity and contractility of the cells, processes that rely on persistent and more constant forces, were not affected, suggesting that p114RhoGEF mediates process-specific myosin activation. Locomotion was p114RhoGEF-dependent on Matrigel, which favors more roundish cells and amoeboid-like actinomyosin-driven movement, but not on fibronectin, which stimulates flatter cells and lamellipodia-driven, mesenchymal-like migration. Accordingly, depletion of p114RhoGEF led to reduced RhoA, but increased Rac activity. Invasion of 3D matrices was p114RhoGEF-dependent under conditions that do not require metalloproteinase activity, supporting a role of p114RhoGEF in myosin-dependent, amoeboid-like locomotion. Our data demonstrate that p114RhoGEF drives cortical myosin activation by stimulating myosin light chain double phosphorylation and, thereby, collective cell migration of epithelial sheets and amoeboid-like motility of tumor cells. PMID:23185572

  6. Sociodemographic characterization of ECT utilization in Hawaii.

    PubMed

    Ona, Celia M; Onoye, Jane M; Goebert, Deborah; Hishinuma, Earl; Bumanglag, R Janine; Takeshita, Junji; Carlton, Barry; Fukuda, Michael

    2014-03-01

    Minimal research has been done on sociodemographic differences in utilization of electroconvulsive therapy (ECT) for refractory depression, especially among Asian Americans and Pacific Islanders. This study examined sociodemographic and diagnostic variables using retrospective data from Hawaii, an island state with predominantly Asian Americans and Pacific Islanders. Retrospective data were obtained from an inpatient and outpatient database of ECT patients from 2008 to 2010 at a tertiary care community hospital on O'ahu, Hawaii. There was a significant increase in overall ECT utilization from 2008 to 2009, with utilization remaining stable from 2009 to 2010. European Americans (41%) and Japanese Americans (29%) have relatively higher rates of receiving ECT, and Filipino Americans and Native Hawaiians have relatively lower rates in comparison with their population demographics. Japanese Americans received significantly more ECT procedures than European Americans. Electroconvulsive therapy is underutilized by certain sociodemographic groups that may benefit most from the treatment. There are significant differences in ECT usage based on ethnicity. Such differences may be related to help-seeking behavior, economic differences, and/or attitudes regarding mental illness. Further research is needed to elucidate the reasons for differences in utilization.

  7. Twice versus thrice weekly ECT in a clinical population: an evaluation of patient outcomes.

    PubMed

    Siskind, Dan; Charlson, Fiona; Saraf, Sudeep; Scheurer, Roman; Lie, David Charles

    2012-10-30

    Increasing demand on electroconvulsive therapy (ECT) services led to a recommendation that low risk patients be considered for twice weekly ECT rather than the usual thrice weekly. We evaluated whether practice changed and compared patient clinical outcomes for twice and thrice weekly ECT. Medical records for all patients receiving ECT in the 2-year study period (1/9/08 to 30/8/10) were reviewed to determine ECT protocol, diagnosis, admission duration and readmission rates. During the study period, 119 patients received 150 treatment courses. Patient outcomes were compared for twice weekly ECT and thrice weekly ECT protocols, as well as for 1 year before and after the recommendation (1/9/09). Twice weekly ECT courses increased (8-20) after the recommendation while thrice weekly ECT courses decreased (64-30). The recommendation had no significant effect on patient outcomes. Comparing twice and thrice weekly ECT, patient clinical outcomes were similar between the two groups, though non-affective twice weekly patients waited longer before starting ECT. In the context of resource constraints, psychiatrists can be influenced to examine and change their ECT prescribing practice. This bodes well for the implementation of evidence-based treatment into mental health services. Secondly, for adults, there appear to be no significant differences in clinical outcomes for twice versus thrice weekly ECT. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  8. Comparing ECT data of two different inpatient clinics: propofol or thiopental?

    PubMed

    Yazici, Esra; Bosgelmez, Sukriye; Tas, Halil Ibrahim; Karabulut, Umit; Yazici, Ahmet Bulent; Yildiz, Mustafa; Kirpinar, Ismet

    2013-10-01

    This study compares the data of (modified) electroconvulsive theraphy (ECT) applications from two different inpatient clinics in Turkey: Kocaeli Derince Training and Research Hospital (Clinic-I) and Kocaeli University (Clinic-II). Recorded files of patients from the two clinics were compared in terms of ECT indications, number and duration of seizures, and anesthetic agents used (propofol vs. thiopental). ECT applications occurring between January 2011 and January 2013 were included in the study. A total of 86 patients (9.5% of the inpatients) received ECT in Clinic-I and 103 patients (21.1% of the inpatients) in Clinic-II during the period studied. The yearly ECT rate (treated person rate per 10,000 per year) was 0.59/10,000 for Kocaeli (Turkey) as a whole. The overall number of ECT applications was 539 in Clinic-I and 999 in Clinic-II, and the average number of ECT sessions for each patient was 6.4 ± 2.33 in Clinic-I and 9.69 ± 4.66 in Clinic-II. The majority of indications were depressive disorders and insufficient response to medicine. Patients in the clinic which utilized thiopental as the anesthetic agent experienced more cardiovascular and respiratory side effects than the one which used propofol. The number of ECT sessions required was greater for patients with schizoaffective disorder than for others. The administration of ECT was considered to be a reliable method of treatment in these clinics. With respect to specific anesthetic agents, propofol was found to have less hemodynamic side effects and shorter seizure durations than thiopental.

  9. Synthesis of 5-hydroxyectoine from ectoine: crystal structure of the non-heme iron(II) and 2-oxoglutarate-dependent dioxygenase EctD.

    PubMed

    Reuter, Klaus; Pittelkow, Marco; Bursy, Jan; Heine, Andreas; Craan, Tobias; Bremer, Erhard

    2010-05-14

    As a response to high osmolality, many microorganisms synthesize various types of compatible solutes. These organic osmolytes aid in offsetting the detrimental effects of low water activity on cell physiology. One of these compatible solutes is ectoine. A sub-group of the ectoine producer's enzymatically convert this tetrahydropyrimidine into a hydroxylated derivative, 5-hydroxyectoine. This compound also functions as an effective osmostress protectant and compatible solute but it possesses properties that differ in several aspects from those of ectoine. The enzyme responsible for ectoine hydroxylation (EctD) is a member of the non-heme iron(II)-containing and 2-oxoglutarate-dependent dioxygenases (EC 1.14.11). These enzymes couple the decarboxylation of 2-oxoglutarate with the formation of a high-energy ferryl-oxo intermediate to catalyze the oxidation of the bound organic substrate. We report here the crystal structure of the ectoine hydroxylase EctD from the moderate halophile Virgibacillus salexigens in complex with Fe(3+) at a resolution of 1.85 A. Like other non-heme iron(II) and 2-oxoglutarate dependent dioxygenases, the core of the EctD structure consists of a double-stranded beta-helix forming the main portion of the active-site of the enzyme. The positioning of the iron ligand in the active-site of EctD is mediated by an evolutionarily conserved 2-His-1-carboxylate iron-binding motif. The side chains of the three residues forming this iron-binding site protrude into a deep cavity in the EctD structure that also harbours the 2-oxoglutarate co-substrate-binding site. Database searches revealed a widespread occurrence of EctD-type proteins in members of the Bacteria but only in a single representative of the Archaea, the marine crenarchaeon Nitrosopumilus maritimus. The EctD crystal structure reported here can serve as a template to guide further biochemical and structural studies of this biotechnologically interesting enzyme family.

  10. An extracellular-matrix-specific GEF-GAP interaction regulates Rho GTPase crosstalk for 3D collagen migration.

    PubMed

    Kutys, Matthew L; Yamada, Kenneth M

    2014-09-01

    Rho-family GTPases govern distinct types of cell migration on different extracellular matrix proteins in tissue culture or three-dimensional (3D) matrices. We searched for mechanisms selectively regulating 3D cell migration in different matrix environments and discovered a form of Cdc42-RhoA crosstalk governing cell migration through a specific pair of GTPase activator and inhibitor molecules. We first identified βPix, a guanine nucleotide exchange factor (GEF), as a specific regulator of migration in 3D collagen using an affinity-precipitation-based GEF screen. Knockdown of βPix specifically blocks cell migration in fibrillar collagen microenvironments, leading to hyperactive cellular protrusion accompanied by increased collagen matrix contraction. Live FRET imaging and RNAi knockdown linked this βPix knockdown phenotype to loss of polarized Cdc42 but not Rac1 activity, accompanied by enhanced, de-localized RhoA activity. Mechanistically, collagen phospho-regulates βPix, leading to its association with srGAP1, a GTPase-activating protein (GAP), needed to suppress RhoA activity. Our results reveal a matrix-specific pathway controlling migration involving a GEF-GAP interaction of βPix with srGAP1 that is critical for maintaining suppressive crosstalk between Cdc42 and RhoA during 3D collagen migration.

  11. Differences in Cognitive Outcomes After ECT Depending on BDNF and COMT Polymorphisms.

    PubMed

    Bennett, Daniel Mark; Currie, James; Fernie, Gordon; Perrin, Jennifer S; Reid, Ian C

    2016-12-01

    The study aimed to explore cognitive outcomes after electroconvulsive therapy (ECT) depending on which version of common single nucleotide polymorphisms the patient expressed for brain-derived neurotrophic factor (BDNF) and catechol-O-methyltransferase (COMT). A total of 87 patients from the clinical ECT service in Aberdeen, Scotland, were included in the study. Cognitive function testing (using Spatial Recognition Memory task from the Cambridge Neuropsychological Test Automated Battery and Mini-Mental State Examination) and mood ratings (Montgomery-Åsberg Depression Rating Scale) were performed before ECT, after 4 treatments, at the end of ECT and 1 and 3 months after the end of treatment. These scores were compared depending on BDNF and COMT variant at each time point using the Student t test and using a time series generalized least squares random effects model. No differences were found between the val and met versions of the BDNF or COMT polymorphism in either cognitive or mood outcomes at any time point during ECT treatment or up to 3 months of follow-up. This study did not detect significant differences in cognitive or mood outcomes between patients who have the val66val or met versions of the BDNF polymorphism. Our results suggest that these polymorphisms will not be helpful in clinical practice for predicting cognitive outcomes after ECT.

  12. Cost reduction with maintenance ECT in refractory bipolar disorder.

    PubMed

    Bonds, C; Frye, M A; Coudreaut, M F; Cunningham, M; Spearing, M; McGuire, M; Guze, B

    1998-03-01

    A case report of outpatient maintenance electroconvulsive therapy (ECT) is presented in a patient with bipolar disorder type I refractory to conventional medication treatment but responsive to ECT. A cost comparison is made showing substantial savings when outpatient maintenance ECT is used in lieu of inpatient hospitalization with ECT. A detailed life chart illustrating multiple medication trials that failed to stabilize the patient accompanies the financial summary. This case highlights the advantages of outpatient maintenance ECT for bipolar depression particularly with regard to safety, efficacy, and significant health care cost reduction.

  13. Efficacy of right unilateral ultrabrief pulse width ECT: a preliminary report.

    PubMed

    Magid, Michelle; Truong, Liz; Trevino, Kenneth; Husain, Mustafa

    2013-12-01

    Ultrabrief (right unilateral) electroconvulsive therapy (UB-RU ECT) is a newer form of ECT, which uses a shorter pulse width than the standard ECT (0.3 vs 1.0 millisecond, respectively). As a result, the use of UB ECT may provide a means of further decreasing ECT-related cognitive adverse effects. In 2011, the University of Texas Southwestern Department of ECT in Austin adopted a UB ECT protocol. The purpose of this study was to perform a preliminary evaluation of the effectiveness and efficiency of UB-RU ECT. This study also examined whether sex, age, or diagnosis affected response rates. This retrospective chart review identified 62 patients treated with the UB ECT protocol. An analysis of ECT response rates and demographic characteristics was conducted based on the data from clinical evaluations and Patient Health Questionnaire 9. Sixty-eight percent of patients in the study responded to ECT; 55% responded to UB pulse width RU ECT with another 13% responding when switched to standard pulse width bilateral ECT. The mean number of treatments in an index ECT series was 12.5. There was no statistically significant difference in response rates between bipolar and unipolar depressed patients. Men required progression to bilateral treatment more than women. This UB ECT protocol demonstrated a similar response rate when compared to standard ECT protocols; however, an increase in the number of treatments was required. Ultrabrief protocols are a viable option for both bipolar and unipolar depression. In men, UB ECT protocols may be less advantageous due to a need to overcome a potentially higher seizure threshold in men; however, additional research is needed to confirm this finding.

  14. Successful use of right unilateral ECT for catatonia: a case series.

    PubMed

    Cristancho, Pilar; Jewkes, Delaina; Mon, Thetsu; Conway, Charles

    2014-03-01

    Catatonia is a neuropsychiatric syndrome involving motor signs in association with disorders of mood, behavior, or thought. Bitemporal electrode placement electroconvulsive therapy (ECT) is a proven effective treatment for catatonia, and this mode of ECT delivery is the preferred method of treatment in this condition. Studies in major depressive disorder have demonstrated that suprathreshold, nondominant (right) hemisphere, unilateral electrode placement ECT has fewer adverse effects, especially cognitive adverse effects, than bitemporal ECT. This case series describes the use of right unilateral (RUL) ECT in 5 patients with catatonia. Before ECT, all 5 patients in this series initially failed therapy with benzodiazepines and psychotropic medications. Each catatonic patient received a series of 8 to 12 RUL ECT in an every-other-day series. After ECT, 4 of the 5 patients had a full recovery from catatonia. One patient achieved only partial response to RUL ECT, and no additional benefit was obtained with bitemporal ECT. All patients in this case series tolerated RUL ECT without major adverse effects. This case series illustrates successful use of RUL ECT in patients with catatonia and adds to the early literature demonstrating its effective use in treating this complex condition.

  15. AKAP13 Rho-GEF and PKD-Binding Domain Deficient Mice Develop Normally but Have an Abnormal Response to β-Adrenergic-Induced Cardiac Hypertrophy

    PubMed Central

    Spindler, Matthew J.; Burmeister, Brian T.; Huang, Yu; Hsiao, Edward C.; Salomonis, Nathan; Scott, Mark J.; Srivastava, Deepak; Carnegie, Graeme K.; Conklin, Bruce R.

    2013-01-01

    Background A-kinase anchoring proteins (AKAPs) are scaffolding molecules that coordinate and integrate G-protein signaling events to regulate development, physiology, and disease. One family member, AKAP13, encodes for multiple protein isoforms that contain binding sites for protein kinase A (PKA) and D (PKD) and an active Rho-guanine nucleotide exchange factor (Rho-GEF) domain. In mice, AKAP13 is required for development as null embryos die by embryonic day 10.5 with cardiovascular phenotypes. Additionally, the AKAP13 Rho-GEF and PKD-binding domains mediate cardiomyocyte hypertrophy in cell culture. However, the requirements for the Rho-GEF and PKD-binding domains during development and cardiac hypertrophy are unknown. Methodology/Principal Findings To determine if these AKAP13 protein domains are required for development, we used gene-trap events to create mutant mice that lacked the Rho-GEF and/or the protein kinase D-binding domains. Surprisingly, heterozygous matings produced mutant mice at Mendelian ratios that had normal viability and fertility. The adult mutant mice also had normal cardiac structure and electrocardiograms. To determine the role of these domains during β-adrenergic-induced cardiac hypertrophy, we stressed the mice with isoproterenol. We found that heart size was increased similarly in mice lacking the Rho-GEF and PKD-binding domains and wild-type controls. However, the mutant hearts had abnormal cardiac contractility as measured by fractional shortening and ejection fraction. Conclusions These results indicate that the Rho-GEF and PKD-binding domains of AKAP13 are not required for mouse development, normal cardiac architecture, or β-adrenergic-induced cardiac hypertrophic remodeling. However, these domains regulate aspects of β-adrenergic-induced cardiac hypertrophy. PMID:23658642

  16. Catatonia with schizophrenia: From ECT to rTMS.

    PubMed

    Stip, E; Blain-Juste, M-E; Farmer, O; Fournier-Gosselin, M-P; Lespérance, P

    2018-04-01

    Electroconvulsive therapy is indicated in cases of catatonic schizophrenia following a failure of the challenge test with lorazepam or Zolpidem ® . Some patients need maintenance treatment with ECT. Repetitive Transcranial Magnetic Stimulation (rTMS) and anodal Transcranial direct-current stimulation (tDCS) might be effective against catatonia. Consider an alternative to ECT for a refractory patient. Twenty-one articles were identified mainly based on case reports series were found using search on Medline, Google Scholar, PsychInfo, CAIRNS. Key words were:"catatonia", and "rTMS", and more generally with"ECT","tDCS","Zolpidem ® ". At the end there were only six case reports with rTMS and three with tDCS. We discussed the alternative to ECT and follow up rTMS strategies illustrated by these case reports. Patients mean age was 35; numbers of previous ECT vary from zero to 556; the most common motor threshold (MT) is 80%, with two patients with 110%, the most common treatment placement is L DLPFC. In one of them, ECT was the only acute-state or maintenance treatment effective in this patient, who underwent 556 ECT sessions over 20 years. High-frequency rTMS was considered as a possible alternative, given the potential adverse effects of chronic maintenance ECT in a patient with comorbid epilepsy. rTMS treatment was 3-4×/week and over time extended to once every two weeks. A persistent objective improvement in catatonia was observed on the Bush-Francis Catatonia Rating Scale. rTMS is helpful for acute and maintenance treatment for catatonic schizophrenia who both failed multiple pharmacologic interventions and had safety concerns with continuing maintenance ECT. Clinicians should consider rTMS as a potential treatment option for refractory catatonia. Copyright © 2017 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

  17. Efficacy of ECT in bipolar and unipolar depression in a real life hospital setting.

    PubMed

    Narayanaswamy, Janardhanan C; Viswanath, Biju; Reddy, Preethi V; Kumar, K Raghavendra; Thirthalli, Jagadisha; Gangadhar, Bangalore N

    2014-04-01

    It has been debated as to whether the polarity of mood disorder (bipolar versus unipolar) has prognostic significance for electroconvulsive therapy (ECT) outcome. In the treatment guidelines, ECT is recommended more readily for unipolar depression and not so for bipolar depression. This study aims to examine efficacy of bipolar and unipolar depression to ECT in a real life naturalistic setting. We studied the ECT parameters of all consecutive patients with a diagnosis of unipolar depression (recurrent depressive disorder, ≥2 episodes of depression) and bipolar depression referred for ECT between the months of July 2008 and December 2010 (BP-D: n=44) and (UP-D: n=106). When bipolar depression was compared to unipolar depression, the average motor seizure duration (mean=46.9 and 46.7, t=-0.06, p=0.94), number of ECTs required for improvement (mean=6.4 and 6.5, t=0.17, p=0.86), duration of inpatient stay after ECT initiation in days (mean=16.2 and 16.6, t=0.23, p=0.81) and improvement as assessed using a Likert scale (Mann-Whitney U, Z=-0.09, p=0.92) were not statistically different between the groups. We did not find any difference in efficacy of ECT between the two forms of depression in real life setting. This calls for justification of use of ECT in all patients with depression irrespective of the type of illness polarity and inclusion of ECT as a routine treatment option in bipolar depression guidelines. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. End-tidal carbon dioxide monitoring stabilized hemodynamic changes during ECT.

    PubMed

    Saito, Shigeru; Kadoi, Yuji; Nihishara, Fumio; Aso, Chizu; Goto, Fumio

    2003-03-01

    Accumulation of carbon dioxide (CO2) can disturb systemic and cerebral hemodynamics in patients receiving electroconvulsive therapy (ECT). The purpose of this study was to identify the effects of end-tidal CO2 monitoring on hemodynamic changes in patients who received ECT under propofol anesthesia. ECT was prescribed to 40 patients under propofol anesthesia. Ventilation was assisted using a face mask and 100% oxygen, with or without end-tidal CO2 monitoring. Heart rate was significantly increased in patients without end-tidal CO2 monitoring at 1 to 5 minutes after electrical stimulation (p < 0.01). Mean arterial blood pressure and middle cerebral artery blood flow velocity in the group without end-tidal CO2 monitoring were significantly larger than the values in the group with the monitor at 1 to 5 minutes after electrical stimulation. Arterial CO2 tension in the group without end-tidal CO2 monitoring was larger than the value in the group with the monitoring at 1 minute (45+/-5 mm Hg with the monitor and 56+/-8 without the monitor) and 5 minutes (37+/-4 mm Hg with the monitor and 51+/-8 without the monitor) after electrical stimulation (p < 0.01). Application of end-tidal CO2 monitoring is considered beneficial for safe and effective anesthesia management of patients undergoing ECT, especially patients with an intracranial disorder or ischemic heart disease.

  19. Comparative Study of Multiplet Structures of Mn4+ in K2SiF6, K2GeF6, and K2TiF6 Based on First-Principles Configuration-Interaction Calculations

    NASA Astrophysics Data System (ADS)

    Novita, Mega; Ogasawara, Kazuyoshi

    2012-02-01

    We performed first-principles configuration-interaction calculations of multiplet energies for Mn4+ in K2SiF6, K2GeF6, and K2TiF6 crystals. The results indicate that corrections based on a single-electron calculation are effective for the prediction of 4A2 → 4T2 and 4A2 → 4T1a transition energies, while such corrections are not necessary for the prediction of the 4A22E transition energy. The cluster size dependence of the multiplet energies is small. However, the 4A22E transition energy is slightly improved by using larger clusters including K ions. The theoretical multiplet energies are improved further by considering the lattice relaxation effect. As a result, the characteristic multiplet energy shifts depending on the host crystal are well reproduced without using any empirical parameters. Although K2GeF6 and K2TiF6 have lower symmetry than K2SiF6, the results indicate that the variation of the multiplet energy is mainly determined by the Mn-F bond length.

  20. A report on mood and cognitive outcomes with right unilateral ultrabrief pulsewidth (0.3 ms) ECT and retrospective comparison with standard pulsewidth right unilateral ECT.

    PubMed

    Loo, Colleen; Sheehan, Patrick; Pigot, Melissa; Lyndon, William

    2007-11-01

    Electroconvulsive therapy (ECT) is a highly effective treatment for depression but its use is limited by the risk of cognitive side effects. This study explored the potential of a novel approach, ultrabrief pulsewidth (0.3 ms) right unilateral (RUL-UB) ECT, to minimise cognitive effects while preserving efficacy. Mood and neuropsychological functioning were objectively rated in 30 patients over a course of RUL-UB ECT at 6 times seizure threshold. Results (mood outcomes, ECT treatment parameters) were compared with a retrospectively assessed group of 30 age and gender matched patients who received RUL ECT (1.0 ms pulsewidth, 3.5 times seizure threshold) at the same hospital. Six treatments of RUL-UB ECT resulted in relatively few cognitive side effects, compared to reports of previous studies. The number of responders did not differ between groups but significantly more treatments were required in the RUL-UB group, suggesting a slower speed of response. Patients were not randomised to the two forms of ECT and data was obtained retrospectively in the RUL ECT comparison group. This study suggests that RUL-UB ECT can be effective in treating depression while incurring lesser cognitive side effects than a commonly used form of RUL ECT, but a greater number of treatments may be required for response.

  1. Acute antidepressant effects of right unilateral ultra-brief ECT: a double-blind randomised controlled trial.

    PubMed

    Mayur, Prashanth; Byth, Karen; Harris, Anthony

    2013-07-01

    Shortening the pulse width to 0.3 ms holds neurophysiological and clinical promise of making ECT safer by limiting cognitive side effects. However, the antidepressant effects of right ultra-brief unilateral ECT are under contention. In an acute ECT course, antidepressant equivalence of ultra-brief right unilateral ECT to the high-dose brief pulse right unilateral ECT was investigated. Severely depressed patients were randomised to 1 ms-brief pulse (n=18) or 0.3 ms ultra-brief pulse (n=17) right unilateral ECT, both at high-dose (6 times threshold stimulus dose) given thrice weekly. Depression severity was measured using the Montgomery Asberg Depression Rating Scale at baseline, after 8 treatments and after the acute course of ECT. Depression severity declined equally in both groups: F (1.27,41.97)=0.31, p=0.63. Median time in days to remission (95%CI) was in brief pulse ECT: 26 (18.6-33.4) and ultra-brief pulse ECT:28 (17.9-38.0). The small sample study in the study increases the likelihood of type 2 error. In severe depression, high-dose ultra-brief right unilateral ECT appears to show matching acute antidepressant response to an equally high-dose brief pulse right unilateral ECT. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Safety and efficacy of caffeine-augmented ECT in elderly depressives: a retrospective study.

    PubMed

    Kelsey, M C; Grossberg, G T

    1995-07-01

    Prior studies have shown that in younger depressives undergoing ECT whose seizure durations declined despite maximum settings on three different ECT devices, pretreatment with caffeine lengthened seizures and resulted in clinical improvement. Caffeine (half life, 140-270 minutes) was well tolerated even in patients with pre-existing cardiovascular disease. The purpose of this retrospective study was to determine the safety and efficacy of caffeine augmented ECT in elderly depressed patients. The charts of 14 elderly depressives (average age 75.6, range 59-83; 2 males, 12 females) who received caffeine-augmented ECT were reviewed. Patients pre- and post-ECT medications, blood pressure, pulse, and seizure times (cuff and EEG) for each ECT performed were noted. The following conclusions were drawn from our study: (1) Caffeine definitely increases the seizure length and was useful in our setting when the energy settings could not be increased anymore. (2) Caffeine augmentation inconsistently causes an increase in pulse rate, on average, in the elderly. (3) Caffeine inconsistently produces an increase in mean arterial pressure. (4) Caffeine did not consistently produce an increase in the maximum rate-pressure product. We conclude from this study that caffeine-augmented ECT is safe and effective in increasing seizure duration in the elderly. However, more research needs to be done to determine optimal dosing and tolerability.

  3. A non-typical sequence of phase transitions in (NH4)3GeF7: optical and structural characterization.

    PubMed

    Mel'nikova, S V; Molokeev, M S; Laptash, N M; Misyul, S V

    2016-03-28

    Single crystals of germanium double salt (NH4)3GeF7 = (NH4)2GeF6·NH4F = (NH4)3[GeF6]F were grown and studied by the methods of polarization optics and X-ray diffraction. The birefringence Δn = (no - ne), the rotation angle of the optical indicatrix ϕ(T) and unit cell parameters were measured in the temperature range 100-400 K. Three structural phase transitions were found at the temperatures: T1↓ = 279.2 K (T1↑ = 279.4 K), T2↑ = 270 K (T2↓ = 268.9 K), T3↓ = 218 K (T3↑ = 227 K). An unusual sequence of symmetry transformations with temperature change was established: P4/mbm (Z = 2) (G1) ↔ Pbam (Z = 4) (G2) ↔ P21/c (Z = 4) (G3) ↔ Pa3[combining macron] (Z = 8) (G4). The crystal structures of different phases were determined. The experimental data were additionally interpreted by a group-theoretical analysis of the complete condensate of order parameters taking into account the critical and noncritical atomic displacements. Strengthening of the N-HF hydrogen bonds can be a driving force of the observed phase transitions.

  4. Combined use of clozapine and ECT: a review.

    PubMed

    Grover, Sandeep; Hazari, Nandita; Kate, Natasha

    2015-06-01

    This paper aims to review the available evidence for the use of clozapine and electroconvulsive therapy (ECT) in combination. Electronic searches were carried out to identify reports describing the combined use of clozapine and ECT. Forty reports including 208 patients were identified. The majority of reports were in the form of case reports and case series, with few retrospective and open-label studies. The majority of patients were aged between 18 and 65 years and diagnosed with schizophrenia or schizoaffective disorder. Most of the patients refractory to clozapine were started on ECT as an augmentation therapy; however, in some reports, both ECT and clozapine were started concurrently, and in few cases clozapine was started after ECT. In terms of effectiveness, 37.5-100% patients improved in short-term, and sustained long-term improvement (3 weeks to 24 months) was described in few studies. In terms of the side-effect profile, five patients each had delirium and tachycardia and only four patients were described to have prolonged seizures. Overall, the combination was considered effective and safe. There is evidence for the effectiveness and safety of the clozapine-ECT combination and it should be used in patients with treatment-resistant schizophrenia who do not respond to clozapine.

  5. Effectiveness of Electroconvulsive Therapy (ECT) in Parkinsonian Symptoms: A Case Series.

    PubMed

    Grover, Sandeep; Somani, Aditya; Sahni, Neeru; Mehta, Sahil; Choudhary, Swati; Chakravarty, Rahul Kumar; Rabha, Anju Moni

    2018-02-01

    Depression is a common comorbidity in patients suffering from Parkinson's disease (PD). Available evidence suggests that electroconvulsive therapy (ECT) is an effective treatment for depression and also improves symptoms of PD. However, literature on usefulness of ECT in parkinsonian symptoms is limited. A review of records of all patients receiving ECT from 2010 to April 2017 in the authors' clinic yielded six cases (0.63% of all patients who received ECT at the authors' center over last 7 years) of depression with PD who were treated with ECT. All six patients had improvement in both depression and symptoms of PD following ECT treatment. The improvement achieved with ECT was sustained in four patients. Worsening of PD symptoms 3 to 4 months post-treatment was seen in two patients. ECT appears to be an effective treatment option for management of motoric symptoms in patients with PD, especially those with comorbid psychiatric disorders.

  6. ECT IN MENTALLY RETARDED SUBJECTS WITH PSYCHIATRIC ILLNESS

    PubMed Central

    Chopra, V.K; Sinha, V.K.

    2002-01-01

    The mentally retarded subjects show a much higher prevalence of full range of psychiatric disorders than the non-retarded population. Whereas the role of psychotropic drugs in such patients is well discussed, the reports on the use of ECT are scarce. Many psychiatrists dealing with the mentally retarded psychiatric patients are reluctant to consider ECT due to lack of adequate experience. We report five mentally retarded patients with different psychiatric disorders who were successfully treated with ECT after failing adequate trials of pharmacotherapy. No disproportionately higher adverse events on account of mental retardation were observed. ECT need to be favorably considered in mentally retarded persons with psychiatric morbidity especially when treatment with psychotropic drugs either fail or is intolerable. PMID:21206883

  7. A qualitative study of experience of parents of adolescents who received ECT.

    PubMed

    Grover, Sandeep; Varadharajan, Natarajan; Avasthi, Ajit

    2017-12-01

    To evaluate the experience of parents of adolescents who received ECT for severe mental illness. Using qualitative methods, 6 parents of 5 adolescents were interviewed by using a self-designed semi-structured interview after the completion of ECT course. The clinicians involved in the ECT procedure, i.e., seeking informed consent and administration of ECT were not aware about the study. All the interviews were recorded and the content was analysed and themes were generated. Parents of all the 5 adolescents expressed that their children were considered for ECT only after the patient had not responded to medication and were unmanageable. Prior to ECT the treating doctors did explain to them about the ECT procedure, they were given information booklet and they were not coerced to consent for ECT. Some of the parents reported that they had dilemma prior to giving consent and were scared prior to the first ECT. However, as the clinical condition of their children improved, they felt that ECT was a good treatment. Majority of the parents felt that ECT was delayed for their children. When asked about restriction in use of ECT in children and adolescents, the parents expressed that it is important for law makers to understand the distress of the parents,when their children are acutely ill. They expressed that decision of administration of ECT must be left to the family and the treating clinicians. Parents of adolescents considered for ECT are generally satisfied with the treatment procedure. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Emergency ECT in an incapacitated, medically compromised patient with Huntington's disease.

    PubMed

    Magid, Michelle; Trevino, Kenneth; Reid, William H; Jalalat, Sheila; Husain, Mustafa M; Kahn, David A

    2014-11-01

    Electroconvulsive therapy (ECT) is infrequently considered an "emergency" medical procedure; however, there are certain conditions in which there is considerable urgency to initiate ECT. For example, prompt administration of ECT to treat neuroleptic malignant syndrome and malignant catatonia is necessary to improve a patient's overall prognosis and potentially save the patient's life. In this case, a 57-year-old woman with Huntington's disease was admitted to our medical intensive care unit for failure to thrive due to severe psychotic symptoms. Prior to her admission, the patient had become increasingly psychotic and agitated, resulting in her refusal and/or inability to eat. Efforts to treat her severe psychiatric and behavioral symptoms with various psychopharmacological strategies were largely unsuccessful. As the patient's physical health continued to decline, with loss of approximately 35 pounds over 2 months, her family began making arrangements to transfer her to a hospice facility. The day before she was to be transferred, the psychiatry consultation-liaison service recommended ECT. Unfortunately, this recommendation was complicated because the patient was unable to provide consent. This case report describes the legal and administrative process used to ethically and legally administer ECT without consent from the patient or a court-appointed guardian in order to treat a life-threatening condition. To the best of our knowledge, this report documents the first time ECT has been granted "medical emergency" status in Texas.

  9. Focus on ECT seizure quality: serum BDNF as a peripheral biomarker in depressed patients.

    PubMed

    Bumb, Jan Malte; Aksay, Suna Su; Janke, Christoph; Kranaster, Laura; Geisel, Olga; Gass, Peter; Hellweg, Rainer; Sartorius, Alexander

    2015-04-01

    Electroconvulsive therapy (ECT) is a well-established, safe and effective treatment in severest or drug-resistant affective disorders. The potential relation between any peripheral biological marker and the seizure quality as a surrogate for treatment efficacy has not been investigated so far. We prospectively examined serum brain-derived neurotrophic factor (BDNF) levels in 20 patients with major depression before and after electroconvulsive therapy. A seizure quality sum score for every ECT session was build up on the basis of the seizure duration, seizure amplitude, central inhibition, interhemispheric coherence and sympathetic activation. Serum BDNF levels were significantly higher after ECT (P = 0.036). In the linear regression analysis, a significant correlation of the serum BDNF levels and the time between the last ECT and the blood withdrawal (P = 0.01) was observed. The ANOVA revealed a significant influence of the interval between the last ECT and the blood withdrawal (P = 0.0017) as well as the seizure quality (P = 0.038) on the variance of BDNF serum levels. Our data corroborate the neurotrophin hypothesis suggesting an ECT-induced central BDNF rise leading to a delayed (>6 days) and increased equilibrium of the peripheral BDNF. The association of seizure adequacy with a BDNF rise might underline the importance of monitoring seizure quality markers in daily practice.

  10. Electroconvulsive Therapy Part I: A Perspective on the Evolution and Current Practice of ECT

    PubMed Central

    Payne, Nancy A.; Prudic, Joan

    2010-01-01

    The concept of inducing convulsions, mainly through chemical means, to promote mental wellness has existed since the 16th century. In 1938, Italian scientists first applied electrically induced therapeutic seizures. Although electroconvulsive therapy (ECT) is employed in the treatment of several psychiatric disorders, it is most frequently used today to treat severe depressive episodes and remains the most effective treatment available for those disorders. Despite this, ECT continues to be the most stigmatized treatment available in psychiatry, resulting in restrictions on and reduced accessibility to a helpful and potentially life-saving treatment. The psychiatric and psychosocial ramifications of this stigmatization may include the exacerbation of the increasingly serious, global health problem of major depressive disorders as well as serious consequences for individual patients who may not be offered, or may refuse, a potentially beneficial treatment. The goal of this first article in this two-part series is to provide an overview of ECT's historical development and discuss the current state of knowledge about ECT, including technical aspects of delivery, patient selection, its side-effect profile, and factors that may contribute to underuse of ECT. PMID:19820553

  11. Electroconvulsive therapy: Part I. A perspective on the evolution and current practice of ECT.

    PubMed

    Payne, Nancy A; Prudic, Joan

    2009-09-01

    The concept of inducing convulsions, mainly through chemical means, to promote mental wellness has existed since the 16th century. In 1938, Italian scientists first applied electrically induced therapeutic seizures. Although electroconvulsive therapy (ECT) is employed in the treatment of several psychiatric disorders, it is most frequently used today to treat severe depressive episodes and remains the most effective treatment available for those disorders. Despite this, ECT continues to be the most stigmatized treatment available in psychiatry, resulting in restrictions on and reduced accessibility to a helpful and potentially life-saving treatment. The psychiatric and psychosocial ramifications of this stigmatization may include the exacerbation of the increasingly serious, global health problem of major depressive disorders as well as serious consequences for individual patients who may not be offered, or may refuse, a potentially beneficial treatment. The goal of this first article in this two-part series is to provide an overview of ECT's historical development and discuss the current state of knowledge about ECT, including technical aspects of delivery, patient selection, its side-effect profile, and factors that may contribute to underuse of ECT.

  12. Predictors of regained occupational functioning after electroconvulsive therapy (ECT) in patients with major depressive disorder--a population based cohort study.

    PubMed

    Nordenskjöld, Axel; von Knorring, Lars; Brus, Ole; Engström, Ingemar

    2013-10-01

    The aim of the present study is to investigate the rate of regained occupational functioning among patients treated with electroconvulsive therapy (ECT) for major depression and to define predictors of time to regained occupational functioning. A nested cohort study was performed of patients treated by ECT for unipolar major depressive disorder registered in the Quality register for ECT and in the Swedish Social Insurance Agency registry. Predictive values of single clinical variables and their relative importance were tested with Cox regression analysis. 394 patients were identified. Of those, 266 were on non-permanent sick leave and 128 on disability pension during ECT. Within 1 year post-ECT, 71% of the patients with non-permanent sick leave regained occupational functioning. Factors independently associated with a statistically significant increased time to regained occupational functioning were longer duration of sick leave pre-ECT, milder depression pre-ECT, less complete improvement with ECT, benzodiazepine treatment after ECT and co-morbid substance dependence. A large proportion of the patients do not return to work within several months post-ECT. Paradoxically, patients with more severe depression pre-ECT had a reduced time to regained occupational functioning, indicating a larger effect in this patients group of the treatment. Moreover, the period with sick leave compensation might be reduced if ECT is initiated within the first 3 months of sick leave. Most patients on non-permanent sick leave regain occupational functioning after ECT. However, it usually takes a few months even in symptomatically improved patients.

  13. Heat induced temperature dysregulation and seizures in Dravet Syndrome/GEFS+ Gabrg2+/Q390X mice.

    PubMed

    Warner, Timothy A; Liu, Zhong; Macdonald, Robert L; Kang, Jing-Qiong

    2017-08-01

    It has been established that febrile seizures and its extended syndromes like generalized epilepsy with febrile seizures (FS) plus (GEFS+) and Dravet syndrome have been associated with mutations especially in SCN1A and GABRG2 genes. In patients, the onset of FS is likely due to the combined effect of temperature and inflammation in genetically vulnerable individuals because fever is often associated with infection. Much effort has been spent to understand the mechanisms underlying fever induction of seizures. In addition to the role of cytokines in FS, previous studies in Scn1a +/- knockout mice, a model of Dravet syndrome, indicated that temperature elevation alone could result in seizure generation, and the effect of elevated temperature inducing seizures was age-dependent. Here, we report the thermal effect in a different mouse model of Dravet syndrome, the Gabrg2 +/Q390X knockin mouse. We demonstrated age-dependent dysregulated temperature control and that temperature elevation produced myoclonic jerks, generalized tonic clonic seizures (GTCSs) and heightened anxiety-like symptoms in Gabrg2 +/Q390X mice. The study indicated that regardless of other inflammatory factors, brief heat alone increased brain excitability and induced multiple types of seizures in Gabrg2 +/Q390X mice, suggesting that mutations like GABRG2(Q390X) may alter brain thermal regulation and precipitate seizures during temperature elevations. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. The Evolutionary Landscape of Dbl-Like RhoGEF Families: Adapting Eukaryotic Cells to Environmental Signals

    PubMed Central

    Blangy, Anne

    2017-01-01

    Abstract The dynamics of cell morphology in eukaryotes is largely controlled by small GTPases of the Rho family. Rho GTPases are activated by guanine nucleotide exchange factors (RhoGEFs), of which diffuse B-cell lymphoma (Dbl)-like members form the largest family. Here, we surveyed Dbl-like sequences from 175 eukaryotic genomes and illuminate how the Dbl family evolved in all eukaryotic supergroups. By combining probabilistic phylogenetic approaches and functional domain analysis, we show that the human Dbl-like family is made of 71 members, structured into 20 subfamilies. The 71 members were already present in ancestral jawed vertebrates, but several members were subsequently lost in specific clades, up to 12% in birds. The jawed vertebrate repertoire was established from two rounds of duplications that occurred between tunicates, cyclostomes, and jawed vertebrates. Duplicated members showed distinct tissue distributions, conserved at least in Amniotes. All 20 subfamilies have members in Deuterostomes and Protostomes. Nineteen subfamilies are present in Porifera, the first phylum that diverged in Metazoa, 14 in Choanoflagellida and Filasterea, single-celled organisms closely related to Metazoa and three in Fungi, the sister clade to Metazoa. Other eukaryotic supergroups show an extraordinary variability of Dbl-like repertoires as a result of repeated and independent gain and loss events. Last, we observed that in Metazoa, the number of Dbl-like RhoGEFs varies in proportion of cell signaling complexity. Overall, our analysis supports the conclusion that Dbl-like RhoGEFs were present at the origin of eukaryotes and evolved as highly adaptive cell signaling mediators. PMID:28541439

  15. General Description of Fission Observables: GEF Model Code

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Schmidt, K.-H.; Jurado, B., E-mail: jurado@cenbg.in2p3.fr; Amouroux, C.

    2016-01-15

    The GEF (“GEneral description of Fission observables”) model code is documented. It describes the observables for spontaneous fission, neutron-induced fission and, more generally, for fission of a compound nucleus from any other entrance channel, with given excitation energy and angular momentum. The GEF model is applicable for a wide range of isotopes from Z = 80 to Z = 112 and beyond, up to excitation energies of about 100 MeV. The results of the GEF model are compared with fission barriers, fission probabilities, fission-fragment mass- and nuclide distributions, isomeric ratios, total kinetic energies, and prompt-neutron and prompt-gamma yields and energymore » spectra from neutron-induced and spontaneous fission. Derived properties of delayed neutrons and decay heat are also considered. The GEF model is based on a general approach to nuclear fission that explains a great part of the complex appearance of fission observables on the basis of fundamental laws of physics and general properties of microscopic systems and mathematical objects. The topographic theorem is used to estimate the fission-barrier heights from theoretical macroscopic saddle-point and ground-state masses and experimental ground-state masses. Motivated by the theoretically predicted early localisation of nucleonic wave functions in a necked-in shape, the properties of the relevant fragment shells are extracted. These are used to determine the depths and the widths of the fission valleys corresponding to the different fission channels and to describe the fission-fragment distributions and deformations at scission by a statistical approach. A modified composite nuclear-level-density formula is proposed. It respects some features in the superfluid regime that are in accordance with new experimental findings and with theoretical expectations. These are a constant-temperature behaviour that is consistent with a considerably increased heat capacity and an increased pairing condensation energy

  16. Right Unilateral Ultrabrief Pulse ECT in Geriatric Depression: Phase 1 of the PRIDE Study.

    PubMed

    Kellner, Charles H; Husain, Mustafa M; Knapp, Rebecca G; McCall, W Vaughn; Petrides, Georgios; Rudorfer, Matthew V; Young, Robert C; Sampson, Shirlene; McClintock, Shawn M; Mueller, Martina; Prudic, Joan; Greenberg, Robert M; Weiner, Richard D; Bailine, Samuel H; Rosenquist, Peter B; Raza, Ahmad; Kaliora, Styliani; Latoussakis, Vassilios; Tobias, Kristen G; Briggs, Mimi C; Liebman, Lauren S; Geduldig, Emma T; Teklehaimanot, Abeba A; Lisanby, Sarah H

    2016-11-01

    The Prolonging Remission in Depressed Elderly (PRIDE) study evaluated the efficacy of right unilateral ultrabrief pulse electroconvulsive therapy (ECT) combined with venlafaxine for the treatment of geriatric depression. PRIDE was a two-phase multisite study. Phase 1 was an acute course of right unilateral ultrabrief pulse ECT, combined with open-label venlafaxine at seven academic medical centers. In phase 2 (reported separately), patients who had remitted were randomly assigned to receive pharmacotherapy (venlafaxine plus lithium) or pharmacotherapy plus continuation ECT. In phase 1, depressed patients received high-dose ECT (at six times the seizure threshold) three times per week. Venlafaxine was started during the first week of treatment and continued throughout the study. The primary outcome measure was remission, assessed with the 24-item Hamilton Depression Rating Scale (HAM-D), which was administered three times per week. Secondary outcome measures were post-ECT reorientation and safety. Paired t tests were used to estimate and evaluate the significance of change from baseline in HAM-D scores. Of 240 patients who entered phase 1 of the study, 172 completed it. Overall, 61.7% (148/240) of all patients met remission criteria, 10.0% (24/240) did not remit, and 28.3% (68/240) dropped out; 70% (169/240) met response criteria. Among those who remitted, the mean decrease in HAM-D score was 24.7 points (95% CI=23.4, 25.9), with a mean final score of 6.2 (SD=2.5) and an average change from baseline of 79%. The mean number of ECT treatments to remission was 7.3 (SD=3.1). Right unilateral ultrabrief pulse ECT, combined with venlafaxine, is a rapidly acting and highly effective treatment option for depressed geriatric patients, with excellent safety and tolerability. These data add to the evidence base supporting the efficacy of ECT to treat severe depression in elderly patients.

  17. Gamma and x-ray irradiation effects on different Ge and Ge/F doped optical fibers

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Alessi, A., E-mail: antonino.alessi@univ-st-etienne.fr; Girard, S.; Di Francesca, D.

    2015-08-28

    We performed electron paramagnetic resonance (EPR) measurements on γ and X ray irradiated Ge doped and Ge/F co-doped optical fibers. We considered three different drawing conditions (speed and tension), and for each type of drawing, we studied Ge and Ge/F doped samples having Ge doping level above 4% by weight. The EPR data recorded for the γ ray irradiated fibers confirm that all the samples exhibit a very close radiation response regardless of the drawing conditions corresponding to values used for the production of specialty fibers. Furthermore, as for the X irradiated materials, in the γ ray irradiated F co-dopedmore » fibers, we observed that the Ge(1) and the Ge(2) defects generation is unchanged, whereas it was enhanced for the E'Ge. In the various fibers, the comparison of the γ and X-ray induced concentrations of these kinds of Ge related defects indicates that the two irradiations induce similar effects regardless of the different employed dose rates and sources. Confocal microscopy luminescence results show that the starting content of the Germanium Lone Pair Center (GLPC) is neither strongly affected by the Ge content nor by the drawing conditions, and we consider the similarity of the GLPC content as key factor in determining many of the above reported similarities.« less

  18. Use of ECT in Nepal: A One Year Study From the Country's Largest Psychiatric Facility.

    PubMed

    Subedi, Sandip; Aich, Tapas Kumar; Sharma, Niru

    2016-02-01

    Electro-Convulsive Therapy (ECT) refers to the electrical stimulation of the brain to produce seizures for therapeutic purpose. Since the development of ECT, it's use has been consistent. Inspite of the common use, data pertaining to the use of ECT in Nepal is lacking. This study was undertaken with the aim of exploring the clinico-demographic profile of patients treated with ECT in the largest psychiatry facility in the country. It is a retrospective descriptive study of patients who were treated with ECT after admission in the inpatient psychiatry unit of Universal College of Medical Sciences Teaching Hospital, Bhairahawa, Nepal during a period of one year (August 2012 to July 2013). Out of 1095 patients admitted during the specified period, 81 (7.39%) patients received ECT. About 44.44% of the patients belonged to 20-29 years age group. Female patients constituted more than half of the subjects (55.56%). Review of diagnostic profile showed that majority of patients receiving ECT were suffering from Schizophrenia (44.4%), followed by Bipolar Affective Disorder/Mania (29.6%), Depressive disorder (11.1%), Acute and Transient Psychotic Disorder (6.2%), Post-partum Psychosis (3.7%) and substance induced mood/psychotic disorders (3.7%). A significant majority of subjects (75.3%) received about 5-7 ECT treatments. The mean seizure duration after ECT treatment was 31.13±5.79 seconds. No any major complications were noted during ECT treatment. This study suggests that ECT, use, as a treatment modality is common in young adults and females with Schizophrenia being the most common indication. Direct ECT is safe when used judiciously.

  19. Study on automatic ECT data evaluation by using neural network

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Komatsu, H.; Matsumoto, Y.; Badics, Z.

    1994-12-31

    At the in--service inspection of the steam generator (SG) tubings in Pressurized Water Reactor (PWR) plant, eddy current testing (ECT) has been widely used at each outage. At present, ECT data evaluation is mainly performed by ECT data analyst, therefore it has the following problems. Only ECT signal configuration on the impedance trajectory is used in the evaluation. It is an enormous time consuming process. The evaluation result is influenced by the ability and experience of the analyst. Especially, it is difficult to identify the true defect signal hidden in background signals such as lift--off noise and deposit signals. Inmore » this work, the authors performed the study on the possibility of the application of neural network to ECT data evaluation. It was demonstrated that the neural network proved to be effective to identify the nature of defect, by selecting several optimum input parameters to categorize the raw ECT signals.« less

  20. Based on a True Story? The Portrayal of ECT in International Movies and Television Programs.

    PubMed

    Sienaert, Pascal

    Movies and television (TV) programs are an important source of public information about ECT. To narratively review the portrayal of ECT in international movies and TV programs from 1948 until present. Several Internet movie databases and a database of phrases appearing in movies and TV programs were searched, supplemented with a Medline-search. No language restrictions were applied. ECT was portrayed in 52 movies (57 scenes), 21 TV programs (23 scenes), and 2 animated sitcoms (2 scenes). In movies, the main indication for ECT is behavioral control or torture (17/57, 29.8%), whereas in TV programs, the most frequent indication is erasing memories (7/25, 28%). In most scenes (47/82; 57.3%) ECT is given without consent, and without anesthesia (59/82; 72%). Unmodified ECT is depicted more frequently in American scenes (48/64, 75%), as opposed to scenes from other countries (11/18; 64.7%). Bilateral electrode placement is used in almost all (89%, 73/82) scenes. The vast majority of movies (46/57, 80.7%) and TV programs (18/25, 72%) show a negative and inaccurate image of the treatment. In the majority of scenes, ECT is used as a metaphor for repression, mind and behavior control, and is shown as a memory-erasing, painful and damaging treatment, adding to the stigma already associated with ECT. Only a few exceptions paint a truthful picture of this indispensable treatment in modern psychiatry. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Use of electroconvulsive therapy (ECT) in postpartum psychosis--a naturalistic prospective study.

    PubMed

    Babu, Girish N; Thippeswamy, Harish; Chandra, Prabha S

    2013-06-01

    Postpartum psychosis (PPP) is a severe psychiatric condition requiring rapid restoration of health in view of significant risks to both mother and the infant. Electroconvulsive therapy (ECT) is often used for treatment of severe PPP. The aims of the study were to describe the indications for ECT among women admitted with PPP to a psychiatric hospital in India. It also aimed at assessing whether women with PPP who received ECT differed in their clinical history, diagnosis, severity of illness, psychopathology, drug dosage, and duration of hospital stay, compared to women who did not receive ECT. Infants of mothers who were breast-feeding their infants while receiving ECT were assessed for adverse effects. This was a naturalistic prospective study of 78 women admitted with PPP, 34 (43.6 %) of whom received ECT. Presence of catatonia, augmentation of medications, and suicidality were common indications for ECT. Catatonic symptoms were significantly higher among women who received ECT. There was no significant difference in duration of hospitalization or severity of psychopathology between women who did and did not receive ECT. Transient side effects to ECT were observed in few women, with no adverse effects noted in infants who were breast-fed. The current study supports the use of ECT as an effective and safe treatment for women with severe PPP.

  2. Supraventricular tachycardia in a patient receiving ECT, clozapine, and caffeine.

    PubMed

    Beale, M D; Pritchett, J T; Kellner, C H

    1994-09-01

    A patient receiving electroconvulsive therapy (ECT), clozapine, and intravenous caffeine sodium benzoate developed supraventricular tachycardia. This was rapidly treated with intravenous verapamil. Subsequent maintenance ECT given without caffeine was well tolerated. We believe the combination of clozapine and caffeine at the time of ECT was responsible for the arrhythmia.

  3. Robuste Verzweigungserkennung von Gefäßen in CTA-Datensätzen zur modellbasierten Extraktion der Centerline

    NASA Astrophysics Data System (ADS)

    Beck, Thomas; Fritz, Dominik; Biermann, Christina; Dillmann, Rüdiger

    Bei der Befundung und Visualisierung von Blutgefäßen ist deren Centerline von zentraler Bedeutung. Die Unterscheidung zwischen unverzweigten Abschnitten des Gefäßes und Verzweigungsbereichen ermöglicht den Einsatz spezialisierter und sehr effizienter Algorithmen zur modellbasierten Extraktion der Centerline. In diesem Artikel wird ein robustes Verfahren zur Verzweigungserkennung vorgestellt. Das Verfahren beruht auf einem Front-Propagation-Ansatz mit dynamisch angepassten Schwellwerten und einer anschließenden Clusteranalyse. Die vorgestellte Methode zur Verzweigungserkennung wurde als Komponente einer Architektur zur Extraktion der Centerline auf handannotierten Datensätzen getestet. Erste Ergebnisse sind sehr vielversprechend und ermöglichen auch bei pathologischen Gefäßen eine robuste Detektion von Gefäßverzweigungen.

  4. Use of ECT in the presence of acute bilateral posterior vitreous detachmanet.

    PubMed

    Taye, Tesema; Dobranici, Letitia; Fisher, Mark; Cullum, Sarah

    2018-04-01

    We describe a case of acute bilateral posterior vitreous detachment (PVD) in a 71-year-old female, which developed during a course of electroconvulsive therapy (ECT) for treatment-resistant depression. The risks and benefits of continuing ECT were assessed and the patient completed the full course of 16 ECT treatments without further ophthalmic complications. As the incidence of PVD increases with age, and ECT is used more frequently in elderly people with depression, we recommend paying attention to ophthalmic symptoms as part of the routine clinical monitoring of ECT side effects. If ophthalmic symptoms occur, the risks and benefits of ECT need to be weighed up including consultation with an ophthalmologist.

  5. TGF-β regulates LARG and GEF-H1 during EMT to affect stiffening response to force and cell invasion

    PubMed Central

    Osborne, Lukas D.; Li, George Z.; How, Tam; O'Brien, E. Tim; Blobe, Gerard C.; Superfine, Richard; Mythreye, Karthikeyan

    2014-01-01

    Recent studies implicate a role for cell mechanics in cancer progression. The epithelial-to-mesenchymal transition (EMT) regulates the detachment of cancer cells from the epithelium and facilitates their invasion into stromal tissue. Although classic EMT hallmarks include loss of cell–cell adhesions, morphology changes, and increased invasion capacity, little is known about the associated mechanical changes. Previously, force application on integrins has been shown to initiate cytoskeletal rearrangements that result in increased cell stiffness and a stiffening response. Here we demonstrate that transforming growth factor β (TGF-β)–induced EMT results in decreased stiffness and loss of the normal stiffening response to force applied on integrins. We find that suppression of the RhoA guanine nucleotide exchange factors (GEFs) LARG and GEF-H1 through TGF-β/ALK5–enhanced proteasomal degradation mediates these changes in cell mechanics and affects EMT-associated invasion. Taken together, our results reveal a functional connection between attenuated stiffness and stiffening response and the increased invasion capacity acquired after TGF-β–induced EMT. PMID:25143398

  6. Use of ECT in Nepal: A One Year Study From the Country’s Largest Psychiatric Facility

    PubMed Central

    Aich, Tapas Kumar; Sharma, Niru

    2016-01-01

    Introduction Electro-Convulsive Therapy (ECT) refers to the electrical stimulation of the brain to produce seizures for therapeutic purpose. Since the development of ECT, it’s use has been consistent. Inspite of the common use, data pertaining to the use of ECT in Nepal is lacking. Aim This study was undertaken with the aim of exploring the clinico-demographic profile of patients treated with ECT in the largest psychiatry facility in the country. Materials and Methods It is a retrospective descriptive study of patients who were treated with ECT after admission in the inpatient psychiatry unit of Universal College of Medical Sciences Teaching Hospital, Bhairahawa, Nepal during a period of one year (August 2012 to July 2013). Results Out of 1095 patients admitted during the specified period, 81 (7.39%) patients received ECT. About 44.44% of the patients belonged to 20-29 years age group. Female patients constituted more than half of the subjects (55.56%). Review of diagnostic profile showed that majority of patients receiving ECT were suffering from Schizophrenia (44.4%), followed by Bipolar Affective Disorder/Mania (29.6%), Depressive disorder (11.1%), Acute and Transient Psychotic Disorder (6.2%), Post-partum Psychosis (3.7%) and substance induced mood/psychotic disorders (3.7%). A significant majority of subjects (75.3%) received about 5-7 ECT treatments. The mean seizure duration after ECT treatment was 31.13±5.79 seconds. No any major complications were noted during ECT treatment. Conclusion This study suggests that ECT, use, as a treatment modality is common in young adults and females with Schizophrenia being the most common indication. Direct ECT is safe when used judiciously. PMID:27042563

  7. Dynamic Control of Excitatory Synapse Development by a Rac1 GEF/GAP Regulatory Complex

    PubMed Central

    Um, Kyongmi; Niu, Sanyong; Duman, Joseph G.; Cheng, Jinxuan; Tu, Yen-Kuei; Schwechter, Brandon; Liu, Feng; Hiles, Laura; Narayanan, Anjana; Ash, Ryan T.; Mulherkar, Shalaka; Alpadi, Kannan; Smirnakis, Stelios M.; Tolias, Kimberley F.

    2014-01-01

    SUMMARY The small GTPase Rac1 orchestrates actin-dependent remodeling essential for numerous cellular processes including synapse development. While precise spatiotemporal regulation of Rac1 is necessary for its function, little is known about the mechanisms that enable Rac1 activators (GEFs) and inhibitors (GAPs) to act in concert to regulate Rac1 signaling. Here we identify a regulatory complex composed of a Rac-GEF (Tiam1) and a Rac-GAP (Bcr) that cooperate to control excitatory synapse development. Disruption of Bcr function within this complex increases Rac1 activity and dendritic spine remodeling, resulting in excessive synaptic growth that is rescued by Tiam1 inhibition. Notably, EphB receptors utilize the Tiam1-Bcr complex to control synaptogenesis. Following EphB activation, Tiam1 induces Rac1-dependent spine formation, whereas Bcr prevents Rac1-mediated receptor internalization, promoting spine growth over retraction. The finding that a Rac-specific GEF/GAP complex is required to maintain optimal levels of Rac1 signaling provides an important insight into the regulation of small GTPases. PMID:24960694

  8. Health Related Quality of Life after ECT for depression: A study exploring the role of different electrode-placements and pulse-widths.

    PubMed

    Gálvez, Verònica; Li, Adrienne; Oxley, Cristal; Waite, Susan; De Felice, Nick; Hadzi-Pavlovic, Dusan; Kumar, Divya; Page, Andrew C; Hooke, Geoff; Loo, Colleen K

    2016-12-01

    Prior research has shown large improvements in HRQOL after a course of ECT for depression. However, the effect of different types of ECT on HRQOL outcomes has not been explored. This is important due to the considerable range of ECT treatment modalities that currently exist in clinical practice. HRQOL data from 355 depressed patients in three Australian clinical hospitals, who received ECT given with a range of treatment modalities (combinations of pulse-width and electrode-placement), were analysed. HRQOL was measured at baseline and after ECT, using the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF). The association between type of ECT and HRQOL after ECT was examined by regression analysis, controlling for variables that may affect HRQOL outcomes. There was a significant increase in HRQOL scores after ECT (p<0.0001; t=-23.4). The magnitude of change was large (54% increase, Cohen's d=1.43). Multiple regression analysis yielded a significant model (P<0.001, R 2 =0.18). Baseline HRQOL score (t=4.83; p<0.0001), age (t=2.75, p<0.01) and type of ECT received [Right Unilateral brief vs Bitemporal Ultrabrief (t=-2.99; p<0.01) and Right Unilateral brief vs Bifrontal Ultrabrief (t=-2.70; p<0.01)] were significant predictors of HRQOL after the ECT course. Data was collected naturalistically from clinical services, thus ECT modality was not randomly assigned. Site could have confounded results. An acute course of ECT for depression produced statistically and clinically significant improvements in HRQOL. ECT treatment modality can substantially impact HRQOL outcomes, with the possibility of bilateral ultrabrief forms of ECT being less beneficial. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Viral Activation of MK2-hsp27-p115RhoGEF-RhoA Signaling Axis Causes Cytoskeletal Rearrangements, P-body Disruption and ARE-mRNA Stabilization

    PubMed Central

    Corcoran, Jennifer A.; Johnston, Benjamin P.; McCormick, Craig

    2015-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) is the infectious cause of several AIDS-related cancers, including the endothelial cell (EC) neoplasm Kaposi's sarcoma (KS). KSHV-infected ECs secrete abundant host-derived pro-inflammatory molecules and angiogenic factors that contribute to tumorigenesis. The precise contributions of viral gene products to this secretory phenotype remain to be elucidated, but there is emerging evidence for post-transcriptional regulation. The Kaposin B (KapB) protein is thought to contribute to the secretory phenotype in infected cells by binding and activating the stress-responsive kinase MK2, thereby selectively blocking decay of AU-rich mRNAs (ARE-mRNAs) encoding pro-inflammatory cytokines and angiogenic factors. Processing bodies (PBs) are cytoplasmic ribonucleoprotein foci in which ARE-mRNAs normally undergo rapid 5′ to 3′ decay. Here, we demonstrate that PB dispersion is a feature of latent KSHV infection, which is dependent on kaposin protein expression. KapB is sufficient to disperse PBs, and KapB-mediated ARE-mRNA stabilization could be partially reversed by treatments that restore PBs. Using a combination of genetic and chemical approaches we provide evidence that KapB-mediated PB dispersion is dependent on activation of a non-canonical Rho-GTPase signaling axis involving MK2, hsp27, p115RhoGEF and RhoA. PB dispersion in latently infected cells is likewise dependent on p115RhoGEF. In addition to PB dispersion, KapB-mediated RhoA activation in primary ECs caused actin stress fiber formation, increased cell motility and angiogenesis; these effects were dependent on the activity of the RhoA substrate kinases ROCK1/2. By contrast, KapB-mediated PB dispersion occurred in a ROCK1/2-independent manner. Taken together, these observations position KapB as a key contributor to viral reprogramming of ECs, capable of eliciting many of the phenotypes characteristic of KS tumor cells, and strongly contributing to the post

  10. Electroconvulsive Therapy in Sweden 2013: Data From the National Quality Register for ECT.

    PubMed

    Nordanskog, Pia; Hultén, Martin; Landén, Mikael; Lundberg, Johan; von Knorring, Lars; Nordenskjöld, Axel

    2015-12-01

    The use of electroconvulsive therapy (ECT) varies across countries. The aim of this study was to describe and explore the use of ECT in Sweden in 2013. The Swedish mandatory patient register of the National Board of Health and Welfare includes information on diagnoses and treatments, including ECT. All 56 hospitals that provide ECT in Sweden also report to the nonmandatory national quality register for ECT, which contains information on patient and treatment characteristics. In this study, we combined data from both registers. In addition, all hospitals responded to a survey concerning equipment and organization of ECT. We identified 3972 unique patients who received ECT in Sweden in 2013. This translates into 41 ECT-treated individuals per 100,000 inhabitants. Of these patients, 85% opted to participate in the quality register. The median age was 55 years (range, 15-94 years), and 63% were women. The indication was depression in 78% of the treatment series. Of 4 711 hospitalized patients with severe depression, 38% received ECT. The median number of treatments per index series was 7. Unilateral treatment was used in 86% of the series. In Sweden, ECT is used at a relatively high rate as compared with other western countries, and the rate was unchanged from the last survey in 1975. However, there is room for improvement in the specificity of use and availability of ECT for disorders where ECT is considered a first-line treatment.

  11. Electroconvulsive therapy (ECT) in Parkinson's disease: ECS and dopamine enhancement.

    PubMed

    Cumper, Samantha K; Ahle, Gabriella M; Liebman, Lauren S; Kellner, Charles H

    2014-06-01

    In addition to its effects in major psychiatric illness, electroconvulsive therapy (ECT) is known to have a beneficial effect on the core motor symptoms of Parkinson's disease (PD). This effect is believed to be mediated via dopamine in the striatum. Electroconvulsive shock (ECS), the animal analogue of ECT, is the model in which investigators have sought to elucidate the specific dopaminergic mechanisms by which ECT exerts its therapeutic effect in PD. Electroconvulsive shock has been given to intact animals as well as to animals with neurotoxic lesions that create parkinsonism. In this paper, we selectively review the electroconvulsive shock literature on dopamine in the striatum. Electroconvulsive shock, and by extension, ECT, is associated with increased dopamine release and modulation of dopamine receptors. Better understanding of how ECT works to enhance dopaminergic systems in the brain could help to make it a more accepted treatment for PD.

  12. The use of ketamine in ECT anaesthesia: A systematic review and critical commentary on efficacy, cognitive, safety and seizure outcomes.

    PubMed

    Gálvez, Verònica; McGuirk, Lucy; Loo, Colleen K

    2017-09-01

    This review will discuss ECT efficacy and cognitive outcomes when using ketamine as an ECT anaesthetic compared to other anaesthetics, taking into account important moderator variables that have often not been considered to date. It will also include information on safety and other ECT outcomes (seizure threshold and quality). A systematic search through MEDLINE, PubMed, PsychINFO, Cochrane Databases and reference lists from retrieved articles was performed. Search terms were: "ketamine" and "Electroconvulsive Therapy", from 1995 to September 2016. Meta-analyses, randomised controlled trials, open-label and retrospective studies published in English of depressed samples receiving ECT with ketamine anaesthesia were included (n = 24). Studies were heterogeneous in the clinical populations included and ECT treatment and anaesthetic methods. Frequently, studies did not report on ECT factors (i.e., pulse-width, treatment schedule). Findings regarding efficacy were mixed. Tolerance from repeated use may explain why several studies found that ketamine enhanced efficacy early in the ECT course but not at the end. The majority of studies did not comprehensively examine cognition and adverse effects were not systematically studied. Only a minority of the studies reported on seizure threshold and expression. The routine use of ketamine anaesthesia for ECT in clinical settings cannot yet be recommended based on published data. Larger randomised controlled trials, taking into account moderator variables, specifically reporting on ECT parameters and systematically assessing outcomes are encouraged.

  13. The Incidence and Predictors of Headache and Myalgia in Patients After Electroconvulsive Therapy (ECT).

    PubMed

    Haghighi, Mohammad; Sedighinejad, Abbas; Naderi Nabi, Bahram; Emiralavi, Cyrus; Biazar, Gelareh; Mirmozaffari, Kaveh; Zahedan, Cyrus; Jafari, Mehdi

    2016-06-01

    Electroconvulsive therapy (ECT) is a safe and effective mode of therapy for a wide variety of psychiatric disorders. However, it is associated with some disturbing side effects, such as nausea and vomiting, dental and tongue injury, confusion, dizziness, headache, and myalgia. The present study focused on the evaluation of myalgia and headache and their predictors after ECT. A prospective analytical descriptive study was conducted from October 2014 to January 2015, in an academic hospital in northern Iran. Before sampling, the study was approved by the ethics committee of Guilan University of Medical Sciences. 621 patients with psychiatric disorders who were referred to Shafa hospital enrolled in the study. They were evaluated based on a verbal rating scale (4 point scales) 6 hours after ECT, regarding headache and myalgia side effects. 6 hours after ECT, 126 patients (21.9%) reported headaches, and 56 patients (9%) reported myalgia. The presence of headache or myalgia 6 hours after ECT was not correlated to the duration of convulsion, treatment sessions, sex, or age. But myalgia at 2 hours after treatment was correlated with sex (0.04). Sex, age, duration of seizure, and treatment sessions were not predictors of headache and myalgia 6 hours after ECT (log regression, enter mode). The intensity and frequency of headaches decreased during 6 hours after ECT (P = 0.0001 and P = 0.0001, respectively), and myalgia frequency decreased (P = 0.062) but the intensity increased (P = 0.87). The results of the present study demonstrate that headache after ECT procedures was more common than myalgia, but it was mild, tolerable, and decreased within 6 hours of the treatment. It is also notable that we did not found any predictors for post-ECT headache and myalgia.

  14. The Incidence and Predictors of Headache and Myalgia in Patients After Electroconvulsive Therapy (ECT)

    PubMed Central

    Haghighi, Mohammad; Sedighinejad, Abbas; Naderi Nabi, Bahram; Emiralavi, Cyrus; Biazar, Gelareh; Mirmozaffari, Kaveh; Zahedan, Cyrus; Jafari, Mehdi

    2016-01-01

    Background: Electroconvulsive therapy (ECT) is a safe and effective mode of therapy for a wide variety of psychiatric disorders. However, it is associated with some disturbing side effects, such as nausea and vomiting, dental and tongue injury, confusion, dizziness, headache, and myalgia. Objectives: The present study focused on the evaluation of myalgia and headache and their predictors after ECT. Patients and Methods: A prospective analytical descriptive study was conducted from October 2014 to January 2015, in an academic hospital in northern Iran. Before sampling, the study was approved by the ethics committee of Guilan University of Medical Sciences. 621 patients with psychiatric disorders who were referred to Shafa hospital enrolled in the study. They were evaluated based on a verbal rating scale (4 point scales) 6 hours after ECT, regarding headache and myalgia side effects. Results: 6 hours after ECT, 126 patients (21.9%) reported headaches, and 56 patients (9%) reported myalgia. The presence of headache or myalgia 6 hours after ECT was not correlated to the duration of convulsion, treatment sessions, sex, or age. But myalgia at 2 hours after treatment was correlated with sex (0.04). Sex, age, duration of seizure, and treatment sessions were not predictors of headache and myalgia 6 hours after ECT (log regression, enter mode). The intensity and frequency of headaches decreased during 6 hours after ECT (P = 0.0001 and P = 0.0001, respectively), and myalgia frequency decreased (P = 0.062) but the intensity increased (P = 0.87). Conclusions: The results of the present study demonstrate that headache after ECT procedures was more common than myalgia, but it was mild, tolerable, and decreased within 6 hours of the treatment. It is also notable that we did not found any predictors for post-ECT headache and myalgia. PMID:27761416

  15. Propofol for ECT anesthesia a review of the literature.

    PubMed

    Rasmussen, Keith G

    2014-09-01

    Propofol is a commonly used anesthetic drug for electroconvulsive therapy (ECT), as evidenced by the frequency with which its use is reported in ECT literature. Concerns have been raised over its propensity to be associated with shortened seizure duration vis-à-vis other anesthetic drugs, thus limiting its use in some settings. However, in the surgical anesthesia literature, propofol has shown distinct advantages such as improved hemodynamics and postanesthesia recovery. Given the capricious availability of standard barbiturate anesthetics in some countries, propofol use has probably increased. Thus, a review of its profile for a number of outcome measures in ECT is appropriate. Herein, the author reviews the extensive literature for propofol in ECT, focusing on 5 outcome measures: seizure duration, hemodynamics, postanesthesia recovery, cognitive adverse effects, and therapeutic efficacy. Results indicate that propofol is indeed robustly associated with shorter seizures than other anesthetics but that antidepressant efficacy does not seem to be compromised. Heart rate and blood pressure changes are not as high with propofol, and postanesthesia recovery may be quicker with propofol as well. Not enough data are available regarding cognitive adverse effects to make definitive conclusions, but so far, there does not seem to be a worsened cognitive profile when it is used in ECT. Propofol seems to be an acceptable anesthetic for ECT with advantages for some situations. Using the lowest effective anesthetic dosage minimizes its effect on seizure elicitation and duration.

  16. A report on the introduction of ultrabrief pulse width ECT in a private psychiatric hospital.

    PubMed

    Galletly, Cherrie; Paterson, Tom; Burton, Cassandra

    2012-03-01

    We report on 6 months of data since the introduction of ultrabrief pulse width electroconvulsive therapy (UB ECT) at a private psychiatric hospital in Adelaide. Results suggest that psychiatrists welcomed the availability of UB ECT, with an increase in prescription of ECT. About a quarter of UB ECT patients changed to standard pulse width (SPW) ECT, but those who did respond to UB ECT had an equivalent response to those who had SPW ECT. Courses of treatment were longer with UB ECT, which was reflected in an increased length of stay.

  17. Defect images by planar ECT probe of meander-mesh coils

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yamada, Sotoshi; Katou, Masaki; Iwahara, Masayoshi

    1996-09-01

    This paper presents results pertaining to image data obtained from a planar meander-mesh coupled coil type ECT probe. The image data makes it possible to detect not only the existence of a defect but also to extract detailed information regarding the nature of the defect, such as its position, shape, length, and direction. In order to recognize a defect distinctly, the authors have fabricated the high sensitive planar coil which can be used to image a 2-D representation of the ECT signal. The relationships between the image pattern and defect shape are discussed.

  18. An Assessment of the Subseasonal Forecast Performance in the Extended Global Ensemble Forecast System (GEFS)

    NASA Astrophysics Data System (ADS)

    Sinsky, E.; Zhu, Y.; Li, W.; Guan, H.; Melhauser, C.

    2017-12-01

    Optimal forecast quality is crucial for the preservation of life and property. Improving monthly forecast performance over both the tropics and extra-tropics requires attention to various physical aspects such as the representation of the underlying SST, model physics and the representation of the model physics uncertainty for an ensemble forecast system. This work focuses on the impact of stochastic physics, SST and the convection scheme on forecast performance for the sub-seasonal scale over the tropics and extra-tropics with emphasis on the Madden-Julian Oscillation (MJO). A 2-year period is evaluated using the National Centers for Environmental Prediction (NCEP) Global Ensemble Forecast System (GEFS). Three experiments with different configurations than the operational GEFS were performed to illustrate the impact of the stochastic physics, SST and convection scheme. These experiments are compared against a control experiment (CTL) which consists of the operational GEFS but its integration is extended from 16 to 35 days. The three configurations are: 1) SPs, which uses a Stochastically Perturbed Physics Tendencies (SPPT), Stochastic Perturbed Humidity (SHUM) and Stochastic Kinetic Energy Backscatter (SKEB); 2) SPs+SST_bc, which uses a combination of SPs and a bias-corrected forecast SST from the NCEP Climate Forecast System Version 2 (CFSv2); and 3) SPs+SST_bc+SA_CV, which combines SPs, a bias-corrected forecast SST and a scale aware convection scheme. When comparing to the CTL experiment, SPs shows substantial improvement. The MJO skill has improved by about 4 lead days during the 2-year period. Improvement is also seen over the extra-tropics due to the updated stochastic physics, where there is a 3.1% and a 4.2% improvement during weeks 3 and 4 over the northern hemisphere and southern hemisphere, respectively. Improvement is also seen when the bias-corrected CFSv2 SST is combined with SPs. Additionally, forecast performance enhances when the scale aware

  19. ECT and Pronounced Impairment in Spatial Cognition: The Fallacy of Drawing Conclusions From a Single Case.

    PubMed

    Andrade, Chittaranjan; Prasad, Yameni; Devaraj, Aathira; Pinto, Ekta Franscina; Shukla, Lekhansh

    2018-06-01

    Electroconvulsive therapy (ECT) is associated with memory deficits on neuropsychological assessment. The association of ECT with nonmemory cognitive deficits has been poorly studied. We present a 40-year-old woman who showed a bizarre form of spatial cognition impairment on a subtest of the Tactual Performance Test (TPT) after recovering from depression with 6 alternate day, thrice-weekly, inpatient ECT treatments. This woman was part of a naturalistic, nonblind study that examined nonmemory cognitive deficits in antidepressant-treated depressed patients who did and did not receive ECT. The impairment was in the form of bizarrely drawn reproductions of differently shaped wooden blocks that had been presented to the patient when she was blindfolded. The impairment was still evident when she was retested (3 hours later) under substantially simplified conditions but was much attenuated approximately 2.5 weeks later. On the surface, it seems that ECT had induced severe impairment in spatial cognition and that the impairment showed the familiar pattern of attenuation with the passage of time. However, another recovered patient in the study, who did not receive ECT, also showed substantial spatial deficits on the same subtest of the TPT, and the attenuation of the deficits across time in the ECT-treated patient was probably a result of repeated exposure to the task. We suggest that not all patients who seem to experience spectacular cognitive impairment after ECT have deficits that are attributable to ECT.

  20. Crystallization and preliminary X-ray analysis of CTP:phosphoethanolamine cytidylyltransferase (ECT) from Saccharomyces cerevisiae

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ohtsuka, Jun; Nagata, Koji; Lee, Woo Cheol

    2006-10-01

    CTP:phosphoethanolamine cytidylyltransferase from S. cerevisiae has been expressed, purified and crystallized. CTP:phosphoethanolamine cytidylyltransferase (ECT) is the enzyme that catalyzes the conversion of phosphoethanolamine to CDP-ethanolamine in the phosphatidylethanolamine-biosynthetic pathway (Kennedy pathway). ECT from Saccharomyces cerevisiae was crystallized by the sitting-drop vapour-diffusion method using PEG 4000 as precipitant. The crystals diffracted X-rays from a synchrotron-radiation source to 1.88 Å resolution. The space group was assigned as primitive tetragonal, P4{sub 1}2{sub 1}2 or P4{sub 3}2{sub 1}2, with unit-cell parameters a = b = 66.3, c = 150.8 Å. The crystals contain one ECT molecule in the asymmetric unit (V{sub M} = 2.2more » Å{sup 3} Da{sup −1}), with a solvent content of 43%.« less

  1. "Side effects" of ECT are mainly depressive phenomena and are independent of age.

    PubMed

    Brodaty, H; Berle, D; Hickie, I; Mason, C

    2001-10-01

    The aetiology of reported side effects of electroconvulsive therapy (ECT) is unclear. We examined the interaction of depression and age on adverse neuropsychological and putative side effects of ECT. Inpatients (N=81; median age 70 years) with major depression were assessed prospectively pre-ECT, immediately post-ECT and 1-3 years later. Patients were administered the Hamilton Rating Scale for Depression (HRSD), the Global Assessment of Functioning scale (GAF) and neuropsychological tests from the Wechsler Memory Scale. Side effects and total burden scores were rated pre- and post-treatment. HRSD and GAF scores improved with treatment after ECT, but the prevalence and total burden of side effects were unchanged. Side effect burden was related to depression level before and after ECT. Improvement in depression correlated with reduction in side effect burden. There was a significant decline in side effect burden after controlling for change in depression. Patients' scores on neuropsychological measures did not appear to change after ECT or between pre-ECT and follow-up. Re-analysis, allowing for age, chronicity of depression, medication use and development of dementia, did not alter the findings. lack of a control group, lack of information on ECT technique, incomplete data sets and limited neuropsychological testing. ECT, an effective treatment for depression, does not cause significant side effects or neuropsychological impairment, which are more likely to be depressive phenomena. ECT appears to be safe for old (> or =65 years) and very old (> or =75 years) patients, who do not appear to be more susceptible to adverse effects.

  2. Emerging Communication Technologies (ECT) Phase 4 Report

    NASA Technical Reports Server (NTRS)

    Bastin, Gary L.; Harris, William G.; Marin, Jose A.; Nelson, Richard A.

    2005-01-01

    The Emerging Communication Technology (ECT) project investigated three First Mile communication technologies in support of NASA s Crew Exploration Vehicle (CEV), Advanced Range Technology Working Group (ARTWG), and the Advanced Spaceport Technology Working Group (ASTWG). These First Mile technologies have the purpose of interconnecting mobile users with existing Range Communication infrastructures on a 24/7 basis. ECT is a continuation of the Range Information System Management (RISM) task started in 2002. This is the fourth year of the project.

  3. From Information to Simulation: Improving Competency in ECT Training Using High-Fidelity Simulation.

    PubMed

    Raysin, Anetta; Gillett, Brian; Carmody, Joseph; Goel, Nidhi; McAfee, Scot; Jacob, Theresa

    2017-12-18

    This study was intended to develop a new educational model that supplements ECT didactics with simulation-based procedural training and to evaluate the learning gains conferred by such a curriculum. Two types of curricula were evaluated for educational efficacy in this prospective randomized controlled trial. Psychiatry residents (n = 35) completed surveys to ascertain their baseline experience, knowledge, and proficiency with the ECT procedure. They were then block-randomized to receive either a didactic ECT curriculum (non-SIM) or one augmented by simulation training (SIM). Three months post-completion of the two types of instruction, all residents were re-administered the surveys and a procedural post-assessment. The median number of ECTs performed prior to the study was similar between the two groups (SIM group = 3, non-SIM group = 4.) The SIM group showed significant improvement on pre- and post- survey theoretical knowledge scores: 51% (95% CI = 41 to 61%) and 69% (95% CI = 64 to 74%), respectively, p = .02; this difference was not significant in the non-SIM group, p = .2. Improvement between pre- and post- proficiency scores were seen in the SIM group: 22% (95% CI = 13 to 32%) and 51% (95% CI = 53 to 59%), p < .001 while the effect was less pronounced in the non-SIM group. Inter-rater agreement for the proficiency assessment was excellent: k, = .9. Residents showed significant improvement in knowledge, comfort, and skills following ECT simulation training. With the proposed curriculum, residents would receive comprehensive education not only in the theory behind ECT but also in procedural skills. This curriculum can be modeled in other programs that do not have extensive ECT facilities.

  4. Knowledge of and attitudes towards electroconvulsive therapy (ECT) among psychiatrists and family physicians in Saudi Arabia.

    PubMed

    AlHadi, Ahmad N; AlShahrani, Fahad M; Alshaqrawi, Ali A; Sharefi, Mohanned A; Almousa, Saud M

    2017-01-01

    To assess the knowledge of and attitudes towards ECT among psychiatrists and family physicians in Saudi Arabia. The study is quantitative observational cross-sectional with a convenient sample that included psychiatrists and family physicians (including residents) in Saudi Arabia. Of the 434 questionnaires emailed, a total of 126 returned completed questionnaires (29% response rate). The mean age of respondents was 35 years old. Psychiatrists accounted for 68.3%. The majority were Saudis (95.2%) and male (70.6%). Around half were consultants and about two-thirds (62.7%) had worked in a facility that used ECT. Psychiatrists showed better knowledge than family physicians in their answers, with a mean total knowledge scoring of 8.12 (±1.25) out of 10 and 6.15 (±1.25), respectively ( P  < 0.0001). Among psychiatrists, 87% thought that ECT required general anesthesia, while 35% of family physicians believed so ( P  < 0.0001). Other items of ECT knowledge are discussed. Psychiatrists displayed a better attitude towards ECT than family physicians in all answers, with a mean score of 9.54 (±1.16) and 7.85 (±2.39), respectively ( P  < 0.0001). Psychiatrists scored better than family physicians in both knowledge and attitude regarding ECT.

  5. Speed of response in ultrabrief and brief pulse width right unilateral ECT.

    PubMed

    Loo, Colleen K; Garfield, Joshua B B; Katalinic, Natalie; Schweitzer, Isaac; Hadzi-Pavlovic, Dusan

    2013-05-01

    Ultrabrief pulse width stimulation electroconvulsive therapy (ECT) results in less cognitive side-effects than brief pulse ECT, but recent work suggests that more treatment sessions may be required to achieve similar efficacy. In this retrospective analysis of subjects pooled from three research studies, time to improvement was analysed in 150 depressed subjects who received right unilateral ECT with a brief pulse width (at five times seizure threshold) or ultrabrief pulse width (at six times seizure threshold). Multivariate Cox regression analyses compared the number of treatments required for 50% reduction in depression scores (i.e. speed of response) in these two samples. The analyses controlled for clinical, demographic and treatment variables that differed between the samples or that were found to be significant predictors of speed of response in univariate analyses. In the multivariate analysis, older age predicted faster speed of response. There was a non-significant trend for faster time to 50% improvement with brief pulse ECT (p = 0.067). Remission rates were higher after brief pulse ECT than ultrabrief pulse ECT (p = 0.007) but response rates were similar. This study, the largest of its kind reported to date, suggests that fewer treatments may be needed to attain response with brief than ultrabrief pulse ECT and that remission rates are higher with brief pulse ECT. Further research with a larger randomized and blinded study is recommended.

  6. A naturalistic study of high-dose unilateral ECT among severely depressed inpatients: how does it work in the clinical practice?

    PubMed

    Alves, Lucas P C; Freire, Thiago F V; Fleck, Marcelo P A; Rocha, Neusa S

    2016-11-11

    Naturalistic studies can be useful tools to understand how an intervention works in the real clinical practice. This study aims to investigate the outcomes in a naturalistically treated depressed inpatients cohort, who were referred, or not, to unilateral ECT. Depressed adults according to MINI admitted in a psychiatric unit were divided in unilateral ECT treated and non-ECT treated. Main outcomes were: depression improvement in Hamilton Rating Scale for Depression (HDRS-17) scores; response (HDRS-17 improvement ≥50 %); remission (HDRS-17 score ≤7); length of hospitalization. Forty-three patients were included in unilateral ECT group and 104 in non-ECT group. No differences of psychotic symptoms, melancholic features or past maniac episode were found between groups. Unilateral ECT group had a mean HDRS-17 score higher than non-ECT group at admission (ECT: 25.05 ± 1.03; non-ECT: 21.61 ± 0.69; p = 0.001), but no significant difference was found at discharge (ECT: 7.70 ± 0.81; non-ECT: 7.40 ± 0.51; p = 0.75). Unilateral ECT group had a larger HDRS-17 score reduction during treatment (ECT: 18.24 ± 1.18; non-ECT:14.20 ± 0.76; p = 0.004). There were no significant differences in response and remission rates between groups. Unilateral ECT group had longer mean duration of hospitalization in days (ECT: 35.48 ± 2.48; non-ECT: 24.57 ± 1.50; p < 0.001), but there were no difference in mean time of treatment (ECT group:27.66 ± 1.95; non-ECT: 24.57 ± 1.50; p = 0.25). Unilateral high-dose ECT is still a useful treatment option, in the real world clinical practice, to reduce the intensity of depressive symptoms in highly depressed inpatients.

  7. 7 CFR 985.31 - Research and development proj-ects.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Research and development proj-ects. 985.31 Section 985.31 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING... Research § 985.31 Research and development proj-ects. The Committee, with the approval of the Secretary...

  8. 7 CFR 985.31 - Research and development proj-ects.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Research and development proj-ects. 985.31 Section 985.31 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING... Research § 985.31 Research and development proj-ects. The Committee, with the approval of the Secretary...

  9. 7 CFR 985.31 - Research and development proj-ects.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Research and development proj-ects. 985.31 Section 985.31 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING... Research § 985.31 Research and development proj-ects. The Committee, with the approval of the Secretary...

  10. 7 CFR 985.31 - Research and development proj-ects.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Research and development proj-ects. 985.31 Section 985.31 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING... Research § 985.31 Research and development proj-ects. The Committee, with the approval of the Secretary...

  11. The Global ECT-MRI Research Collaboration (GEMRIC): Establishing a multi-site investigation of the neural mechanisms underlying response to electroconvulsive therapy.

    PubMed

    Oltedal, Leif; Bartsch, Hauke; Sørhaug, Ole Johan Evjenth; Kessler, Ute; Abbott, Christopher; Dols, Annemieke; Stek, Max L; Ersland, Lars; Emsell, Louise; van Eijndhoven, Philip; Argyelan, Miklos; Tendolkar, Indira; Nordanskog, Pia; Hamilton, Paul; Jorgensen, Martin Balslev; Sommer, Iris E; Heringa, Sophie M; Draganski, Bogdan; Redlich, Ronny; Dannlowski, Udo; Kugel, Harald; Bouckaert, Filip; Sienaert, Pascal; Anand, Amit; Espinoza, Randall; Narr, Katherine L; Holland, Dominic; Dale, Anders M; Oedegaard, Ketil J

    2017-01-01

    Major depression, currently the world's primary cause of disability, leads to profound personal suffering and increased risk of suicide. Unfortunately, the success of antidepressant treatment varies amongst individuals and can take weeks to months in those who respond. Electroconvulsive therapy (ECT), generally prescribed for the most severely depressed and when standard treatments fail, produces a more rapid response and remains the most effective intervention for severe depression. Exploring the neurobiological effects of ECT is thus an ideal approach to better understand the mechanisms of successful therapeutic response. Though several recent neuroimaging studies show structural and functional changes associated with ECT, not all brain changes associate with clinical outcome. Larger studies that can address individual differences in clinical and treatment parameters may better target biological factors relating to or predictive of ECT-related therapeutic response. We have thus formed the Global ECT-MRI Research Collaboration (GEMRIC) that aims to combine longitudinal neuroimaging as well as clinical, behavioral and other physiological data across multiple independent sites. Here, we summarize the ECT sample characteristics from currently participating sites, and the common data-repository and standardized image analysis pipeline developed for this initiative. This includes data harmonization across sites and MRI platforms, and a method for obtaining unbiased estimates of structural change based on longitudinal measurements with serial MRI scans. The optimized analysis pipeline, together with the large and heterogeneous combined GEMRIC dataset, will provide new opportunities to elucidate the mechanisms of ECT response and the factors mediating and predictive of clinical outcomes, which may ultimately lead to more effective personalized treatment approaches.

  12. The use of ECT and MST in treating depression.

    PubMed

    Allan, Charlotte L; Ebmeier, Klaus P

    2011-10-01

    Electroconvulsive therapy (ECT) has been used clinically since 1938. Its most common use is in the treatment of depression: first line treatment where rapid recovery is a priority, but more frequently as an effective treatment for patients who do not respond to pharmacological and psychological approaches. Whilst it is widely hailed as an effective treatment, concerns about its effect on cognition remain. The development of magnetic seizure therapy (MST) over the past decade has attempted to devise a therapy with comparable efficacy to ECT, but without the associated cognitive side effects. The rationale for this is that MST uses magnetic fields to induce seizures in the cortex, without electrical stimulation of brain structures involved with memory. MST has been used successfully in the treatment of depression, yet there is a dearth of literature in comparison with ECT. We present a systematic review of the literature on ECT (from 2009-2011) and MST (from 2001-2011).

  13. Representations of ECT in English-Language Film and Television in the New Millennium.

    PubMed

    Matthews, Avery Madeleine; Rosenquist, Peter B; McCall, William Vaughn

    2016-09-01

    The aim of the study was to survey the media landscape to determine whether visual depictions of electroconvulsive therapy (ECT) are becoming more or less medically accurate in the new millennium. English-language film and television shows depicting ECT were analyzed for patient demographics, administrator roles, indication, consent, anesthesia, paralytics, bite block, lead placement, electroencephalogram, and outcome. Thirty-nine ECT scenes were viewed, and just 3 included all 5 essential tools of modern ECT: anesthesia, paralytic, electrodes, electroencephalogram, and a bite block. Media depictions of ECT do not reflect current practice. Too often, ECT is portrayed as a torture technique rather than an evidenced-based therapy, and even in a therapeutic setting, it is too often shown with outdated techniques.

  14. An audit of ECT in England 2011-2015: Usage, demographics, and adherence to guidelines and legislation.

    PubMed

    Read, John; Harrop, Christopher; Geekie, Jim; Renton, Julia

    2017-10-20

    Electroconvulsive therapy (ECT) continues to be used in England, but without comprehensive national auditing. Therefore, information was gathered on usage, demographics, consent, and adherence to the guidelines of the National Institute of Clinical Excellence (N.I.C.E.) and to the Mental Health Act. Freedom of Information Act requests were sent to 56 National Health Service Trusts. Thirty-two trusts provided some usable data. Only 10 were able to report how many people received psychological therapy prior to ECT in accordance with N.I.C.E. recommendations, with figures ranging from 0% to 100%. The number of people currently receiving ECT in England annually is between 2,100 and 2,700, and falling. There was a 12-fold difference between the Trusts with the highest and lowest usage rates per capita. Most recipients are still women (66%) and over 60 (56%). More than a third (39%) is given without consent, with 30% of Trusts not adhering to mental health legislation concerning second opinions. At least 44% were not using validated measures of efficacy, and at least 33% failed to do so for adverse effects. Only four provided any actual data for positive outcomes or adverse effects. None provided any data on efficacy beyond the end of treatment. National audits should be reinstated. Independent, objective monitoring of adverse effects is urgently required. An investigation into why ECT is still administered excessively to older people and women seems long overdue. Mental health staff should seek to ensure that all depressed people in their service are offered evidence-based psychological treatments before being offered E.C.T. Staff should lobby managers to ensure proper auditing of E.C.T. within their service Individuals receiving ECT should be closely monitored for adverse cognitive effects Overuse of ECT with women and older people should be avoided. © 2017 The British Psychological Society.

  15. What was learned: studies by the consortium for research in ECT (CORE) 1997-2011.

    PubMed

    Fink, M

    2014-06-01

    To review the findings of the four-hospital collaborative studies of electroconvulsive therapy (ECT) in unipolar depressed patients known as CORE between 1997 and 2011. Unipolar depressed patients were treated with bilateral ECT, and on remission were randomly assigned to a fixed schedule continuation ECT or to combined lithium and nortriptyline for 6 months. A second study compared three electrode placements in unipolar and bipolar depressed patients. Nineteen published reports were reviewed. The findings are compared with those of a parallel multi-hospital study of ECT led by a Columbia University Collaboration (CUC) team that studied right unilateral ECT in a similar population with similar inclusion/exclusion and remission criteria. Successful ECT was followed by placebo, nortriptyline alone, or combined lithium, and nortriptyline. Relapse rates after remission were similar with fixed schedule ECT as with medications. Predictors of outcome (psychosis, suicide risk, polarity, melancholia, atypical depression, age) and technical aspects (electrode placement, seizure threshold, speed of response) are discussed, The findings offer criteria to optimize the selection of patients, the technique, and outcome of ECT for unipolar and bipolar depressed patients. Continuation ECT is an effective alternative to continuation treatment with lithium and nortriptyline. Bilateral electrode placement is more efficient than alternative placements. ECT relieves both bipolar and unipolar depression. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Electroconvulsive therapy (ECT) in literature: Sylvia Plath's The Bell Jar.

    PubMed

    Kellner, Charles H

    2013-01-01

    Sylvia Plath's well-known novel, The Bell Jar, recounts her experience of a severe depressive episode. In the novel, the protagonist is treated with electroconvulsive therapy (ECT), as was Plath in life. The first ECT is given in the now-obsolete "unmodified" form, without general anesthesia. Later in the story, she receives ECT again, this time with full general anesthesia and muscle relaxation, as is the standard of care today. This chapter examines how the novelistic descriptions of the treatment compare with actual clinical practice. © 2013 Elsevier B.V. All rights reserved.

  17. Low-dose right unilateral electroconvulsive therapy (ECT): effectiveness of the first treatment.

    PubMed

    Lapidus, Kyle A B; Shin, Joseph S W; Pasculli, Rosa M; Briggs, Mimi C; Popeo, Dennis M; Kellner, Charles H

    2013-06-01

    Electroconvulsive therapy (ECT) is a widely used, highly effective antidepressant treatment. Except for the most severely ill patients, right unilateral (RUL) electrode placement is the most frequent initial treatment choice. In current practice, RUL ECT is administered at several multiples of seizure threshold (ST) based on reports that lower stimulus intensity results in lower response/remission rates. Many patients, as part of an initial dose titration to determine ST, will receive a single treatment with low-dose RUL ECT and subsequent treatments with a stimulus at a multiple of ST. To assess response to the first ECT. A retrospective analysis of charts from clinical practice at Mount Sinai Medical Center was performed. A single treatment with low-dose (presumably near ST) RUL ECT had a significant and immediate antidepressant effect in our sample of patients with major depression. We determined that this response is similar to that of patients receiving a single initial treatment with high-dose RUL ECT (at a multiple of ST). These data suggest, contrary to commonly held belief, that RUL ECT may be effective at a low stimulus dose. This argues against restimulating at 6 times ST in the initial session, based on the belief that the near-threshold seizure has no antidepressant efficacy. Our findings suggest a need for further investigation of cases in which low-dose RUL ECT may be an effective antidepressant treatment. Further prospective studies, including larger numbers of patients who receive randomized treatment with low- or high-dose RUL with longer follow-up, are indicated.

  18. Fronto-Temporal Connectivity Predicts ECT Outcome in Major Depression.

    PubMed

    Leaver, Amber M; Wade, Benjamin; Vasavada, Megha; Hellemann, Gerhard; Joshi, Shantanu H; Espinoza, Randall; Narr, Katherine L

    2018-01-01

    Electroconvulsive therapy (ECT) is arguably the most effective available treatment for severe depression. Recent studies have used MRI data to predict clinical outcome to ECT and other antidepressant therapies. One challenge facing such studies is selecting from among the many available metrics, which characterize complementary and sometimes non-overlapping aspects of brain function and connectomics. Here, we assessed the ability of aggregated, functional MRI metrics of basal brain activity and connectivity to predict antidepressant response to ECT using machine learning. A radial support vector machine was trained using arterial spin labeling (ASL) and blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) metrics from n = 46 (26 female, mean age 42) depressed patients prior to ECT (majority right-unilateral stimulation). Image preprocessing was applied using standard procedures, and metrics included cerebral blood flow in ASL, and regional homogeneity, fractional amplitude of low-frequency modulations, and graph theory metrics (strength, local efficiency, and clustering) in BOLD data. A 5-repeated 5-fold cross-validation procedure with nested feature-selection validated model performance. Linear regressions were applied post hoc to aid interpretation of discriminative features. The range of balanced accuracy in models performing statistically above chance was 58-68%. Here, prediction of non-responders was slightly higher than for responders (maximum performance 74 and 64%, respectively). Several features were consistently selected across cross-validation folds, mostly within frontal and temporal regions. Among these were connectivity strength among: a fronto-parietal network [including left dorsolateral prefrontal cortex (DLPFC)], motor and temporal networks (near ECT electrodes), and/or subgenual anterior cingulate cortex (sgACC). Our data indicate that pattern classification of multimodal fMRI metrics can successfully predict ECT

  19. Transient febrile reaction after electroconvulsive therapy (ECT) in a young adult with intellectual disability and bipolar disorder.

    PubMed

    Majeske, Matthew F; Garakani, Amir; Maloutas, Eleni; Bryson, Ethan O; Kellner, Charles H

    2013-12-01

    We report the case of a 27-year-old man with mild-moderate intellectual disability (ID) and bipolar disorder treated with electroconvulsive therapy (ECT). He was psychiatrically hospitalized for agitation, aggression, and manic symptoms including insomnia, rapid and pressured speech, and hyperactivity. After multiple medication trials, ECT was recommended. The treatment was delayed owing to the need to obtain evaluation for incapacity and then substituted consent from the patient's mother. He received 2 ECT treatments with marked improvement but complicated by transient fevers, which resolved without treatment. Fever workup was unremarkable. The patient became calm and cooperative and was discharged home. He was readmitted 3 weeks later, again in an agitated manic state. He received 5 additional ECT treatments, but this time with no post-ECT fevers. Once again, his manic symptoms resolved, and he was safely discharged. Whereas patients with ID pose special challenges, our case is in keeping with the previous literature, which supports the use of ECT in patients with ID and comorbid psychiatric disorders.

  20. I was told it restarts your brain: knowledge, power, and women's experiences of ECT.

    PubMed

    Ejaredar, Maede; Hagen, Brad

    2014-02-01

    A discrepancy exists between clinician-led studies of people's experience of electroconvulsive therapy (ECT) and consumer-led studies, with the former typically being much more positive about the efficacy and side effects of ECT compared with the latter. Qualitative in-depth explorations of people's experiences of ECT are relatively rare, particularly those looking specifically at women's experience of ECT. The aim of this qualitative study was to explore women's experiences of ECT, particularly their experience of knowledge and power related to ECT. Qualitative analysis of the interviews with nine women resulted in four main themes emerging from the interviews with the women: (i) "he really didn't say much," (ii) "I'm going to be very upset with you," (iii) "I was just desperate," and (iv) "it was like we were cattle." Overall, participants found their experiences with ECT to be quite negative, and characterized by a lack of knowledge during the procedure, and a lack of power throughout the entire process.

  1. Effects of desmopressin (DDAVP) on memory impairment following electroconvulsive therapy (ECT).

    PubMed

    Abdollahian, Ebrahim; Sargolzaee, Mohammad R; Hajzade, Moosareza; Mohebbi, Mohammad D; Javanbakht, Arash

    2004-06-01

    Memory impairment is a common adverse effect of electroconvulsive therapy (ECT). Studies on animals and humans suggest that vasopressin improves the cognitive function, and positive effects of desmopressin on memory and learning have been reported. This research was performed for evaluation of the effects of desmopressin in the prevention of memory impairment following ECT. This randomized, double-blind controlled clinical trial with placebo administration was performed on 50 patients with psychiatric disorders who were candidates for ECT. Subjects in the case group received 60 µm of intranasal desmopressin daily (in three doses of 20 µm). For the control group 0.9% saline solution was administered in the same way. Memory function was evaluated using Wechsler's Memory Scale three times a week (the first time before the start of ECT and the second and third times after the third and sixth sessions, respectively). Results were analyzed by t-test and Paired t-test. The mean age of patients was 29 years (range 20-40). During the course of ECT, patients in the control group demonstrated a meaningful decrease in memory scores (from a base score of 80.15-75.45 in the second test and 72.60 in the third test). Despite this, a meaningful increase in memory scores was observed during the treatment with desmopressin in the case group (from a base score of 73.27-75.70 and 79.13 in the second and the third tests, respectively). There was a meaningful difference between the two groups (P < 0.0001). This study confirms the protective effect of desmopressin against memory impairment. The results confirm that memory impairment is a common side-effect of ECT and suggest that desmopressin may prevent ECT-induced memory impairment by its effects on memory and the learning process.

  2. The role of ECT in posttraumatic stress disorder: A systematic review.

    PubMed

    Youssef, Nagy A; McCall, W Vaughn; Andrade, Chittaranjan

    2017-02-01

    Posttraumatic stress disorder (PTSD) is associated with a high burden of disability and mortality and frequently is treatment resistant. There is little to offer patients who are not responding to standard interventions. Thus, the objective of this report is to systematically review human data on whether electroconvulsive therapy (ECT) is effective in PTSD. We performed a systematic literature review from 1958 through August 2016 for clinical studies and case reports published in English examining the efficacy of ECT in improving PTSD symptoms. The literature search generated 3 retrospective studies, 1 prospective uncontrolled clinical trial, and 5 case reports. It is not clear, given the small sample size and lack of a large randomized trial, whether favorable outcomes were attributed to improvement in depression (as opposed to core PTSD symptoms). Current efficacy data do not separate conclusively the effects of ECT on PTSD symptoms from those on depression. Randomized controlled trials are necessary to examine the use of ECT in medication-refractory PTSD patients with and without comorbid depression. Subsequent studies may address response in PTSD subtypes, and the use of novel techniques, such as memory reactivation, before ECT.

  3. A homogeneous quenching resonance energy transfer assay for the kinetic analysis of the GTPase nucleotide exchange reaction.

    PubMed

    Kopra, Kari; Ligabue, Alessio; Wang, Qi; Syrjänpää, Markku; Blaževitš, Olga; Veltel, Stefan; van Adrichem, Arjan J; Hänninen, Pekka; Abankwa, Daniel; Härmä, Harri

    2014-07-01

    A quenching resonance energy transfer (QRET) assay for small GTPase nucleotide exchange kinetic monitoring is demonstrated using nanomolar protein concentrations. Small GTPases are central signaling proteins in all eukaryotic cells acting as a "molecular switches" that are active in the GTP-state and inactive in the GDP-state. GTP-loading is highly regulated by guanine nucleotide exchange factors (GEFs). In several diseases, most prominently cancer, this process in misregulated. The kinetics of the nucleotide exchange reaction reports on the enzymatic activity of the GEF reaction system and is, therefore, of special interest. We determined the nucleotide exchange kinetics using europium-labeled GTP (Eu-GTP) in the QRET assay for small GTPases. After GEF catalyzed GTP-loading of a GTPase, a high time-resolved luminescence signal was found to be associated with GTPase bound Eu-GTP, whereas the non-bound Eu-GTP fraction was quenched by soluble quencher. The association kinetics of the Eu-GTP was measured after GEF addition, whereas the dissociation kinetics could be determined after addition of unlabeled GTP. The resulting association and dissociation rates were in agreement with previously published values for H-Ras(Wt), H-Ras(Q61G), and K-Ras(Wt), respectively. The broader applicability of the QRET assay for small GTPases was demonstrated by determining the kinetics of the Ect2 catalyzed RhoA(Wt) GTP-loading. The QRET assay allows the use of nanomolar protein concentrations, as more than 3-fold signal-to-background ratio was achieved with 50 nM GTPase and GEF proteins. Thus, small GTPase exchange kinetics can be efficiently determined in a HTS compatible 384-well plate format.

  4. Significantly improved neurocognitive function in major depressive disorders 6 weeks after ECT.

    PubMed

    Mohn, Christine; Rund, Bjørn Rishovd

    2016-09-15

    Cognitive side effects may occur after electroconvulsive treatment (ECT) in depressive disorder patients. Previous studies have been limited by small numbers of cognitive functions assessed. The present study reports the first results from a prospective project monitoring cognitive effects of ECT using a comprehensive neuropsychological test battery and subjective report of everyday cognitive function. Thirty-one patients with major depressive disorder were assessed with the MATRICS Consensus Cognitive Battery (MCCB). Subjective cognitive complaints were described with the Everyday Memory Questionnaire (EMQ). Severity of depression symptoms were assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS). These assessments were performed prior to and 6 weeks after non-standardized ECT. Compared to baseline, the mean depression severity level was nearly halved and there were significant improvements in mean levels of Speed of Processing, Attention/Vigilance, and Visual Learning 6 weeks after ECT. The other cognitive domains were not altered from baseline. There was no significant change in subjective cognitive complaints. At baseline, there were several significant correlations between the MADRS and MCCB scores. There was no strong association between the EMQ and MCCB scores at either assessment point, but the post-ECT EMQ score was significantly correlated with depression severity. Major limitations were low N and lack of uniform ECT procedure. There was significant improvement in Speed of Processing, Attention/Vigilance, and Visual Learning 6 weeks after ECT. Cognitive tests scores were related to severity of depression, but not to subjective memory complaints. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Structure of Shigella IpgB2 in Complex with Human RhoA

    PubMed Central

    Klink, Björn U.; Barden, Stephan; Heidler, Thomas V.; Borchers, Christina; Ladwein, Markus; Stradal, Theresia E. B.; Rottner, Klemens; Heinz, Dirk W.

    2010-01-01

    A common theme in bacterial pathogenesis is the manipulation of eukaryotic cells by targeting the cytoskeleton. This is in most cases achieved either by modifying actin, or indirectly via activation of key regulators controlling actin dynamics such as Rho-GTPases. A novel group of bacterial virulence factors termed the WXXXE family has emerged as guanine nucleotide exchange factors (GEFs) for these GTPases. The precise mechanism of nucleotide exchange, however, has remained unclear. Here we report the structure of the WXXXE-protein IpgB2 from Shigella flexneri and its complex with human RhoA. We unambiguously identify IpgB2 as a bacterial RhoA-GEF and dissect the molecular mechanism of GDP release, an essential prerequisite for GTP binding. Our observations uncover that IpgB2 induces conformational changes on RhoA mimicking DbI- but not DOCK family GEFs. We also show that dissociation of the GDP·Mg2+ complex is preceded by the displacement of the metal ion to the α-phosphate of the nucleotide, diminishing its affinity to the GTPase. These data refine our understanding of the mode of action not only of WXXXE GEFs but also of mammalian GEFs of the DH/PH family. PMID:20363740

  6. Electroconvulsive therapy (ECT) and aerobic exercise training (AET) increased plasma BDNF and ameliorated depressive symptoms in patients suffering from major depressive disorder.

    PubMed

    Salehi, Iraj; Hosseini, Seyed Mohammad; Haghighi, Mohammad; Jahangard, Leila; Bajoghli, Hafez; Gerber, Markus; Pühse, Uwe; Holsboer-Trachsler, Edith; Brand, Serge

    2016-05-01

    To treat patients suffering from major depressive disorder (MDD), research has focused on electroconvulsive therapy (ECT) and aerobic exercise training (AET). Brain derived neurotrophic factor (BDNF) seems to be key in MDD. The aims of the present study were therefore two-fold, to investigate in a three-arm interventional study the differential effects of ECT, ECT plus AET, and AET alone in patients suffering from TR-MDD on 1. depressive symptoms and 2. plasma BDNF (pBDNF). 60 patients with MDD (mean age: 31 years; 31.6% female patients) were randomly assigned either to the ECT, ECT + AET, or AET condition. The AET condition consisted of treadmill exercise for 45 min, three times a week. Both depression severity and pBDNF levels were assessed at baseline and 4 weeks later. All patients were further treated with an SSRI standard medication. pBDNF levels increased over time in all three study conditions, though, highest increase was observed in the ECT + EAT condition, and lowest increase was observed in the AET condition. Depressive symptoms decreased in all three conditions over time, though, strongest decrease was observed in the ECT + AET condition. The combination of ECT + AET led to significantly greater remission rates than in either the ECT or AET alone conditions. BDNF levels were not associated with symptoms of depression. The pattern of results suggests that ECT, AET and particularly their combination are promising directions for the treatment of patients suffering from MDD, and that it remains unclear to what extent pBDNF is key and a reliable biomarker for MDD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Maintenance ECT as a therapeutic approach to medication-refractory epilepsy in an adult with mental retardation: case report and review of literature.

    PubMed

    Shah, Nilesh; Pande, Nikhil; Bhat, Tushar; Murke, Mukund; Andrade, Chittaranjan

    2012-06-01

    Electroconvulsive therapy (ECT) raises the seizure threshold. This physiological change may benefit patients with seizure disorders. Whereas ECT has recently been used to terminate medication-refractory status epilepticus, there is little current literature on its planned administration as a specific maintenance treatment for medication-refractory epilepsy. We used maintenance ECT to treat an 18-year-old man with a long-standing generalized tonic-clonic seizure disorder who had shown poor response to several antiepileptic drugs administered in combination with antiepileptic medication compliance confirmed through drug level monitoring. A total of 52 ECTs were administered across nearly 20 months at a mean frequency of once in nearly 12 days. From the very outset, ECT dramatically decreased the frequency of spontaneous seizures from approximately 6 to 24 per week at baseline to approximately 1 to 2 per week after ECT initiation. The efficacy of maintenance ECT in spontaneous seizure prophylaxis was greater when the ECT treatment interval was narrower. Improvement with ECT was associated with improved behavior and improved psychosocial functioning on clinical report. No cognitive or other adverse effects were reported or clinically ascertained. The ECT charge administered at the last 10 treatment sessions was 1434 millicoulombs. This is probably the highest electrical stimulus dose recorded in literature. Maintenance ECT may reduce the frequency of breakthrough seizures in patients with seizure disorder that is inadequately responsive to antiepileptic medication regimes. Very high ECT seizure thresholds may be observed when many antiepileptic drugs are concurrently administered in high doses.

  8. Maintenance electroconvulsive therapy (M-ECT) after acute response: examining the evidence for who, what, when, and how?

    PubMed

    Rabheru, Kiran

    2012-03-01

    To examine the evidence for maintenance electroconvulsive therapy (M-ECT) to help determine who, when, and how long ECT should be continued. A review of published literature on the use of maintenance ECT (M-ECT) was conducted. It focused primarily on trials published since 1997, meeting the following additional criteria: randomized controlled trial or cohort study with a comparison (matched group or before and after), and at least 10 patients receiving M-/continuation ECT. Where such data are not available, recent case series were reviewed. Relapse rates after discontinuation of ECT are very high. Maintenance ECT is an underused treatment option that can substantially reduce risks of relapse in patients with major depressive disorder and likely in bipolar disorder and schizophrenia as well. Little data are available for the use of M-ECT in neurological disorders, and no cost-effectiveness analyses in the maintenance setting were found. Whereas no clear answers emerge from the literature, there is now a growing body of evidence to suggest that for those who have not responded well to medications but have responded to ECT, M-ECT must be presented as an option to the patient and the family for consideration. Clear consensus guidelines for the use of M-ECT are needed.

  9. Orchestrated Regulation of Nogo Receptors, Lotus, AMPA Receptors and BDNF in an ECT Model Suggests Opening and Closure of a Window of Synaptic Plasticity

    PubMed Central

    Nordgren, Max; Karlsson, Tobias; Svensson, Maria; Koczy, Josefin; Josephson, Anna; Olson, Lars; Tingström, Anders; Brené, Stefan

    2013-01-01

    Electroconvulsive therapy (ECT) is an efficient and relatively fast acting treatment for depression. However, one severe side effect of the treatment is retrograde amnesia, which in certain cases can be long-term. The mechanisms behind the antidepressant effect and the amnesia are not well understood. We hypothesized that ECT causes transient downregulation of key molecules needed to stabilize synaptic structure and to prevent Ca2+ influx, and a simultaneous increase in neurotrophic factors, thus providing a short time window of increased structural synaptic plasticity. Here we followed regulation of NgR1, NgR3, LOTUS, BDNF, and AMPA subunits GluR1 and GluR2 flip and flop mRNA levels in hippocampus at 2, 4, 12, 24, and 72 hours after a single episode of induced electroconvulsive seizures (ECS) in rats. NgR1 and LOTUS mRNA levels were transiently downregulated in the dentate gyrus 2, 4, 12 and 4, 12, 24 h after ECS treatment, respectively. GluR2 flip, flop and GluR1 flop were downregulated at 4 h. GluR2 flip remained downregulated at 12 h. In contrast, BDNF, NgR3 and GluR1 flip mRNA levels were upregulated. Thus, ECS treatment induces a transient regulation of factors important for neuronal plasticity. Our data provide correlations between ECS treatment and molecular events compatible with the hypothesis that both effects and side effects of ECT may be caused by structural synaptic rearrangements. PMID:24244357

  10. Orchestrated regulation of Nogo receptors, LOTUS, AMPA receptors and BDNF in an ECT model suggests opening and closure of a window of synaptic plasticity.

    PubMed

    Nordgren, Max; Karlsson, Tobias; Svensson, Maria; Koczy, Josefin; Josephson, Anna; Olson, Lars; Tingström, Anders; Brené, Stefan

    2013-01-01

    Electroconvulsive therapy (ECT) is an efficient and relatively fast acting treatment for depression. However, one severe side effect of the treatment is retrograde amnesia, which in certain cases can be long-term. The mechanisms behind the antidepressant effect and the amnesia are not well understood. We hypothesized that ECT causes transient downregulation of key molecules needed to stabilize synaptic structure and to prevent Ca2+ influx, and a simultaneous increase in neurotrophic factors, thus providing a short time window of increased structural synaptic plasticity. Here we followed regulation of NgR1, NgR3, LOTUS, BDNF, and AMPA subunits GluR1 and GluR2 flip and flop mRNA levels in hippocampus at 2, 4, 12, 24, and 72 hours after a single episode of induced electroconvulsive seizures (ECS) in rats. NgR1 and LOTUS mRNA levels were transiently downregulated in the dentate gyrus 2, 4, 12 and 4, 12, 24 h after ECS treatment, respectively. GluR2 flip, flop and GluR1 flop were downregulated at 4 h. GluR2 flip remained downregulated at 12 h. In contrast, BDNF, NgR3 and GluR1 flip mRNA levels were upregulated. Thus, ECS treatment induces a transient regulation of factors important for neuronal plasticity. Our data provide correlations between ECS treatment and molecular events compatible with the hypothesis that both effects and side effects of ECT may be caused by structural synaptic rearrangements.

  11. ReProTool Version 2.0: Re-Engineering Academic Curriculum Using Learning Outcomes, ECTS and Bologna Process Concepts

    ERIC Educational Resources Information Center

    Pouyioutas, Philippos; Gjermundrod, Harald; Dionysiou, Ioanna

    2012-01-01

    Purpose: The purpose of this paper is to present ReProTool Version 2.0, a software tool that is used for the European Credit Transfer System (ECTS) and the Bologna Process re-engineering of academic programmes. The tool is the result of an 18 months project (February 2012-July 2013) project, co-financed by the European Regional Development Fund…

  12. Efficacy of 67 gallium ECT imaging in lymphoma, infection, and lung carcinoma: A comparison with planar imaging

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Harwood, S.J.; Anderson, M.W.; Klein, R.C.

    1984-01-01

    Emission computed tomography (ECT) studies were performed on a GE 400 A/T camera and ADAC computers (system 3 and system 3300). Thirty-three sets of ECT and planar images were obtained in 20 patients over a six month period. Imaging was performed 48 hours after the intravenous administration of 5 mc of Gallium 67 citrate. No bowel preparation was employed. Comparison is made of the initial nuclear medicine report derived from planar and ECT imaging aided by clinical knowledge versus the consensus opinion of two nuclear medicine physicians reading the planar images along with minimal clinical information. The lymphoma series consistsmore » of 18 scans in 10 patients. There were 5 scans in which a false negative planar interpretation was changed to a true positive ECT interpretation. Sensitivity of planar imaging for lymphoma was 58% which rose to 100% with addition of ECT information. There were no false positives by either technique. There were 5 sets of scans in 5 lung carcinoma patients. Sensitivity of the planar images was 60% because of 2 false negative results. Sensitivity of the ECT technique was 100%. There were no false positives. The infection series consists of 10 scans in 5 patients. Sensitivity of ECT was 100%, sensitivity of planar was 66%. There was 1 false positive planar. For the total series the accuracy of planar imaging was 69% and the predictive value of a negative planar interpretation was 44%. Corresponding values for ECT imaging were 100%. The authors' experience demonstrates significant increase in sensitivity without loss of specificity resulting from the use of Emission Computed Tomography in both chest and abdomen in patients with lymphoma, infection, and lung cancer.« less

  13. Agonist-induced Ca2+ Sensitization in Smooth Muscle

    PubMed Central

    Artamonov, Mykhaylo V.; Momotani, Ko; Stevenson, Andra; Trentham, David R.; Derewenda, Urszula; Derewenda, Zygmunt S.; Read, Paul W.; Gutkind, J. Silvio; Somlyo, Avril V.

    2013-01-01

    Many agonists, acting through G-protein-coupled receptors and Gα subunits of the heterotrimeric G-proteins, induce contraction of smooth muscle through an increase of [Ca2+]i as well as activation of the RhoA/RhoA-activated kinase pathway that amplifies the contractile force, a phenomenon known as Ca2+ sensitization. Gα12/13 subunits are known to activate the regulator of G-protein signaling-like family of guanine nucleotide exchange factors (RhoGEFs), which includes PDZ-RhoGEF (PRG) and leukemia-associated RhoGEF (LARG). However, their contributions to Ca2+-sensitized force are not well understood. Using permeabilized blood vessels from PRG(−/−) mice and a new method to silence LARG in organ-cultured blood vessels, we show that both RhoGEFs are activated by the physiologically and pathophysiologically important thromboxane A2 and endothelin-1 receptors. The co-activation is the result of direct and independent activation of both RhoGEFs as well as their co-recruitment due to heterodimerization. The isolated recombinant C-terminal domain of PRG, which is responsible for heterodimerization with LARG, strongly inhibited Ca2+-sensitized force. We used photolysis of caged phenylephrine, caged guanosine 5′-O-(thiotriphosphate) (GTPγS) in solution, and caged GTPγS or caged GTP loaded on the RhoA·RhoGDI complex to show that the recruitment and activation of RhoGEFs is the cause of a significant time lag between the initial Ca2+ transient and phasic force components and the onset of Ca2+-sensitized force. PMID:24106280

  14. What does the electroencephalogram tell us about the mechanisms of action of ECT in major depressive disorders?

    PubMed

    Farzan, Faranak; Boutros, Nash N; Blumberger, Daniel M; Daskalakis, Zafiris J

    2014-06-01

    Electroconvulsive therapy (ECT) remains to be one of the most effective treatment options in treatment-resistant major depressive disorder (MDD). From the early days, researchers have embarked on extracting information from electroencephalography (EEG) recordings before, during, and after ECT to identify neurophysiological targets of ECT and discover EEG predictors of response to ECT in patients with MDD. In this article, we provide an overview of visually detected and quantitative EEG features that could help in furthering our understanding of the mechanisms of action of ECT in MDD. We further discuss the EEG findings in the context of postulated hypotheses of ECT therapeutic pathways. We introduce an alternative and unifying hypothesis suggesting that ECT may exert its therapeutic efficacy through resetting the aberrant functional connectivity and promoting the generation of new and healthy connections in brain regions implicated in MDD pathophysiology, a mechanism that may be in part mediated by the ECT-induced activation of inhibitory and neuroplasticity mechanisms. We further discuss the added value of EEG markers in the larger context of ECT research and as complementary to neuroimaging and genetic markers. We conclude by drawing attention to the need for longitudinal studies in large cohort of patients and the need for standardization and validation of EEG algorithms of functional connectivity across studies to facilitate the translation of EEG correlates of ECT response in routine clinical practice.

  15. Electroconvulsive therapy (ECT) for treating agitation in dementia (major neurocognitive disorder) - a promising option.

    PubMed

    Glass, Oliver M; Forester, Brent P; Hermida, Adriana P

    2017-05-01

    Agitation in patients with dementia increases caretaker burden, increases healthcare costs, and worsens the patient's quality of life. Antipsychotic medications, commonly used for the treatment of agitation in patients with dementia have a box warning from the FDA for elevated mortality risk. Electroconvulsive therapy (ECT) has made significant advances over the past several years, and is efficacious in treating a wide range of psychiatric conditions. We provide a systematic review of published literature regarding the efficacy of ECT for the treatment of agitation in patients with dementia (major neurocognitive disorder). We searched PubMed, Medline, Google Scholar, UptoDate, Embase, and Cochrane for literature concerning ECT for treating agitation in dementia using the title search terms "ECT agitation dementia;" "ECT aggression dementia;" "ECT Behavior and Psychological Symptoms of Dementia;" and "ECT BPSD." The term "dementia" was also interchanged with "Major Neurocognitive Disorder." No time frame restriction was placed. We attempted to include all publications that were found to ensure a comprehensive review. We found 11 papers, with a total (N) of 216 patients. Limited to case reports, case series, retrospective chart review, retrospective case-control, and an open label prospective study, ECT has demonstrated promising results in decreasing agitation in patients with dementia. Patients who relapsed were found to benefit from maintenance ECT. Available studies are often limited by concomitant psychotropic medications, inconsistent use of objective rating scales, short follow-up, lack of a control group, small sample sizes, and publication bias. A future randomized controlled trial will pose ethical and methodological challenges. A randomized controlled trial must carefully consider the definition of usual care as a comparison group. Well-documented prospective studies and/or additional case series with explicit selection criteria, a wide range of outcome

  16. Seizure threshold increases can be predicted by EEG quality in right unilateral ultrabrief ECT.

    PubMed

    Gálvez, Verònica; Hadzi-Pavlovic, Dusan; Waite, Susan; Loo, Colleen K

    2017-12-01

    Increases in seizure threshold (ST) over a course of brief pulse ECT can be predicted by decreases in EEG quality, informing ECT dose adjustment to maintain adequate supra-threshold dosing. ST increases also occur over a course of right unilateral ultrabrief (RUL UB) ECT, but no data exist on the relationship between ST increases and EEG indices. This study (n = 35) investigated if increases in ST over RUL UB ECT treatments could be predicted by a decline in seizure quality. ST titration was performed at ECT session one and seven, with treatment dosing maintained stable (at 6-8 times ST) in intervening sessions. Seizure quality indices (slow-wave onset, mid-ictal amplitude, regularity, stereotypy, and post-ictal suppression) were manually rated at the first supra-threshold treatment, and last supra-threshold treatment before re-titration, using a structured rating scale, by a single trained rater blinded to the ECT session being rated. Twenty-one subjects (60%) had a ST increase. The association between ST changes and EEG quality indices was analysed by logistic regression, yielding a significant model (p < 0.001). Initial ST (p < 0.05) and percentage change in mid-ictal amplitude (p < 0.05) were significant predictors of change in ST. Percentage change in post-ictal suppression reached trend level significance (p = 0.065). Increases in ST over a RUL UB ECT course may be predicted by decreases in seizure quality, specifically decline in mid-ictal amplitude and potentially in post-ictal suppression. Such EEG indices may be able to inform when dose adjustments are necessary to maintain adequate supra-threshold dosing in RUL UB ECT.

  17. Maintained Improvement of Neurocognitive Function in Major Depressive Disorders 6 Months after ECT.

    PubMed

    Mohn, Christine; Rund, Bjørn Rishovd

    2016-01-01

    Both impaired and improved cognitive function after electroconvulsive therapy (ECT) in major depressive disorder (MDD) patients may occur. We have previously found improved cognitive function 6 weeks after ECT in this group. The aim of this study was to report 6-month follow-up results from the same prospective project monitoring cognitive effects of ECT. Thirty-one patients with MDD were assessed with the MATRICS Consensus Cognitive Battery (MCCB), the Everyday Memory Questionnaire (EMQ), and the Montgomery-Åsberg Depression Rating Scale prior to, 6 weeks, and 6 months after ECT. Compared to baseline, the speed of processing, attention/vigilance, and reasoning/problem solving test results were significantly improved. The depression score was significantly reduced. There were no changes in subjective memory complaint. There was no significant relationship between the EMQ and the MCCB subtests, but a significant correlation between current depression level and the EMQ. Six months after ECT the cognitive improvement reported at 6-week follow-up was maintained and extended. The corresponding decrease in depressive symptoms and stability in subjectively reported memory complaints suggest that the antidepressant effects of ECT do not occur at the expense of cognitive function.

  18. On an image reconstruction method for ECT

    NASA Astrophysics Data System (ADS)

    Sasamoto, Akira; Suzuki, Takayuki; Nishimura, Yoshihiro

    2007-04-01

    An image by Eddy Current Testing(ECT) is a blurred image to original flaw shape. In order to reconstruct fine flaw image, a new image reconstruction method has been proposed. This method is based on an assumption that a very simple relationship between measured data and source were described by a convolution of response function and flaw shape. This assumption leads to a simple inverse analysis method with deconvolution.In this method, Point Spread Function (PSF) and Line Spread Function(LSF) play a key role in deconvolution processing. This study proposes a simple data processing to determine PSF and LSF from ECT data of machined hole and line flaw. In order to verify its validity, ECT data for SUS316 plate(200x200x10mm) with artificial machined hole and notch flaw had been acquired by differential coil type sensors(produced by ZETEC Inc). Those data were analyzed by the proposed method. The proposed method restored sharp discrete multiple hole image from interfered data by multiple holes. Also the estimated width of line flaw has been much improved compared with original experimental data. Although proposed inverse analysis strategy is simple and easy to implement, its validity to holes and line flaw have been shown by many results that much finer image than original image have been reconstructed.

  19. Autobiographical Memory and ECT: Don’t Throw Out the Baby

    PubMed Central

    Sackeim, Harold A.

    2014-01-01

    Retrograde amnesia for autobiographical information is the most critical side effect of ECT. Much, if not most, modern research demonstrating long-term autobiographical amnesia following ECT has used either the Columbia University Autobiographical Memory Interview (CUAMI) or the short form of this scale (CUAMI-SF). Semkovska and McLoughlin claimed that studies using these instruments should be dismissed and the findings ignored due to a lack of normative data, as well as concerns about the reliability and validity of these instruments. In this commentary, the development and use of these scales is reviewed. It is shown that Semkovska and McLoughlin’s critique is factually incorrect, as normative data were simultaneously collected in virtually all studies using these instruments. Furthermore, there is substantial evidence supporting the reliability and validity of these scales. Indeed, these instruments are the only neuropsychological tests repeatedly shown to covary with patient self-evaluations of ECT’s effects on memory, and have repeatedly demonstrated long-term differences in the magnitude of amnesia as a function of ECT technique. Findings with the CUAMI and CUAMI-SF provide key evidence regarding ECT’s cognitive side effect profile. It is inaccurate and inadvisable to continue to deny that ECT can exert long-term adverse effects in this domain. PMID:24755727

  20. A randomized, double-blind, placebo-controlled trial on the role of preemptive analgesia with acetaminophen [paracetamol] in reducing headache following electroconvulsive therapy [ECT].

    PubMed

    Isuru, Amila; Rodrigo, Asiri; Wijesinghe, Chamara; Ediriweera, Dileepa; Premadasa, Shan; Wijesekara, Carmel; Kuruppuarachchi, Lalith

    2017-07-28

    Electroconvulsive therapy (ECT) is a safe and efficient treatment for several severe psychiatric disorders, but its use is limited by side effects. Post-ECT headache is one of the commonest side effects. Preemptive analgesia is effective in post-surgical pain management. The most commonly used analgesic is acetaminophen (paracetamol). However, acetaminophen as a preemptive analgesic for post-ECT headache has not been studied adequately. This study was conducted to compare the incidence and severity of post-ECT headache in patients who were administered acetaminophen pre-ECT with a placebo group. This study was a randomised, double-blind, placebo-controlled trial. Sixty-three patients received 1 g acetaminophen and 63 patients received a placebo identical to acetaminophen. The incidence and severity of headache 2 h before and after ECT were compared between placebo and acetaminophen groups. The severity was measured using a visual analog scale. Generalised linear models were used to evaluate variables associated with post ECT headache. Demographic and clinical variables of placebo and acetaminophen groups were comparable except for the energy level used to induce a seizure. Higher proportion of the placebo group (71.4%) experienced post-ECT headache when compared to the acetaminophen group (p < 0.001). The median pain score for headache was 0 (Inter quartile range: 0-2) in acetaminophen group whereas the score was 2 (IQR: 0-4) in placebo group (P < 0.001). Model fitting showed that the administration of acetaminophen is associated with less post-ECT headache (odds ratio = 0.23, 95% CI: 0.11-0.48, P < 0.001). A significant reduction was seen in both the incidence and severity of post-ECT headache with preemptive analgesia with acetaminophen. Ethical approval was granted by an Ethic review committee, University of Kelaniya, Sri Lanka (P/166/10/2015) and the trial was registered in the Sri Lanka Clinical Trials Registry ( SLCTR/2015/27 ).

  1. Efficacy and cognitive side effects of electroconvulsive therapy (ECT) in depressed elderly inpatients with coexisting mild cognitive impairment or dementia.

    PubMed

    Hausner, Lucrezia; Damian, Marinella; Sartorius, Alexander; Frölich, Lutz

    2011-01-01

    To study cognitive performance in depressed geriatric inpatients with or without preexisting cognitive impairment who received a first course of electroconvulsive therapy (ECT). Forty-four elderly inpatients with major depressive disorder (ICD-10 criteria) were included in a prospective consecutive case series of a university hospital. The patients were divided into 3 groups (no cognitive impairment [NCI], mild cognitive impairment [MCI], dementia) and rated for cognitive performance with the MMSE before first ECT, after sixth ECT, and 6 weeks and 6 months after ECT termination. Affective symptoms were rated by 21-item Hamilton Depression Rating Scale (HDRS-21) before and 6 weeks after ECT. Analysis of variance or Kruskal-Wallis tests on ECT-induced MMSE and HDRS-21 score changes were compared to baseline. Binary logistic regression was used for predictor analysis. The study was conducted from April 2004 to April 2008. After initial nonsignificant cognitive deterioration in all 3 groups, the NCI group improved cognitively 6 weeks (P = .018) and 6 months (P = .027) after ECT. The MCI group improved in cognition 6 months (P = .036) after ECT. In the dementia group, mean MMSE scores also improved numerically over the course of ECT without significance. Dementia patients with antidementia treatment improved in cognition to a clinically relevant extent after the sixth ECT. Dementia subjects without antidementia treatment deteriorated. After the sixth ECT, 70.0% of dementia patients (P = .004) presented a cognitive decline, and 68.8% of MCI patients (P < .001) presented a decline 6 weeks after ECT. Six months after ECT, one-third of the dementia patients (P < .036) still had a cognitive decline. Affective symptoms remitted after ECT in all 3 groups (P < .001). Pre-ECT cognitive deficits were the best predictor of MMSE decline (6 weeks after ECT, P = .007; 6 months after ECT, P = .055). ECT is effective and well tolerated in geriatric depressed inpatients regardless of

  2. Detection and Sizing of Defects in Structural Components of a Nuclear Power Plant by ECT

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chen Zhenmao; Miya, Kenzo

    2005-04-09

    In this paper, progress of ECT technique for inspection of stress corrosion cracks in a structural component of a nuclear power plant is reported. Access and scanning vehicle (robot), advanced probes for SG tube inspection, development and evaluation of new probes for welding joint, and ECT based crack sizing technique are described respectively. Based on these new techniques, it is clarified that ECT can play as a supplement of UT for the welding zone inspection. It is also proved in this work that new ECT sensors are efficient even for a stainless plate as thick as 15mm.

  3. Effects of stimulus intensity on the efficacy and safety of twice-weekly, bilateral electroconvulsive therapy (ECT) combined with antipsychotics in acute mania: a randomised controlled trial.

    PubMed

    Mohan, Titus S P; Tharyan, Prathap; Alexander, Jacob; Raveendran, Nirmal S

    2009-03-01

    To examine differences in speed of improvement and remission in people with mania undergoing bilateral, brief-pulse, twice-weekly electroconvulsive therapy (ECT) at stimulus intensities administered just above and 2.5 times their individually titrated seizure threshold. Consecutive, eligible subjects with mania, prescribed ECT, were randomised to receive treatments at stimulus doses either just above or 2.5 times their individually titrated seizure thresholds. Main outcomes were the speed of improvement and remission as measured by the Young Mania Rating Scale (YMRS) and the Clinical Global Impressions-Improvement scale (CGI-I) and cognitive side effects assessed by the Mini-Mental State Exam, the Wechsler Memory Scale, and a scale for autobiographical memory. A total of 24/26 subjects (92.3%) given threshold ECT and 22/24 subjects (91.7%) given suprathreshold ECT were significantly improved [CGI = 2; odds ratio (OR) = 1.1, 95% confidence interval (CI): 0.1-8.4; p = 1.0] at the end of ECT. A total of 88% of the sample had remitted [YMRS < 10; threshold 23/26 (88.5%) versus suprathreshold 21/24 (87.5%)], with no significant differences between interventions (OR = 1.1, 95% CI: 0.2- 6.0; p = 1.0). The interventions did not differ significantly in the time or number of ECT treatments required for improvement or remission. Both interventions were equally safe. Bilateral, twice-weekly ECT delivered at stimulus intensities just above individually titrated seizure threshold was as effective and safe as ECT administered at stimulus intensities 2.5 times seizure threshold in rapidly resolving the symptoms of acute mania.

  4. Supporting Open Access to European Academic Courses: The ASK-CDM-ECTS Tool

    ERIC Educational Resources Information Center

    Sampson, Demetrios G.; Zervas, Panagiotis

    2013-01-01

    Purpose: This paper aims to present and evaluate a web-based tool, namely ASK-CDM-ECTS, which facilitates authoring and publishing on the web descriptions of (open) academic courses in machine-readable format using an application profile of the Course Description Metadata (CDM) specification, namely CDM-ECTS. Design/methodology/approach: The paper…

  5. Propofol interruption of ECT seizure to reduce side-effects: a pilot study.

    PubMed

    Warnell, Ronald L; Swartz, Conrad M; Thomson, Alice

    2010-01-30

    Fifteen depressed subjects received six bitemporal electroconvulsive therapy (ECT) treatments under etomidate anesthesia. They were randomized to blindly either receive propofol 0.5mg/kg 15s post-stimulus or not. Propofol infusion significantly prevented long seizures, and prevented cognitive decrements in most neuropsychological tests, several significantly. Propofol interruption may clinically help reduce ECT side-effects.

  6. Contrasting patterns of deficits in visuospatial memory and executive function in patients with major depression with and without ECT referral.

    PubMed

    Tsaltas, E; Kalogerakou, S; Papakosta, V-M; Kontis, D; Theochari, E; Koutroumpi, M; Anyfandi, E; Michopoulos, I; Poulopoulou, C; Papadimitriou, G; Oulis, P

    2011-05-01

    The pretreatment neuropsychological profile of drug-resistant patients with major depressive disorder (MDD) referred for electroconvulsive therapy (ECT) may differ from that of their drug-respondent MDD counterparts. Such differences could help in identifying distinct MDD subtypes, thus offering insights into the neuropathology underlying differential treatment responses. Depressed patients with ECT referral (ECTs), depressed patients with no ECT referral (NECTs) and non-psychiatric Controls (matched groups, n=15) were assessed with memory and executive function tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB). ECTs scored significantly lower than NECTs in the Mini-Mental State Examination (MMSE; p=0.01). NECTs performed worse than Controls in the Paired Associates Learning (PAL) task (p<0.03; Control/NECT p<0.01) and the Spatial Recognition Memory (SRM) task (p<0.05; Controls/NECTs p<0.05); ECTs performed between Controls and NECTs, not differing from either. In the Intra/Extradimensional (IED) set-shifting task, ECTs performed worse that Controls and NECTS (IED: p<0.01; Controls/ECTs p<0.01), particularly in the shift phases, which suggests reduced attentional flexibility. In Stockings of Cambridge (SOC), ECTs abandoned the test early more often than Controls and NECTs (H=11, p<0.01) but ECTs who completed SOC performed comparably to the other two groups. A double dissociation emerged from the comparison of cognitive profiles of ECT and NECT patients. ECTs showed executive deficits, particularly in attentional flexibility, but mild deficits in tests of visuospatial memory. NECTs presented the opposite pattern. This suggests predominantly frontostriatal involvement in ECT versus temporal involvement in NECT depressives.

  7. Multiple roles of the Rho GEF ephexin1 in synapse remodeling

    PubMed Central

    Shi, Lei; Fu, Amy KY

    2010-01-01

    Synapse remodeling, which involves changes in the synaptic structure and their molecular composition, is required for the maturation and refinement of neural circuits. Although synapse remodeling is known to be tightly dependent on the assembly of local actin cytoskeleton, how actin directs the structural changes of synapse and targeting of synaptic proteins are not fully understood. Recently, we identified ephexin1, a Rho guanine nucleotide exchange factor (GEF) that regulates actin dynamics, to play an essential role in the maturation and functioning of the mammalian neuromuscular junction (NMJ). We showed that ephexin1 regulates the synaptic organization of the neurotransmitter receptor acetylcholine receptor (AChR) clusters through RhoA-dependent actin reorganization. Interestingly, ephexin1 has been implicated in the regulation of postsynaptic structure as well as the presynaptic vesicle release at various types of synapses. Our findings thus establish a novel function of ephexin1 in synapse remodeling through regulating the synaptic targeting of neurotransmitter receptors, revealing a versatile role of ephexin1 at synapses. PMID:21331259

  8. Consent, competency and ECT: a psychiatrist's view

    PubMed Central

    Taylor, P J

    1983-01-01

    Dr Taylor, an English psychiatrist, considers the issue of the symposium in the context of the Mental Health (Amendment) Act 1982. This, she says, gives little guidance on how judgment of a patient's competency or capability to consent to treatment should be made, although it specifies that unless compulsorily detained patients competently consent to ECT a special second medical opinion is required. Although some guidelines from the Department of Health may be offered before implementation of the Act in September 1983 all those working with psychiatric patients will have to consider the issues. After discussing her criteria for informed consent, some practical approaches for obtaining it and problems arising from these, and problems of surrogate consent, Dr Taylor concludes that there is no single or simple solution to the dilemma. She ends by asking: `Can refusal of ECT for severe depression ever be a competent decision?' PMID:6620319

  9. Pre- and Post-Clerkship Knowledge, Perceptions, and Acceptability of Electroconvulsive Therapy (ECT) in 3rd Year Medical Students.

    PubMed

    Ithman, Muaid; O'Connell, Chris; Ogunleye, Ayodeji; Lee, Suhwon; Chamberlain, Brett; Ramalingam, Anupama

    2018-05-26

    To examine the impact of the third year psychiatry clerkship on medical students' knowledge and opinion of ECT at University of Missouri-Columbia School of Medicine. Despite overwhelming evidence of ECT's efficacy and safety for refractory affective illnesses, (among other conditions), it remains a misunderstood and underutilized intervention. Several studies indicate that ECT stigma and misinformation, unfortunately, does not spare the medical community. Medical students are an optimal group to study, as they are forming their perspectives on different specialties. Few studies have measured the effect of education programs (e.g., clerkships, lectures, observation of ECT) on medical students' perspectives on ECT.

  10. The Clinical and Service Outcomes of Unilateral and Bilateral ECT Electrode Placements in Australian Aged Psychiatry Services.

    PubMed

    D'Cunha, Craig; Plakiotis, Christos; Macfarlane, Stephen; Moss, Francine; Reddy, Murali; Singh, Dhiren; Tofler, David; White, Erica; O'Connor, Daniel W

    2016-03-01

    The aim of the study was to determine whether depressed aged inpatients treated with brief pulse unilateral electroconvulsive therapy (ECT) differed from those treated with bilateral (bitemporal or bifrontal) ECT with respect to numbers of treatments, length of hospital admission, changes in scores on depression and cognitive scales, and serious adverse effects. An audit of routinely collected data regarding 221 acute ECT courses in 7 public aged psychiatry services in Victoria, Australia. Patients given unilateral, bifrontal, and bitemporal treatments were similar with respect to personal, clinical, and treatment characteristics. Most treatments were administered in line with local clinical guidelines and were rated as effective. Psychiatrists preferred unilateral ECT in the first instance with stimulus dosing based on patients' seizure thresholds. Approximately a quarter of unilateral courses were switched later to bitemporal placement, most probably because of insufficient progress. Bilateral treatments were associated with a larger number of treatments, less improvement in scores on mood and cognitive scales, and more refusals to continue treatment than unilateral-only ECT. Brief pulse unilateral ECT proved more effective than bitemporal and bifrontal ECT for most aged patients, especially when coupled with stimulus dosing based on seizure threshold.

  11. Magnetic Inclination E Ects In Star-Planet Magnetic Interactions

    NASA Astrophysics Data System (ADS)

    Strugarek, Antoine

    2017-10-01

    A large fraction of the exoplanets discovered today are in a close-in orbit around their host star. This proximity allows them to be magnetically connected to their host, which lead to e cient energy and angular momentum exchanges between the star and the planet. We carry out three-dimensional magneto-hydrodynamic simulations of close-in star-planet systems to characterize the e ect of the inclination of the planetary magnetic eld on the star-planet magnetic interaction. We parametrize this e ect in scaling laws depending on the star, planet, and stellar wind properties that can be applied to any exoplanetary systems around cool stars.

  12. Clinical efficacy and cognitive side effects of bifrontal versus right unilateral electroconvulsive therapy (ECT): a short-term randomised controlled trial in pharmaco-resistant major depression.

    PubMed

    Eschweiler, Gerhard W; Vonthein, Reinhard; Bode, Ruediger; Huell, Michael; Conca, Andreas; Peters, Oliver; Mende-Lechler, Stefan; Peters, Julia; Klecha, Dorothee; Prapotnik, Michael; DiPauli, Jan; Wild, Barbara; Plewnia, Christian; Bartels, Mathias; Schlotter, Wilfried

    2007-08-01

    In most studies right unilateral electroconvulsive therapy (ECT) has been shown to cause fewer cognitive side effects but less antidepressant efficacy compared with bi(fronto)temporal ECT at certain intensities. To compare the short-term efficacy and side effects of right unilateral ECT and bifrontal ECT. In a double-blind randomised controlled clinical trial, 92 patients diagnosed with pharmaco-resistant major depression received either six right unilateral ECT treatments (250% stimulus intensity of titrated threshold) or six bifrontal ECT (150% of threshold) treatments over a 3-week period. Concomitant psychotropic medications were continued during ECT treatments. The severity of depression and cognitive status was assessed prior to the first ECT and one day after the sixth ECT using the 21-item Hamilton Depression Rating Scale and the modified Mini Mental State Examination. Eight patients did not complete the course of the study due to minor side effects or withdrawal of consent. The mean Hamilton Depression score decreased from 27 to 17 points in both groups of 46 patients, resulting in 12 responders (primary endpoint defined as a decrease >50%) in each patient group (95% confidence interval for the odds ratio from 0.35 to 2.8). There was no reduction in the modified Mini Mental State score (mean score 86 of 100 points). Both bifrontal and right unilateral electrode placements in ECT were reasonably safe and moderately efficacious in reducing symptoms of pharmaco-resistant major depression.

  13. Electroconvulsive therapy (ECT) in a six-year-old girl suffering from major depressive disorder with catatonic features.

    PubMed

    Esmaili, Taghi; Malek, Ayyoub

    2007-02-01

    ECT is generally both effective and safe in the treatment of adolescents, but treatment using ECT in children of pre-pubertal age has been less reported and is a controversial treatment. This article reports a 6-year-old girl who has been diagnosed as having major depressive disorder with catatonic features and 50% loss of weight due to food refusal. The seven-session ECT treatment with bilateral and brief pulse stimulation was successfully done. Propofol 1% was used for anesthesia. After the third session, the patient's clinical improvement began by eating. As the ECT sessions went on the signs of depression and catatonic features completely resolved. There were no noticeable clinical side effects. ECT should be considered in severe cases of child psychiatric disorders where it is life threatening, as an effective and safe method.

  14. Model-based estimation for dynamic cardiac studies using ECT.

    PubMed

    Chiao, P C; Rogers, W L; Clinthorne, N H; Fessler, J A; Hero, A O

    1994-01-01

    The authors develop a strategy for joint estimation of physiological parameters and myocardial boundaries using ECT (emission computed tomography). They construct an observation model to relate parameters of interest to the projection data and to account for limited ECT system resolution and measurement noise. The authors then use a maximum likelihood (ML) estimator to jointly estimate all the parameters directly from the projection data without reconstruction of intermediate images. They also simulate myocardial perfusion studies based on a simplified heart model to evaluate the performance of the model-based joint ML estimator and compare this performance to the Cramer-Rao lower bound. Finally, the authors discuss model assumptions and potential uses of the joint estimation strategy.

  15. A Generic Method for Distribution and Transfer of ECTS and Other Norm-Referenced Grades within Student Cohorts

    ERIC Educational Resources Information Center

    Warfvinge, Per

    2008-01-01

    The ECTS grade transfer scale is an interface grade scale to help European universities, students and employers to understand the level of student achievement. Hence, the ECTS scale can be seen as an interface, transforming local scales to a common system where A-E denote passing grades. By definition, ECTS should distribute the passing students…

  16. Neurodevelopmental disease-associated de novo mutations and rare sequence variants affect TRIO GDP/GTP exchange factor activity.

    PubMed

    Katrancha, Sara M; Wu, Yi; Zhu, Minsheng; Eipper, Betty A; Koleske, Anthony J; Mains, Richard E

    2017-12-01

    Bipolar disorder, schizophrenia, autism and intellectual disability are complex neurodevelopmental disorders, debilitating millions of people. Therapeutic progress is limited by poor understanding of underlying molecular pathways. Using a targeted search, we identified an enrichment of de novo mutations in the gene encoding the 330-kDa triple functional domain (TRIO) protein associated with neurodevelopmental disorders. By generating multiple TRIO antibodies, we show that the smaller TRIO9 isoform is the major brain protein product, and its levels decrease after birth. TRIO9 contains two guanine nucleotide exchange factor (GEF) domains with distinct specificities: GEF1 activates both Rac1 and RhoG; GEF2 activates RhoA. To understand the impact of disease-associated de novo mutations and other rare sequence variants on TRIO function, we utilized two FRET-based biosensors: a Rac1 biosensor to study mutations in TRIO (T)GEF1, and a RhoA biosensor to study mutations in TGEF2. We discovered that one autism-associated de novo mutation in TGEF1 (K1431M), at the TGEF1/Rac1 interface, markedly decreased its overall activity toward Rac1. A schizophrenia-associated rare sequence variant in TGEF1 (F1538Intron) was substantially less active, normalized to protein level and expressed poorly. Overall, mutations in TGEF1 decreased GEF1 activity toward Rac1. One bipolar disorder-associated rare variant (M2145T) in TGEF2 impaired inhibition by the TGEF2 pleckstrin-homology domain, resulting in dramatically increased TGEF2 activity. Overall, genetic damage to both TGEF domains altered TRIO catalytic activity, decreasing TGEF1 activity and increasing TGEF2 activity. Importantly, both GEF changes are expected to decrease neurite outgrowth, perhaps consistent with their association with neurodevelopmental disorders. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Influence of depressed patients' expectations prior to electroconvulsive therapy on its effectiveness and tolerability (Exp-ECT): a prospective study.

    PubMed

    Krech, Lisa; Belz, Michael; Besse, Matthias; Methfessel, Isabel; Wedekind, Dirk; Zilles, David

    2017-09-22

    Electroconvulsive therapy (ECT) is the most effective therapy for severe depressive disorders. Though there are known clinical predictors of response (e.g., higher age, presence of psychotic symptoms), there is a lack of knowledge concerning the impact of patients' expectations on treatment outcome and tolerability in terms of possible placebo/nocebo effects. In 31 patients with unipolar or bipolar depressive disorder, we used a questionnaire to investigate the patients' expectations of ECT effectiveness and tolerability prior to and in the course of the treatment. Additionally, the questionnaire was used after the ECT course for a final assessment. Depressive symptoms and putative side-effects were measured at each time point. General linear models were used to analyze the course of depressive symptoms and patients' expectation of ECT effectiveness and tolerability. ECT significantly reduced depressive symptoms with large effect sizes. Patients' rating of ECT effectiveness decreased in parallel: While responders' rating of ECT effectiveness remained stable on a high level, non-responders' rating decreased significantly. Group difference was significant after, but not prior to and during the treatment. Regarding tolerability, there was a (temporary) significant increase in the severity of self-rated symptoms such as headache and memory impairment. In contrast, patients' expectation and assessment of ECT tolerability remained unchanged, and their expectations prior to ECT had no impact on the occurrence of side-effects. These findings contradict the presence of relevant placebo/nocebo effects in the context of ECT when investigating a population of mostly chronic or treatment resistant patients with moderate to severe depressive disorder.

  18. Numerical evaluation of ECT impedance signal due to minute cracks

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fukutomi, Hiroyuki; Takagi, Toshiyuki; Tani, Junji

    1997-03-01

    This paper describes an experimental and analytical study on minute crack inspection with Eddy Current Testing (ECT). Measurement and simulation using a 3D FEM program are applied for the evaluation of the detecting signal with a minute crack in a test piece. Parameters such as mesh division, ICCG convergence criteria, etc. are evaluated to achieve high accuracy in numerical calculation. The simulation results agreed with experimental ones. ECT is used for in-service inspection of tubes in steam generators, heat exchangers and condensers in nuclear or conventional power plants as well as in chemical installations.

  19. Plasma BDNFs level initially and post treatment in acute mania: comparison between ECT and atypical antipsychotic treatment and healthy controls.

    PubMed

    Karamustafalioglu, Nesrin; Genc, Abdullah; Kalelioglu, Tevfik; Tasdemir, Akif; Umut, Gokhan; Incir, Said; Akkuş, Mustafa; Emul, Murat

    2015-08-01

    Inconsistent findings concerning brain-derived neurotrophic factor (BDNF) levels across different episodes in bipolar disorder have been reported, which is also in line with the treatment effects on BDNF levels in acute mania. We aimed to compare plasma BDNF level alterations after pure antipsychotic drug or ECT plus antipsychotic drug treatment in acute mania. Sixty-eight patients with mania were divided into two treatment arms: the antipsychotic treatment arm (AP) and electroconvulsive therapy (ECT)+AP arm. In addition, 30 healthy controls were included in the study. There was no significant statistical difference according to mean age, education level, marital and working status between patients and healthy controls. The initial serum BDNF level in patients with acute mania was significantly lower than healthy controls. The initial BDNF level between the ECT arm and AP arm was not significant. The BDNF level decreased significantly after reaching remission in patients with acute mania. The change in BDNF level in the AP arm was not significant while in the ECT arm it was significant after treatment. In this study, for the first time we revealed a significant decrease in BDNF levels after ECT sessions in acute manic patients. Besides clinical remission after treatment in acute mania, the decrement in BDNF levels does not seem to be related to clinical response. Thus cumulative effects of mood episodes for the ongoing decrease in BDNF levels might be borne in mind despite the achievement of remission and/or more time being required for an increase in BDNF levels after treatment. © The Author(s) 2015.

  20. In vitro guanine nucleotide exchange activity of DHR-2/DOCKER/CZH2 domains.

    PubMed

    Côté, Jean-François; Vuori, Kristiina

    2006-01-01

    Rho family GTPases regulate a large variety of biological processes, including the reorganization of the actin cytoskeleton. Like other members of the Ras superfamily of small GTP-binding proteins, Rho GTPases cycle between a GDP-bound (inactive) and a GTP-bound (active) state, and, when active, the GTPases relay extracellular signals to a large number of downstream effectors. Guanine nucleotide exchange factors (GEFs) promote the exchange of GDP for GTP on Rho GTPases, thereby activating them. Most Rho-GEFs mediate their effects through their signature domain known as the Dbl Homology-Pleckstrin Homology (DH-PH) module. Recently, we and others identified a family of evolutionarily conserved, DOCK180-related proteins that also display GEF activity toward Rho GTPases. The DOCK180-family of proteins lacks the canonical DH-PH module. Instead, they rely on a novel domain, termed DHR-2, DOCKER, or CZH2, to exchange GDP for GTP on Rho targets. In this chapter, the experimental approach that we used to uncover the exchange activity of the DHR-2 domain of DOCK180-related proteins will be described.

  1. The efficacy and safety of ECT in population before and after 60 years of age.

    PubMed

    Antosik-Wójcińska, Anna; Święcicki, Łukasz

    2016-10-31

    The aim of the study was to evaluate efficacy and safety of electroconvulsive therapy (ECT), in two age groups: before and after 60 years of age. The study included 107 patients, 62 women and 45 men hospitalized in the Institute of Psychiatry and Neurology and treated with ECT in 2013 and 2014. 76 people were below 60 years; 31 people - above 60. The authors analyzed the course of 1086 ECTs, 747 sessions for patients before 60 and 339 in patients over 60 years of age. The efficacy of ECT was diagnosed using CGI Scale. No serious complications such as death, life-threatening condition, hospitalization in another ward or permanent injury occurred. In 67.11% of patients below 60 and 42% of patients after 60 years of age no side effects were observed. Below 60 years of age most frequently reported adverse reactions were headaches (13.16% of patients), above 60 years of age - memory impairment (22.58% of respondents). Arrhythmias occurred in 6 patients aged over 60. Disturbances of consciousness occurred among older patients slightly less frequently than in younger patients (3.25% vs. 3.95%). In patients over 60 years of age remission rate was similar as in younger age group (32.89% vs 32.26%) and significant improvement rate was even higher (61.29% over 60 vs. 48.68 before 60 years of age). No improvement of mental state occurred in 7.89% and worsening occurred in 2.63% of younger patients. All patients ged over 60 years benefited from the treatment. The effectiveness of ECT in elderly was similar as in younger age group. The tolerance was slightly worse in patients aged over 60 years than in younger patients. The biggest problem in the elderly was not cognitive impairment, but the cardiovascular complications.

  2. A simulation of orientation dependent, global changes in camera sensitivity in ECT

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bieszk, J.A.; Hawman, E.G.; Malmin, R.E.

    1984-01-01

    ECT promises the abilities to: 1) observe radioisotope distributions in a patient without the summation of overlying activity to reduce contrast, and 2) measure quantitatively these distributions to further and more accurately assess organ function. Ideally, camera-based ECT systems should have a performance that is independent of camera orientation or gantry angle. This study is concerned with ECT quantitation errors that can arise from angle-dependent variations of camera sensitivity. Using simulated phantoms representative of heart and liver sections, the effects of sensitivity changes on reconstructed images were assessed both visually and quantitatively based on ROI sums. The sinogram for eachmore » test image was simulated with 128 linear digitization and 180 angular views. The global orientation-dependent sensitivity was modelled by applying an angular sensitivity dependence to the sinograms of the test images. Four sensitivity variations were studied. Amplitudes of 0% (as a reference), 5%, 10%, and 25% with a costheta dependence were studied as well as a cos2theta dependence with a 5% amplitude. Simulations were done with and without Poisson noise to: 1) determine trends in the quantitative effects as a function of the magnitude of the variation, and 2) to see how these effects are manifested in studies having statistics comparable to clinical cases. For the most realistic sensitivity variation (costheta, 5% ampl.), the ROIs chosen in the present work indicated changes of <0.5% in the noiseless case and <5% for the case with Poisson noise. The effects of statistics appear to dominate any effects due to global, sinusoidal, orientation-dependent sensitivity changes in the cases studied.« less

  3. Model-based estimation for dynamic cardiac studies using ECT

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chiao, P.C.; Rogers, W.L.; Clinthorne, N.H.

    1994-06-01

    In this paper, the authors develop a strategy for joint estimation of physiological parameters and myocardial boundaries using ECT (Emission Computed Tomography). The authors construct an observation model to relate parameters of interest to the projection data and to account for limited ECT system resolution and measurement noise. The authors then use a maximum likelihood (ML) estimator to jointly estimate all the parameters directly from the projection data without reconstruction of intermediate images. The authors also simulate myocardial perfusion studies based on a simplified heart model to evaluate the performance of the model-based joint ML estimator and compare this performancemore » to the Cramer-Rao lower bound. Finally, model assumptions and potential uses of the joint estimation strategy are discussed.« less

  4. Comparative study of clozapine, electroshock and the combination of ECT with clozapine in treatment-resistant schizophrenic patients.

    PubMed

    Masoudzadeh, A; Khalilian, A R

    2007-12-01

    The aim of this study was to compare the results of treatment with clozapine alone, Electroshock (ECT) alone and the combination of clozapine with ECT in treatment-resistant schizophrenic patients. Eighteen treatment-resistant schizophrenic patients were assigned to three equal groups: one group was given clozapine; one group was treated with ECT and one group was treated with the combination of clozapine and ECT. The treatment response was evaluated using the PANSS criteria and the data were analyzed with ANOVA. Combination therapy was superior to single modality therapy. The reduction of PANSS scores was 46% in the clozapine group, 40% in the ECT groups and 71% in the combination group, the difference between the combination group and the other groups was statistically significant (p < 0.05). Patients had a quick response to combination treatment, which resulted in a higher cure rate of positive and negative symptoms and improved the patients general performance. There were no significant adverse effects with combination treatment. Combination treatment with clozapine and ECT was safe and effective in treatment-resistant schizophrenic patients. It should be considered for the treatment of treatment-resistant schizophrenic patients.

  5. European Credit Transfer and Accumulation System: An Alternative Way to Calculate the ECTS Grades

    ERIC Educational Resources Information Center

    Grosges, Thomas; Barchiesi, Dominique

    2007-01-01

    The European Credit Transfer and Accumulation System (ECTS) has been developed and instituted to facilitate student mobility and academic recognition. This paper presents, discusses, and illustrates the pertinence and the limitation of the current statistical distribution of the ECTS grades, and we propose an alternative way to calculate the ECTS…

  6. The Role of Electroconvulsive Therapy (ECT) in Bipolar Disorder: Effectiveness in 522 Patients with Bipolar Depression, Mixed-state, Mania and Catatonic Features

    PubMed Central

    Perugi, Giulio; Medda, Pierpaolo; Toni, Cristina; Mariani, Michela Giorgi; Socci, Chiara; Mauri, Mauro

    2017-01-01

    Objective: We evaluated the effectiveness of Electroconvulsive Therapy (ECT) in the treatment of Bipolar Disorder (BD) in a large sample of bipolar patients with drug resistant depression, mania, mixed state and catatonic features. Method: 522 consecutive patients with DSM-IV-TR BD were evaluated prior to and after the ECT course. Responders and nonresponders were compared in subsamples of depressed and mixed patients. Descriptive analyses were reported for patients with mania and with catatonic features. Results: Of the original sample only 22 patients were excluded for the occurrence of side effects or consent withdrawal. After the ECT course, 344 (68.8%) patients were considered responders (final CGIi score ≤2) and 156 (31.2%) nonresponders. Response rates were respectively 68.1% for BD depression, 72.9% for mixed state, 75% for mania and 80.8% for catatonic features. Length of current episode and global severity of the illness were the only statistically significant predictors of nonresponse. Conclusion: ECT resulted to be an effective and safe treatment for all the phases of severe and drug-resistant BD. Positive response was observed in approximately two-thirds of the cases and in 80% of the catatonic patients. The duration of the current episode was the major predictor of nonresponse. The risk of ECT-induced mania is virtually absent and mood destabilization very unlikely. Our results clearly indicate that current algorithms for the treatment of depressive, mixed, manic and catatonic states should be modified and, at least for the most severe patients, ECT should not be considered as a “last resort”. PMID:28503107

  7. The Role of Electroconvulsive Therapy (ECT) in Bipolar Disorder: Effectiveness in 522 Patients with Bipolar Depression, Mixed-state, Mania and Catatonic Features.

    PubMed

    Perugi, Giulio; Medda, Pierpaolo; Toni, Cristina; Mariani, Michela Giorgi; Socci, Chiara; Mauri, Mauro

    2017-04-01

    We evaluated the effectiveness of Electroconvulsive Therapy (ECT) in the treatment of Bipolar Disorder (BD) in a large sample of bipolar patients with drug resistant depression, mania, mixed state and catatonic features. 522 consecutive patients with DSM-IV-TR BD were evaluated prior to and after the ECT course. Responders and nonresponders were compared in subsamples of depressed and mixed patients. Descriptive analyses were reported for patients with mania and with catatonic features. Of the original sample only 22 patients were excluded for the occurrence of side effects or consent withdrawal. After the ECT course, 344 (68.8%) patients were considered responders (final CGIi score ≤2) and 156 (31.2%) nonresponders. Response rates were respectively 68.1% for BD depression, 72.9% for mixed state, 75% for mania and 80.8% for catatonic features. Length of current episode and global severity of the illness were the only statistically significant predictors of nonresponse. ECT resulted to be an effective and safe treatment for all the phases of severe and drug-resistant BD. Positive response was observed in approximately two-thirds of the cases and in 80% of the catatonic patients. The duration of the current episode was the major predictor of nonresponse. The risk of ECT-induced mania is virtually absent and mood destabilization very unlikely. Our results clearly indicate that current algorithms for the treatment of depressive, mixed, manic and catatonic states should be modified and, at least for the most severe patients, ECT should not be considered as a "last resort".

  8. Emulsion Chamber Technology Experiment (ECT)

    NASA Technical Reports Server (NTRS)

    Gregory, John C.; Takahashi, Yoshiyuki

    1996-01-01

    The experimental objective of Emulsion Chamber Technology (ECT) was to develop space-borne emulsion chamber technology so that cosmic rays and nuclear interactions may subsequently be studied at extremely high energies with long exposures in space. A small emulsion chamber was built and flown on flight STS-62 of the Columbia in March 1994. Analysis of the several hundred layers of radiation-sensitive material has shown excellent post-flight condition and suitability for cosmic ray physics analysis at much longer exposures. Temperature control of the stack was 20 +/-1 C throughout the active control period and no significant deviations of temperature or pressure in the chamber were observed over the entire mission operations period. The unfortunate flight attitude of the orbiter (almost 90% Earth viewing) prevented any significant number of heavy particles (Z greater than or equal to 10) reaching the stack and the inverted flow of shower particles in the calorimeter has not allowed evaluation of absolute primary cosmic ray-detection efficiency nor of the practical time limits of useful exposure of these calorimeters in space to the level of detail originally planned. Nevertheless, analysis of the observed backgrounds and quality of the processed photographic and plastic materials after the flight show that productive exposures of emulsion chambers are feasible in low orbit for periods of up to one year or longer. The engineering approaches taken in the ECT program were proven effective and no major environmental obstacles to prolonged flight are evident.

  9. Rapid Response of Long-Standing, Treatment-Resistant Non-Catatonic Mutism in Paranoid Schizophrenia with Single ECT session.

    PubMed

    Dar, Mansoor Ahmad; Rather, Yasir Hassan; Shah, Majid Shafi; Wani, Rayees Ahmad; Hussain, Arshad

    2014-11-01

    Mutism is a common manifestation of catatonia, but mutism due to other forms of psychopathology and neurological disorders have also been described. Although not common, long-standing mutism has also been a feature of non-catatonic schizophrenia and traditionally responds less to conventional therapies. We describe a rare case of paranoid schizophrenia presenting with continuous mutism for about 4 years. This 26-year-old male had symptoms of schizophrenia without catatonia. After failed trial of adequate pharmacotherapy and psychological intervention and considering his level of dysfunction, he was started on electroconvulsive therapy (ECT). To our surprise, he improved with a single session of ECT while he was on concurrent pharmacotherapy. We also discuss the possible explanation for this rapid effect of ECT in such clinical presentation. To our knowledge, this is the first case of non-catatonic mutism of schizophrenia of this long duration responding so promptly to ECT, although there are other reports as well in literature, but multiple ECT sessions were applied in those cases. Non-catatonic mutism is perhaps presenting as a cultural variant in this part of the world and whenever encountered, ECT should be an option. Further research should be carried out to validate this idea.

  10. Some considerations of the tolerability of ketamine for ECT anesthesia: a case series and review of the literature.

    PubMed

    Rasmussen, Keith G; Ritter, Matthew J

    2014-12-01

    Most anesthetic agents used for electroconvulsive therapy (ECT) have few intrinsic adverse effects. Ketamine, however, is well known to be associated with a variety of adverse effects including nausea, dizziness, and psychotomimetic phenomena. Over the past several decades, there have been numerous reports on the use of ketamine for ECT anesthesia, with varied assessments on how prominent these adverse effects are in the ECT situation. Ketamine has received a resurgence of interest as an ECT anesthetic of late owing to its established independent antidepressant effects and to theoretical reasons why it might lessen the cognitive adverse effects of ECT. In this case series, the author reviews the experience with 14 patients who had undergone ECT who were switched to ketamine as anesthetic from methohexital at the preference of the treating anesthesiologist. All 14 patients spontaneously reported a strong preference not to be given ketamine again due to bothersome adverse effects. The latter consisted of either vestibular-type symptoms (nausea/vomiting, dizziness, and vertigo) or psychotomimetic effects (dissociative phenomena). It is concluded that ketamine is not free of adverse effects when used as an ECT anesthetic. Electroconvulsive therapy clinicians should be vigilant about assessing for these effects when ketamine is used, and consideration should be given to using a benzodiazepine such as diazepam or midazolam at seizure termination when ketamine anesthesia is used to prevent bothersome adverse effects seen upon awakening.

  11. A High-Throughput Assay for Rho Guanine Nucleotide Exchange Factors Based on the Transcreener GDP Assay.

    PubMed

    Reichman, Melvin; Schabdach, Amanda; Kumar, Meera; Zielinski, Tom; Donover, Preston S; Laury-Kleintop, Lisa D; Lowery, Robert G

    2015-12-01

    Ras homologous (Rho) family GTPases act as molecular switches controlling cell growth, movement, and gene expression by cycling between inactive guanosine diphosphate (GDP)- and active guanosine triphosphate (GTP)-bound conformations. Guanine nucleotide exchange factors (GEFs) positively regulate Rho GTPases by accelerating GDP dissociation to allow formation of the active, GTP-bound complex. Rho proteins are directly involved in cancer pathways, especially cell migration and invasion, and inhibiting GEFs holds potential as a therapeutic strategy to diminish Rho-dependent oncogenesis. Methods for measuring GEF activity suitable for high-throughput screening (HTS) are limited. We developed a simple, generic biochemical assay method for measuring GEF activity based on the fact that GDP dissociation is generally the rate-limiting step in the Rho GTPase catalytic cycle, and thus addition of a GEF causes an increase in steady-state GTPase activity. We used the Transcreener GDP Assay, which relies on selective immunodetection of GDP, to measure the GEF-dependent stimulation of steady-state GTP hydrolysis by small GTPases using Dbs (Dbl's big sister) as a GEF for Cdc42, RhoA, and RhoB. The assay is well suited for HTS, with a homogenous format and far red fluorescence polarization (FP) readout, and it should be broadly applicable to diverse Rho GEF/GTPase pairs. © 2015 Society for Laboratory Automation and Screening.

  12. The role of APOE-ɛ4 and beta amyloid in the differential rate of recovery from ECT: a review

    PubMed Central

    Sutton, T A; Sohrabi, H R; Rainey-Smith, S R; Bird, S M; Weinborn, M; Martins, R N

    2015-01-01

    Individual biological differences may contribute to the variability of outcomes, including cognitive effects, observed following electroconvulsive treatment (ECT). A narrative review of the research literature on carriage of the apolipoprotein E ɛ4 allele (APOE-ɛ4) and the protein biomarker beta amyloid (Aβ) with ECT cognitive outcome was undertaken. ECT induces repeated brain seizures and there is debate as to whether this causes brain injury and long-term cognitive disruption. The majority of ECT is administered to the elderly (over age 65 years) with drug-resistant depression. Depression in the elderly may be a symptom of the prodromal stage of Alzheimer's disease (AD). Carriage of the APOE-ɛ4 allele and raised cerebral Aβ are consistently implicated in AD, but inconsistently implicated in brain injury (and related syndromes) recovery rates. A paucity of brain-related recovery, genetic and biomarker research in ECT responses in the elderly was found: three studies have examined the effect of APOE-ɛ4 allele carriage on cognition in the depressed elderly receiving ECT, and two have examined Aβ changes after ECT, with contradictory findings. Cognitive changes in all studies of ECT effects were measured by a variety of psychological tests, making comparisons of such changes between studies problematic. Further, psychological test data-validity measures were not routinely administered, counter to current testing recommendations. The methodological issues of the currently available literature as well as the need for well-designed, hypothesis driven, longitudinal studies are discussed. PMID:25826114

  13. The role of APOE-ɛ4 and beta amyloid in the differential rate of recovery from ECT: a review.

    PubMed

    Sutton, T A; Sohrabi, H R; Rainey-Smith, S R; Bird, S M; Weinborn, M; Martins, R N

    2015-03-31

    Individual biological differences may contribute to the variability of outcomes, including cognitive effects, observed following electroconvulsive treatment (ECT). A narrative review of the research literature on carriage of the apolipoprotein E ɛ4 allele (APOE-ɛ4) and the protein biomarker beta amyloid (Aβ) with ECT cognitive outcome was undertaken. ECT induces repeated brain seizures and there is debate as to whether this causes brain injury and long-term cognitive disruption. The majority of ECT is administered to the elderly (over age 65 years) with drug-resistant depression. Depression in the elderly may be a symptom of the prodromal stage of Alzheimer's disease (AD). Carriage of the APOE-ɛ4 allele and raised cerebral Aβ are consistently implicated in AD, but inconsistently implicated in brain injury (and related syndromes) recovery rates. A paucity of brain-related recovery, genetic and biomarker research in ECT responses in the elderly was found: three studies have examined the effect of APOE-ɛ4 allele carriage on cognition in the depressed elderly receiving ECT, and two have examined Aβ changes after ECT, with contradictory findings. Cognitive changes in all studies of ECT effects were measured by a variety of psychological tests, making comparisons of such changes between studies problematic. Further, psychological test data-validity measures were not routinely administered, counter to current testing recommendations. The methodological issues of the currently available literature as well as the need for well-designed, hypothesis driven, longitudinal studies are discussed.

  14. NASA's Van Allen Probes RBSP-ECT and NSF's FIREBIRD Data Products and Access to Them: An Insider's Outlook on the Inner and Outer Belts.

    NASA Astrophysics Data System (ADS)

    Smith, S. S.; Spence, H. E.; Geoffrey, R.; Klumpar, D. M.

    2017-12-01

    In this poster, we present a summary of access to data products Radiation Belt Storm Probes - Energetic Particle Composition, and Thermal plasma (RBSP-ECT) suite of NASA's Van Allen Probes mission. The RBSP-ECT science investigation (http://rbsp-ect.sr.unh.edu) measures comprehensively the near-Earth charged particle environment in order to understand the processes that control the acceleration, global distribution, and variability of radiation belt electrons and ions. RBSP-ECT data products derive from the three instrument elements that comprise the suite, which collectively covers the broad energies that define the source and seed populations, the core radiation belts, and also their highest energy ultra-relativistic extensions. These RBSP-ECT instruments include, from lowest to highest energies: the Helium, Oxygen, Proton, and Electron (HOPE) sensor, the Magnetic Electron and Ion Spectrometer (MagEIS), and the Relativistic Electron and Proton Telescope (REPT). We provide a brief overview of their principles of operation, as well as a description of the Level 1-3 data products that the HOPE, MagEIS, and REPT instruments produce, both separately and together. We provide a summary of how to access these RBSP-ECT data products at our Science Operation Center and Science Data Center (http://www.rbsp-ect.lanl.gov/rbsp_ect.php ) as well as caveats for their use. In addition, we also provide a summary of access to the data products from NSF's CubeSat mission called Focused Investigation of Relativistic Electron Burst: Intensity, Range, and Dynamics (FIREBIRD). The dual CubeSat FIREBIRD missions provide data on energetic radiation belt electrons precipitating into the atmosphere at low altitudes, which complements and is contemporary with RBSP-ECT measurements. We provide a similar summary of how to access these data (https://ssel.montana.edu/firebird2.html). Finally, in the spirit of efficiently and effectively promoting and encouraging new collaborations, we present a

  15. Diverse roles of guanine nucleotide exchange factors in regulating collective cell migration

    PubMed Central

    Tseng, Yun-Yu; Rabadán, M. Angeles; Krishna, Shefali; Hall, Alan

    2017-01-01

    Efficient collective migration depends on a balance between contractility and cytoskeletal rearrangements, adhesion, and mechanical cell–cell communication, all controlled by GTPases of the RHO family. By comprehensive screening of guanine nucleotide exchange factors (GEFs) in human bronchial epithelial cell monolayers, we identified GEFs that are required for collective migration at large, such as SOS1 and β-PIX, and RHOA GEFs that are implicated in intercellular communication. Down-regulation of the latter GEFs differentially enhanced front-to-back propagation of guidance cues through the monolayer and was mirrored by down-regulation of RHOA expression and myosin II activity. Phenotype-based clustering of knockdown behaviors identified RHOA-ARHGEF18 and ARHGEF3-ARHGEF28-ARHGEF11 clusters, indicating that the latter may signal through other RHO-family GTPases. Indeed, knockdown of RHOC produced an intermediate between the two phenotypes. We conclude that for effective collective migration, the RHOA-GEFs → RHOA/C → actomyosin pathways must be optimally tuned to compromise between generation of motility forces and restriction of intercellular communication. PMID:28512143

  16. Serum BDNF as a peripheral biomarker of treatment-resistant depression and the rapid antidepressant response: A comparison of ketamine and ECT.

    PubMed

    Allen, A P; Naughton, M; Dowling, J; Walsh, A; Ismail, F; Shorten, G; Scott, L; McLoughlin, D M; Cryan, J F; Dinan, T G; Clarke, G

    2015-11-01

    Ketamine is associated with rapid antidepressant efficacy but the biological mechanisms underpinning this effect are unclear. Serum brain-derived neurotrophic factor (sBDNF) is a potential circulating biomarker of treatment-resistant depression (TRD) and ketamine response but it is unclear if this is a common target of both ketamine and electroconvulsive therapy (ECT), the current gold standard for TRD. Moreover, the impact of multiple ketamine infusions on sBDNF has not yet been established. Thirty five TRD patients with a current DSM-IV diagnosis of recurrent depressive disorder received up to 12 ECT sessions (N=17) or up to three intravenous infusions of low-dose (0.5mg/kg) ketamine (N=18). Blood samples were taken over the course of the study for assessment of sBDNF. Symptom severity and response were monitored using the 17-item Hamilton Depression Rating Scale (HDRS). sBDNF was assessed in 20 healthy controls to allow comparison with TRD patients. As expected, sBDNF was lower in TRD patients at baseline compared to healthy controls. Ketamine and ECT treatment were both associated with significant reductions in depressive symptoms. However, sBDNF was significantly elevated only at one week following the first ketamine infusion in those classified as responders one week later. sBDNF was not elevated following subsequent infusions. ECT reduced depressive symptoms, as expected, but was not associated with an enhancement in BDNF. Patients continued with their psychotropic medications throughout this trial. SBDNF normalisation does not appear to be a prerequisite for symptomatic improvement in TRD following ketamine or ECT treatment. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Strain E?ect on the Instability of Island Formation in Submonolayer Heteroepitaxy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yao, yugui; Li, Maozhi; Wu, Biao

    2009-01-01

    Strain e ect on the instability of island formation in submonolayer heteroepitaxy is studied in both thermodynamic and kinetic regimes. By using linear stability analysis, the energy change of an island due to small perturbations is analyzed. A phase diagram is constructed to illustrate the interplay between kinetic processes and strain e ect on the shape instability. Critical island sizes beyond which islands grow unstable are also derived for various growth conditions and can be used to estimate energy parameters. The scaling forms of shape instability are also discussed.

  18. 7 CFR 985.31 - Research and development proj-ects.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., may establish or provide for the establishment of production research, marketing research and... 7 Agriculture 8 2010-01-01 2010-01-01 false Research and development proj-ects. 985.31 Section 985.31 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING...

  19. The anticoagulant effect of therapeutic levels of dabigatran in atrial fibrillation evaluated by thrombelastography (TEG®), Hemoclot Thrombin Inhibitor (HTI) assay and Ecarin Clotting Time (ECT).

    PubMed

    Solbeck, Sacha; Jensen, Annette Schophuus; Maschmann, Christian; Stensballe, Jakob; Ostrowski, Sisse Rye; Johansson, Pär I

    Monitoring the effect of dabigatran (Pradaxa ® ) is challenging. The aim of this study was to evaluate if thrombelastography reaction time (TEG ® R) could detect the anticoagulant effect of dabigatran showing a correlation between TEG ® R, Hemoclot Thrombin Inhibitor (HTI) assay and Ecarin Clotting Time (ECT) in patients with non-valvular atrial fibrillation (NVAF). Blood samples from 35 AF patients receiving either 110 mg (n 19) or 150 mg (n 16) dabigatran twice daily were analyzed with TEG ® , HTI and ECT 2-3 h after dabigatran intake. All patients had prolonged TEG ® R. The patients receiving dabigatran 110 mg ×2 had a TEG ® R mean 14.2 min (range 9.1-25), a mean dabigatran concentration measured by HTI of 268.5 ng/mL (range 54-837 ng/mL) and by ECT of 355.7 ng/mL (range 40-1020 ng/mL). The corresponding numbers for patients receiving dabigatran 150 mg ×2 were TEG ® R mean of 12.5 min (range 9.2-23.2 min), mean dabigatran concentration of 179.2 ng/mL by HTI (range 26-687 ng/mL) and by ECT 225.1 ng/mL (range 42-1020 ng/mL). The two dosage groups had comparable anticoagulation demonstrated by equally prolonged TEG ® R (p = .909), HTI (p = .707) and ECT (p = .567). No difference in creatinine levels in the two dosage groups was observed (p = .204) though patients with dabigatran concentration >400 ng/mL had significantly higher creatinine levels (p = .001). Large individual variation of the anticoagulant response was observed. Some patients had TEG ® R values up to three times upper normal limit with immediate risk of bleeding. Our data indicate that TEG ® R reflected dabigatran levels in NVAF patients and that TEG ® R correlated to HTI and ECT.

  20. Focal electrically administered seizure therapy: a novel form of ECT illustrates the roles of current directionality, polarity, and electrode configuration in seizure induction.

    PubMed

    Spellman, Timothy; Peterchev, Angel V; Lisanby, Sarah H

    2009-07-01

    Electroconvulsive therapy (ECT) is a mainstay in the treatment of severe, medication-resistant depression. The antidepressant efficacy and cognitive side effects of ECT are influenced by the position of the electrodes on the head and by the degree to which the electrical stimulus exceeds the threshold for seizure induction. However, surprisingly little is known about the effects of other key electrical parameters such as current directionality, polarity, and electrode configuration. Understanding these relationships may inform the optimization of therapeutic interventions to improve their risk/benefit ratio. To elucidate these relationships, we evaluated a novel form of ECT (focal electrically administered seizure therapy, FEAST) that combines unidirectional stimulation, control of polarity, and an asymmetrical electrode configuration, and contrasted it with conventional ECT in a nonhuman primate model. Rhesus monkeys had their seizure thresholds determined on separate days with ECT conditions that crossed the factors of current directionality (unidirectional or bidirectional), electrode configuration (standard bilateral or FEAST (small anterior and large posterior electrode)), and polarity (assignment of anode and cathode in unidirectional stimulation). Ictal expression and post-ictal suppression were quantified through scalp EEG. Findings were replicated and extended in a second experiment with the same subjects. Seizures were induced in each of the 75 trials, including 42 FEAST procedures. Seizure thresholds were lower with unidirectional than with bidirectional stimulation (p<0.0001), and lower in FEAST than in bilateral ECS (p=0.0294). Ictal power was greatest in posterior-anode unidirectional FEAST, and post-ictal suppression was strongest in anterior-anode FEAST (p=0.0008 and p=0.0024, respectively). EEG power was higher in the stimulated hemisphere in posterior-anode FEAST (p=0.0246), consistent with the anode being the site of strongest activation. These

  1. Computational models of Bitemporal, Bifrontal and Right Unilateral ECT predict differential stimulation of brain regions associated with efficacy and cognitive side effects.

    PubMed

    Bai, S; Gálvez, V; Dokos, S; Martin, D; Bikson, M; Loo, C

    2017-03-01

    Extensive clinical research has shown that the efficacy and cognitive outcomes of electroconvulsive therapy (ECT) are determined, in part, by the type of electrode placement used. Bitemporal ECT (BT, stimulating electrodes placed bilaterally in the frontotemporal region) is the form of ECT with relatively potent clinical and cognitive side effects. However, the reasons for this are poorly understood. This study used computational modelling to examine regional differences in brain excitation between BT, Bifrontal (BF) and Right Unilateral (RUL) ECT, currently the most clinically-used ECT placements. Specifically, by comparing similarities and differences in current distribution patterns between BT ECT and the other two placements, the study aimed to create an explanatory model of critical brain sites that mediate antidepressant efficacy and sites associated with cognitive, particularly memory, adverse effects. High resolution finite element human head models were generated from MRI scans of three subjects. The models were used to compare differences in activation between the three ECT placements, using subtraction maps. In this exploratory study on three realistic head models, Bitemporal ECT resulted in greater direct stimulation of deep midline structures and also left temporal and inferior frontal regions. Interpreted in light of existing knowledge on depressive pathophysiology and cognitive neuroanatomy, it is suggested that the former sites are related to efficacy and the latter to cognitive deficits. We hereby propose an approach using binarised subtraction models that can be used to optimise, and even individualise, ECT therapies. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  2. Regulation of Ras Exchange Factors and Cellular Localization of Ras Activation by Lipid Messengers in T Cells

    PubMed Central

    Jun, Jesse E.; Rubio, Ignacio; Roose, Jeroen P.

    2013-01-01

    The Ras-MAPK signaling pathway is highly conserved throughout evolution and is activated downstream of a wide range of receptor stimuli. Ras guanine nucleotide exchange factors (RasGEFs) catalyze GTP loading of Ras and play a pivotal role in regulating receptor-ligand induced Ras activity. In T cells, three families of functionally important RasGEFs are expressed: RasGRF, RasGRP, and Son of Sevenless (SOS)-family GEFs. Early on it was recognized that Ras activation is critical for T cell development and that the RasGEFs play an important role herein. More recent work has revealed that nuances in Ras activation appear to significantly impact T cell development and selection. These nuances include distinct biochemical patterns of analog versus digital Ras activation, differences in cellular localization of Ras activation, and intricate interplays between the RasGEFs during distinct T cell developmental stages as revealed by various new mouse models. In many instances, the exact nature of these nuances in Ras activation or how these may result from fine-tuning of the RasGEFs is not understood. One large group of biomolecules critically involved in the control of RasGEFs functions are lipid second messengers. Multiple, yet distinct lipid products are generated following T cell receptor (TCR) stimulation and bind to different domains in the RasGRP and SOS RasGEFs to facilitate the activation of the membrane-anchored Ras GTPases. In this review we highlight how different lipid-based elements are generated by various enzymes downstream of the TCR and other receptors and how these dynamic and interrelated lipid products may fine-tune Ras activation by RasGEFs in developing T cells. PMID:24027568

  3. Initial evaluation of discrete orthogonal basis reconstruction of ECT images

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Moody, E.B.; Donohue, K.D.

    1996-12-31

    Discrete orthogonal basis restoration (DOBR) is a linear, non-iterative, and robust method for solving inverse problems for systems characterized by shift-variant transfer functions. This simulation study evaluates the feasibility of using DOBR for reconstructing emission computed tomographic (ECT) images. The imaging system model uses typical SPECT parameters and incorporates the effects of attenuation, spatially-variant PSF, and Poisson noise in the projection process. Sample reconstructions and statistical error analyses for a class of digital phantoms compare the DOBR performance for Hartley and Walsh basis functions. Test results confirm that DOBR with either basis set produces images with good statistical properties. Nomore » problems were encountered with reconstruction instability. The flexibility of the DOBR method and its consistent performance warrants further investigation of DOBR as a means of ECT image reconstruction.« less

  4. Effectiveness and clinical predictors of response to combined ECT and antipsychotic therapy in patients with treatment-resistant schizophrenia and dominant negative symptoms.

    PubMed

    Pawełczyk, Tomasz; Kołodziej-Kowalska, Emilia; Pawełczyk, Agnieszka; Rabe-Jabłońska, Jolanta

    2014-12-15

    The effectiveness and predictors of response to electroconvulsive therapy (ECT) combined with antipsychotics (AP) in treatment-resistant schizophrenia patients with the dominance of negative symptoms (TRS-NS) have not been studied systematically so far. 29 patients aged 21-55 years diagnosed with TRS-NS underwent ECT combined with antipsychotics (ECT+AP). Prior to the ECT, the symptom profile and severity were evaluated using Positive and Negative Syndrome Scale (PANSS). Demographic and medical data was collected; ECT parameters and pharmacotherapy results were evaluated. After the combined ECT+AP therapy a significant decrease in symptom severity was found. A response to treatment was achieved by 60% of patients. The greatest reductions were obtained in general and positive PANSS subscale (median change: 11 and 7 pts.) and the smallest, but still significant, ones in negative symptoms subscale (median: 3.5 pts.). Patients who responded to ECT+AP demonstrated a significantly shorter duration of the current episode in comparison with patients who did not experience at least a 25% reduction in symptom severity (median: 4 vs. 8 months). A combination of ECT and antipsychotic therapy can provide a useful treatment option for patients with TRS-NS. The only significant predictor of response to treatment was a shorter duration of the current episode. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. NASA's RBSP-ECT Science Investigation of the Van Allen Probes Mission: Highlights of the Prime Mission Phase, Data Access Overview, and Opportunities to Collaborate in the Extended Mission Phase

    NASA Astrophysics Data System (ADS)

    Smith, S. S.; Friedel, R. H.; Larsen, B.; Reeves, G.; Spence, H. E.

    2015-12-01

    In this poster, we present a summary of access to the data products of the Radiation Belt Storm Probes - Energetic Particle Composition, and Thermal plasma (RBSP-ECT) suite of NASA's Van Allen Probes mission. The RBSP-ECT science investigation (http://rbsp-ect.sr.unh.edu) measures comprehensively the near-Earth charged particle environment in order to understand the processes that control the acceleration, global distribution, and variability of radiation belt electrons and ions. RBSP-ECT data products derive from the three instrument elements that comprise the suite, which collectively covers the broad energies that define the source and seed populations, the core radiation belts, and also their highest energy ultra-relativistic extensions. These RBSP-ECT instruments include, from lowest to highest energies: the Helium, Oxygen, Proton, and Electron (HOPE) sensor, the Magnetic Electron and Ion Spectrometer (MagEIS), and the Relativistic Electron and Proton Telescope (REPT). We provide a brief overview of their principles of operation, as well as a description of the Level 2-3 data products that the HOPE, MagEIS, and REPT instruments produce, both separately and together. We provide a summary of how to access these RBSP-ECT data products at our Science Operation Center and Science Data Center (http://www.rbsp-ect.lanl.gov/rbsp_ect.php ) as well as caveats for their use. Finally, in the spirit of efficiently and effectively promoting and encouraging new collaborations, we present a summary of past publications, current studies, and opportunities for your future participation in RBSP-ECT extended mission phase science.

  6. Focal Electrically Administered Seizure Therapy (FEAST): A novel form of ECT illustrates the roles of current directionality, polarity, and electrode configuration in seizure induction

    PubMed Central

    Spellman, Timothy; Peterchev, Angel V.; Lisanby, Sarah H.

    2009-01-01

    Electroconvulsive therapy (ECT) is a mainstay in the treatment of severe, medication resistant depression. The antidepressant efficacy and cognitive side effects of ECT are influenced by the position of the electrodes on the head and by the degree to which the electrical stimulus exceeds the threshold for seizure induction. However, surprisingly little is known about the effects of other key electrical parameters such as current directionality, polarity, and electrode configuration. Understanding these relationships may inform the optimization of therapeutic interventions to improve their risk/benefit ratio. To elucidate these relationships, we evaluated a novel form of ECT (focal electrically administered seizure therapy, FEAST) that combines unidirectional stimulation, control of polarity, and an asymmetrical electrode configuration, and contrasted it with conventional ECT in a nonhuman primate model. Rhesus monkeys had their seizure thresholds determined on separate days with ECT conditions that crossed the factors of current directionality (unidirectional or bidirectional), electrode configuration (standard bilateral or FEAST (small anterior and large posterior electrode)), and polarity (assignment of anode and cathode in unidirectional stimulation). Ictal expression and post-ictal suppression were quantified via scalp EEG. Findings were replicated and extended in a second experiment with the same subjects. Seizures were induced in each of 75 trials, including 42 FEAST procedures. Seizure thresholds were lower with unidirectional than with bidirectional stimulation (p<0.0001), and lower in FEAST than in bilateral ECS (p=0.0294). Ictal power was greatest in posterior-anode unidirectional FEAST, and post-ictal suppression was strongest in anterior-anode FEAST (p=0.0008 and p=0.0024, respectively). EEG power was higher in the stimulated hemisphere in posterior-anode FEAST (p=0.0246), consistent with the anode being the site of strongest activation. These findings

  7. Is electroconvulsive therapy (ECT) effective and safe for treatment of depression in dementia? A short review.

    PubMed

    Oudman, Erik

    2012-03-01

    Depression is one of the most frequently diagnosed psychiatric disorders in patients with dementia with a prevalence of up to 50%. The detrimental effects of depression in dementia include disability in daily living, worse quality of life, and faster cognitive decline. Although electroconvulsive therapy (ECT) is a well-established and effective treatment for depression in the elderly, it is currently an overlooked treatment option in the elderly with dementia and depression. The aim of this review was to provide a critical analysis of the efficacy and safety of ECT in depression superimposed on dementia by reviewing the current literature on this topic. Current evidence suggests that ECT is an effective treatment for depression in dementia, although the relatively small number of controlled studies hampers the comparison of effectiveness between healthy nongeriatric patients and those with dementia. Moreover, the systematic reports on cognitive side effects are very limited in number and currently only apply to moderately mild or mild dementia of nonvascular origin. Some studies do suggest that cognitive side effects are likely in later stages of dementia and in patients with vascular dementia. It is therefore of crucial relevance to prospectively study effects of ECT in different types and phases of dementia in controlled trials. From a clinical perspective, it is essential to inform and educate patients and family about the possible risks and benefits of ECT treatment for depression in dementia.

  8. Top Ten Reasons a Graduate Student Should Apply to Be an ECT Foundation Intern

    ERIC Educational Resources Information Center

    York, Cindy S.

    2009-01-01

    In this article, the author encourages graduate students to apply for the ECT Foundation Internship. She presents a list of the top ten benefits the internship offers a graduate student's career: (1) It could change your life. It changed mine; (2) Networking; (3) Mentoring; (4) Leadership opportunities; (5) Behind the scenes pass; (6) Shadowing;…

  9. GlnR-Mediated Regulation of ectABCD Transcription Expands the Role of the GlnR Regulon to Osmotic Stress Management.

    PubMed

    Shao, ZhiHui; Deng, WanXin; Li, ShiYuan; He, JuanMei; Ren, ShuangXi; Huang, WeiRen; Lu, YinHua; Zhao, GuoPing; Cai, ZhiMing; Wang, Jin

    2015-10-01

    Ectoine and hydroxyectoine are excellent compatible solutes for bacteria to deal with environmental osmotic stress and temperature damages. The biosynthesis cluster of ectoine and hydroxyectoine is widespread among microorganisms, and its expression is activated by high salinity and temperature changes. So far, little is known about the mechanism of the regulation of the transcription of ect genes and only two MarR family regulators (EctR1 in methylobacteria and the EctR1-related regulator CosR in Vibrio cholerae) have been found to negatively regulate the expression of ect genes. Here, we characterize GlnR, the global regulator for nitrogen metabolism in actinomycetes, as a negative regulator for the transcription of ectoine/hydroxyectoine biosynthetic genes (ect operon) in Streptomyces coelicolor. The physiological role of this transcriptional repression by GlnR is proposed to protect the intracellular glutamate pool, which acts as a key nitrogen donor for both the nitrogen metabolism and the ectoine/hydroxyectoine biosynthesis. High salinity is deleterious, and cells must evolve sophisticated mechanisms to cope with this osmotic stress. Although production of ectoine and hydroxyectoine is one of the most frequently adopted strategies, the in-depth mechanism of regulation of their biosynthesis is less understood. So far, only two MarR family negative regulators, EctR1 and CosR, have been identified in methylobacteria and Vibrio, respectively. Here, our work demonstrates that GlnR, the global regulator for nitrogen metabolism, is a negative transcriptional regulator for ect genes in Streptomyces coelicolor. Moreover, a close relationship is found between nitrogen metabolism and osmotic resistance, and GlnR-mediated regulation of ect transcription is proposed to protect the intracellular glutamate pool. Meanwhile, the work reveals the multiple roles of GlnR in bacterial physiology. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  10. GlnR-Mediated Regulation of ectABCD Transcription Expands the Role of the GlnR Regulon to Osmotic Stress Management

    PubMed Central

    Shao, ZhiHui; Deng, WanXin; Li, ShiYuan; He, JuanMei; Ren, ShuangXi; Huang, WeiRen; Lu, YinHua; Zhao, GuoPing

    2015-01-01

    ABSTRACT Ectoine and hydroxyectoine are excellent compatible solutes for bacteria to deal with environmental osmotic stress and temperature damages. The biosynthesis cluster of ectoine and hydroxyectoine is widespread among microorganisms, and its expression is activated by high salinity and temperature changes. So far, little is known about the mechanism of the regulation of the transcription of ect genes and only two MarR family regulators (EctR1 in methylobacteria and the EctR1-related regulator CosR in Vibrio cholerae) have been found to negatively regulate the expression of ect genes. Here, we characterize GlnR, the global regulator for nitrogen metabolism in actinomycetes, as a negative regulator for the transcription of ectoine/hydroxyectoine biosynthetic genes (ect operon) in Streptomyces coelicolor. The physiological role of this transcriptional repression by GlnR is proposed to protect the intracellular glutamate pool, which acts as a key nitrogen donor for both the nitrogen metabolism and the ectoine/hydroxyectoine biosynthesis. IMPORTANCE High salinity is deleterious, and cells must evolve sophisticated mechanisms to cope with this osmotic stress. Although production of ectoine and hydroxyectoine is one of the most frequently adopted strategies, the in-depth mechanism of regulation of their biosynthesis is less understood. So far, only two MarR family negative regulators, EctR1 and CosR, have been identified in methylobacteria and Vibrio, respectively. Here, our work demonstrates that GlnR, the global regulator for nitrogen metabolism, is a negative transcriptional regulator for ect genes in Streptomyces coelicolor. Moreover, a close relationship is found between nitrogen metabolism and osmotic resistance, and GlnR-mediated regulation of ect transcription is proposed to protect the intracellular glutamate pool. Meanwhile, the work reveals the multiple roles of GlnR in bacterial physiology. PMID:26170409

  11. Intrathecal Pump Exposure to Electromagnetic Interference: A Report of Device Interrogation following Multiple ECT Sessions.

    PubMed

    Bicket, Mark C; Hanna, George M

    2016-02-01

    Intrathecal drug delivery systems represent an increasingly common treatment modality for patients with a variety of conditions, including chronic pain and spasticity. Pumps rely on electronic programming to properly control and administer highly concentrated medications. Electromagnetic interference (EMI) is a known exposure that may cause a potential patient safety issue stemming from direct patient injury, pump damage, or changes to pump operation or flow rate. The objective of our case report was to describe an approach to evaluating a patient with a pump prior to and following exposure to EMI from electroconvulsive therapy (ECT), as well as to document findings from device interrogations associated with this event. Case report. Academic university-based pain management center. We present the case of a patient with an intrathecal pump who underwent multiple exposures to EMI in the form of 42 ECT sessions. Interrogation of the intrathecal drug delivery system revealed no safety issues following ECT sessions. At no time were error messages, unintentional changes in event logs, unintentional changes in pump settings, or evidence of pump stall or over-infusion noted. Communication with multiple entities (patient, family, consulting physicians, and device manufacturer) and maintaining vigilance through device interrogation both before and after EMI exposure are appropriate safeguards to mitigate the risk and detect potential adverse events of EMI with intrathecal drug delivery systems. Given the infrequent reports of device exposure to ECT, best practices may be derived from experience with EMI exposure from magnetic resonance imaging (MRI). Although routine EMI exposure to intrathecal drug delivery systems should be avoided, we describe one patient with repeated exposure to ECT without apparent complication.

  12. Characterization of the Edge Crack Torsion (ECT) Test for Mode III Fracture Toughness Measurement of Laminated Composites

    NASA Technical Reports Server (NTRS)

    Ratcliffe, James G.

    2004-01-01

    The edge crack torsion (ECT) test is designed to initiate mode III delamination growth in composite laminates. The test has undergone several design changes during its development. The objective of this paper was to determine the suitability of the current ECT test design a mode III fracture test. To this end, ECT tests were conducted on specimens manufactured from IM7/8552 and S2/8552 tape laminates. Three-dimensional finite element analyses were performed. The analysis results were used to calculate the distribution of mode I, mode II, and mode III strain energy release rate along the delamination front. The results indicated that mode IIIdominated delamination growth would be initiated from the specimen center. However, in specimens of both material types, the measured values of GIIIc exhibited significant dependence on delamination length. Load-displacement response of the specimens exhibited significant deviation from linearity before specimen failure. X-radiographs of a sample of specimens revealed that damage was initiated in the specimens prior to failure. Further inspection of the failure surfaces is required to identify the damage and determine that mode III delamination is initiated in the specimens.

  13. [Efficacy of continuation and maintenance electroconvulsive therapy (c/m ECT) in the treatment of patients with therapy-resistant affective disorders: a retrospective analysis].

    PubMed

    Post, Thomas; Kemmler, Georg; Krassnig, Tristan; Brugger, Anita; Hausmann, Armand

    2015-01-01

    Continuation and maintenance electroconvulsive therapy (c/m ECT) is a long-term treatment option in severely and chronically ill patients with mood disorders, who are unresponsive or intolerant to medication. Due to the current lack of empirical studies, c/m ECT is still a clinical tool with little evidence. We conducted a retrospective analysis of patients' charts who received c/m ECT over a 10-year period. Outcome was measured by comparing the number of pre-c/m ECT and post-c/m ECT hospitalizations, as well as inpatient days per year and mean duration of hospital stays. In 19 patients (63% female; mean age 53.5 ± 12.0 years) with either bipolar (42%) or unipolar (58%) mood disorder, with the majority of patients suffering from a depressive episode at hospital admission (95%), c/m ECT was initiated after a successful series of ECT. In a 5-year interval before and after starting c/m ECT the number of hospitalizations per year (0.87 vs. 0.28, p < 0.001), inpatient days per year (30.8 vs. 4.5 days, p < 0.001), as well as the mean duration of hospital days (30.5 vs. 16.7 days, p = 0.02) decreased significantly. Our data support previous results showing that c/m ECT is an efficacious option in treating and favourably altering the course of therapy-resistant affective disorders. Further research using a controlled study design and larger sample sizes are needed to convincingly define indication and performance of c/m ECT.

  14. A dual role for the RhoGEF Ephexin5 in regulation of dendritic spine outgrowth

    PubMed Central

    Hamilton, AM; Lambert, JT; Parajuli, LK; Vivas, O; Park, DK; Stein, IS; Jahncke, JN; Greenberg, ME; Margolis, SS; Zito, K

    2017-01-01

    The outgrowth of new dendritic spines is closely linked to the formation of new synapses, and is thought to be a vital component of the experience-dependent circuit plasticity that supports learning. Here, we examined the role of the RhoGEF Ephexin5 in driving activity-dependent spine outgrowth. We found that reducing Ephexin5 levels increased spine outgrowth, and increasing Ephexin5 levels decreased spine outgrowth in a GEF-dependent manner, suggesting that Ephexin5 acts as an inhibitor of spine outgrowth. Notably, we found that increased neural activity led to a proteasome-dependent reduction in the levels of Ephexin5 in neuronal dendrites, which could facilitate the enhanced spine outgrowth observed following increased neural activity. Surprisingly, we also found that Ephexin5-GFP levels were elevated on the dendrite at sites of future new spines, prior to new spine outgrowth. Moreover, lowering neuronal Ephexin5 levels inhibited new spine outgrowth in response to both global increases in neural activity and local glutamatergic stimulation of the dendrite, suggesting that Ephexin5 is necessary for activity-dependent spine outgrowth. Our data support a model in which Ephexin5 serves a dual role in spinogenesis, acting both as a brake on overall spine outgrowth and as a necessary component in the site-specific formation of new spines. PMID:28185854

  15. A dual role for the RhoGEF Ephexin5 in regulation of dendritic spine outgrowth.

    PubMed

    Hamilton, A M; Lambert, J T; Parajuli, L K; Vivas, O; Park, D K; Stein, I S; Jahncke, J N; Greenberg, M E; Margolis, S S; Zito, K

    2017-04-01

    The outgrowth of new dendritic spines is closely linked to the formation of new synapses, and is thought to be a vital component of the experience-dependent circuit plasticity that supports learning. Here, we examined the role of the RhoGEF Ephexin5 in driving activity-dependent spine outgrowth. We found that reducing Ephexin5 levels increased spine outgrowth, and increasing Ephexin5 levels decreased spine outgrowth in a GEF-dependent manner, suggesting that Ephexin5 acts as an inhibitor of spine outgrowth. Notably, we found that increased neural activity led to a proteasome-dependent reduction in the levels of Ephexin5 in neuronal dendrites, which could facilitate the enhanced spine outgrowth observed following increased neural activity. Surprisingly, we also found that Ephexin5-GFP levels were elevated on the dendrite at sites of future new spines, prior to new spine outgrowth. Moreover, lowering neuronal Ephexin5 levels inhibited new spine outgrowth in response to both global increases in neural activity and local glutamatergic stimulation of the dendrite, suggesting that Ephexin5 is necessary for activity-dependent spine outgrowth. Our data support a model in which Ephexin5 serves a dual role in spinogenesis, acting both as a brake on overall spine outgrowth and as a necessary component in the site-specific formation of new spines. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Baseline cognitive function does not predict the treatment outcome of electroconvulsive therapy (ECT) in late-life depression.

    PubMed

    Bjølseth, Tor Magne; Engedal, Knut; Benth, Jūratė Šaltytė; Dybedal, Gro Strømnes; Gaarden, Torfinn Lødøen; Tanum, Lars

    2015-10-01

    No prior study has investigated whether impairment of specific cognitive functions at baseline may predict the short-term treatment outcome of electroconvulsive therapy (ECT) in elderly non-demented patients with major depression (MD). This longitudinal cohort study included 65 elderly patients with unipolar or bipolar MD, aged 60-85 years, treated with formula-based ECT. Treatment outcome was assessed using the 17-item Hamilton Rating Scale for Depression (HRSD17). Cognitive function at baseline was assessed using nine neuropsychological tests or subtests measuring information processing speed, verbal learning and memory, and aspects of executive function. A poorer performance on the word reading task of the Color Word Interference Test rendered higher odds of achieving remission during the ECT course (p=0.021). Remission was defined as an HRSD17 score of 7 or less. There were no other significant associations between the treatment outcome of ECT and cognitive performance parameters assessed at baseline. The limited number of subjects may have reduced the generalizability of the findings. Multiple statistical tests increase the risk for making a type I error. How well patients perform on neuropsychological tests at baseline is most likely not a predictor of, or otherwise not significantly associated with the treatment outcome of formula-based ECT in elderly patients with MD. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  17. Efficacy and acceptability of high frequency repetitive transcranial magnetic stimulation (rTMS) versus electroconvulsive therapy (ECT) for major depression: a systematic review and meta-analysis of randomized trials.

    PubMed

    Berlim, Marcelo T; Van den Eynde, Frederique; Daskalakis, Zafiris J

    2013-07-01

    Clinical trials comparing the efficacy and acceptability of high frequency repetitive transcranial magnetic stimulation (HF-rTMS) and electroconvulsive therapy (ECT) for treating major depression (MD) have yielded conflicting results. As this may have been the result of limited statistical power, we have carried out this meta-analysis to examine this issue. We searched the literature for randomized trials on head-to-head comparisons between HF-rTMS and ECT from January 1995 through September 2012 using MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, and SCOPUS. The main outcome measures were remission rates, pre-post changes in depression ratings, as well as overall dropout rates at study end. We used a random-effects model, Odds Ratios (OR), Number Needed to Treat (NNT), and Hedges' g effect sizes. Data were obtained from 7 randomized trials, totalling 294 subjects with MD. After an average of 15.2 HF-rTMS and 8.2 ECT sessions, 33.6% (38/113) and 52% (53/102) of subjects were classified as remitters (OR = 0.46; p = 0.04), respectively. The associated NNT for remission was 6 and favoured ECT. Also, reduction of depressive symptomatology was significantly more pronounced in the ECT group (Hedges' g = -0.93; p = 0.007). No differences on dropout rates for HF-rTMS and ECT groups were found. In conclusion, ECT seems to be more effective than HF-rTMS for treating MD, although they did not differ in terms of dropout rates. Nevertheless, future comparative trials with larger sample sizes and better matching at baseline, longer follow-ups and more intense stimulation protocols are warranted. © 2013 Wiley Periodicals, Inc.

  18. Rapid amelioration of severe manic episodes with right unilateral ultrabrief pulse ECT: a case series of four patients.

    PubMed

    Sidorov, Alexey; Mayur, Prashanth

    2017-02-01

    The aim of this small case series is to describe four cases of severe mania, where ultrabrief pulse electroconvulsive therapy (ECT) was used as a primary mode of treatment. A retrospective file review was undertaken of four patients identified as having received ultrabrief pulse ECT for severe mania. The outcome measures for treatment efficacy were the Young Mania Rating Scale (YMRS) and Clinical Global Impression (CGI). All the patients showed significant clinical improvement. A comparison of pre- and post-treatment YMRS and CGI scores showed a dramatic decrease in all four cases. However, one patient was shifted to brief pulse ECT due to inadequate response. Ultrabrief pulse ECT may be an effective treatment in cases of severe mania. Due to the very small number of cases in the current case series, no specific conclusions regarding efficacy may be drawn; however, larger, controlled studies would be indicated.

  19. ECT imaging with Tc(V)-99m dimercaptosuccinic acid useful to detect lung metastases of osteosarcoma

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ohta, H.; Ishii, M.; Yoshizumi, M.

    1985-01-01

    ECT imaging, using Tc(V)-99m dimercaptosuccinic acid (Tc(V)-DMS) was performed in two patients with lung metastasis of osteosarcoma, and the results were compared with those of CT scan. Clear accumulation of Tc(V)-DMS was recognized in all cases in the same area that CT scans demonstrated. Tc(V)-DMS was labeled under optimal pH 8, had very low SnCl/sub 2/ concentrations, an equilibrium between a stable form and a dissociated form of anion TcO/sub 4/(3-) structurally similar to PO/sub 4/(3-), and was postulated for tumor uptake. Considering this proposed mechanism for Tc(V)-DMS uptake by tumor cells, ECT imaging using this tracer could be ofmore » use in the early detection of lung metastasis of osteosarcoma.« less

  20. Open Ocean Assessments for Management in the GEF Transboundary Waters Assessment Project (TWAP)

    NASA Astrophysics Data System (ADS)

    Fischer, A. S.; Alverson, K. D.

    2010-12-01

    A methodology for a thematic and scientifically-credible assessment of Open Ocean waters as a part of the Global Environment Facility (GEF) Transboundary Waters Assessment Project (TWAP) has been developed in the last 18 months by the Intergovernmental Oceanographic Commission of UNESCO, and is presented for feedback and comment. While developed to help the GEF International Waters focal area target investment to manage looming environmental threats in interlinked freshwater and marine systems (a very focused decision support system), the assessment methodology could contribute to other assessment and management efforts in the UN system and elsewhere. Building on a conceptual framework that describes the relationships between human systems and open ocean natural systems, and on mapping of the human impact on the marine environment, the assessment will evaluate and make projections on a thematic basis, identifying key metrics, indices, and indicators. These themes will include the threats on key ecosystem services of climate change through sea level rise, changed stratification, warming, and ocean acidification; vulnerabilities of ecosystems, habitats, and living marine resources; the impact and sustainability of fisheries; and pollution. Global-level governance arrangements will also be evaluated, with an eye to identifying scope for improved global-level management. The assessment will build on sustained ocean observing systems, model projections, and an assessment of scientific literature, as well as tools for combining knowledge to support identification of priority concerns and in developing scenarios for management. It will include an assessment of key research and observing needs as one way to deal with the scientific uncertainty inherent in such an exercise, and to better link policy and science agendas.

  1. Electroconvulsive therapy modulates plasma pigment epithelium-derived factor in depression: a proteomics study

    PubMed Central

    Ryan, K M; Glaviano, A; O'Donovan, S M; Kolshus, E; Dunne, R; Kavanagh, A; Jelovac, A; Noone, M; Tucker, G M; Dunn, M J; McLoughlin, D M

    2017-01-01

    Electroconvulsive therapy (ECT) is the most effective treatment for severe depression, yet its mechanism of action is not fully understood. Peripheral blood proteomic analyses may offer insights into the molecular mechanisms of ECT. Patients with a major depressive episode were recruited as part of the EFFECT-Dep trial (enhancing the effectiveness of electroconvulsive therapy in severe depression; ISRCTN23577151) along with healthy controls. As a discovery-phase study, patient plasma pre-/post-ECT (n=30) was analyzed using 2-dimensional difference in gel electrophoresis and mass spectrometry. Identified proteins were selected for confirmation studies using immunodetection methods. Samples from a separate group of patients (pre-/post-ECT; n=57) and matched healthy controls (n=43) were then used to validate confirmed changes. Target protein mRNA levels were also assessed in rat brain and blood following electroconvulsive stimulation (ECS), the animal model of ECT. We found that ECT significantly altered 121 protein spots with 36 proteins identified by mass spectrometry. Confirmation studies identified a post-ECT increase (P<0.01) in the antiangiogenic and neuroprotective mediator pigment epithelium-derived factor (PEDF). Validation work showed an increase (P<0.001) in plasma PEDF in depressed patients compared with the controls that was further increased post-ECT (P=0.03). PEDF levels were not associated with mood scores. Chronic, but not acute, ECS increased PEDF mRNA in rat hippocampus (P=0.02) and dentate gyrus (P=0.03). This study identified alterations in blood levels of PEDF in depressed patients and further alterations following ECT, as well as in an animal model of ECT. These findings implicate PEDF in the biological response to ECT for depression. PMID:28350398

  2. Electroconvulsive therapy modulates plasma pigment epithelium-derived factor in depression: a proteomics study.

    PubMed

    Ryan, K M; Glaviano, A; O'Donovan, S M; Kolshus, E; Dunne, R; Kavanagh, A; Jelovac, A; Noone, M; Tucker, G M; Dunn, M J; McLoughlin, D M

    2017-03-28

    Electroconvulsive therapy (ECT) is the most effective treatment for severe depression, yet its mechanism of action is not fully understood. Peripheral blood proteomic analyses may offer insights into the molecular mechanisms of ECT. Patients with a major depressive episode were recruited as part of the EFFECT-Dep trial (enhancing the effectiveness of electroconvulsive therapy in severe depression; ISRCTN23577151) along with healthy controls. As a discovery-phase study, patient plasma pre-/post-ECT (n=30) was analyzed using 2-dimensional difference in gel electrophoresis and mass spectrometry. Identified proteins were selected for confirmation studies using immunodetection methods. Samples from a separate group of patients (pre-/post-ECT; n=57) and matched healthy controls (n=43) were then used to validate confirmed changes. Target protein mRNA levels were also assessed in rat brain and blood following electroconvulsive stimulation (ECS), the animal model of ECT. We found that ECT significantly altered 121 protein spots with 36 proteins identified by mass spectrometry. Confirmation studies identified a post-ECT increase (P<0.01) in the antiangiogenic and neuroprotective mediator pigment epithelium-derived factor (PEDF). Validation work showed an increase (P<0.001) in plasma PEDF in depressed patients compared with the controls that was further increased post-ECT (P=0.03). PEDF levels were not associated with mood scores. Chronic, but not acute, ECS increased PEDF mRNA in rat hippocampus (P=0.02) and dentate gyrus (P=0.03). This study identified alterations in blood levels of PEDF in depressed patients and further alterations following ECT, as well as in an animal model of ECT. These findings implicate PEDF in the biological response to ECT for depression.

  3. Incidence and risk factors for oxygen desaturation during recovery from modified electroconvulsive therapy: A prospective observational study.

    PubMed

    Surve, Rohini; Bansal, Sonia; Sriganesh, Kamath; Subbakrishna, Doddaballapur Kumaraswamy; Thirthalli, Jagadisha; Umamaheswara Rao, Ganne Sesha

    2015-01-01

    Electroconvulsive therapy (ECT) is an established modality of treatment for severe psychiatric illnesses. Among the various complications associated with ECT, oxygen desaturation is often under reported. None of the previous studies has evaluated the predictive factors for oxygen desaturation during ECT. The objective of this study was to evaluate the incidence of oxygen desaturation during recovery from anesthesia for modified ECT and evaluate its risk factors in a large sample. All patients aged above 15 years who were prescribed a modified ECT for their psychiatric illness over 1 year were prospectively included in this observational study. The association between age, body mass index (BMI), doses of thiopentone and suxamethonium, stimulus current, ECT session number, pre- and post-ECT heart rate and mean arterial pressure, seizure duration, and pre- and post ECT oxygen saturation, was systematically studied. The incidence of oxygen desaturation was 29% (93/316 patients). Seizure duration and BMI were found to be significantly correlated with post ECT desaturation. In this prospective observational study, the incidence of oxygen desaturation during recovery from anesthesia for ECT was high. The study identified obesity and duration of seizure as the independent predictors of this complication. This knowledge is likely to help in identifying and optimizing such patients before subsequent ECT sessions.

  4. Missouri University Multi-Plane Imager (MUMPI): A high sensitivity rapid dynamic ECT brain imager

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Logan, K.W.; Holmes, R.A.

    1984-01-01

    The authors have designed a unique ECT imaging device that can record rapid dynamic images of brain perfusion. The Missouri University Multi-Plane Imager (MUMPI) uses a single crystal detector that produces four orthogonal two-dimensional images simultaneously. Multiple slice images are reconstructed from counts recorded from stepwise or continuous collimator rotation. Four simultaneous 2-d image fields may also be recorded and reviewed. The cylindrical sodium iodide crystal and the rotating collimator concentrically surround the source volume being imaged with the collimator the only moving part. The design and function parameters of MUMPI have been compared to other competitive tomographic head imagingmore » devices. MUMPI's principal advantages are: 1) simultaneous direct acquisition of four two-dimensional images; 2) extremely rapid project set acquisition for ECT reconstruction; and 3) instrument practicality and economy due to single detector design and the absence of heavy mechanical moving components (only collimator rotation is required). MUMPI should be ideal for imaging neutral lipophilic chelates such as Tc-99m-PnAO which passively diffuses across the intact blood-brain-barrier and rapidly clears from brain tissue.« less

  5. Structural diversities induced by cation sizes in a series of fluorogermanophosphates: A2[GeF2(HPO4)2] (A = Na, K, Rb, NH4, and Cs).

    PubMed

    Chen, Zhang-Gai; Huang, Xia; Zhuang, Rong-Chuan; Zhang, Yu; Liu, Xin; Shi, Tao; Wang, Shuai-Hua; Wu, Shao-Fan; Mi, Jin-Xiao; Huang, Ya-Xi

    2017-09-12

    Germanophosphates, in comparison with other metal phosphates, have been less studied but potentially exhibit more diverse structural chemistry with wide applications. Herein we applied a hydro-/solvo-fluorothermal route to make use of both the "tailor effect" of fluoride for the formation of low dimensional anionic clusters and the presence of alkali cations of different sizes to align the anionic clusters to control the overall crystal symmetries of germanophosphates. The synergetic effects of fluoride and alkali cations led to structural changes from chain-like structures to layered structures in a series of five novel fluorogermanophosphates: A 2 [GeF 2 (HPO 4 ) 2 ] (A = Na, K, Rb, NH 4 , and Cs, denoted as Na, K, Rb, NH4, and Cs). Although these fluorogermanophosphates have stoichiometrically equivalent formulas, they feature different anionic clusters, diverse structural dimensionalities, and contrasting crystal symmetries. Chain-like structures were observed for the compounds with the smaller sized alkali ions (Na + , K + , and Rb + ), whereas layered structures were found for those containing the larger sized cations ((NH 4 ) + and Cs + ). Specifically, monoclinic space groups were observed for the Na, K, Rb, and NH4 compounds, whereas a tetragonal space group P4/mbm was found for the Cs compound. These compounds provide new insights into the effects of cation sizes on the anionic clusters built from GeO 4 F 2 octahedra and HPO 4 tetrahedra as well as their influences on the overall structural symmetries in germanophosphates. Further characterization including IR spectroscopy and thermal analyses for all five compounds is also presented.

  6. Activator-inhibitor coupling between Rho signaling and actin assembly make the cell cortex an excitable medium

    PubMed Central

    Bement, William M.; Leda, Marcin; Moe, Alison M.; Kita, Angela M.; Larson, Matthew E.; Golding, Adriana E.; Pfeuti, Courtney; Su, Kuan-Chung; Miller, Ann L.; Goryachev, Andrew B.; von Dassow, George

    2016-01-01

    Animal cell cytokinesis results from patterned activation of the small GTPase Rho, which directs assembly of actomyosin in the equatorial cortex. Cytokinesis is restricted to a portion of the cell cycle following anaphase onset in which the cortex is responsive to signals from the spindle. We show that shortly after anaphase onset oocytes and embryonic cells of frogs and echinoderms exhibit cortical waves of Rho activity and F-actin polymerization. The waves are modulated by cyclin-dependent kinase 1 (Cdk1) activity and require the Rho GEF (guanine nucleotide exchange factor), Ect2. Surprisingly, during wave propagation, while Rho activity elicits F-actin assembly, F-actin subsequently inactivates Rho. Experimental and modeling results show that waves represent excitable dynamics of a reaction diffusion system with Rho as the activator and F-actin the inhibitor. We propose that cortical excitability explains fundamental features of cytokinesis including its cell cycle regulation. PMID:26479320

  7. Electronic Current Transducer (ECT) for high voltage dc lines

    NASA Astrophysics Data System (ADS)

    Houston, J. M.; Peters, P. H., Jr.; Summerayes, H. R., Jr.; Carlson, G. J.; Itani, A. M.

    1980-02-01

    The development of a bipolar electronic current transducer (ECT) for measuring the current in a high voltage dc (HVDC) power line at line potential is discussed. The design and construction of a free standing ECT for use on a 400 kV line having a nominal line current of 2000 A is described. Line current is measured by a 0.0001 ohm shunt whose voltage output is sampled by a 14 bit digital data link. The high voltage interface between line and ground is traversed by optical fibers which carry digital light signals as far as 300 m to a control room where the digital signal is converted back to an analog representation of the shunt voltage. Two redundant electronic and optical data links are used in the prototype. Power to operate digital and optical electronics and temperature controlling heaters at the line is supplied by a resistively and capacitively graded 10 stage cascade of ferrite core transformers located inside the hollow, SF6 filled, porcelain support insulator. The cascade is driven by a silicon controlled rectifier inverter which supplies about 100 W of power at 30 kHz.

  8. Characterization of the Edge Crack Torsion (ECT) Test for Mode III Fracture Toughness Measurement of Laminated Composites

    NASA Technical Reports Server (NTRS)

    Ratcliffe, James G.

    2004-01-01

    The edge crack torsion (ECT) test is designed to initiate mode III delamination growth in composite laminates. An ECT specimen is a rectangular laminate, containing an edge delamination at the laminate mid-plane. Torsion load is applied to the specimens, resulting in relative transverse shear sliding of the delaminated faces. The test data reduction schemes are intended to yield initiation values of critical mode III strain energy release rate, G(sub IIIc), that are constant with delamination length. The test has undergone several design changes during its development. The objective of this paper was to determine the suitability of the current ECT test design as a mode III fracture test. To this end, ECT tests were conducted on specimens manufactured from IM7/8552 and specimens made from S2/8552 tape laminates. Several specimens, each with different delamination lengths are tested. Detailed, three-dimensional finite element analyses of the specimens were performed. The analysis results were used to calculate the distribution of mode I, mode II, and mode III strain energy release rate along the delamination front. The results indicated that mode III-dominated delamination growth would be initiated from the specimen center. However, in specimens of both material types, the measured values of G(sub IIIc) exhibited significant dependence on delamination length. Furthermore, there was a large amount of scatter in the data. Load-displacement response of the specimens exhibited significant deviation from linearity before specimen failure. X-radiographs of a sample of specimens revealed that damage was initiated in the specimens prior to failure. Further inspection of the failure surfaces is required to identify the damage and determine that mode III delamination is initiated in the specimens.

  9. Evaluation of the Edge Crack Torsion (ECT) Test for Mode 3 Interlaminar Fracture Toughness of Laminated Composites

    NASA Technical Reports Server (NTRS)

    Li, Jian; Lee, Edward W.; OBrien, T. Kevin; Lee, Shaw Ming

    1996-01-01

    An analytical and experimental investigation was carried out on G40-800/R6376 graphite epoxy laminates to evaluate the Edge Crack Torsion (ECT) test as a candidate for a standard Mode 3 interlaminar fracture toughness test for laminated composites. The ECT test consists of a (90/(+/- 45)(sub 3)/(+/- 45)(sub 3)/90))(sub s) laminate with a delamination introduced by a non-adhesive film at the mid-plane along one edge and loaded in a special fixture to create torsion along the length of the laminate. Dye penetrate enhanced X-radiograph of failed specimens revealed that the delamination initiated at the middle of the specimen length and propagated in a self similar manner along the laminate mid-plane. A three-dimensional finite element analysis was performed that indicated that a pure Mode 3 delamination exists at the middle of specimen length away from both ends. At the ends near the loading point a small Mode 2 component exists. However, the magnitude of this Mode 2 strain energy release rate at the loading point is small compared to the magnitude of Mode 3 component in the mid-section of the specimen. Hence, the ECT test yielded the desired Mode 3 delamination. The Mode 3 fracture toughness was obtained from a compliance calibration method and was in good agreement with the finite element results. Mode 2 End-Notched Flexure (ENF) tests and Mode 1 Double Cantilever Beam (DCB) tests were also performed for the same composite material. The Mode 1 fracture toughness was much smaller than both the Mode 2 and Mode 3 fracture toughness. The Mode 2 fracture toughness was found to be 75% of the Mode 3 fracture toughness.

  10. A BAC transgenic mouse model reveals neuron subtype-specific effects of a Generalized Epilepsy with Febrile Seizures Plus (GEFS+) mutation

    PubMed Central

    Tang, Bin; Dutt, Karoni; Papale, Ligia; Rusconi, Raffaella; Shankar, Anupama; Hunter, Jessica; Tufik, Sergio; Yu, Frank H.; Catterall, William A.; Mantegazza, Massimo; Goldin, Alan L.; Escayg, Andrew

    2009-01-01

    Mutations in the voltage-gated sodium channel SCN1A are responsible for a number of seizure disorders including Generalized Epilepsy with Febrile Seizures Plus (GEFS+) and Severe Myoclonic Epilepsy of Infancy (SMEI). To determine the effects of SCN1A mutations on channel function in vivo, we generated a bacterial artificial chromosome (BAC) transgenic mouse model that expresses the human SCN1A GEFS+ mutation, R1648H. Mice with the R1648H mutation exhibit a more severe response to the proconvulsant kainic acid compared with mice expressing a control Scn1a transgene. Electrophysiological analysis of dissociated neurons from mice with the R1648H mutation reveal delayed recovery from inactivation and increased use-dependent inactivation only in inhibitory bipolar neurons, as well as a hyperpolarizing shift in the voltage dependence of inactivation only in excitatory pyramidal neurons. These results demonstrate that the effects of SCN1A mutations are cell type-dependent and that the R1648H mutation specifically leads to a reduction in interneuron excitability. PMID:19409490

  11. Phosphorylation-dependent Regulation of Connecdenn/DENND1 Guanine Nucleotide Exchange Factors*

    PubMed Central

    Kulasekaran, Gopinath; Nossova, Nadya; Marat, Andrea L.; Lund, Ingrid; Cremer, Christopher; Ioannou, Maria S.; McPherson, Peter S.

    2015-01-01

    Connecdenn 1/2 are DENN (differentially expressed in normal and neoplastic cells) domain-bearing proteins that function as GEFs (guanine nucleotide exchange factors) for the small GTPase Rab35. Disruption of connecdenn/Rab35 function leads to defects in the recycling of multiple cargo proteins from endosomes with altered cell function, yet the regulation of connecdenn GEF activity is unexplored. We now demonstrate that connecdenn 1/2 are autoinhibited such that the purified, full-length proteins have significantly less Rab35 binding and GEF activity than the isolated DENN domain. Both proteins are phosphorylated with prominent phosphorylation sites between residues 500 and 600 of connecdenn 1. A large scale proteomics screen revealed that connecdenn 1 is phosphorylated at residues Ser-536 and Ser-538 in an Akt-dependent manner in response to insulin stimulation of adipocytes. Interestingly, we find that an Akt inhibitor reduces connecdenn 1 interaction with Rab35 after insulin treatment of adipocytes. Remarkably, a peptide flanking Ser-536/Ser-538 binds the DENN domain of connecdenn 1, whereas a phosphomimetic peptide does not. Moreover, connecdenn 1 interacts with 14-3-3 proteins, and this interaction is also disrupted by Akt inhibition and by mutation of Ser-536/Ser-538. We propose that Akt phosphorylation of connecdenn 1 downstream of insulin activation regulates connecdenn 1 function through an intramolecular interaction. PMID:26055712

  12. Wsc1 and Mid2 Are Cell Surface Sensors for Cell Wall Integrity Signaling That Act through Rom2, a Guanine Nucleotide Exchange Factor for Rho1

    PubMed Central

    Philip, Bevin; Levin, David E.

    2001-01-01

    Wsc1 and Mid2 are highly O-glycosylated cell surface proteins that reside in the plasma membrane of Saccharomyces cerevisiae. They have been proposed to function as mechanosensors of cell wall stress induced by wall remodeling during vegetative growth and pheromone-induced morphogenesis. These proteins are required for activation of the cell wall integrity signaling pathway that consists of the small G-protein Rho1, protein kinase C (Pkc1), and a mitogen-activated protein kinase cascade. We show here by two-hybrid experiments that the C-terminal cytoplasmic domains of Wsc1 and Mid2 interact with Rom2, a guanine nucleotide exchange factor (GEF) for Rho1. At least with regard to Wsc1, this interaction is mediated by the Rom2 N-terminal domain. This domain is distinct from the Rho1-interacting domain, suggesting that the GEF can interact simultaneously with a sensor and with Rho1. We also demonstrate that extracts from wsc1 and mid2 mutants are deficient in the ability to catalyze GTP loading of Rho1 in vitro, providing evidence that the function of the sensor-Rom2 interaction is to stimulate nucleotide exchange toward this G-protein. In a related line of investigation, we identified the PMT2 gene in a genetic screen for mutations that confer an additive cell lysis defect with a wsc1 null allele. Pmt2 is a member of a six-protein family in yeast that catalyzes the first step in O mannosylation of target proteins. We demonstrate that Mid2 is not mannosylated in a pmt2 mutant and that this modification is important for signaling by Mid2. PMID:11113201

  13. Effects of ECT in treatment of depression: study protocol for a prospective neuroradiological study of acute and longitudinal effects on brain structure and function.

    PubMed

    Oltedal, Leif; Kessler, Ute; Ersland, Lars; Grüner, Renate; Andreassen, Ole A; Haavik, Jan; Hoff, Per Ivar; Hammar, Åsa; Dale, Anders M; Hugdahl, Kenneth; Oedegaard, Ketil J

    2015-05-01

    Major depression can be a serious and debilitating condition. For some patients in a treatment resistant depressive episode, electroconvulsive treatment (ECT) is the only treatment that is effective. Although ECT has shown efficacy in randomized controlled trials, the treatment is still controversial and stigmatized. This can in part be attributed to our lack of knowledge of the mechanisms of action. Some reports also suggest potential harmful effects of ECT treatment and memory related side effects have been documented. The present study will apply state of the art radiology through advanced magnetic resonance imaging (MRI) techniques to investigate structural and functional brain effects of ECT. As a multi-disciplinary collaboration, imaging findings will be correlated to psychiatric response parameters, neuropsychological functioning as well as neurochemical and genetic biomarkers that can elucidate the underlying mechanisms. The aim is to document both treatment effects and potential harmful effects of ECT. n = 40 patients in a major depressive episode (bipolar and major depressive disorder). Two control groups with n = 15 in each group: age and gender matched healthy volunteers not receiving ECT and patients undergoing electrical cardioversion (ECV) for atrial fibrillation (AF). Observation time: six months. The study will contribute to our understanding of the pathophysiology of major depression as well as mechanisms of action for the most effective treatment for the disorder; ECT.

  14. Comparative phylogenetic analyses of Halomonas variabilis and related organisms based on 16S rRNA, gyrB and ectBC gene sequences.

    PubMed

    Okamoto, Takuji; Maruyama, Akihiko; Imura, Satoshi; Takeyama, Haruko; Naganuma, Takeshi

    2004-05-01

    Halomonas variabilis and phylogenetically related organisms were isolated from various habitats such as Antarctic terrain and saline ponds, deep-sea sediment, deep-sea waters affected by hydrothermal plumes, and hydrothermal vent fluids. Ten strains were selected for physiological and phylogenetic characterization in detail. All of those strains were found to be piezotolerant and psychrotolerant, as well as euryhaline halophilic or halotolerant. Their stress tolerance may facilitate their wide occurrence, even in so-called extreme environments. The 16S rDNA-based phylogenetic relationship was complemented by analyses of the DNA gyrase subunit B gene (gyrB) and genes involved in the synthesis of the major compatible solute, ectoine: diaminobutyric acid aminotransferase gene (ectB) and ectoine synthase gene (ectC). The phylogenetic relationships of H. variabilis and related organisms were very similar in terms of 16S rDNA, gyrB, and ectB. The ectC-based tree was inconsistent with the other phylogenetic trees. For that reason, ectC was inferred to derive from horizontal transfer.

  15. An AST-ELM Method for Eliminating the Influence of Charging Phenomenon on ECT.

    PubMed

    Wang, Xiaoxin; Hu, Hongli; Jia, Huiqin; Tang, Kaihao

    2017-12-09

    Electrical capacitance tomography (ECT) is a promising imaging technology of permittivity distributions in multiphase flow. To reduce the effect of charging phenomenon on ECT measurement, an improved extreme learning machine method combined with adaptive soft-thresholding (AST-ELM) is presented and studied for image reconstruction. This method can provide a nonlinear mapping model between the capacitance values and medium distributions by using machine learning but not an electromagnetic-sensitive mechanism. Both simulation and experimental tests are carried out to validate the performance of the presented method, and reconstructed images are evaluated by relative error and correlation coefficient. The results have illustrated that the image reconstruction accuracy by the proposed AST-ELM method has greatly improved than that by the conventional methods under the condition with charging object.

  16. Novel Role for p21-activated Kinase 2 in Thrombin-induced Monocyte Migration*

    PubMed Central

    Gadepalli, Ravisekhar; Kotla, Sivareddy; Heckle, Mark R.; Verma, Shailendra K.; Singh, Nikhlesh K.; Rao, Gadiparthi N.

    2013-01-01

    To understand the role of thrombin in inflammation, we tested its effects on migration of THP-1 cells, a human monocytic cell line. Thrombin induced THP-1 cell migration in a dose-dependent manner. Thrombin induced tyrosine phosphorylation of Pyk2, Gab1, and p115 RhoGEF, leading to Rac1- and RhoA-dependent Pak2 activation. Downstream to Pyk2, Gab1 formed a complex with p115 RhoGEF involving their pleckstrin homology domains. Furthermore, inhibition or depletion of Pyk2, Gab1, p115 RhoGEF, Rac1, RhoA, or Pak2 levels substantially attenuated thrombin-induced THP-1 cell F-actin cytoskeletal remodeling and migration. Inhibition or depletion of PAR1 also blocked thrombin-induced activation of Pyk2, Gab1, p115 RhoGEF, Rac1, RhoA, and Pak2, resulting in diminished THP-1 cell F-actin cytoskeletal remodeling and migration. Similarly, depletion of Gα12 negated thrombin-induced Pyk2, Gab1, p115 RhoGEF, Rac1, RhoA, and Pak2 activation, leading to attenuation of THP-1 cell F-actin cytoskeletal remodeling and migration. These novel observations reveal that thrombin induces monocyte/macrophage migration via PAR1-Gα12-dependent Pyk2-mediated Gab1 and p115 RhoGEF interactions, leading to Rac1- and RhoA-targeted Pak2 activation. Thus, these findings provide mechanistic evidence for the role of thrombin and its receptor PAR1 in inflammation. PMID:24025335

  17. An Assessment of the ECTS in Software Engineering: A Teaching Experience

    ERIC Educational Resources Information Center

    Salas-Morera, L.; Berral-Yeron, J.; Serrano-Gomez, I.; Martinez-Jimenez, P.

    2009-01-01

    Spain is currently implementing the regulatory modifications promulgated by the Declaration of Bologna, which should result in the updating of the structure of university degrees, and the inclusion of the European Credit Transfer and Accumulation System (ECTS) methodology. In some Spanish universities, the experimental adoption of this methodology…

  18. The tight-adhesion proteins TadGEF of Bradyrhizobium diazoefficiens USDA 110 are involved in cell adhesion and infectivity on soybean roots.

    PubMed

    Mongiardini, Elías J; Parisi, Gustavo D; Quelas, Juan I; Lodeiro, Aníbal R

    2016-01-01

    Adhesion of symbiotic bacteria to host plants is an essential early step of the infection process that leads to the beneficial interaction. In the Bradyrhizobium diazoefficiens-soybean symbiosis few molecular determinants of adhesion are known. Here we identified the tight-adhesion gene products TadGEF in the open-reading frames blr3941-blr3943 of the B. diazoefficiens USDA 110 complete genomic sequence. Predicted structure of TadG indicates a transmembrane domain and two extracytosolic domains, from which the C-terminal has an integrin fold. TadE and TadF are also predicted as bearing transmembrane segments. Mutants in tadG or the small cluster tadGEF were impaired in adhesion to soybean roots, and the root infection was delayed. However, nodule histology was not compromised by the mutations, indicating that these effects were restricted to the earliest contact of the B. diazoefficiens and root surfaces. Knowledge of preinfection determinants is important for development of inoculants that are applied to soybean crops worldwide. Copyright © 2015 Elsevier GmbH. All rights reserved.

  19. Debunking EHEA Myths: Common ECTS Misconceptions and Why They Are Wrong

    ERIC Educational Resources Information Center

    Pérez Cañado, María Luisa

    2009-01-01

    The present article seeks to overcome some of the most common misconceptions which are currently proliferating in the application of the "European Credit Transfer System" (ECTS) at tertiary level. It presents and unpacks seven false myths affecting all the main curricular and organizational levels of the implementation of the new credit…

  20. An ECT/ERT dual-modality sensor for oil-water two-phase flow measurement

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang, Pitao; Wang, Huaxiang; Sun, Benyuan

    2014-04-11

    This paper presents a new sensor for ECT/ERT dual-modality system which can simultaneously obtain the permittivity and conductivity of the materials in the pipeline. Quasi-static electromagnetic fields are produced by the inner electrodes array sensor of electrical capacitance tomography (ECT) system. The results of simulation show that the data of permittivity and conductivity can be simultaneously obtained from the same measurement electrode and the fusion of two kinds of data may improve the quality of the reconstructed images. For uniform oil-water mixtures, the performance of designed dual-modality sensor for measuring the various oil fractions has been tested on representative datamore » and the results of experiments show that the designed sensor broadens the measurement range compared to single modality.« less

  1. An AST-ELM Method for Eliminating the Influence of Charging Phenomenon on ECT

    PubMed Central

    Wang, Xiaoxin; Hu, Hongli; Jia, Huiqin; Tang, Kaihao

    2017-01-01

    Electrical capacitance tomography (ECT) is a promising imaging technology of permittivity distributions in multiphase flow. To reduce the effect of charging phenomenon on ECT measurement, an improved extreme learning machine method combined with adaptive soft-thresholding (AST-ELM) is presented and studied for image reconstruction. This method can provide a nonlinear mapping model between the capacitance values and medium distributions by using machine learning but not an electromagnetic-sensitive mechanism. Both simulation and experimental tests are carried out to validate the performance of the presented method, and reconstructed images are evaluated by relative error and correlation coefficient. The results have illustrated that the image reconstruction accuracy by the proposed AST-ELM method has greatly improved than that by the conventional methods under the condition with charging object. PMID:29232850

  2. Comparison of the effect of intravenous anesthetics used for anesthesia during electroconvulsive therapy on the hemodynamic safety and the course of ECT.

    PubMed

    Wojdacz, Rafał; Święcicki, Łukasz; Antosik-Wójcińska, Anna

    2017-12-30

    Electroconvulsive therapy (ECT) is the treatment method widely used in psychiatric disorders such as depression, bipolar disorder, schizophrenia and schizoaffective disorder. The advantage of ECT is therapeutic response that occurs significantly earlier than during pharmacotherapy. Initially ECTwas used without anesthesia. Then, in the 1950s procedures with general anesthesia were introduced to reduce the complications that may occur during a seizure caused by ECT, such as broken bones, teeth, tendon rupture, muscle damage. Currently, in general anesthesia for ECTseveral medications are used interchangeably: thiopental, propofol, etomidate and ketamine. In different resorts and different countries different anestethics are used, the choice is determined mainly by the experience of each resort and a kind of tradition. The authors provide an overview of objective data showing how various anesthetics affect the quality of ECT and the presence of any hemodynamic complications after ETC. Selection of articles included in this paper was made by searching Medline and PubMed databases using specific keywords: electroconvulsive therapy, general anesthesia, the risks and benefits of thiopental, ketamine, propofol and etomidate. The results of this review are inconclusive when it comes to the effect of intravenous anesthetics on the quality of the ECT treatment and side effects relating to respiratory and cardiovascular system. On this basis it is impossible to determine which of intravenous anesthetics is most advantageous from the point of view of the patient. To develop the optimum scheme of anesthesia for ECT, it is necessary to conduct further, methodologically correct studies.

  3. TH-EF-207A-06: High-Resolution Optical-CT/ECT Imaging of Unstained Mice Femur, Brain, Spleen, and Tumor

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yoon, S; Dewhirst, M; Oldham, M

    2016-06-15

    Purpose: Optical transmission and emission computed tomography (optical-CT/ECT) provides high-resolution 3D attenuation and emission maps in unsectioned large (∼1cm{sup 3}) ex vivo tissue samples at a resolution of 12.9µm{sup 3} per voxel. Here we apply optical-CT/ECT to investigate high-resolution structure and auto-fluorescence in a range of optically cleared mice organs, including, for the first time, mouse bone (femur), opening the potential for study of bone metastasis and bone-mediated immune response. Methods: Three BALBc mice containing 4T1 flank tumors were sacrificed to obtain spleen, brain, tumor, and femur. Tissues were washed in 4% PFA, fixed in EtOH solution (for 5, 10,more » 10, and 2 days respectively), and then optically cleared for 3 days in BABBs. The femur was also placed in 0.25M aqueous EDTA for 15–30 days to remove calcium. Optical-CT/ECT attenuation and emission maps at 633nm (the latter using 530nm excitation light) were obtained for all samples. Bi-telecentric optical-CT was compared side-by-side with conventional optical projection tomography (OPT) imaging to evaluate imaging capability of these two rival techniques. Results: Auto-fluorescence mapping of femurs reveals vasculatures and fluorescence heterogeneity. High signals (A.U.=10) are reported in the medullary cavity but not in the cortical bone (A.U.=1). The brain strongly and uniform auto-fluoresces (A.U.=5). Thick, optically dense organs such as the spleen and the tumor (0.12, 0.46OD/mm) are reconstructed at depth without significant loss of resolution, which we attribute to the bi-telecentric optics of optical-CT. The attenuation map of tumor reveals vasculature, attenuation heterogeneity, and possibly necrotic tissue. Conclusion: We demonstrate the feasibility of optical-CT/ECT imaging of un-sectioned mice bones (femurs) and spleen with high resolution. This result, and the characterization of unstained organs, are important steps enabling future studies involving optical-CT/ECT

  4. A long-term longitudinal follow-up of depressed patients treated with ECT with special focus on development of dementia.

    PubMed

    Berggren, Åke; Gustafson, Lars; Höglund, Peter; Johanson, Aki

    2016-08-01

    In this study, the long term effects of ECT on patients with depression were investigated through repeated rCBF and EEG measures as well as clinical characteristics over several years. The aim of the investigation was to establish an association with the eventual development of dementia. A cohort of forty-nine patients (21 men and 28 women) with a mean age of 61 years underwent ECT. A subsequent evaluation from medical records and three rating-scales for diagnosis of Alzheimer´s disease (AD), fronto-temporal dementia (FTD), and for vascular dementia (VaD), revealed that 17 patients (8 men and 9 women), had developed dementia. These cases were compared to the 32 patients (13 men and 19 women), who had not developed dementia. Initially, the dementia group, compared to those without dementia, showed a lower hemispheric CBF (left side; p=.029, right side; p=.033), and a lower mean occipital EEG frequency (p=.048). After the first ECT-series, an increase in general disorientation (p=.015), personal disorientation (p=.009), and subsequently, spatial disorientation (p=.021), were seen in the dementia group. There were no differences in the clinical response or remissions after treatment in the groups. The small sample-size, which did not allow for the comparison of characteristics between different dementias. Depressed older patients who later developed dementia showed lower hemispheric mean level of CBF and EEG mean frequency before ECT and higher personal and spatial disorientation following ECT. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. The MAP kinase pathway coordinates crossover designation with disassembly of synaptonemal complex proteins during meiosis

    PubMed Central

    Nadarajan, Saravanapriah; Mohideen, Firaz; Tzur, Yonatan B; Ferrandiz, Nuria; Crawley, Oliver; Montoya, Alex; Faull, Peter; Snijders, Ambrosius P; Cutillas, Pedro R; Jambhekar, Ashwini; Blower, Michael D; Martinez-Perez, Enrique; Harper, J Wade; Colaiacovo, Monica P

    2016-01-01

    Asymmetric disassembly of the synaptonemal complex (SC) is crucial for proper meiotic chromosome segregation. However, the signaling mechanisms that directly regulate this process are poorly understood. Here we show that the mammalian Rho GEF homolog, ECT-2, functions through the conserved RAS/ERK MAP kinase signaling pathway in the C. elegans germline to regulate the disassembly of SC proteins. We find that SYP-2, a SC central region component, is a potential target for MPK-1-mediated phosphorylation and that constitutively phosphorylated SYP-2 impairs the disassembly of SC proteins from chromosomal domains referred to as the long arms of the bivalents. Inactivation of MAP kinase at late pachytene is critical for timely disassembly of the SC proteins from the long arms, and is dependent on the crossover (CO) promoting factors ZHP-3/RNF212/Zip3 and COSA-1/CNTD1. We propose that the conserved MAP kinase pathway coordinates CO designation with the disassembly of SC proteins to ensure accurate chromosome segregation. DOI: http://dx.doi.org/10.7554/eLife.12039.001 PMID:26920220

  6. Speed of recovery from disorientation may predict the treatment outcome of electroconvulsive therapy (ECT) in elderly patients with major depression.

    PubMed

    Magne Bjølseth, Tor; Engedal, Knut; Šaltytė Benth, Jūratė; Bergsholm, Per; Strømnes Dybedal, Gro; Lødøen Gaarden, Torfinn; Tanum, Lars

    2016-01-15

    No study has previously investigated whether the speed of recovery from disorientation in the post-ictal period may predict the short-term treatment outcome of electroconvulsive therapy (ECT). This longitudinal cohort study included 57 elderly patients with unipolar or bipolar major depression, aged 60-85 years, treated with formula-based ECT. Treatment outcome was assessed weekly during the ECT course using the 17-item Hamilton Rating Scale for Depression (HRSD17). The post-ictal reorientation time (PRT) was assessed at the first and third treatments. Longer PRTs at the first and third treatments predicted a more rapid decline and a lower end-point in continuous HRSD17 scores (p=0.002 and 0.019, respectively). None of the patients who recovered from disorientation in less than 5 min met the remission criterion, defined as an HRSD17 score of 7 or less. A greater increment in stimulus dosage from the first to the third ECT session rendered a smaller relative decline in PRT (p<0.001). The limited number of subjects may reduce the generalizability of the findings. The speed of recovery from disorientation at the first and third sessions seems to be a predictor of the treatment outcome of formula-based ECT, at least in elderly patients with major depression. It remains to be clarified how the PRT may be utilized to guide stimulus dosing. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  7. The Radiation Belt Storm Probes (RBSP) Energetic Particle, Composition, and Thermal plasma (ECT) Suite: Upcoming Opportunties for Testing Radiation Belt Acceleration Mechanisms

    NASA Astrophysics Data System (ADS)

    Spence, Harlan; Reeves, Geoffrey

    2012-07-01

    The Radiation Belt Storm Probes (RBSP) mission will launch in late summer 2012 and begin its exploration of acceleration and dynamics of energetic particles in the inner magnetosphere. In this presentation, we discuss opportunities afforded by the RBSP Energetic Particle, Composition, and Thermal plasma (ECT) instrument suite to advance our understanding of acceleration processes in the radiation belts. The RBSP-ECT instrument suite comprehensively measures the electron and major ion populations of the inner magnetosphere, from the lowest thermal plasmas of the plasmasphere, to the hot plasma of the ring current, to the relativistic populations of the radiation belts. Collectively, the ECT measurements will reveal the complex cross-energy coupling of these colocated particle populations, which along with concurrent RBSP wave measurements, will permit various wave-particle acceleration mechanisms to be tested. We review the measurement capabilities of the RBSP-ECT instrument suite, and demonstrate several examples of how these measurements will be used to explore candidate acceleration mechanisms and dynamics of radiation belt particles.

  8. NASA's Van Allen Probes RBSP-ECT Data Products and Access to Them: An Insider's Outlook on the Inner and Outer Belts (and We Don't Mean the Nation's Beltway...)

    NASA Astrophysics Data System (ADS)

    Smith, S. S.; Friedel, R. H. W.; Henderson, M. G.; Larsen, B.; Reeves, G. D.; Spence, H. E.

    2014-12-01

    In this poster, we present a summary of access to the data products of the Radiation Belt Storm Probes - Energetic Particle Composition, and Thermal plasma (RBSP-ECT) suite of NASA's Van Allen Probes mission. The RBSP-ECT science investigation (http://rbsp-ect.sr.unh.edu) measures comprehensively the near-Earth charged particle environment in order to understand the processes that control the acceleration, global distribution, and variability of radiation belt electrons and ions. RBSP-ECT data products derive from the three instrument elements that comprise the suite, which collectively covers the broad energies that define the source and seed populations, the core radiation belts, and also their highest energy ultra-relativistic extensions. These RBSP-ECT instruments include, from lowest to highest energies: the Helium, Oxygen, Proton, and Electron (HOPE) sensor, the Magnetic Electron and Ion Spectrometer (MagEIS), and the Relativistic Electron and Proton Telescope (REPT). We provide a brief overview of their principles of operation, as well as a description of the Level 1-3 data products that the HOPE, MagEIS, and REPT instruments produce, both separately and together. We provide a summary of how to access these RBSP-ECT data products at our Science Operation Center and Science Data Center (http://www.rbsp-ect.lanl.gov/rbsp_ect.php ) as well as caveats for their use. Finally, in the spirit of efficiently and effectively promoting and encouraging new collaborations, we present a summary of past publications, current studies, and opportunities for your future participation in RBSP-ECT science analyses.

  9. Ketamine augmentation of electroconvulsive therapy to improve neuropsychological and clinical outcomes in depression (Ketamine-ECT): a multicentre, double-blind, randomised, parallel-group, superiority trial.

    PubMed

    Anderson, Ian M; Blamire, Andrew; Branton, Tim; Clark, Ross; Downey, Darragh; Dunn, Graham; Easton, Andrew; Elliott, Rebecca; Elwell, Clare; Hayden, Katherine; Holland, Fiona; Karim, Salman; Loo, Colleen; Lowe, Jo; Nair, Rajesh; Oakley, Timothy; Prakash, Antony; Sharma, Parveen K; Williams, Stephen R; McAllister-Williams, R Hamish

    2017-05-01

    The use of electroconvulsive therapy (ECT) is limited by concerns about its cognitive adverse effects. Preliminary evidence suggests that administering the glutamate antagonist ketamine with ECT might alleviate cognitive adverse effects and accelerate symptomatic improvement; we tested this in a randomised trial of low-dose ketamine. In this multicentre, randomised, parallel-group study in 11 ECT suites serving inpatient and outpatient care settings in seven National Health Service trusts in the North of England, we recruited severely depressed patients, who were diagnosed as having unipolar or bipolar depressive episodes defined as moderate or severe by DSM-IV criteria, aged at least 18 years, and were able and willing to provide written consent to participate in the study. Patients were randomly assigned (1:1) to ketamine (0·5 mg/kg intravenous bolus) or saline adjunctive to the anaesthetic for the duration of their ECT course. Patients and assessment and ECT treatment teams were masked to treatment allocation, although anaesthetists administering the study medication were not. We analysed the primary outcome, Hopkins Verbal Learning Test-Revised delayed verbal recall (HVLT-R-DR) after four ECT treatments, using a Gaussian repeated measures model in all patients receiving the first ECT treatment. In the same population, safety was assessed by adverse effect monitoring. This trial was registered with International Standard Randomised Controlled Trial Number, number ISRCTN14689382. Between early December, 2012, and mid-June, 2015, 628 patients were screened for eligibility, of whom 79 were randomly assigned to treatment (40 in the ketamine group vs 39 in the saline group). Ketamine (mean 5·17, SD 2·92), when compared with saline (5·54, 3·42), had no benefit on the primary outcome (HVLT-R-DR; difference in means -0·43 [95% CI -1·73 to 0·87]). 15 (45%) of 33 ketamine-treated patients compared with 10 (27%) of 37 patients receiving saline experienced at least

  10. The product of C9orf72, a gene strongly implicated in neurodegeneration, is structurally related to DENN Rab-GEFs.

    PubMed

    Levine, Timothy P; Daniels, Rachel D; Gatta, Alberto T; Wong, Louise H; Hayes, Matthew J

    2013-02-15

    Fronto-temporal dementia (FTD) and amyotrophic lateral sclerosis (ALS, also called motor neuron disease, MND) are severe neurodegenerative diseases that show considerable overlap at the clinical and cellular level. The most common single mutation in families with FTD or ALS has recently been mapped to a non-coding repeat expansion in the uncharacterized gene C9ORF72. Although a plausible mechanism for disease is that aberrant C9ORF72 mRNA poisons splicing, it is important to determine the cellular function of C9ORF72, about which nothing is known. Sensitive homology searches showed that C9ORF72 is a full-length distant homologue of proteins related to Differentially Expressed in Normal and Neoplasia (DENN), which is a GDP/GTP exchange factor (GEF) that activates Rab-GTPases. Our results suggest that C9ORF72 is likely to regulate membrane traffic in conjunction with Rab-GTPase switches, and we propose to name the gene and its product DENN-like 72 (DENNL72).

  11. Levels of mania and cognitive performance two years after ECT in patients with bipolar I disorder - results from a follow-up study.

    PubMed

    Haghighi, Mohammad; Barikani, Reza; Jahangard, Leila; Ahmadpanah, Mohammad; Bajoghli, Hafez; Sadeghi Bahmani, Dena; Holsboer-Trachsler, Edith; Brand, Serge

    2016-08-01

    There is limited evidence on the long-term outcomes for patients with bipolar I disorder (BP-I-D) and treated with ECT. Therefore, we asked whether mania scores and cognitive performance at the end of ECT treatment (baseline/BL) predicted mania scores, cognitive performance, recurrence, treatment adherence, and mood (depression; hypomania) two years later (follow-up/FU). 38 patients with BP-I-D undergoing ECT at baseline were followed up two years later. A brief psychiatric and cognitive assessment (Mini Mental State Examination; short-term verbal memory test) was performed; patients completed questionnaires covering recurrence, treatment adherence, and mood (depression; hypomania). High cognitive performance at BL predicted high cognitive performance at FU; low mania scores at BL predicted low mania scores at FU. By FU, cognitive performance had increased and mania scores decreased. Mania scores and cognitive performance at BL did not predict recurrence, or adherence to medication, or mood (depression; hypomania). The pattern of results suggests that after two years of successful treatment of acute mania with ECT, cognitive impairment, measured by MMSE and a short-term verbal memory test, is not impaired and mood symptom recurrence seems to be improved. Mania scores and cognitive performance at the end of ECT treatment predicted neither mood (depression; hypomania), nor recurrence, or adherence to medication two years later. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. A phantom for quantitation of partial volume effects in ECT

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mullani, N.A.

    1989-02-01

    A special phantom has been designed, built and tested to measure the quantitative recovery of ECT data from the heart as a function of the size of the object and the angulation of a 1 cm thick simulated myocardium inclined with respect to the image plane. The phantom consists of five objects of 0.5, 1.0, 1.5. 2.0, and 3.0 cm width and six 1 cm thick strips inclined at 0, 30, 45, 60, 90, and -90 degrees with respect to the axial direction. Recovery coefficients for different object sizes and simulated 1 cm thick myocardium inclined at different angles canmore » be obtained from a single scan. Adequacy of axial sampling can be observed visually by creating the long axis view of the phantom.« less

  13. Applying the ECTS System to the Childhood Education Teaching Degree in Andalusia

    ERIC Educational Resources Information Center

    Serrano, Rosario Merida; Romero, Julia Angulo; Del Pino, Carmen Gil

    2008-01-01

    This article presents the research conducted as part of a Pilot Experiment regarding the application of the ECTS to the Childhood Education Teaching Degree taught at the University of Cordoba (Spain). It analyses the Experiment, which was carried out in the Education Faculty over the course of three academic years (2004/05, 2005/06 and 2006/07).…

  14. Somatic therapies for treatment-resistant depression: ECT, TMS, VNS, DBS.

    PubMed

    Cusin, Cristina; Dougherty, Darin D

    2012-08-17

    The field of non-pharmacological therapies for treatment resistant depression (TRD) is rapidly evolving and new somatic therapies are valuable options for patients who have failed numerous other treatments. A major challenge for clinicians (and patients alike) is how to integrate the results from published clinical trials in the clinical decision-making process.We reviewed the literature for articles reporting results for clinical trials in particular efficacy data, contraindications and side effects of somatic therapies including electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), vagal nerve stimulation (VNS) and deep brain stimulation (DBS). Each of these devices has an indication for patients with different level of treatment resistance, based on acuteness of illness, likelihood of response, costs and associated risks. ECT is widely available and its effects are relatively rapid in severe TRD, but its cognitive adverse effects may be cumbersome. TMS is safe and well tolerated, and it has been approved by FDA for adults who have failed to respond to one antidepressant, but its use in TRD is still controversial as it is not supported by rigorous double-blind randomized clinical trials. The options requiring surgical approach are VNS and DBS. VNS has been FDA-approved for TRD, however it is not indicated for management of acute illness. DBS for TRD is still an experimental area of investigation and double-blind clinical trials are underway.

  15. Brain Region and Isoform-Specific Phosphorylation Alters Kalirin SH2 Domain Interaction Sites and Calpain Sensitivity

    PubMed Central

    Miller, Megan B.; Yan, Yan; Machida, Kazuya; Kiraly, Drew D.; Levy, Aaron D.; Wu, Yi I.; Lam, TuKiet T.; Abbott, Thomas; Koleske, Anthony J.; Eipper, Betty A.; Mains, Richard E.

    2017-01-01

    Kalirin7 (Kal7), a postsynaptic Rho GDP/GTP exchange factor (RhoGEF), plays a crucial role in long term potentiation and in the effects of cocaine on behavior and spine morphology. The KALRN gene has been linked to schizophrenia and other disorders of synaptic function. Mass spectrometry was used to quantify phosphorylation at 26 sites in Kal7 from individual adult rat nucleus accumbens and prefrontal cortex before and after exposure to acute or chronic cocaine. Region- and isoform-specific phosphorylation was observed along with region-specific effects of cocaine on Kal7 phosphorylation. Evaluation of the functional significance of multi-site phosphorylation in a complex protein like Kalirin is difficult. With the identification of five tyrosine phosphorylation (pY) sites, a panel of 71 SH2 domains was screened, identifying subsets that interacted with multiple pY sites in Kal7. In addition to this type of reversible interaction, endoproteolytic cleavage by calpain plays an essential role in long-term potentiation. Calpain cleaved Kal7 at two sites, separating the N-terminal domain, which affects spine length, and the PDZ binding motif from the GEF domain. Mutations preventing phosphorylation did not affect calpain sensitivity or GEF activity; phosphomimetic mutations at specific sites altered protein stability, increased calpain sensitivity and reduced GEF activity. PMID:28418645

  16. Simplified data reduction methods for the ECT test for mode 3 interlaminar fracture toughness

    NASA Technical Reports Server (NTRS)

    Li, Jian; Obrien, T. Kevin

    1995-01-01

    Simplified expressions for the parameter controlling the load point compliance and strain energy release rate were obtained for the Edge Crack Torsion (ECT) specimen for mode 3 interlaminar fracture toughness. Data reduction methods for mode 3 toughness based on the present analysis are proposed. The effect of the transverse shear modulus, G(sub 23), on mode 3 interlaminar fracture toughness characterization was evaluated. Parameters influenced by the transverse shear modulus were identified. Analytical results indicate that a higher value of G(sub 23) results in a low load point compliance and lower mode 3 toughness estimation. The effect of G(sub 23) on the mode 3 toughness using the ECT specimen is negligible when an appropriate initial delamination length is chosen. A conservative estimation of mode 3 toughness can be obtained by assuming G(sub 23) = G(sub 12) for any initial delamination length.

  17. Vascular risk factors in older patients with depression: outcome of electroconvulsive therapy versus medication.

    PubMed

    Spaans, Harm-Pieter; Kok, Rob M; Bouckaert, Filip; Van Den Berg, Julia F; Tunney, Orlaith C; Sienaert, Pascal; Verwijk, Esmée; Kho, King H; Stek, Max L

    2018-02-01

    Research suggests that in depression, vascular burden predicts a lower efficacy for medication (MED) and a more favourable outcome for electroconvulsive therapy (ECT). Therefore, we investigated the influence of the following vascular risk factors (VRF): hypercholesterolemia, hypertension, smoking, diabetes mellitus, cardiovascular disease, and cerebral vascular accident/transient ischemic attack, on remission from major depression after ECT versus MED. The study sample consisted of 81 inpatients with a DSM-IV unipolar major depression diagnosis (mean age 72.2 years, SD = 7.6, mean Montgomery-Åsberg Depression Rating Scale score 32.9, SD = 6.2) participating in a randomized controlled trial comparing nortriptyline versus venlafaxine and 43 inpatients (mean age 73.7 years, SD = 7.5, mean Montgomery-Åsberg Depression Rating Scale score 30.6, SD = 7.1) from an randomized controlled trial comparing brief pulse versus ultrabrief pulse ECT. The presence of VRF was established from the medical records. The remission rate of patients with VRF was compared with those of patients without VRF. The remission rate was 58% (19/33) in the ECT group with ≥1 VRF and 32% (23/73) in the MED group with ≥1 VRF (χ 2  = 6.456, p = 0.011). Comparing patients with no VRF versus ≥1 VRF, the remission rate decreased from 80 to 58% (χ 2  = 1.652, p = 0.276) in ECT patients and from 38 to 32% (χ 2  = 0.119, p = 0.707) in MED patients. Applying different cut-offs for the number of VRFs yielded the same trends. Logistic regression revealed no interaction between VRF and treatment condition. The superior efficacy of ECT over pharmacotherapy in major depression in older age was independent of the presence of VRF. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  18. Anomalous behaviour of thermodynamic properties at successive phase transitions in (NH4)3GeF7

    NASA Astrophysics Data System (ADS)

    Bogdanov, Evgeniy V.; Kartashev, Andrey V.; Pogoreltsev, Evgeniy I.; Gorev, Mikhail V.; Laptash, Natalia M.; Flerov, Igor N.

    2017-12-01

    Heat capacity, thermal dilatation, susceptibility to hydrostatic pressure and dielectric properties associated with succession of three phase transitions below room temperature in double fluoride salt (NH4)3GeF7 were studied. A possible transformation into the parent Pm-3m cubic phase was not observed up to the decomposition of compound. Nonferroelectric nature of structural distortions was confirmed. The DTA under pressure studies revealed a high temperature stability of two phases: P4/mbm and Pbam. The entropies of the phase transitions agree well with the model of structural distortions. Analysis of the thermal properties associated with the individual phase transitions in the framework of thermodynamic equations has shown a high reliability of the data obtained.

  19. Preconditioned alternating projection algorithms for maximum a posteriori ECT reconstruction

    NASA Astrophysics Data System (ADS)

    Krol, Andrzej; Li, Si; Shen, Lixin; Xu, Yuesheng

    2012-11-01

    We propose a preconditioned alternating projection algorithm (PAPA) for solving the maximum a posteriori (MAP) emission computed tomography (ECT) reconstruction problem. Specifically, we formulate the reconstruction problem as a constrained convex optimization problem with the total variation (TV) regularization. We then characterize the solution of the constrained convex optimization problem and show that it satisfies a system of fixed-point equations defined in terms of two proximity operators raised from the convex functions that define the TV-norm and the constraint involved in the problem. The characterization (of the solution) via the proximity operators that define two projection operators naturally leads to an alternating projection algorithm for finding the solution. For efficient numerical computation, we introduce to the alternating projection algorithm a preconditioning matrix (the EM-preconditioner) for the dense system matrix involved in the optimization problem. We prove theoretically convergence of the PAPA. In numerical experiments, performance of our algorithms, with an appropriately selected preconditioning matrix, is compared with performance of the conventional MAP expectation-maximization (MAP-EM) algorithm with TV regularizer (EM-TV) and that of the recently developed nested EM-TV algorithm for ECT reconstruction. Based on the numerical experiments performed in this work, we observe that the alternating projection algorithm with the EM-preconditioner outperforms significantly the EM-TV in all aspects including the convergence speed, the noise in the reconstructed images and the image quality. It also outperforms the nested EM-TV in the convergence speed while providing comparable image quality.

  20. ARF6 Activated by the LHCG Receptor through the Cytohesin Family of Guanine Nucleotide Exchange Factors Mediates the Receptor Internalization and Signaling*

    PubMed Central

    Kanamarlapudi, Venkateswarlu; Thompson, Aiysha; Kelly, Eamonn; López Bernal, Andrés

    2012-01-01

    The luteinizing hormone chorionic gonadotropin receptor (LHCGR) is a Gs-coupled GPCR that is essential for the maturation and function of the ovary and testis. LHCGR is internalized following its activation, which regulates the biological responsiveness of the receptor. Previous studies indicated that ADP-ribosylation factor (ARF)6 and its GTP-exchange factor (GEF) cytohesin 2 regulate LHCGR internalization in follicular membranes. However, the mechanisms by which ARF6 and cytohesin 2 regulate LHCGR internalization remain incompletely understood. Here we investigated the role of the ARF6 signaling pathway in the internalization of heterologously expressed human LHCGR (HLHCGR) in intact cells using a combination of pharmacological inhibitors, siRNA and the expression of mutant proteins. We found that human CG (HCG)-induced HLHCGR internalization, cAMP accumulation and ARF6 activation were inhibited by Gallein (βγ inhibitor), Wortmannin (PI 3-kinase inhibitor), SecinH3 (cytohesin ARF GEF inhibitor), QS11 (an ARF GAP inhibitor), an ARF6 inhibitory peptide and ARF6 siRNA. However, Dynasore (dynamin inhibitor), the dominant negative mutants of NM23-H1 (dynamin activator) and clathrin, and PBP10 (PtdIns 4,5-P2-binding peptide) inhibited agonist-induced HLHCGR and cAMP accumulation but not ARF6 activation. These results indicate that heterotrimeric G-protein, phosphatidylinositol (PI) 3-kinase (PI3K), cytohesin ARF GEF and ARF GAP function upstream of ARF6 whereas dynamin and clathrin act downstream of ARF6 in the regulation of HCG-induced HLHCGR internalization and signaling. In conclusion, we have identified the components and molecular details of the ARF6 signaling pathway required for agonist-induced HLHCGR internalization. PMID:22523074

  1. Activated RhoA Is a Positive Feedback Regulator of the Lbc Family of Rho Guanine Nucleotide Exchange Factor Proteins*

    PubMed Central

    Medina, Frank; Carter, Angela M.; Dada, Olugbenga; Gutowski, Stephen; Hadas, Jana; Chen, Zhe; Sternweis, Paul C.

    2013-01-01

    The monomeric Rho GTPases are essential for cellular regulation including cell architecture and movement. A direct mechanism for hormonal regulation of the RhoA-type GTPases is their modulation by the G12 and G13 proteins via RH (RGS homology) containing RhoGEFs. In addition to the interaction of the G protein α subunits with the RH domain, activated RhoA also binds to the pleckstrin homology (PH) domain of PDZRhoGEF. The latter interaction is now extended to all seven members of the homologous Lbc family of RhoGEFs which includes the RH-RhoGEFs. This is evinced by direct measurements of binding or through effects on selected signaling pathways in cells. Overexpression of these PH domains alone can block RhoA-dependent signaling in cells to various extents. Whereas activated RhoA does not modulate the intrinsic activity of the RhoGEFs, activated RhoA associated with phospholipid vesicles can facilitate increased activity of soluble RhoGEFs on vesicle-delimited substrate (RhoA-GDP). This demonstrates feasibility of the hypothesis that binding of activated RhoA to the PH domains acts as a positive feedback mechanism. This is supported by cellular studies in which mutation of this binding site on PH strongly attenuates the stimulation of RhoA observed by overexpression of five of the RhoGEF DH-PH domains. This mutation is even more dramatic in the context of full-length p115RhoGEF. The utilization of this mechanism by multiple RhoGEFs suggests that this regulatory paradigm may be a common feature in the broader family of RhoGEFs. PMID:23493395

  2. RhoA GTPase inhibition organizes contraction during epithelial morphogenesis

    PubMed Central

    Mason, Frank M.; Xie, Shicong; Vasquez, Claudia G.; Tworoger, Michael

    2016-01-01

    During morphogenesis, contraction of the actomyosin cytoskeleton within individual cells drives cell shape changes that fold tissues. Coordination of cytoskeletal contractility is mediated by regulating RhoA GTPase activity. Guanine nucleotide exchange factors (GEFs) activate and GTPase-activating proteins (GAPs) inhibit RhoA activity. Most studies of tissue folding, including apical constriction, have focused on how RhoA is activated by GEFs to promote cell contractility, with little investigation as to how GAPs may be important. Here, we identify a critical role for a RhoA GAP, Cumberland GAP (C-GAP), which coordinates with a RhoA GEF, RhoGEF2, to organize spatiotemporal contractility during Drosophila melanogaster apical constriction. C-GAP spatially restricts RhoA pathway activity to a central position in the apical cortex. RhoGEF2 pulses precede myosin, and C-GAP is required for pulsation, suggesting that contractile pulses result from RhoA activity cycling. Finally, C-GAP expression level influences the transition from reversible to irreversible cell shape change, which defines the onset of tissue shape change. Our data demonstrate that RhoA activity cycling and modulating the ratio of RhoGEF2 to C-GAP are required for tissue folding. PMID:27551058

  3. Preconditioned Alternating Projection Algorithms for Maximum a Posteriori ECT Reconstruction

    PubMed Central

    Krol, Andrzej; Li, Si; Shen, Lixin; Xu, Yuesheng

    2012-01-01

    We propose a preconditioned alternating projection algorithm (PAPA) for solving the maximum a posteriori (MAP) emission computed tomography (ECT) reconstruction problem. Specifically, we formulate the reconstruction problem as a constrained convex optimization problem with the total variation (TV) regularization. We then characterize the solution of the constrained convex optimization problem and show that it satisfies a system of fixed-point equations defined in terms of two proximity operators raised from the convex functions that define the TV-norm and the constrain involved in the problem. The characterization (of the solution) via the proximity operators that define two projection operators naturally leads to an alternating projection algorithm for finding the solution. For efficient numerical computation, we introduce to the alternating projection algorithm a preconditioning matrix (the EM-preconditioner) for the dense system matrix involved in the optimization problem. We prove theoretically convergence of the preconditioned alternating projection algorithm. In numerical experiments, performance of our algorithms, with an appropriately selected preconditioning matrix, is compared with performance of the conventional MAP expectation-maximization (MAP-EM) algorithm with TV regularizer (EM-TV) and that of the recently developed nested EM-TV algorithm for ECT reconstruction. Based on the numerical experiments performed in this work, we observe that the alternating projection algorithm with the EM-preconditioner outperforms significantly the EM-TV in all aspects including the convergence speed, the noise in the reconstructed images and the image quality. It also outperforms the nested EM-TV in the convergence speed while providing comparable image quality. PMID:23271835

  4. The Aarskog-Scott Syndrome Protein Fgd1 Regulates Podosome Formation and Extracellular Matrix Remodeling in Transforming Growth Factor β-Stimulated Aortic Endothelial Cells ▿

    PubMed Central

    Daubon, Thomas; Buccione, Roberto; Génot, Elisabeth

    2011-01-01

    Podosomes are dynamic actin-rich adhesion plasma membrane microdomains endowed with extracellular matrix-degrading activities. In aortic endothelial cells, podosomes are induced by transforming growth factor β (TGF-β), but how this occurs is largely unknown. It is thought that, in endothelial cells, podosomes play a role in vessel remodeling and/or in breaching anatomical barriers. We demonstrate here that, in bovine aortic endothelial cells, that the Cdc42-specific guanine exchange factor (GEF) Fgd1 is expressed and regulated by TGF-β to induce Cdc42-dependent podosome assembly. Within 15 min of TGF-β stimulation, Fgd1, but none of the other tested Cdc42 GEFs, undergoes tyrosine phosphorylation, associates with Cdc42, and translocates to the subcortical cytoskeleton via a cortactin-dependent mechanism. Small interfering RNA-mediated Fgd1 knockdown inhibits TGF-β-induced Cdc42 activation. Fgd1 depletion also reduces podosome formation and associated matrix degradation and these defects are rescued by reexpression of Fgd1. Although overexpression of Fgd1 does not promote podosome formation per se, it enhances TGF-β-induced matrix degradation. Our results identify Fgd1 as a TGF-β-regulated GEF and, as such, the first GEF to be involved in the process of cytokine-induced podosome formation. Our findings reveal the involvement of Fgd1 in endothelial cell biology and open up new avenues to study its role in vascular pathophysiology. PMID:21911474

  5. Development of ECT/UT inspection system for bottom mounted instrumentation nozzle of PWR reactor vessels

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tanaka, H.; Fukui, S.; Iwahashi, Y.

    1994-12-31

    The development of inspection technique and tool for Bottom Mounted Instrument (BMI) nozzle of PWR plant was performed for countermeasure of leakage accident at incore instrument nozzle of Hamaoka-1 (BWR). MHI achieved the following development, of which object was PWR Plant R/V: (1) development of ECT/UT Multi-sensored Probe; (2) development of Inspection System (3) development of Data Processing System. The Inspection System had been functionally tested using full scale mock-up. As the result of the functional test, this system was confirmed to be very effective, and assumed to be hopeful for the actual application on site.

  6. Envisioning a New Foundation for Gifted Education: Evolving Complexity Theory (ECT) of Talent Development

    ERIC Educational Resources Information Center

    Dai, David Yun

    2017-01-01

    This article presents a new theory of talent development, evolving complexity theory (ECT), in the context of the changing theoretical directions as well as the landscape of gifted education. I argue that gifted education needs a new foundation that provides a broad psychosocial basis than what the notion of giftedness can afford. A focus on…

  7. Numerical approach for ECT by using boundary element method with Laplace transform

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Enokizono, M.; Todaka, T.; Shibao, K.

    1997-03-01

    This paper presents an inverse analysis by using BEM with Laplace transform. The method is applied to a simple problem in the eddy current testing (ECT). Some crack shapes in a conductive specimen are estimated from distributions of the transient eddy current on its sensing surface and magnetic flux density in the liftoff space. Because the transient behavior includes information on various frequency components, the method is applicable to the shape estimation of a comparative small crack.

  8. Factors associated with the risk of relapse in schizophrenic patients after a response to electroconvulsive therapy: a retrospective study.

    PubMed

    Shibasaki, Chiyo; Takebayashi, Minoru; Fujita, Yasutaka; Yamawaki, Shigeto

    2015-01-01

    Electroconvulsive therapy (ECT) is an effective treatment for depression and schizophrenia. However, there is a high rate of relapse after an initial response to ECT, even with antidepressant or antipsychotic maintenance therapy. This study was carried out to examine the factors that influence the risk of relapse in schizophrenic patients after a response to ECT. We retrospectively reviewed the records of 43 patients with schizophrenia who received and responded to an acute ECT course. We analyzed the associated clinical variables and relapse after response to the acute ECT. Relapse was defined as a Clinical Global Impressions Improvement score ≥6 or a psychiatric rehospitalization. All patients were treated with neuroleptic medication after the acute ECT course. The relapse-free rate of all 43 patients at 1 year was 57.3%, and the median relapse-free period was 21.5 months. Multivariate analysis showed that the number of ECT sessions was associated with a significant increase in the risk of relapse (hazard ratio: 1.159; P=0.033). Patients who were treated with adjunctive mood stabilizers as maintenance pharmacotherapy after the response to the acute ECT course were at a lower risk of relapse than were those treated without mood stabilizers (hazard ratio: 0.257; P=0.047). Our study on the recurrence of schizophrenia after a response to an acute ECT course suggests that the number of ECT sessions might be related to the risk of relapse and that adjunctive mood stabilizers might be effective in preventing relapse.

  9. [Subgroup Analysis of the Non-interventional REASON Study: PFS and OS According to Age, Smoking History, Gender, and Histology in NSCLC Patients Treated with Gefitinib or Chemotherapy].

    PubMed

    Schuette, W; Eberhardt, W E E; Waller, C; Schirmacher, P; Dietel, M; Zirrgiebel, U; Radke, S; Thomas, M

    2016-09-01

    Assessment of several clinical factors on progression-free (PFS) and overall survival (OS) in NSCLC patients (pts.) (stage IV) with mutated epidermal growth factor receptor (EGFRm+) treated with gefitinib (gef) or with chemotherapy (CT) under real-world conditions. 285 EGFRm+ pts. of the non-interventional REASON study treated with gef (n = 206) or CT (n = 79) as first-line therapy or with gef (n = 213) or CT (n = 61) in any line throughout the course of therapy were analyzed according to age, gender, smoking history and histology. Compared with CT, patients treated with gef showed prolongation of PFS and OS in all subgroups. PFS was significantly increased in women and non-smokers. OS was significantly increased in women, non-smokers, (ex)-smokers, patients with adenocarcinoma and elderly patients when treated with gef compared to CT. Female gender turned out to be an independent positive predictive factor for OS in patients treated with gef (HRmale: 1.74, p = 0.0009). A clinical benefit of gef was shown for all analyzed clinical subgroups of EGFRm+ pts. This was confirmed for the female gender in a multivariate analysis. © Georg Thieme Verlag KG Stuttgart · New York.

  10. Clinical efficacy of formula-based bifrontal versus right unilateral electroconvulsive therapy (ECT) in the treatment of major depression among elderly patients: a pragmatic, randomized, assessor-blinded, controlled trial.

    PubMed

    Bjølseth, Tor Magne; Engedal, Knut; Benth, Jūratė Šaltytė; Dybedal, Gro Strømnes; Gaarden, Torfinn Lødøen; Tanum, Lars

    2015-04-01

    No prior study has compared the efficacy of bifrontal (BF) vs right unilateral (RUL) electroconvulsive therapy (ECT) by including the subgroup that is most likely to receive it: only elderly patients with major depression (MD). This single-site, randomized, assessor-blinded, controlled trial was conducted from 2009 to 2013. Seventy-three elderly patients with MD, unipolar and bipolar, were treated with a course of formula-based BF ECT or RUL ECT. The 17-item Hamilton Rating Scale for Depression (HRSD17) was used to measure efficacy. Safety was assessed with the Mini Mental State Examination (MMSE). Both electrode placements resulted in highly significant downward trends in symptom severity (all p<0.001), with a non-significant difference between methods (p=0.703). At the end of the ECT course, response rates for the BF and RUL group were 63.9% and 67.6%, respectively. Short-term remission, defined as an HRSD17 score≤7, was achieved in 14 (38.9%) patients in the BF group and 19 (51.4%) patients in the RUL group. Global cognitive function, as measured by the MMSE, did not deteriorate in the two treatment groups. The small number of subjects may have led to reduced power to detect real differences. The MMSE is not sufficient to ascertain the negative effect of ECT on cognition. This study indicates that formula-based BF and RUL ECT are equally efficacious, and that remission rates of formula-based dosing are lower than those previously reported for titrated dosing, in a clinical sample of elderly patients with MD. ClinicalTrials.gov NCT01559324. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  11. A 3-D enlarged cell technique (ECT) for elastic wave modelling of a curved free surface

    NASA Astrophysics Data System (ADS)

    Wei, Songlin; Zhou, Jianyang; Zhuang, Mingwei; Liu, Qing Huo

    2016-09-01

    The conventional finite-difference time-domain (FDTD) method for elastic waves suffers from the staircasing error when applied to model a curved free surface because of its structured grid. In this work, an improved, stable and accurate 3-D FDTD method for elastic wave modelling on a curved free surface is developed based on the finite volume method and enlarged cell technique (ECT). To achieve a sufficiently accurate implementation, a finite volume scheme is applied to the curved free surface to remove the staircasing error; in the mean time, to achieve the same stability as the FDTD method without reducing the time step increment, the ECT is introduced to preserve the solution stability by enlarging small irregular cells into adjacent cells under the condition of conservation of force. This method is verified by several 3-D numerical examples. Results show that the method is stable at the Courant stability limit for a regular FDTD grid, and has much higher accuracy than the conventional FDTD method.

  12. Structural basis for activation of trimeric Gi proteins by multiple growth factor receptors via GIV/Girdin

    PubMed Central

    Lin, Changsheng; Ear, Jason; Midde, Krishna; Lopez-Sanchez, Inmaculada; Aznar, Nicolas; Garcia-Marcos, Mikel; Kufareva, Irina; Abagyan, Ruben; Ghosh, Pradipta

    2014-01-01

    A long-standing issue in the field of signal transduction is to understand the cross-talk between receptor tyrosine kinases (RTKs) and heterotrimeric G proteins, two major and distinct signaling hubs that control eukaryotic cell behavior. Although stimulation of many RTKs leads to activation of trimeric G proteins, the molecular mechanisms behind this phenomenon remain elusive. We discovered a unifying mechanism that allows GIV/Girdin, a bona fide metastasis-related protein and a guanine-nucleotide exchange factor (GEF) for Gαi, to serve as a direct platform for multiple RTKs to activate Gαi proteins. Using a combination of homology modeling, protein–protein interaction, and kinase assays, we demonstrate that a stretch of ∼110 amino acids within GIV C-terminus displays structural plasticity that allows folding into a SH2-like domain in the presence of phosphotyrosine ligands. Using protein–protein interaction assays, we demonstrated that both SH2 and GEF domains of GIV are required for the formation of a ligand-activated ternary complex between GIV, Gαi, and growth factor receptors and for activation of Gαi after growth factor stimulation. Expression of a SH2-deficient GIV mutant (Arg 1745→Leu) that cannot bind RTKs impaired all previously demonstrated functions of GIV—Akt enhancement, actin remodeling, and cell migration. The mechanistic and structural insights gained here shed light on the long-standing questions surrounding RTK/G protein cross-talk, set a novel paradigm, and characterize a unique pharmacological target for uncoupling GIV-dependent signaling downstream of multiple oncogenic RTKs. PMID:25187647

  13. Son of sevenless directly links the Robo receptor to rac activation to control axon repulsion at the midline.

    PubMed

    Yang, Long; Bashaw, Greg J

    2006-11-22

    Son of sevenless (Sos) is a dual specificity guanine nucleotide exchange factor (GEF) that regulates both Ras and Rho family GTPases and thus is uniquely poised to integrate signals that affect both gene expression and cytoskeletal reorganization. Here, using genetics, biochemistry, and cell biology, we demonstrate that Sos is recruited to the plasma membrane, where it forms a ternary complex with the Roundabout receptor and the SH3-SH2 adaptor protein Dreadlocks (Dock) to regulate Rac-dependent cytoskeletal rearrangement in response to the Slit ligand. Intriguingly, the Ras and Rac-GEF activities of Sos can be uncoupled during Robo-mediated axon repulsion; Sos axon guidance function depends on its Rac-GEF activity, but not its Ras-GEF activity. These results provide in vivo evidence that the Ras and RhoGEF domains of Sos are separable signaling modules and support a model in which Robo recruits Sos to the membrane via Dock to activate Rac during midline repulsion.

  14. ApoER2 and Reelin are expressed in regenerating peripheral nerve and regulate Schwann cell migration by activating the Rac1 GEF protein, Tiam1.

    PubMed

    Pasten, Consuelo; Cerda, Joaquín; Jausoro, Ignacio; Court, Felipe A; Cáceres, Alfredo; Marzolo, Maria-Paz

    2015-11-01

    ApoER2 and its ligand Reelin participate in neuronal migration during development. Upon receptor binding, Reelin induces the proteolytic processing of ApoER2 as well as the activation of signaling pathway, including small Rho GTPases. Besides its presence in the central nervous system (CNS), Reelin is also secreted by Schwann cells (SCs), the glial cells of the peripheral nervous system (PNS). Reelin deficient mice (reeler) show decreased axonal regeneration in the PNS; however neither the presence of ApoER2 nor the role of the Reelin signaling pathway in the PNS have been evaluated. Interestingly SC migration occurs during PNS development and during injury-induced regeneration and involves activation of small Rho GTPases. Thus, Reelin-ApoER2 might regulate SC migration during axon regeneration in the PNS. Here we demonstrate the presence of ApoER2 in PNS. After sciatic nerve injury Reelin was induced and its receptor ApoER2 was proteolytically processed. In vitro, SCs express both Reelin and ApoER2 and Reelin induces SC migration. To elucidate the molecular mechanism underlying Reelin-dependent SC migration, we examined the involvement of Rac1, a conspicuous small GTPase family member. FRET experiments revealed that Reelin activates Rac1 at the leading edge of SCs. In addition, Tiam1, a major Rac1-specific GEF was required for Reelin-induced SC migration. Moreover, Reelin-induced SC migration was decreased after suppression of the polarity protein PAR3, consistent with its association to Tiam1. Even more interesting, we demonstrated that PAR3 binds preferentially to the full-length cytoplasmic tail of ApoER2 corresponding to the splice-variant containing the exon 19 that encodes a proline-rich insert and that ApoER2 was required for SC migration. Our study reveals a novel function for Reelin/ApoER2 in PNS, inducing cell migration of SCs, a process relevant for PNS development and regeneration. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. The N Termini of a-Subunit Isoforms Are Involved in Signaling between Vacuolar H+-ATPase (V-ATPase) and Cytohesin-2*

    PubMed Central

    Hosokawa, Hiroyuki; Dip, Phat Vinh; Merkulova, Maria; Bakulina, Anastasia; Zhuang, Zhenjie; Khatri, Ashok; Jian, Xiaoying; Keating, Shawn M.; Bueler, Stephanie A.; Rubinstein, John L.; Randazzo, Paul A.; Ausiello, Dennis A.; Grüber, Gerhard; Marshansky, Vladimir

    2013-01-01

    Previously, we reported an acidification-dependent interaction of the endosomal vacuolar H+-ATPase (V-ATPase) with cytohesin-2, a GDP/GTP exchange factor (GEF), suggesting that it functions as a pH-sensing receptor. Here, we have studied the molecular mechanism of signaling between the V-ATPase, cytohesin-2, and Arf GTP-binding proteins. We found that part of the N-terminal cytosolic tail of the V-ATPase a2-subunit (a2N), corresponding to its first 17 amino acids (a2N(1–17)), potently modulates the enzymatic GDP/GTP exchange activity of cytohesin-2. Moreover, this peptide strongly inhibits GEF activity via direct interaction with the Sec7 domain of cytohesin-2. The structure of a2N(1–17) and its amino acids Phe5, Met10, and Gln14 involved in interaction with Sec7 domain were determined by NMR spectroscopy analysis. In silico docking experiments revealed that part of the V-ATPase formed by its a2N(1–17) epitope competes with the switch 2 region of Arf1 and Arf6 for binding to the Sec7 domain of cytohesin-2. The amino acid sequence alignment and GEF activity studies also uncovered the conserved character of signaling between all four (a1–a4) a-subunit isoforms of mammalian V-ATPase and cytohesin-2. Moreover, the conserved character of this phenomenon was also confirmed in experiments showing binding of mammalian cytohesin-2 to the intact yeast V-ATPase holo-complex. Thus, here we have uncovered an evolutionarily conserved function of the V-ATPase as a novel cytohesin-signaling receptor. PMID:23288846

  16. Prediction of alpha factor values for fine pore aeration systems.

    PubMed

    Gillot, S; Héduit, A

    2008-01-01

    The objective of this work was to analyse the impact of different geometric and operating parameters on the alpha factor value for fine bubble aeration systems equipped with EPDM membrane diffusers. Measurements have been performed on nitrifying plants operating under extended aeration and treating mainly domestic wastewater. Measurements performed on 14 nitrifying plants showed that, for domestic wastewater treatment under very low F/M ratios, the alpha factor is comprised between 0.44 and 0.98. A new composite variable (the Equivalent Contact Time, ECT) has been defined and makes it possible for a given aeration tank, knowing the MCRT, the clean water oxygen transfer coefficient and the supplied air flow rate, to predict the alpha factor value. ECT combines the effect on mass transfer of all generally accepted factors affecting oxygen transfer performances (air flow rate, diffuser submergence, horizontal flow). (c) IWA Publishing 2008.

  17. [Asu(1,7)E-CT, an analog of eel calcitonin. A comparative study in man with reference to other synthetic calcitonins].

    PubMed

    Caniggia, A; Nuti, R; Vattimo, A; Galli, M; Turchetti, V; Franci, B; Martorelli, T; Righi, G

    1983-04-28

    (Asu) E-CT is a deaminodicarba-analog of the synthetic eel-calcitonin (E-CT) that shows specific activity and the potency reasonably high in comparison with that of the most potent natural hormone. The structure of its molecule indicates that the disulphide bond in calcitonins is not essential for the biological activity but only for the maintenance of the specific conformation by forming an intramolecular bridge. The instability of calcitonins should mainly be attributed to the presence of the disulfide bond and (Asu)E-CT proved to be more stable "in vitro" than native calcitonins. The more prolonged hypocalcemic effect of E-CT and its aminosuberic analog (Asu)E-CT has been accounted for to a greater stability of and persistence at the receptor site. (Asu) E-CT has been largely studied in Japan on experimental animals and successfully used in the treatment of hypercalcemia in man. On the contrary investigations on human administration of this analog are very scarce. The present paper reports studies carried out in normal subjects and Paget's disease patients to investigate the effects of (Asu)E-CT in man in comparison with the effects of synthetic human calcitonin (H-CT) and synthetic salmon calcitonin (S-CT). Two different experimental procedures have been used: 1) rapid intravenous injection of (Asu)E-CT (80 MRC. U.) or respectively of H-CT and S-CT (100 MRC. U.) in 15 subjects (7 normals and 8 with Paget's disease); 2) slow 7 days continuous subcutaneous infusion of similar daily amounts of (Asu)E-CT, H-CT and S-CT administered by a microjet pump device in 21 subjects (7 normals and 14 with Paget's disease). The intravenous administration of (Asu)E-CT induced a rapid and persistent decrease in total plasma calcium, ionized calcium and plasma phosphate that was more evident in Paget's disease patients than in normal subjects. No clearly cut differences have been observed with the hypocalcemic and hypophosphatemic effect of H-CT and S-CT administered

  18. Site-specific regulation of the GEF Cdc24p by the scaffold protein Far1p during yeast mating

    PubMed Central

    Wiget, Philippe; Shimada, Yukiko; Butty, Anne-Christine; Bi, Efrei; Peter, Matthias

    2004-01-01

    Receptor-mediated cell polarization via heterotrimeric G-proteins induces cytoskeletal rearrangements in a variety of organisms. In yeast, Far1p is required for orienting cell growth towards the mating partner by linking activated Gβγ to the guanine-nucleotide exchange factor (GEF) Cdc24p, which activates the Rho-type GTPase Cdc42p. Here we investigated the role of Far1p in the regulation of Cdc24p in vivo. Using time-lapse microscopy of mating cells and artificial membrane targeting of Far1p, we show that Far1p is necessary and sufficient to recruit Cdc24p to the plasma membrane. Wild-type Far1p contains a PH-like domain, which is required for its membrane localization in vivo. Interestingly, expression of membrane-targeted Far1p causes toxicity, most likely by activating Cdc42p uniformly at the cell cortex. The ability of full-length Far1p to function as an activator of Cdc24p in vivo requires its interaction with Cdc24p and Gβγ. Our results imply that Gβγ not only targets Far1p to the correct site but may also trigger a conformational change in Far1p that is required for its ability to activate Cdc24p in vivo. PMID:14988725

  19. Dbl oncogene expression in MCF-10 A epithelial cells disrupts mammary acinar architecture, induces EMT and angiogenic factor secretion

    PubMed Central

    Vanni, Cristina; Ognibene, Marzia; Finetti, Federica; Mancini, Patrizia; Cabodi, Sara; Segalerba, Daniela; Torrisi, Maria Rosaria; Donnini, Sandra; Bosco, Maria Carla; Varesio, Luigi; Eva, Alessandra

    2015-01-01

    The proteins of the Dbl family are guanine nucleotide exchange factors (GEFs) of Rho GTPases and are known to be involved in cell growth regulation. Alterations of the normal function of these proteins lead to pathological processes such as developmental disorders, neoplastic transformation, and tumor metastasis. We have previously demonstrated that expression of Dbl oncogene in lens epithelial cells modulates genes encoding proteins involved in epithelial-mesenchymal-transition (EMT) and induces angiogenesis in the lens. Our present study was undertaken to investigate the role of Dbl oncogene in epithelial cells transformation, providing new insights into carcinoma progression.To assess how Dbl oncogene can modulate EMT, cell migration, morphogenesis, and expression of pro-apoptotic and angiogenic factors we utilized bi- and 3-dimensional cultures of MCF-10 A cells. We show that upon Dbl expression MCF-10 A cells undergo EMT. In addition, we found that Dbl overexpression sustains Cdc42 and Rac activation inducing morphological alterations, characterized by the presence of lamellipodia and conferring a high migratory capacity to the cells. Moreover, Dbl expressing MCF-10 A cells form altered 3D structures and can induce angiogenesis by producing proangiogenic factors such as CCL2. These results support a role for Dbl oncogene in epithelial cell differentiation and transformation and suggest the relevance of GEF deregulation in tumor onset and progression. PMID:25723869

  20. The R-Ras/RIN2/Rab5 complex controls endothelial cell adhesion and morphogenesis via active integrin endocytosis and Rac signaling

    PubMed Central

    Sandri, Chiara; Caccavari, Francesca; Valdembri, Donatella; Camillo, Chiara; Veltel, Stefan; Santambrogio, Martina; Lanzetti, Letizia; Bussolino, Federico; Ivaska, Johanna; Serini, Guido

    2012-01-01

    During developmental and tumor angiogenesis, semaphorins regulate blood vessel navigation by signaling through plexin receptors that inhibit the R-Ras subfamily of small GTPases. R-Ras is mainly expressed in vascular cells, where it induces adhesion to the extracellular matrix (ECM) through unknown mechanisms. We identify the Ras and Rab5 interacting protein RIN2 as a key effector that in endothelial cells interacts with and mediates the pro-adhesive and -angiogenic activity of R-Ras. Both R-Ras-GTP and RIN2 localize at nascent ECM adhesion sites associated with lamellipodia. Upon binding, GTP-loaded R-Ras converts RIN2 from a Rab5 guanine nucleotide exchange factor (GEF) to an adaptor that first interacts at high affinity with Rab5-GTP to promote the selective endocytosis of ligand-bound/active β1 integrins and then causes the translocation of R-Ras to early endosomes. Here, the R-Ras/RIN2/Rab5 signaling module activates Rac1-dependent cell adhesion via TIAM1, a Rac GEF that localizes on early endosomes and is stimulated by the interaction with both Ras proteins and the vesicular lipid phosphatidylinositol 3-monophosphate. In conclusion, the ability of R-Ras-GTP to convert RIN2 from a GEF to an adaptor that preferentially binds Rab5-GTP allows the triggering of the endocytosis of ECM-bound/active β1 integrins and the ensuing funneling of R-Ras-GTP toward early endosomes to elicit the pro-adhesive and TIAM1-mediated activation of Rac1. PMID:22825554

  1. Pan-European Grading Scales: Lessons from National Systems and the ECTS. The Bologna Process: Retrospect and Prospects

    ERIC Educational Resources Information Center

    Karran, Terence

    2005-01-01

    This article assesses the impact of the Bologna Process on the grading schemes of EU member countries. In light of some problems regarding the implementation of the European Credit Transfer system (ECTS), the author proposes further reforms and offers some elements of a unified grading system for European higher education. The author explores the…

  2. Factors associated with relapse after a response to electroconvulsive therapy in unipolar versus bipolar depression.

    PubMed

    Itagaki, Kei; Takebayashi, Minoru; Shibasaki, Chiyo; Kajitani, Naoto; Abe, Hiromi; Okada-Tsuchioka, Mami; Yamawaki, Shigeto

    2017-01-15

    While electroconvulsive therapy (ECT) treatment for depression is highly effective, the high rate of relapse is a critical problem. The current study investigated factors associated with the risk of relapse in mood disorders in patients in which ECT was initially effective. The records of 100 patients with mood disorders (61 unipolar depression, 39 bipolar depression) who received and responded to an acute ECT course were retrospectively reviewed. Associations between clinical variables and relapse after responding to acute ECT were analyzed. The Ethics Committee of NHO Kure Medical Center approved the study protocol. After one year, the percentage of relapse-free patients was 48.7%. There was no significant difference between patients with either unipolar or bipolar depression who were relapse-free (unipolar: 51.1%, bipolar: 45.5%, P=0.603). Valproate maintenance pharmacotherapy in unipolar depression patients was associated with a lower risk of relapse compared to patients without valproate treatment (multivariate analysis, hazard ratio: 0.091; P=0.022). Lithium treatment, reportedly effective for unipolar depression following a course of ECT, tended to lower the risk of relapse (hazard ratio: 0.378; P=0.060). For bipolar depression, no treatment significantly reduced the risk of relapse. The current findings were retrospective and based on a limited sample size. The relapse-free rate was similar between unipolar and bipolar depression. Valproate could have potential for unipolar depression patients as a maintenance therapeutic in preventing relapse after ECT. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. The Arf GEF GBF1 and Arf4 synergize with the sensory receptor cargo, rhodopsin, to regulate ciliary membrane trafficking.

    PubMed

    Wang, Jing; Fresquez, Theresa; Kandachar, Vasundhara; Deretic, Dusanka

    2017-12-01

    The small GTPase Arf4 and the Arf GTPase-activating protein (GAP) ASAP1 cooperatively sequester sensory receptor cargo into transport carriers targeted to primary cilia, but the input that drives Arf4 activation in this process remains unknown. Here, we show, by using frog retinas and recombinant human proteins, that during the carrier biogenesis from the photoreceptor Golgi/ trans -Golgi network (TGN) a functional complex is formed between Arf4, the Arf guanine nucleotide exchange factor (GEF) GBF1 and the light-sensing receptor, rhodopsin. Rhodopsin and Arf4 bind the regulatory N-terminal dimerization and cyclophillin-binding (DCB)-homology upstream of Sec7 (HUS) domain of GBF1. The complex is sensitive to Golgicide A (GCA), a selective inhibitor of GBF1 that accordingly blocks rhodopsin delivery to the cilia, without disrupting the photoreceptor Golgi. The emergence of newly synthesized rhodopsin in the endomembrane system is essential for GBF1-Arf4 complex formation in vivo Notably, GBF1 interacts with the Arf GAP ASAP1 in a GCA-resistant manner. Our findings indicate that converging signals on GBF1 from the influx of cargo into the Golgi/TGN and the feedback from Arf4, combined with input from ASAP1, control Arf4 activation during sensory membrane trafficking to primary cilia. © 2017. Published by The Company of Biologists Ltd.

  4. Combining Peer-Assessment with Negotiated Learning Activities on a Day-Release Undergraduate-Level Certificate Course (ECTS Level 3)

    ERIC Educational Resources Information Center

    McMahon, Tim

    2010-01-01

    Peer-assessment was used within a negotiated curriculum in a module on training and development at ECTS level 3. The students on the programme were exclusively day-release and all had a major responsibility for the management and delivery of work-based training programmes. Analysis of student evaluations, supplemented by those of university…

  5. The General Environment Fit Scale: A Factor Analysis and Test of Convergent Construct Validity

    PubMed Central

    Beasley, Christopher; Jason, Leonard; Miller, Steven

    2014-01-01

    Person-environment fit (P-E fit) was initially espoused as an important construct in the field of community psychology; however, most of the theoretical and empirical development of the construct has been conducted by industrial/organizational (I/O) psychologists. In the current study, the GEFS—a P-E fit measure was developed from I/O and business management perspectives on fit—was administered to 246 attendees of an annual convention for residents and alumni of Oxford House (OH), a network of over 1400 mutual-help recovery homes. The authors conducted confirmatory factor and convergent construct validity analyses on the GEFS. The results suggested that the theoretical factor structure of the measure adequately fit the data, suggesting that the GEFS is a valid measure of P-E fit. OH resident fit with their recovery home was related to satisfaction, but not expected tenure. Exploratory analyses revealed that the sufficient supply of resident needs by the recovery home and similarity between residents and their housemates predicted satisfaction with the recovery home, but only similarity with housemates predicted how long residents intended to stay in the OHs. PMID:22071911

  6. Arf6 guanine-nucleotide exchange factor, cytohesin-2, interacts with actinin-1 to regulate neurite extension.

    PubMed

    Torii, Tomohiro; Miyamoto, Yuki; Nakamura, Kazuaki; Maeda, Masahiro; Yamauchi, Junji; Tanoue, Akito

    2012-09-01

    Proper regulation of morphological changes in neuronal cells is essential for their differentiation. Complex signaling mechanisms mediate a variety of morphological changes such as formation of neurites. It is well established that a number of small GTPases control neurite behavior before the connection with the target tissue. However, their regulatory mechanisms remain to be fully understood. Here, we show that the Arf6 guanine-nucleotide exchange factor (GEF), cytohesin-2 (CYTH2), interacts with the cytoskeletal protein actinin-1 (ACTN1) and regulates neurite extension in N1E-115 cells used as the model. Knockdown of ACTN1, as well as that of CYTH2, in cells inhibits cellular Arf6 activity and neurite extension. The C-terminal polybasic region of CYTH2 participates in interacting directly with the EFh2 domain of ACTN1. Expression of CYTH2 mutant deficient of the EFh2 domain in cells also inhibits Arf6 activation and neurite extension. Furthermore, FRET analysis detects that the respective interactive region peptides, tagged with cell-permeable short peptides, greatly decrease Arf6 activation at growth cones in a time-dependent manner. Collectively, the signaling through CYTH2 and ACTN1 properly regulates neurite extension in N1E-115 cells, demonstrating the unexpected interaction of CYTH2 and ACTN1 in the regulation of cellular Arf6 activity involved in neurite extension. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Two distinct mTORC2-dependent pathways converge on Rac1 to drive breast cancer metastasis.

    PubMed

    Morrison Joly, Meghan; Williams, Michelle M; Hicks, Donna J; Jones, Bayley; Sanchez, Violeta; Young, Christian D; Sarbassov, Dos D; Muller, William J; Brantley-Sieders, Dana; Cook, Rebecca S

    2017-06-30

    The importance of the mTOR complex 2 (mTORC2) signaling complex in tumor progression is becoming increasingly recognized. HER2-amplified breast cancers use Rictor/mTORC2 signaling to drive tumor formation, tumor cell survival and resistance to human epidermal growth factor receptor 2 (HER2)-targeted therapy. Cell motility, a key step in the metastatic process, can be activated by mTORC2 in luminal and triple negative breast cancer cell lines, but its role in promoting metastases from HER2-amplified breast cancers is not yet clear. Because Rictor is an obligate cofactor of mTORC2, we genetically engineered Rictor ablation or overexpression in mouse and human HER2-amplified breast cancer models for modulation of mTORC2 activity. Signaling through mTORC2-dependent pathways was also manipulated using pharmacological inhibitors of mTOR, Akt, and Rac. Signaling was assessed by western analysis and biochemical pull-down assays specific for Rac-GTP and for active Rac guanine nucleotide exchange factors (GEFs). Metastases were assessed from spontaneous tumors and from intravenously delivered tumor cells. Motility and invasion of cells was assessed using Matrigel-coated transwell assays. We found that Rictor ablation potently impaired, while Rictor overexpression increased, metastasis in spontaneous and intravenously seeded models of HER2-overexpressing breast cancers. Additionally, migration and invasion of HER2-amplified human breast cancer cells was diminished in the absence of Rictor, or upon pharmacological mTOR kinase inhibition. Active Rac1 was required for Rictor-dependent invasion and motility, which rescued invasion/motility in Rictor depleted cells. Rictor/mTORC2-dependent dampening of the endogenous Rac1 inhibitor RhoGDI2, a factor that correlated directly with increased overall survival in HER2-amplified breast cancer patients, promoted Rac1 activity and tumor cell invasion/migration. The mTORC2 substrate Akt did not affect RhoGDI2 dampening, but partially

  8. FgBud3, a Rho4-Interacting Guanine Nucleotide Exchange Factor, Is Involved in Polarity Growth, Cell Division and Pathogenicity of Fusarium graminearum.

    PubMed

    Zhang, Chengkang; Luo, Zenghong; He, Dongdong; Su, Li; Yin, Hui; Wang, Guo; Liu, Hong; Rensing, Christopher; Wang, Zonghua

    2018-01-01

    Rho GTPases are signaling macromolecules that are associated with developmental progression and pathogenesis of Fusarium graminearum . Generally, enzymatic activities of Rho GTPases are regulated by Rho GTPase guanine nucleotide exchange factors (RhoGEFs). In this study, we identified a putative RhoGEF encoding gene ( FgBUD3 ) in F. graminearum database and proceeded further by using a functional genetic approach to generate FgBUD3 targeted gene deletion mutant. Phenotypic analysis results showed that the deletion of FgBUD3 caused severe reduction in growth of FgBUD3 mutant generated during this study. We also observed that the deletion of FgBUD3 completely abolished sexual reproduction and triggered the production of abnormal asexual spores with nearly no septum in ΔFgbud3 strain. Further results obtained from infection assays conducted during this research revealed that the FgBUD3 defective mutant lost its pathogenicity on wheat and hence, suggests FgBud3 plays an essential role in the pathogenicity of F. graminearum . Additional, results derived from yeast two-hybrid assays revealed that FgBud3 strongly interacted with FgRho4 compared to the interaction with FgRho2, FgRho3, and FgCdc42. Moreover, we found that FgBud3 interacted with both GTP-bound and GDP-bound form of FgRho4. From these results, we subsequently concluded that, the Rho4-interacting GEF protein FgBud3 crucially promotes vegetative growth, asexual and sexual development, cell division and pathogenicity in F. graminearum .

  9. Balance and gait in older electroconvulsive therapy recipients: a pilot study

    PubMed Central

    Plakiotis, Chris; Barson, Fay; Vengadasalam, Bharathi; Haines, Terry P; O’Connor, Daniel W

    2013-01-01

    Background Electroconvulsive therapy (ECT) is commonly used to treat depression in older adults. Despite its efficacy in this regard, an associated increase in the risk of falls in this population is a downside of treatment. ECT research has focused on the incidence of falls, but its effect on balance and gait – intrinsic factors in instability and falls – has not been studied. Our aim was to examine changes in balance and gait among older adults before and after a single ECT session and explore the effect of patient-related and treatment factors on any changes found. Methods Participants were 21 older adults requiring ECT for depression in public psychiatric services. Patients with clinically overt mobility problems (impairing test participation or increasing the risk of falls) were excluded. Balance and gait testing 1 hour pre-ECT and 1, 2 and 3 hours post-ECT included: (1) steady standing test; (2) perturbation of standing balance by self-initiated movements; (3) perturbation of standing balance by an external perturbation; and (4) timed up and go test. Results No deterioration in test performance was found, using one-way repeated measures analysis of variance. Conclusion Balance and gait did not deteriorate immediately after ECT. Exclusion of participants with clinically overt mobility problems and falls being better attributable to factors unrelated to balance and gait (such as post-ECT confusion) may account for our findings. This research does not repudiate the occurrence of ECT-related falls but calls into question the utility of introducing routine balance and gait assessment among older ECT recipients without pre-existing mobility problems as a means of preventing them. PMID:23766650

  10. BLOC-3 Mutated in Hermansky-Pudlak Syndrome Is a Rab32/38 Guanine Nucleotide Exchange Factor

    PubMed Central

    Gerondopoulos, Andreas; Langemeyer, Lars; Liang, Jin-Rui; Linford, Andrea; Barr, Francis A.

    2012-01-01

    Summary Hermansky-Pudlak syndrome (HPS) is a human disease characterized by partial loss of pigmentation and impaired blood clotting [1–3]. These symptoms are caused by defects in the biogenesis of melanosomes and platelet dense granules, often referred to as lysosome-related organelles [2]. Genes mutated in HPS encode subunits of the biogenesis of lysosome-related organelles complexes (BLOCs). BLOC-1 and BLOC-2, together with the AP-3 clathrin adaptor complex, act at early endosomes to sort components required for melanin formation and melanosome biogenesis away from the degradative lysosomal pathway toward early stage melanosomes [4–6]. However the molecular functions of the Hps1-Hps4 complex BLOC-3 remain mysterious [7–9]. Like other trafficking pathways, melanosome biogenesis and transport of enzymes involved in pigmentation involves specific Rab GTPases, in this instance Rab32 and Rab38 [10–12]. We now demonstrate that BLOC-3 is a Rab32 and Rab38 guanine nucleotide exchange factor (GEF). Silencing of the BLOC-3 subunits Hps1 and Hps4 results in the mislocalization of Rab32 and Rab38 and reduction in pigmentation. In addition, we show that BLOC-3 can promote specific membrane recruitment of Rab32/38. BLOC-3 therefore defines a novel Rab GEF family with a specific function in the biogenesis of lysosome-related organelles. PMID:23084991

  11. Structural Dynamics Control Allosteric Activation of Cytohesin Family Arf GTPase Exchange Factors

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Malaby, Andrew W.; Das, Sanchaita; Chakravarthy, Srinivas

    Membrane dynamic processes including vesicle biogenesis depend on Arf guanosine triphosphatase (GTPase) activation by guanine nucleotide exchange factors (GEFs) containing a catalytic Sec7 domain and a membrane-targeting module such as a pleckstrin homology (PH) domain. The catalytic output of cytohesin family Arf GEFs is controlled by autoinhibitory interactions that impede accessibility of the exchange site in the Sec7 domain. These restraints can be relieved through activator Arf-GTP binding to an allosteric site comprising the PH domain and proximal autoinhibitory elements (Sec7-PH linker and C-terminal helix). Small-angle X-ray scattering and negative-stain electron microscopy were used to investigate the structural organization andmore » conformational dynamics of cytohesin-3 (Grp1) in autoinhibited and active states. The results support a model in which hinge dynamics in the autoinhibited state expose the activator site for Arf-GTP binding, while subsequent C-terminal helix unlatching and repositioning unleash conformational entropy in the Sec7-PH linker to drive exposure of the exchange site.« less

  12. Cell wall integrity modulates RHO1 activity via the exchange factor ROM2.

    PubMed Central

    Bickle, M; Delley, P A; Schmidt, A; Hall, M N

    1998-01-01

    The essential phosphatidylinositol kinase homologue TOR2 of Saccharomyces cerevisiae controls the actin cytoskeleton by activating a GTPase switch consisting of RHO1 (GTPase), ROM2 (GEF) and SAC7 (GAP). We have identified two mutations, rot1-1 and rot2-1, that suppress the loss of TOR2 and are synthetic-lethal. The wild-type ROT1 and ROT2 genes and a multicopy suppressor, BIG1, were isolated by their ability to rescue the rot1-1 rot2-1 double mutant. ROT2 encodes glucosidase II, and ROT1 and BIG1 encode novel proteins. We present evidence that cell wall defects activate RHO1. First, rot1, rot2, big1, cwh41, gas1 and fks1 mutations all confer cell wall defects and suppress tor2(ts). Second, destabilizing the cell wall by supplementing the growth medium with 0.005% SDS also suppresses a tor2(ts) mutation. Third, disturbing the cell wall with SDS or a rot1, rot2, big1, cwh41, gas1 or fks1 mutation increases GDP/GTP exchange activity toward RHO1. These results suggest that cell wall defects suppress a tor2 mutation by activating RHO1 independently of TOR2, thereby inducing TOR2-independent polarization of the actin cytoskeleton and cell wall synthesis. Activation of RHO1, a subunit of the cell wall synthesis enzyme glucan synthase, by a cell wall alteration would ensure that cell wall synthesis occurs only when and where needed. The mechanism of RHO1 activation by a cell wall alteration is via the exchange factor ROM2 and could be analogous to signalling by integrin receptors in mammalian cells. PMID:9545237

  13. The Juxtamembrane and carboxy-terminal domains of Arabidopsis PRK2 are critical for ROP-induced growth in pollen tubes

    USDA-ARS?s Scientific Manuscript database

    Polarized growth of pollen tubes is a critical step for successful reproduction in angiosperms and is controlled by ROP GTPases. Spatiotemporal activation of ROP (Rho GTPases of plants) necessitates a complex and sophisticated regulatory system, in which guanine nucleotide exchange factors (RopGEFs)...

  14. Application of ECT inspection to the first wall of a fusion reactor with wavelet analysis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chen, G.; Yoshida, Y.; Miya, K.

    1994-12-31

    The first wall of a fusion reactor will be subjected to intensive loads during fusion operations. Since these loads may cause defects in the first wall, nondestructive evaluation techniques of the first wall should be developed. In this paper, we try to apply eddy current testing (ECT) technique to the inspection of the first wall. A method based on current vector potential and wavelet analysis is proposed. Owing to the use of wavelet analysis, a new theory developed recently, the accuracy of the present method is shown to be better than a conventional one.

  15. Centralspindlin and α-catenin regulate Rho signalling at the epithelial zonula adherens

    PubMed Central

    Priya, Rashmi; Verma, Suzie; Kovacs, Eva M.; Jiang, Kai; Brown, Nicholas H.; Akhmanova, Anna; Stehbens, Samantha J.; Yap, Alpha S.

    2014-01-01

    Summary The biological impact of Rho depends critically on the precise subcellular localization of its active, GTP-loaded form. The spatio-temporal balance between molecules that promote nucleotide exchange or GTP hydrolysis can potentially determine the sites of Rho signalling. But how these activities may be coordinated is poorly understood. We now report a molecular pathway that achieves exactly this coordination at the epithelial zonula adherens. We identify an extramitotic activity of the centralspindlin complex, better understood as a cytokinetic regulator, which localises to the zonula adherens during interphase by interacting with the cadherin-associated protein, α-catenin. Centralspindlin recruits the Rho GEF, Ect2, to the zonula adherens to activate Rho and support junctional integrity through myosin IIA. Centralspindlin also inhibits the junctional localisation of p190RhoGAP B, which can inactivate Rho. Thus, a conserved molecular ensemble that governs Rho activation during cytokinesis is utilized in interphase cells to control the Rho GTPase cycle at the zonula adherens. PMID:22750944

  16. Identification of a Novel, Putative Rho-specific GDP/GTP Exchange Factor and a RhoA-binding Protein: Control of Neuronal Morphology

    PubMed Central

    Gebbink, Martijn F.B.G.; Kranenburg, Onno; Poland, Mieke; van Horck, Francis P.G.; Houssa, Brahim; Moolenaar, Wouter H.

    1997-01-01

    The small GTP-binding protein Rho has been implicated in the control of neuronal morphology. In N1E-115 neuronal cells, the Rho-inactivating C3 toxin stimulates neurite outgrowth and prevents actomyosin-based neurite retraction and cell rounding induced by lysophosphatidic acid (LPA), sphingosine-1-phosphate, or thrombin acting on their cognate G protein–coupled receptors. We have identified a novel putative GDP/GTP exchange factor, RhoGEF (190 kD), that interacts with both wild-type and activated RhoA, but not with Rac or Cdc42. RhoGEF, like activated RhoA, mimics receptor stimulation in inducing cell rounding and in preventing neurite outgrowth. Furthermore, we have identified a 116-kD protein, p116Rip, that interacts with both the GDP- and GTP-bound forms of RhoA in N1E-115 cells. Overexpression of p116Rip stimulates cell flattening and neurite outgrowth in a similar way to dominant-negative RhoA and C3 toxin. Cells overexpressing p116Rip fail to change their shape in response to LPA, as is observed after Rho inactivation. Our results indicate that (a) RhoGEF may link G protein–coupled receptors to RhoA activation and ensuing neurite retraction and cell rounding; and (b) p116Rip inhibits RhoA-stimulated contractility and promotes neurite outgrowth. PMID:9199174

  17. Assessment of the Activation State of Rho Family GTP-Binding Proteins in Breast Cancer Cells and Specimens

    DTIC Science & Technology

    2004-08-01

    AF038388 Vav3 GEF for Rho and Rac Proto-oncogene product NM020505 hPEM -2 GEF for Cdc42 Predominantly expressed in brain AB007884 GEF-H1 GEF for Rac and Rho...fence tions, and desmosomes play a fundamental role in maintain- function). A functional tight junction is crucial to maintain ing the polarized phenotype

  18. Mouse repeated electroconvulsive seizure (ECS) does not reverse social stress effects but does induce behavioral and hippocampal changes relevant to electroconvulsive therapy (ECT) side-effects in the treatment of depression

    PubMed Central

    Sigrist, Hannes; Seifritz, Erich; Fikse, Lianne; Bosker, Fokko J.; Schoevers, Robert A.; Klein, Hans C.

    2017-01-01

    Electroconvulsive therapy (ECT) is an effective treatment for depression, but can have negative side effects including amnesia. The mechanisms of action underlying both the antidepressant and side effects of ECT are not well understood. An equivalent manipulation that is conducted in experimental animals is electroconvulsive seizure (ECS). Rodent studies have provided valuable insights into potential mechanisms underlying the antidepressant and side effects of ECT. However, relatively few studies have investigated the effects of ECS in animal models with a depression-relevant manipulation such as chronic stress. In the present study, mice were first exposed to chronic social stress (CSS) or a control procedure for 15 days followed by ECS or a sham procedure for 10 days. Behavioral effects were investigated using an auditory fear conditioning (learning) and expression (memory) test and a treadmill-running fatigue test. Thereafter, immunohistochemistry was conducted on brain material using the microglial marker Iba-1 and the cholinergic fibre marker ChAT. CSS did not increase fear learning and memory in the present experimental design; in both the control and CSS mice ECS reduced fear learning and fear memory expression. CSS induced the expected fatigue-like effect in the treadmill-running test; ECS induced increased fatigue in CSS and control mice. In CSS and control mice ECS induced inflammation in hippocampus in terms of increased expression of Iba-1 in radiatum of CA1 and CA3. CSS and ECS both reduced acetylcholine function in hippocampus as indicated by decreased expression of ChAT in several hippocampal sub-regions. Therefore, CSS increased fatigue and reduced hippocampal ChAT activity and, rather than reversing these effects, a repeated ECS regimen resulted in impaired fear learning-memory, increased fatigue, increased hippocampal Iba-1 expression, and decreased hippocampal ChAT expression. As such, the current model does not provide insights into the

  19. Mouse repeated electroconvulsive seizure (ECS) does not reverse social stress effects but does induce behavioral and hippocampal changes relevant to electroconvulsive therapy (ECT) side-effects in the treatment of depression.

    PubMed

    van Buel, Erin M; Sigrist, Hannes; Seifritz, Erich; Fikse, Lianne; Bosker, Fokko J; Schoevers, Robert A; Klein, Hans C; Pryce, Christopher R; Eisel, Ulrich Lm

    2017-01-01

    Electroconvulsive therapy (ECT) is an effective treatment for depression, but can have negative side effects including amnesia. The mechanisms of action underlying both the antidepressant and side effects of ECT are not well understood. An equivalent manipulation that is conducted in experimental animals is electroconvulsive seizure (ECS). Rodent studies have provided valuable insights into potential mechanisms underlying the antidepressant and side effects of ECT. However, relatively few studies have investigated the effects of ECS in animal models with a depression-relevant manipulation such as chronic stress. In the present study, mice were first exposed to chronic social stress (CSS) or a control procedure for 15 days followed by ECS or a sham procedure for 10 days. Behavioral effects were investigated using an auditory fear conditioning (learning) and expression (memory) test and a treadmill-running fatigue test. Thereafter, immunohistochemistry was conducted on brain material using the microglial marker Iba-1 and the cholinergic fibre marker ChAT. CSS did not increase fear learning and memory in the present experimental design; in both the control and CSS mice ECS reduced fear learning and fear memory expression. CSS induced the expected fatigue-like effect in the treadmill-running test; ECS induced increased fatigue in CSS and control mice. In CSS and control mice ECS induced inflammation in hippocampus in terms of increased expression of Iba-1 in radiatum of CA1 and CA3. CSS and ECS both reduced acetylcholine function in hippocampus as indicated by decreased expression of ChAT in several hippocampal sub-regions. Therefore, CSS increased fatigue and reduced hippocampal ChAT activity and, rather than reversing these effects, a repeated ECS regimen resulted in impaired fear learning-memory, increased fatigue, increased hippocampal Iba-1 expression, and decreased hippocampal ChAT expression. As such, the current model does not provide insights into the

  20. Dissociation of Rac1(GDP)·RhoGDI Complexes by the Cooperative Action of Anionic Liposomes Containing Phosphatidylinositol 3,4,5-Trisphosphate, Rac Guanine Nucleotide Exchange Factor, and GTP*

    PubMed Central

    Ugolev, Yelena; Berdichevsky, Yevgeny; Weinbaum, Carolyn; Pick, Edgar

    2008-01-01

    Rac plays a pivotal role in the assembly of the superoxide-generating NADPH oxidase of phagocytes. In resting cells, Rac is found in the cytosol in complex with Rho GDP dissociation inhibitor (RhoGDI). NADPH oxidase assembly involves dissociation of the Rac·RhoGDI complex and translocation of Rac to the membrane. We reported that liposomes containing high concentrations of monovalent anionic phospholipids cause Rac·RhoGDI complex dissociation (Ugolev, Y., Molshanski-Mor, S., Weinbaum, C., and Pick, E. (2006) J. Biol. Chem.281 ,19204 -1921916702219). We now designed an in vitro model mimicking membrane phospholipid remodeling during phagocyte stimulation in vivo. We showed that liposomes of “resting cell membrane” composition (less than 20 mol % monovalent anionic phospholipids), supplemented with 1 mol % of polyvalent anionic phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) in conjunction with constitutively active forms of the guanine nucleotide exchange factors (GEFs) for Rac, Trio, or Tiam1 and a non-hydrolyzable GTP analogue, cause dissociation of Rac1(GDP)·RhoGDI complexes, GDP to GTP exchange on Rac1, and binding of Rac1(GTP) to the liposomes. Complexes were not dissociated in the absence of GEF and GTP, and optimal dissociation required the presence of PtdIns(3,4,5)P3 in the liposomes. Dissociation of Rac1(GDP)·RhoGDI complexes was correlated with the affinity of particular GEF constructs, via the N-terminal pleckstrin homology domain, for PtdIns(3,4,5)P3 and involved GEF-mediated GDP to GTP exchange on Rac1. Phagocyte membranes enriched in PtdIns(3,4,5)P3 responded by NADPH oxidase activation upon exposure in vitro to Rac1(GDP)·RhoGDI complexes, p67phox, GTP, and Rac GEF constructs with affinity for PtdIns(3,4,5)P3 at a level superior to that of native membranes. PMID:18505730

  1. Challenges in comparing the acute cognitive outcomes of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) vs. electroconvulsive therapy (ECT) in major depression: A systematic review.

    PubMed

    Kedzior, Karina Karolina; Schuchinsky, Maria; Gerkensmeier, Imke; Loo, Colleen

    2017-08-01

    The present study aimed to systematically compare the cognitive outcomes of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) and electroconvulsive therapy (ECT) in head-to-head studies with major depression (MDD) patients. A systematic literature search identified six studies with 219 MDD patients that were too heterogeneous to reliably detect meaningful differences in acute cognitive outcomes after ECT vs. HF-rTMS. Cognitive effects of brain stimulation vary depending on the timeframe and methods of assessment, stimulation parameters, and maintenance treatment. Thus, acute and longer-term differences in cognitive outcomes both need to be investigated at precisely defined timeframes and with similar instruments assessing comparable functions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. PSD-Zip70 Deficiency Causes Prefrontal Hypofunction Associated with Glutamatergic Synapse Maturation Defects by Dysregulation of Rap2 Activity.

    PubMed

    Mayanagi, Taira; Yasuda, Hiroki; Sobue, Kenji

    2015-10-21

    Dysregulation of synapse formation and plasticity is closely related to the pathophysiology of psychiatric and neurodevelopmental disorders. The prefrontal cortex (PFC) is particularly important for executive functions such as working memory, cognition, and emotional control, which are impaired in the disorders. PSD-Zip70 (Lzts1/FEZ1) is a postsynaptic density (PSD) protein predominantly expressed in the frontal cortex, olfactory bulb, striatum, and hippocampus. Here we found that PSD-Zip70 knock-out (PSD-Zip70KO) mice exhibit working memory and cognitive defects, and enhanced anxiety-like behaviors. These abnormal behaviors are caused by impaired glutamatergic synapse transmission accompanied by tiny-headed immature dendritic spines in the PFC, due to aberrant Rap2 activation, which has roles in synapse formation and plasticity. PSD-Zip70 modulates the Rap2 activity by interacting with SPAR (spine-associated RapGAP) and PDZ-GEF1 (RapGEF) in the postsynapse. Furthermore, suppression of the aberrant Rap2 activation in the PFC rescued the behavioral defects in PSD-Zip70KO mice. Our data demonstrate a critical role for PSD-Zip70 in Rap2-dependent spine synapse development in the PFC and underscore the importance of this regulation in PFC-dependent behaviors. PSD-Zip70 deficiency causes behavioral defects in working memory and cognition, and enhanced anxiety due to prefrontal hypofunction. This study revealed that PSD-Zip70 plays essential roles in glutamatergic synapse maturation via modulation of the Rap2 activity in the PFC. PSD-Zip70 interacts with both SPAR (spine-associated RapGAP) and PDZ-GEF1 (RapGEF) and modulates the Rap2 activity in postsynaptic sites. Our results provide a novel Rap2-specific regulatory mechanism in synaptic maturation involving PSD-Zip70. Copyright © 2015 the authors 0270-6474/15/3514327-14$15.00/0.

  3. Comparison of the neuropsychological mechanisms of 2,6-diisopropylphenol and N-methyl-D-aspartate receptor antagonist against electroconvulsive therapy-induced learning and memory impairment in depressed rats.

    PubMed

    Liu, Gang; Liu, Chao; Zhang, Xue-Ning

    2015-09-01

    The present study aimed to examine the neurophysiological mechanisms of the 2,6-diisopropylphenol and N-methyl-D-aspartate (NMDA) receptor antagonist against learning and memory impairment, induced by electroconvulsive therapy (ECT). A total of 48 adult depressed rats without olfactory bulbs were randomly divided into six experimental groups: i) saline; ii) 10 mg/kg MK‑801; iii) 10 mg/kg MK‑801 and a course of ECT; iv) 200 mg/kg 2,6‑diisopropylphenol; v) 200 mg/kg 2,6‑diisopropylphenol and a course of ECT; and vi) saline and a course of ECT. The learning and memory abilities of the rats were assessed using a Morris water maze 1 day after a course of ECT. The hippocampus was removed 1 day after assessment using the Morris water maze assessment. The content of glutamate in the hippocampus was detected using high‑performance liquid chromatography. The expression levels of p‑AT8Ser202 and GSK‑3β1H8 in the hippocampus were determined using immunohistochemical staining and western blot analysis. The results demonstrated that the 2,6‑diisopropylphenol NMDA receptor antagonist, MK‑801 and ECT induced learning and memory impairment in the depressed rats. The glutamate content was significantly upregulated by ECT, reduced by 2,6‑diisopropylphenol, and was unaffected by the NMDA receptor antagonist in the hippocampus of the depressed rats. Tau protein hyperphosphorylation in the hippocampus was upregulated by ECT, but was reduced by 2,6‑diisopropylphenol and the MK‑801 NMDA receptor antagonist. It was also demonstrated that 2,6‑diisopropylphenol prevented learning and memory impairment and reduced the hyperphosphorylation of the Tau protein, which was induced by eECT. GSK‑3β was found to be the key protein involved in this signaling pathway. The ECT reduced the learning and memory impairment, caused by hyperphosphorylation of the Tau protein, in the depressed rats by upregulating the glutamate content.

  4. Acetylation of the RhoA GEF Net1A controls its subcellular localization and activity

    PubMed Central

    Song, Eun Hyeon; Oh, Wonkyung; Ulu, Arzu; Carr, Heather S.; Zuo, Yan; Frost, Jeffrey A.

    2015-01-01

    ABSTRACT Net1 isoform A (Net1A) is a RhoA GEF that is required for cell motility and invasion in multiple cancers. Nuclear localization of Net1A negatively regulates its activity, and we have recently shown that Rac1 stimulates Net1A relocalization to the plasma membrane to promote RhoA activation and cytoskeletal reorganization. However, mechanisms controlling the subcellular localization of Net1A are not well understood. Here, we show that Net1A contains two nuclear localization signal (NLS) sequences within its N-terminus and that residues surrounding the second NLS sequence are acetylated. Treatment of cells with deacetylase inhibitors or expression of active Rac1 promotes Net1A acetylation. Deacetylase inhibition is sufficient for Net1A relocalization outside the nucleus, and replacement of the N-terminal acetylation sites with arginine residues prevents cytoplasmic accumulation of Net1A caused by deacetylase inhibition or EGF stimulation. By contrast, replacement of these sites with glutamine residues is sufficient for Net1A relocalization, RhoA activation and downstream signaling. Moreover, the N-terminal acetylation sites are required for rescue of F-actin accumulation and focal adhesion maturation in Net1 knockout MEFs. These data indicate that Net1A acetylation regulates its subcellular localization to impact on RhoA activity and actin cytoskeletal organization. PMID:25588829

  5. Metabolomics reveals the formation of aldehydes and iminium in gefitinib metabolism

    USDA-ARS?s Scientific Manuscript database

    Gefitinib (GEF), an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, is widely used for the treatment of cancers, particularly non-small cell lung cancer. However, its clinical use is limited by multiple adverse effects associated with GEF, such as liver and lung injuries, sever...

  6. [MK-801 or DNQX reduces electroconvulsive shock-induced impairment of learning-memory and hyperphosphorylation of Tau in rats].

    PubMed

    Liu, Chao; Min, Su; Wei, Ke; Liu, Dong; Dong, Jun; Luo, Jie; Liu, Xiao-Bin

    2012-08-25

    This study explored the effect of the excitatory amino acid receptor antagonists on the impairment of learning-memory and the hyperphosphorylation of Tau protein induced by electroconvulsive shock (ECT) in depressed rats, in order to provide experimental evidence for the study on neuropsychological mechanisms improving learning and memory impairment and the clinical intervention treatment. The analysis of variance of factorial design set up two intervention factors which were the electroconvulsive shock (two level: no disposition; a course of ECT) and the excitatory amino acid receptor antagonists (three level: iv saline; iv NMDA receptor antagonist MK-801; iv AMPA receptor antagonist DNQX). Forty-eight adult Wistar-Kyoto (WKY) rats (an animal model for depressive behavior) were randomly divided into six experimental groups (n = 8 in each group): saline (iv 2 mL saline through the tail veins of WKY rats ); MK-801 (iv 2 mL 5 mg/kg MK-801 through the tail veins of WKY rats) ; DNQX (iv 2 mL 5 mg/kg DNQX through the tail veins of WKY rats ); saline + ECT (iv 2 mL saline through the tail veins of WKY rats and giving a course of ECT); MK-801 + ECT (iv 2 mL 5 mg/kg MK-801 through the tail veins of WKY rats and giving a course of ECT); DNQX + ECT (iv 2 mL 5 mg/kg DNQX through the tail veins of WKY rats and giving a course of ECT). The Morris water maze test started within 1 day after the finish of the course of ECT to evaluate learning and memory. The hippocampus was removed from rats within 1 day after the finish of Morris water maze test. The content of glutamate in the hippocampus of rats was detected by high performance liquid chromatography. The contents of Tau protein which included Tau5 (total Tau protein), p-PHF1(Ser396/404), p-AT8(Ser199/202) and p-12E8(Ser262) in the hippocampus of rats were detected by immunohistochemistry staining (SP) and Western blot. The results showed that ECT and the glutamate ionic receptor blockers (NMDA receptor antagonist MK-801 and

  7. Assessment of the Activation of Rho Family GTP-Binding Proteins in Breast Cancer Cells and Specimens

    DTIC Science & Technology

    2001-08-01

    lymphopenia Vav2 GEF for Rho, Rac, and Cdc42 proto-oncogene product; NM009500 Vav3 GEF for Rho and Rac proto-oncogene product; NM020505 hPEM -2 GEF for...junctions, and desmosomes play a fundamental role in maintaining the polarized phenotype and vectorial transport functions of epithelial cells. The tight

  8. Ectoine and 5-hydroxyectoine accumulation in the halophile Virgibacillus halodenitrificans PDB-F2 in response to salt stress.

    PubMed

    Tao, Ping; Li, Hui; Yu, Yunjiang; Gu, Jidong; Liu, Yongdi

    2016-08-01

    The moderately halophilic bacterium Virgibacillus halodenitrificans PDB-F2 copes with salinity by synthesizing or taking up compatible solutes. The main compatible solutes in this strain were ectoine and hydroxyectoine, as determined by (1)H nuclear magnetic resonance spectroscopy ((1)H-NMR). A high-performance liquid chromatography (HPLC) analysis showed that ectoine was the major solute that was synthesized in response to elevated salinity, while hydroxyectoine was a minor solute. However, the hydroxyectoine/ectoine ratio increased from 0.04 at 3 % NaCl to 0.45 at 15 % NaCl in the late exponential growth phase. A cluster of ectoine biosynthesis genes was identified, including three genes in the order of ectA, ectB, and ectC. The hydroxyectoine biosynthesis gene ectD was not part of the ectABC gene cluster. Reverse transcription-quantitative polymerase chain reactions (RT-qPCR) showed that the expression of the ect genes was salinity dependent. The expression of ectABC reached a maximum at 12 % NaCl, while ectD expression increased up to 15 % NaCl. Ectoine and hydroxyectoine production was growth phase dependent. The hydroxyectoine/ectoine ratio increased from 0.018 in the early exponential phase to 0.11 in the stationary phase at 5 % NaCl. Hydroxyectoine biosynthesis started much later than ectoine biosynthesis after osmotic shock, and the temporal expression of the ect genes differed under these conditions, with the ectABC genes being expressed first, followed by ectD gene. Increased culture salinity triggered ectoine or hydroxyectoine uptake when they were added to the medium. Hydroxyectoine was accumulated preferentially when both ectoine and hydroxyectoine were provided exogenously.

  9. Vav1-mediated scaffolding interactions stabilize SLP-76 microclusters and contribute to antigen-dependent T cell responses.

    PubMed

    Sylvain, Nicholas R; Nguyen, Ken; Bunnell, Stephen C

    2011-03-08

    The guanine nucleotide exchange factor (GEF) Vav1 synergizes with the adaptor protein SLP-76 (Src homology 2 domain--containing leukocyte phosphoprotein of 76 kD) to support T cell development and activation. In response to ligation of the T cell receptor (TCR), SLP-76 is assembled into microclusters that provide an essential platform for the signaling events that drive T cell activation. We found that Vav1 selectively entered SLP-76 microclusters, rather than TCR microclusters, influencing their stability and function. The carboxyl terminus of Vav1, which consists of Src homology domains, was both necessary and sufficient for the entry of Vav1 into SLP-76 microclusters; however, this fragment of Vav1 was insufficient to stabilize the microclusters, and it potently suppressed T cell activation. This indicated that the amino terminus of Vav1, which has the GEF domain, also contributed to the integrity of SLP-76 microclusters and thereby to T cell activation. These microcluster-stabilizing functions were independent of the GEF activity in the amino terminus of Vav1 and were unaffected if the GEF function of Vav1 was either inactivated or constitutively activated by mutation. In contrast, Vav1 deletion mutants lacking either the calponin homology domain or the catalytic core of the GEF exhibited mild scaffolding defects, but they differentially affected TCR-dependent calcium ion (Ca²+) responses. We conclude that multiple GEF-independent scaffolding functions distributed throughout the amino terminus of Vav1 contribute to the activation of T cells by acting synergistically to increase the stability and function of SLP-76 microclusters.

  10. A KRAS GTPase K104Q Mutant Retains Downstream Signaling by Offsetting Defects in Regulation*

    PubMed Central

    Kistler, Samantha; George, Samuel D.; Kuhlmann, Nora; Garvey, Leslie; Huynh, Minh; Bagni, Rachel K.; Lammers, Michael; Der, Channing J.; Campbell, Sharon L.

    2017-01-01

    The KRAS GTPase plays a critical role in the control of cellular growth. The activity of KRAS is regulated by guanine nucleotide exchange factors (GEFs), GTPase-activating proteins (GAPs), and also post-translational modification. Lysine 104 in KRAS can be modified by ubiquitylation and acetylation, but the role of this residue in intrinsic KRAS function has not been well characterized. We find that lysine 104 is important for GEF recognition, because mutations at this position impaired GEF-mediated nucleotide exchange. Because the KRAS K104Q mutant has recently been employed as an acetylation mimetic, we conducted a series of studies to evaluate its in vitro and cell-based properties. Herein, we found that KRAS K104Q exhibited defects in both GEF-mediated exchange and GAP-mediated GTP hydrolysis, consistent with NMR-detected structural perturbations in localized regions of KRAS important for recognition of these regulatory proteins. Despite the partial defect in both GEF and GAP regulation, KRAS K104Q did not alter steady-state GTP-bound levels or the ability of the oncogenic KRAS G12V mutant to cause morphologic transformation of NIH 3T3 mouse fibroblasts and of WT KRAS to rescue the growth defect of mouse embryonic fibroblasts deficient in all Ras genes. We conclude that the KRAS K104Q mutant retains both WT and mutant KRAS function, probably due to offsetting defects in recognition of factors that up-regulate (GEF) and down-regulate (GAP) RAS activity. PMID:28154176

  11. Evaluating the influence of geo-environmental factors on gully erosion in a semi-arid region of Iran: An integrated framework.

    PubMed

    Rahmati, Omid; Tahmasebipour, Naser; Haghizadeh, Ali; Pourghasemi, Hamid Reza; Feizizadeh, Bakhtiar

    2017-02-01

    Despite the importance of soil erosion in sustainable development goals in arid and semi-arid areas, the study of the geo-environmental conditions and factors influencing gully erosion occurrence is rarely undertaken. As effort to this challenge, the main objective of this study is to apply an integrated approach of Geographic Object-Based Image Analysis (GEOBIA) together with high-spatial resolution imagery (SPOT-5) for detecting gully erosion features at the Kashkan-Poldokhtar watershed, Iran. We also aimed to apply a Conditional Probability (CP) model for establishing the spatial relationship between gullies and the Geo-Environmental Factors (GEFs). The gully erosion inventory map prepared using GEOBIA and field surveying was randomly partitioned into two subsets: (1) part 1 that contains 70% was used in the training phase of the CP model; (2) part 2 is a validation dataset (30%) for validation of the model and to confirm its accuracy. Prediction performances of the GEOBIA and CP model were checked by overall accuracy and Receiver Operating Characteristics (ROC) curve methods, respectively. In addition, the influence of all GEFs on gully erosion was evaluated by performing a sensitivity analysis model. The validation findings illustrated that overall accuracy for GEOBIA approach and the area under the ROC curve for the CP model were 92.4% and 89.9%, respectively. Also, based on sensitivity analysis, soil texture, drainage density, and lithology represent significantly effects on the gully erosion occurrence. This study has shown that the integrated framework can be successfully used for modeling gully erosion occurrence in a data-poor environment. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Deconstructing Ras Signaling in the Thymus

    PubMed Central

    Kortum, Robert L.; Sommers, Connie L.; Pinski, John M.; Alexander, Clayton P.; Merrill, Robert K.; Li, Wenmei; Love, Paul E.

    2012-01-01

    Thymocytes must transit at least two distinct developmental checkpoints, governed by signals that emanate from either the pre-T cell receptor (pre-TCR) or the TCR to the small G protein Ras before emerging as functional T lymphocytes. Recent studies have shown a role for the Ras guanine exchange factor (RasGEF) Sos1 at the pre-TCR checkpoint. At the second checkpoint, the quality of signaling through the TCR is interrogated to ensure the production of an appropriate T cell repertoire. Although RasGRP1 is the only confirmed RasGEF required at the TCR checkpoint, current models suggest that the intensity and character of Ras activation, facilitated by both Sos and RasGRP1, will govern the boundary between survival (positive selection) and death (negative selection) at this stage. Using mouse models, we have assessed the independent and combined roles for the RasGEFs Sos1, Sos2, and RasGRP1 during thymocyte development. Although Sos1 was the dominant RasGEF at the pre-TCR checkpoint, combined Sos1/RasGRP1 deletion was required to effectively block development at this stage. Conversely, while RasGRP1 deletion efficiently blocked positive selection, combined RasGRP1/Sos1 deletion was required to block negative selection. This functional redundancy in RasGEFs during negative selection may act as a failsafe mechanism ensuring appropriate central tolerance. PMID:22586275

  13. Function of the nucleotide exchange activity of vav1 in T cell development and activation.

    PubMed

    Saveliev, Alexander; Vanes, Lesley; Ksionda, Olga; Rapley, Jonathan; Smerdon, Stephen J; Rittinger, Katrin; Tybulewicz, Victor L J

    2009-12-15

    The guanine nucleotide exchange factor (GEF) Vav1 is essential for transducing T cell antigen receptor (TCR) signals and therefore plays a critical role in the development and activation of T cells. It has been presumed that the GEF activity of Vav1 is important for its function; however, there has been no direct demonstration of this. Here, we generated mice expressing enzymatically inactive, but normally folded, Vav1 protein. Analysis of these mice showed that the GEF activity of Vav1 was necessary for the selection of thymocytes and for the optimal activation of T cells, including signal transduction to Rac1, Akt, and integrins. In contrast, the GEF activity of Vav1 was not required for TCR-induced calcium flux, activation of extracellular signal-regulated kinase and protein kinase D1, and cell polarization. Thus, in T cells, the GEF activity of Vav1 is essential for some, but not all, of its functions.

  14. Function of the Nucleotide Exchange Activity of Vav1 in T cell Development and Activation*

    PubMed Central

    Saveliev, Alexander; Vanes, Lesley; Ksionda, Olga; Rapley, Jonathan; Smerdon, Stephen J.; Rittinger, Katrin; Tybulewicz, Victor L. J.

    2012-01-01

    The guanine nucleotide exchange factor (GEF) Vav1 is essential for transducing T cell antigen receptor (TCR) signals and therefore plays a critical role in the development and activation of T cells. It has been presumed that the GEF activity of Vav1 is important for its function; however, there has been no direct demonstration of this. Here, we generated mice expressing enzymatically inactive, but normally folded, Vav1 protein. Analysis of these mice showed that the GEF activity of Vav1 was necessary for the selection of thymocytes and for the optimal activation of T cells, including signal transduction to Rac1, Akt, and integrins. In contrast, the GEF activity of Vav1 was not required for TCR-induced calcium flux, activation of extracellular signal–regulated kinase (ERK) and protein kinase D1 (PKD1), and cell polarization. Thus, in T cells, the GEF activity of Vav1 is essential for some, but not all, of its functions. PMID:20009105

  15. Operations of the External Conjugate-T Matching System for the A2 ICRH Antennas at JET

    NASA Astrophysics Data System (ADS)

    Monakhov, I.; Graham, M.; Blackman, T.; Mayoral, M.-L.; Nightingale, M.; Sheikh, H.; Whitehurst, A.

    2009-11-01

    The External Conjugate-T (ECT) matching system was successfully commissioned on two A2 ICRH antennas at JET in 2009. The system allows trip-free injection of RF power into ELMy H-mode plasmas in the 32-52 MHz band without antenna phasing restrictions. The ECT demonstrates robust and predictable performance and high load-tolerance during routine operations, injecting up to 4 MW average power into H-mode plasma with Type-I ELMs. The total power coupled to ELMy plasma by all the A2 antennas using the ECT and 3dB systems has been increased to 7 MW. Antenna arcing during ELMs has been identified as a new challenge to high-power ICRH operations in H-mode plasma. The implemented Advanced Wave Amplitude Comparison System (AWACS) has proven to be an efficient protection tool for the ECT scheme.

  16. Small-GTPase-associated signaling by the guanine nucleotide exchange factors CpDock180 and CpCdc24, the GTPase effector CpSte20, and the scaffold protein CpBem1 in Claviceps purpurea.

    PubMed

    Herrmann, Andrea; Tillmann, Britta A M; Schürmann, Janine; Bölker, Michael; Tudzynski, Paul

    2014-04-01

    Monomeric GTPases of the Rho subfamily are important mediators of polar growth and NADPH (Nox) signaling in a variety of organisms. These pathways influence the ability of Claviceps purpurea to infect host plants. GTPase regulators contribute to the nucleotide loading cycle that is essential for proper functionality of the GTPases. Scaffold proteins gather GTPase complexes to facilitate proper function. The guanine nucleotide exchange factors (GEFs) CpCdc24 and CpDock180 activate GTPase signaling by triggering nucleotide exchange of the GTPases. Here we show that CpCdc24 harbors nucleotide exchange activity for both Rac and Cdc42 homologues. The GEFs partly share the cellular distribution of the GTPases and interact with the putative upstream GTPase CpRas1. Interaction studies show the formation of higher-order protein complexes, mediated by the scaffold protein CpBem1. Besides the GTPases and GEFs, these complexes also contain the GTPase effectors CpSte20 and CpCla4, as well as the regulatory protein CpNoxR. Functional characterizations suggest a role of CpCdc24 mainly in polarity, whereas CpDock180 is involved in stress tolerance mechanisms. These findings indicate the dynamic formation of small GTPase complexes and improve the model for GTPase-associated signaling in C. purpurea.

  17. Kinetics of Interaction between ADP-ribosylation Factor-1 (Arf1) and the Sec7 Domain of Arno Guanine Nucleotide Exchange Factor, Modulation by Allosteric Factors, and the Uncompetitive Inhibitor Brefeldin A

    PubMed Central

    Rouhana, Jad; Padilla, André; Estaran, Sébastien; Bakari, Sana; Delbecq, Stephan; Boublik, Yvan; Chopineau, Joel; Pugnière, Martine; Chavanieu, Alain

    2013-01-01

    The GDP/GTP nucleotide exchange of Arf1 is catalyzed by nucleotide exchange factors (GEF), such as Arno, which act through their catalytic Sec7 domain. This exchange is a complex mechanism that undergoes conformational changes and intermediate complex species involving several allosteric partners such as nucleotides, Mg2+, and Sec7 domains. Using a surface plasmon resonance approach, we characterized the kinetic binding parameters for various intermediate complexes. We first confirmed that both GDP and GTP counteract equivalently to the free-nucleotide binary Arf1-Arno complex stability and revealed that Mg2+ potentiates by a factor of 2 the allosteric effect of GDP. Then we explored the uncompetitive inhibitory mechanism of brefeldin A (BFA) that conducts to an abortive pentameric Arf1-Mg2+-GDP-BFA-Sec7 complex. With BFA, the association rate of the abortive complex is drastically reduced by a factor of 42, and by contrast, the 15-fold decrease of the dissociation rate concurs to stabilize the pentameric complex. These specific kinetic signatures have allowed distinguishing the level and nature as well as the fate in real time of formed complexes according to experimental conditions. Thus, we showed that in the presence of GDP, the BFA-resistant Sec7 domain of Arno can also associate to form a pentameric complex, which suggests that the uncompetitive inhibition by BFA and the nucleotide allosteric effect combine to stabilize such abortive complex. PMID:23255605

  18. Neutrophil-mediated oxidative burst and host defense are controlled by a Vav-PLCγ2 signaling axis in mice

    PubMed Central

    Graham, Daniel B.; Robertson, Charles M.; Bautista, Jhoanne; Mascarenhas, Francesca; Diacovo, M. Julia; Montgrain, Vivianne; Lam, Siu Kit; Cremasco, Viviana; Dunne, W. Michael; Faccio, Roberta; Coopersmith, Craig M.; Swat, Wojciech

    2007-01-01

    Oxidative burst, a critical antimicrobial mechanism of neutrophils, involves the rapid generation and release of reactive oxygen intermediates (ROIs) by the NADPH oxidase complex. Genetic mutations in an NADPH oxidase subunit, gp91 (also referred to as NOX2), are associated with chronic granulomatous disease (CGD), which is characterized by recurrent and life-threatening microbial infections. To combat such infections, ROIs are produced by neutrophils after stimulation by integrin-dependent adhesion to the ECM in conjunction with stimulation from inflammatory mediators, or microbial components containing pathogen-associated molecular patterns. In this report, we provide genetic evidence that both the Vav family of Rho GTPase guanine nucleotide exchange factors (GEFs) and phospholipase C–γ2 (PLC-γ2) are critical mediators of adhesion-dependent ROI production by neutrophils in mice. We also demonstrated that Vav was critically required for neutrophil-dependent host defense against systemic infection by Staphylococcus aureus and Pseudomonas aeruginosa, 2 common pathogens associated with fatal cases of hospital-acquired pneumonia. We identified a molecular pathway in which Vav GEFs linked integrin-mediated signaling with PLC-γ2 activation, release of intracellular Ca2+ cations, and generation of diacylglycerol to control assembly of the NADPH oxidase complex and ROI production by neutrophils. Taken together, our data indicate that integrin-dependent signals generated during neutrophil adhesion contribute to the activation of NADPH oxidase by a variety of distinct effector pathways, all of which require Vav. PMID:17932569

  19. Trio combines with dock to regulate Pak activity during photoreceptor axon pathfinding in Drosophila.

    PubMed

    Newsome, T P; Schmidt, S; Dietzl, G; Keleman, K; Asling, B; Debant, A; Dickson, B J

    2000-04-28

    Correct pathfinding by Drosophila photoreceptor axons requires recruitment of p21-activated kinase (Pak) to the membrane by the SH2-SH3 adaptor Dock. Here, we identify the guanine nucleotide exchange factor (GEF) Trio as another essential component in photoreceptor axon guidance. Regulated exchange activity of one of the two Trio GEF domains is critical for accurate pathfinding. This GEF domain activates Rac, which in turn activates Pak. Mutations in trio result in projection defects similar to those observed in both Pak and dock mutants, and trio interacts genetically with Rac, Pak, and dock. These data define a signaling pathway from Trio to Rac to Pak that links guidance receptors to the growth cone cytoskeleton. We propose that distinct signals transduced via Trio and Dock act combinatorially to activate Pak in spatially restricted domains within the growth cone, thereby controlling the direction of axon extension.

  20. Relationship Between Hippocampal Volume, Serum BDNF, and Depression Severity Following Electroconvulsive Therapy in Late-Life Depression

    PubMed Central

    Bouckaert, Filip; Dols, Annemiek; Emsell, Louise; De Winter, François-Laurent; Vansteelandt, Kristof; Claes, Lene; Sunaert, Stefan; Stek, Max; Sienaert, Pascal; Vandenbulcke, Mathieu

    2016-01-01

    Recent structural imaging studies have described hippocampal volume changes following electroconvulsive therapy (ECT). It has been proposed that serum brain-derived neurotrophic factor (sBDNF)-mediated neuroplasticity contributes critically to brain changes following antidepressant treatment. To date no studies have investigated the relationship between changes in hippocampal volume, mood, and sBDNF following ECT. Here, we combine these measurements in a longitudinal study of severe late-life unipolar depression (LLD). We treated 88 elderly patients with severe LLD twice weekly until remission (Montgomery–Åsberg Depression Rating Scale (MADRS) <10). sBDNF and MADRS were obtained before ECT (T0), after the sixth ECT (T1), 1 week after the last ECT (T2), 4 weeks after the last ECT (T3), and 6 months after the last ECT (T4). Hippocampal volumes were quantified by manual segmentation of 3T structural magnetic resonance images in 66 patients at T0 and T2 and in 23 patients at T0, T2, and T4. Linear mixed models (LMM) were used to examine the evolution of MADRS, sBDNF, and hippocampal volume over time. Following ECT, there was a significant decrease in MADRS scores and a significant increase in hippocampal volume. Hippocampal volume decreased back to baseline values at T4. Compared with T0, sBDNF levels remained unchanged at T1, T2, and T3. There was no coevolution between changes in MADRS scores, hippocampal volume, and sBDNF. Hippocampal volume increase following ECT is an independent neurobiological effect unrelated to sBDNF and depressive symptomatology, suggesting a complex mechanism of action of ECT in LLD. PMID:27272769

  1. A KRAS GTPase K104Q Mutant Retains Downstream Signaling by Offsetting Defects in Regulation.

    PubMed

    Yin, Guowei; Kistler, Samantha; George, Samuel D; Kuhlmann, Nora; Garvey, Leslie; Huynh, Minh; Bagni, Rachel K; Lammers, Michael; Der, Channing J; Campbell, Sharon L

    2017-03-17

    The KRAS GTPase plays a critical role in the control of cellular growth. The activity of KRAS is regulated by guanine nucleotide exchange factors (GEFs), GTPase-activating proteins (GAPs), and also post-translational modification. Lysine 104 in KRAS can be modified by ubiquitylation and acetylation, but the role of this residue in intrinsic KRAS function has not been well characterized. We find that lysine 104 is important for GEF recognition, because mutations at this position impaired GEF-mediated nucleotide exchange. Because the KRAS K104Q mutant has recently been employed as an acetylation mimetic, we conducted a series of studies to evaluate its in vitro and cell-based properties. Herein, we found that KRAS K104Q exhibited defects in both GEF-mediated exchange and GAP-mediated GTP hydrolysis, consistent with NMR-detected structural perturbations in localized regions of KRAS important for recognition of these regulatory proteins. Despite the partial defect in both GEF and GAP regulation, KRAS K104Q did not alter steady-state GTP-bound levels or the ability of the oncogenic KRAS G12V mutant to cause morphologic transformation of NIH 3T3 mouse fibroblasts and of WT KRAS to rescue the growth defect of mouse embryonic fibroblasts deficient in all Ras genes. We conclude that the KRAS K104Q mutant retains both WT and mutant KRAS function, probably due to offsetting defects in recognition of factors that up-regulate (GEF) and down-regulate (GAP) RAS activity. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Operations of the External Conjugate-T Matching System for the A2 ICRH Antennas at JET

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Monakhov, I.; Graham, M.; Blackman, T.

    2009-11-26

    The External Conjugate-T (ECT) matching system was successfully commissioned on two A2 ICRH antennas at JET in 2009. The system allows trip-free injection of RF power into ELMy H-mode plasmas in the 32-52 MHz band without antenna phasing restrictions. The ECT demonstrates robust and predictable performance and high load-tolerance during routine operations, injecting up to 4 MW average power into H-mode plasma with Type-I ELMs. The total power coupled to ELMy plasma by all the A2 antennas using the ECT and 3dB systems has been increased to 7 MW. Antenna arcing during ELMs has been identified as a new challengemore » to high-power ICRH operations in H-mode plasma. The implemented Advanced Wave Amplitude Comparison System (AWACS) has proven to be an efficient protection tool for the ECT scheme.« less

  3. Identification of a negative regulatory region for the exchange activity and characterization of T332I mutant of Rho guanine nucleotide exchange factor 10 (ARHGEF10).

    PubMed

    Chaya, Taro; Shibata, Satoshi; Tokuhara, Yasunori; Yamaguchi, Wataru; Matsumoto, Hiroshi; Kawahara, Ichiro; Kogo, Mikihiko; Ohoka, Yoshiharu; Inagaki, Shinobu

    2011-08-26

    The T332I mutation in Rho guanine nucleotide exchange factor 10 (ARHGEF10) was previously found in persons with slowed nerve conduction velocities and thin myelination of peripheral nerves. However, the molecular and cellular basis of the T332I mutant is not understood. Here, we show that ARHGEF10 has a negative regulatory region in the N terminus, in which residue 332 is located, and the T332I mutant is constitutively active. An N-terminal truncated ARHGEF10 mutant, ARHGEF10 ΔN (lacking amino acids 1-332), induced cell contraction that was inhibited by a Rho kinase inhibitor Y27632 and had higher GEF activity for RhoA than the wild type. The T332I mutant also showed the phenotype similar to the N-terminal truncated mutant. These data suggest that the ARHGEF10 T332I mutation-associated phenotype observed in the peripheral nerves is due to activated GEF activity of the ARHGEF10 T332I mutant.

  4. Identification of a Negative Regulatory Region for the Exchange Activity and Characterization of T332I Mutant of Rho Guanine Nucleotide Exchange Factor 10 (ARHGEF10)*

    PubMed Central

    Chaya, Taro; Shibata, Satoshi; Tokuhara, Yasunori; Yamaguchi, Wataru; Matsumoto, Hiroshi; Kawahara, Ichiro; Kogo, Mikihiko; Ohoka, Yoshiharu; Inagaki, Shinobu

    2011-01-01

    The T332I mutation in Rho guanine nucleotide exchange factor 10 (ARHGEF10) was previously found in persons with slowed nerve conduction velocities and thin myelination of peripheral nerves. However, the molecular and cellular basis of the T332I mutant is not understood. Here, we show that ARHGEF10 has a negative regulatory region in the N terminus, in which residue 332 is located, and the T332I mutant is constitutively active. An N-terminal truncated ARHGEF10 mutant, ARHGEF10 ΔN (lacking amino acids 1–332), induced cell contraction that was inhibited by a Rho kinase inhibitor Y27632 and had higher GEF activity for RhoA than the wild type. The T332I mutant also showed the phenotype similar to the N-terminal truncated mutant. These data suggest that the ARHGEF10 T332I mutation-associated phenotype observed in the peripheral nerves is due to activated GEF activity of the ARHGEF10 T332I mutant. PMID:21719701

  5. Predictors of Seizure Threshold in Right Unilateral Ultrabrief Electroconvulsive Therapy: Role of Concomitant Medications and Anaesthesia Used.

    PubMed

    Gálvez, Verònica; Hadzi-Pavlovic, Dusan; Smith, Deidre; Loo, Colleen K

    2015-01-01

    An individualized approach to maximize electroconvulsive therapy (ECT) efficacy and minimize cognitive side effects is to treat patients relative to their seizure threshold (ST). However, although Right Unilateral-Ultrabrief (0.3 ms) (RUL-UB) ECT is increasingly used in clinical settings as an effective form of ECT with minimal cognitive effects, there is sparse data regarding predictors of ST. To analyze the relationship between ST and clinical and demographic factors in a sample of patients treated with RUL-UB ECT. Clinical, demographic and ECT data from 179 patients in ECT research studies were examined. Seizure threshold was titrated at the first ECT session. ECT was performed with a Thymatron(®) or Mecta(®) device, with thiopentone (2.5-5 mg/kg) or propofol (1-2 mg/kg) anaesthesia. Medications taken at the time of ST titration were documented. The association between ST and candidate predictor variables was examined with regression analysis. Multiple regression analyses showed that 34% of the variance in ST (P < 0.001) could be predicted. Older age (R(2) = 0.194, P < 0.001), propofol (vs thiopentone) (R(2) = 0.029, P ≤ 0.01) and higher anaesthetic dose (mg in propofol equivalents) (R(2) = 0.029, P < 0.05) were found to be predictors of higher initial ST. Treatment with lithium (R(2) = 0.043, P < 0.01) and study site (R(2) = 0.019, P < 0.05) significantly predicted lower initial ST. Empirical titration is recommended for accurate determination of ST in patients receiving RUL-UB ECT. Novel findings of this study are that propofol anaesthesia resulted in higher ST than thiopentone and concomitant treatment with lithium treatment lowered ST. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Role of Longwave Cloud-Radiation Feedback in the Simulation of the Madden-Julian Oscillation

    NASA Technical Reports Server (NTRS)

    Kim, Daehyun; Ahn, Min-Seop; Kang, In-Sik; Del Genio, Anthony D.

    2015-01-01

    The role of the cloud-radiation interaction in the simulation of the Madden-Julian oscillation (MJO) is investigated. A special focus is on the enhancement of column-integrated diabatic heating due to the greenhouse effects of clouds and moisture in the region of anomalous convection. The degree of this enhancement, the greenhouse enhancement factor (GEF), is measured at different precipitation anomaly regimes as the negative ratio of anomalous outgoing longwave radiation to anomalous precipitation. Observations show that the GEF varies significantly with precipitation anomaly and with the MJO cycle. The greenhouse enhancement is greater in weak precipitation anomaly regimes and its effectiveness decreases monotonically with increasing precipitation anomaly. The GEF also amplifies locally when convection is strengthened in association with the MJO, especially in the weak precipitation anomaly regime (less than 5 mm day(exp -1)). A robust statistical relationship is found among CMIP5 climate model simulations between the GEF and the MJO simulation fidelity. Models that simulate a stronger MJO also simulate a greater GEF, especially in the weak precipitation anomaly regime (less than 5 mm day(exp -1)). Models with a greater GEF in the strong precipitation anomaly regime (greater than 30 mm day(-1)) represent a slightly slower MJO propagation speed. Many models that lack the MJO underestimate the GEF in general and in particular in the weak precipitation anomaly regime. The results herein highlight that the cloud-radiation interaction is a crucial process for climate models to correctly represent the MJO.

  7. Epidermal wound repair is regulated by the planar cell polarity signaling pathway.

    PubMed

    Caddy, Jacinta; Wilanowski, Tomasz; Darido, Charbel; Dworkin, Sebastian; Ting, Stephen B; Zhao, Quan; Rank, Gerhard; Auden, Alana; Srivastava, Seema; Papenfuss, Tony A; Murdoch, Jennifer N; Humbert, Patrick O; Parekh, Vishwas; Boulos, Nidal; Weber, Thomas; Zuo, Jian; Cunningham, John M; Jane, Stephen M

    2010-07-20

    The mammalian PCP pathway regulates diverse developmental processes requiring coordinated cellular movement, including neural tube closure and cochlear stereociliary orientation. Here, we show that epidermal wound repair is regulated by PCP signaling. Mice carrying mutant alleles of PCP genes Vangl2, Celsr1, PTK7, and Scrb1, and the transcription factor Grhl3, interact genetically, exhibiting failed wound healing, neural tube defects, and disordered cochlear polarity. Using phylogenetic analysis, ChIP, and gene expression in Grhl3(-)(/-) mice, we identified RhoGEF19, a homolog of a RhoA activator involved in PCP signaling in Xenopus, as a direct target of GRHL3. Knockdown of Grhl3 or RhoGEF19 in keratinocytes induced defects in actin polymerization, cellular polarity, and wound healing, and re-expression of RhoGEF19 rescued these defects in Grhl3-kd cells. These results define a role for Grhl3 in PCP signaling and broadly implicate this pathway in epidermal repair. (c) 2010 Elsevier Inc. All rights reserved.

  8. Epidermal wound repair is regulated by the planar cell polarity signaling pathway

    PubMed Central

    Caddy, Jacinta; Wilanowski, Tomasz; Darido, Charbel; Dworkin, Sebastian; Ting, Stephen B.; Zhao, Quan; Rank, Gerhard; Auden, Alana; Srivastava, Seema; Papenfuss, Tony A.; Murdoch, Jennifer N.; Humbert, Patrick O.; Boulos, Nidal; Weber, Thomas; Zuo, Jian; Cunningham, John M.; Jane, Stephen M.

    2010-01-01

    SUMMARY The mammalian PCP pathway regulates diverse developmental processes requiring coordinated cellular movement, including neural tube closure and cochlear stereociliary orientation. Here, we show that epidermal wound repair is regulated by PCP signaling. Mice carrying mutant alleles of PCP genes Vangl2, Celsr1, PTK7, and Scrb1, and the transcription factor Grhl3, interact genetically, exhibiting failed wound healing, neural tube defects and disordered cochlear polarity. Using phylogenetic analysis, ChIP, and gene expression in Grhl3−/− mice, we identified RhoGEF19, a homologue of a RhoA activator involved in PCP signaling in Xenopus, as a direct target of GRHL3. Knockdown of Grhl3 or RhoGEF19 in keratinocytes induced defects in actin polymerisation, cellular polarity and wound healing, and re-expression of RhoGEF19 rescued these defects in Grhl3-kd cells. These results define a role for Grhl3 in PCP signaling, and broadly implicate this pathway in epidermal repair. PMID:20643356

  9. Genome-wide siRNA screen identifies UNC50 as a regulator of Shiga toxin 2 trafficking.

    PubMed

    Selyunin, Andrey S; Iles, Lakesla R; Bartholomeusz, Geoffrey; Mukhopadhyay, Somshuvra

    2017-10-02

    Shiga toxins 1 and 2 (STx1 and STx2) undergo retrograde trafficking to reach the cytosol. Early endosome-to-Golgi transport allows the toxins to evade degradation in lysosomes. Targeting this trafficking step has therapeutic promise, but the mechanism of trafficking for the more potent toxin STx2 is unclear. To identify host factors required for early endosome-to-Golgi trafficking of STx2, we performed a viability-based genome-wide siRNA screen in HeLa cells. 564, 535, and 196 genes were found to be required for toxicity induced by STx1 only, STx2 only, and both toxins, respectively. We focused on validating endosome/Golgi-localized hits specific for STx2 and found that depletion of UNC50 blocked early endosome-to-Golgi trafficking and induced lysosomal degradation of STx2. UNC50 acted by recruiting GBF1, an ADP ribosylation factor-guanine nucleotide exchange factor (ARF-GEF), to the Golgi. These results provide new information about STx2 trafficking mechanisms and may advance efforts to generate therapeutically viable toxin-trafficking inhibitors. © 2017 Selyunin et al.

  10. Short-term Drought Prediction in India.

    NASA Astrophysics Data System (ADS)

    Shah, R.; Mishra, V.

    2014-12-01

    Medium range soil moisture drought forecast helps in decision making in the field of agriculture and water resources management. Part of skills in medium range drought forecast comes from precipitation. Proper evaluation and correction of precipitation forecast may improve drought predictions. Here, we evaluate skills of ensemble mean precipitation forecast from Global Ensemble Forecast System (GEFS) for medium range drought predictions over India. Climatological mean (CLIM) of historic data (OBS) are used as reference forecast to evaluate GEFS precipitation forecast. Analysis was conducted based on forecast initiated on 1st and 15th dates of each month for lead up to 7-days. Correlation and RMSE were used to estimate skill scores of accumulated GEFS precipitation forecast from lead 1 to 7-days. Volumetric indices based on the 2X2 contingency table were used to check missed and falsely predicted historic volume of daily precipitation from GEFS in different regions and at different thresholds. GEFS showed improvement in correlation of 0.44 over CLIM during the monsoon season and 0.55 during the winter season. Lower RMSE was showed by GEFS than CLIM. Ratio of RMSE in GEFS and CLIM comes out as 0.82 and 0.4 (perfect skill is at zero) during the monsoon and winter season, respectively. We finally used corrected GEFS forecast to derive the Variable Infiltration Capacity (VIC) model, which was used to develop short-term forecast of hydrologic and agricultural (soil moisture) droughts in India.

  11. Electroconvulsive Therapy in Women: A Retrospective Study from a Mental Health Hospital in Turkey.

    PubMed

    Özdemir, Armağan; Poyraz, Cana Aksoy; Erten, Evrim; Çırakoğlu, Emre; Tomruk, Nesrin

    2016-12-01

    The aim was to evaluate the clinical profile and effectiveness of ECT in women. A retrospective chart review was carried out to identify female patients who had received ECT during the period September 2013-February 2015. Details regarding their sociodemographic, clinical, and treatment data were extracted from these records for the present study. The total number of patients, admitted to our psychiatry inpatient clinic during the survey period, was 802. During this period, 26 (3.24 %) female patients received ECT. Patients who received ECT were mostly in age group of 25-44 years (76.9 %). Twenty percent of patients were in the postpartum period. Psychotic disorders (46.1 %) was the most common diagnosis for which ECT was used, followed by bipolar affective disorder, current episode manic (19.2 %). At the end of ECT courses, 70 % of the patients showed good response with a CGI-I of 1 or 2, and 30 % showed minimal response with a CGI-I score of 3. The most common side effects were post-ECT confusion (15.4 %) and prolonged seizure (11.5 %). This rate of prolonged seizure was higher the rates reported in the literature. The bronchospasm related with remifentanil, post-ECT bradycardia, hypertensive crisis and oligohydramnios were also reported in one case each. ECT is a safe and effective treatment option in women with severe psychiatric disorders and disorders in the perinatal/postpartum period are a major area of ECT use. The female gender may be a contributing factor for the higher rates of prolonged seizure.

  12. Public attitudes towards electroconvulsive therapy in the Chuvash Republic.

    PubMed

    Golenkov, Andrei; Ungvari, Gabor S; Gazdag, Gábor

    2012-05-01

    Public attitudes towards a given medical procedure can have a significant influence on the employment of that method. Electroconvulsive therapy (ECT) is a medical procedure that has received an exceptionally ambiguous public reception since its inception. To survey the level of information about and attitudes towards ECT in a general population sample of the Chuvash Republic of the Russian Federation. A randomly selected cohort of 5,373 people was contacted by telephone. The respondents were asked three closed and three open questions. The response rate was 74.7%. Only 35.2% of those interviewed said they knew anything about ECT. Health professionals and younger respondents were better informed. The two main sources of information about ECT were foreign films and the mass media. The main indication of ECT was thought to be schizophrenia. The majority (63.3%) of the respondents had negative opinions and emotions about ECT. Limited information about and generally negative attitudes towards ECT were found in the general population of the Chuvash Republic. Gender, age, education level, employment in the health industry, and information source were found to be the determining factors in the knowledge of and attitudes towards ECT.

  13. eIF2β is critical for eIF5-mediated GDP-dissociation inhibitor activity and translational control

    PubMed Central

    Jennings, Martin D.; Kershaw, Christopher J.; White, Christopher; Hoyle, Danielle; Richardson, Jonathan P.; Costello, Joseph L.; Donaldson, Ian J.; Zhou, Yu; Pavitt, Graham D.

    2016-01-01

    In protein synthesis translation factor eIF2 binds initiator tRNA to ribosomes and facilitates start codon selection. eIF2 GDP/GTP status is regulated by eIF5 (GAP and GDI functions) and eIF2B (GEF and GDF activities), while eIF2α phosphorylation in response to diverse signals is a major point of translational control. Here we characterize a growth suppressor mutation in eIF2β that prevents eIF5 GDI and alters cellular responses to reduced eIF2B activity, including control of GCN4 translation. By monitoring the binding of fluorescent nucleotides and initiator tRNA to purified eIF2 we show that the eIF2β mutation does not affect intrinsic eIF2 affinities for these ligands, neither does it interfere with eIF2 binding to 43S pre-initiation complex components. Instead we show that the eIF2β mutation prevents eIF5 GDI stabilizing nucleotide binding to eIF2, thereby altering the off-rate of GDP from eIF2•GDP/eIF5 complexes. This enables cells to grow with reduced eIF2B GEF activity but impairs activation of GCN4 targets in response to amino acid starvation. These findings provide support for the importance of eIF5 GDI activity in vivo and demonstrate that eIF2β acts in concert with eIF5 to prevent premature release of GDP from eIF2γ and thereby ensure tight control of protein synthesis initiation. PMID:27458202

  14. eIF2β is critical for eIF5-mediated GDP-dissociation inhibitor activity and translational control.

    PubMed

    Jennings, Martin D; Kershaw, Christopher J; White, Christopher; Hoyle, Danielle; Richardson, Jonathan P; Costello, Joseph L; Donaldson, Ian J; Zhou, Yu; Pavitt, Graham D

    2016-11-16

    In protein synthesis translation factor eIF2 binds initiator tRNA to ribosomes and facilitates start codon selection. eIF2 GDP/GTP status is regulated by eIF5 (GAP and GDI functions) and eIF2B (GEF and GDF activities), while eIF2α phosphorylation in response to diverse signals is a major point of translational control. Here we characterize a growth suppressor mutation in eIF2β that prevents eIF5 GDI and alters cellular responses to reduced eIF2B activity, including control of GCN4 translation. By monitoring the binding of fluorescent nucleotides and initiator tRNA to purified eIF2 we show that the eIF2β mutation does not affect intrinsic eIF2 affinities for these ligands, neither does it interfere with eIF2 binding to 43S pre-initiation complex components. Instead we show that the eIF2β mutation prevents eIF5 GDI stabilizing nucleotide binding to eIF2, thereby altering the off-rate of GDP from eIF2•GDP/eIF5 complexes. This enables cells to grow with reduced eIF2B GEF activity but impairs activation of GCN4 targets in response to amino acid starvation. These findings provide support for the importance of eIF5 GDI activity in vivo and demonstrate that eIF2β acts in concert with eIF5 to prevent premature release of GDP from eIF2γ and thereby ensure tight control of protein synthesis initiation. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  15. Rab14 and Its Exchange Factor FAM116 Link Endocytic Recycling and Adherens Junction Stability in Migrating Cells

    PubMed Central

    Linford, Andrea; Yoshimura, Shin-ichiro; Bastos, Ricardo Nunes; Langemeyer, Lars; Gerondopoulos, Andreas; Rigden, Daniel J.; Barr, Francis A.

    2012-01-01

    Summary Rab GTPases define the vesicle trafficking pathways underpinning cell polarization and migration. Here, we find that Rab4, Rab11, and Rab14 and the candidate Rab GDP-GTP exchange factors (GEFs) FAM116A and AVL9 are required for cell migration. Rab14 and its GEF FAM116A localize to and act on an intermediate compartment of the transferrin-recycling pathway prior to Rab11 and after Rab5 and Rab4. This Rab14 intermediate recycling compartment has specific functions in migrating cells discrete from early and recycling endosomes. Rab14-depleted cells show increased N-cadherin levels at junctional complexes and cannot resolve cell-cell junctions. This is due to decreased shedding of cell-surface N-cadherin by the ADAM family protease ADAM10/Kuzbanian. In FAM116A- and Rab14-depleted cells, ADAM10 accumulates in a transferrin-positive endocytic compartment, and the cell-surface level of ADAM10 is correspondingly reduced. FAM116 and Rab14 therefore define an endocytic recycling pathway needed for ADAM protease trafficking and regulation of cell-cell junctions. PMID:22595670

  16. Simulation and design of ECT differential bobbin probes for the inspection of cracks in bolts

    NASA Astrophysics Data System (ADS)

    Ra, S. W.; Im, K. H.; Lee, S. G.; Kim, H. J.; Song, S. J.; Kim, S. K.; Cho, Y. T.; Woo, Y. D.; Jung, J. A.

    2015-12-01

    All Various defects could be generated in bolts for a use of oil filters for the manufacturing process and then may affect to the safety and quality in bolts. Also, fine defects may be imbedded in oil filter system during multiple forging manufacturing processes. So it is very important that such defects be investigated and screened during the multiple manufacturing processes. Therefore, in order effectively to evaluate the fine defects, the design parameters for bobbin-types were selected under a finite element method (FEM) simulations and Eddy current testing (ECT). Especially the FEM simulations were performed to make characterization in the crack detection of the bolts and the parameters such as number of turns of the coil, the coil size and applied frequency were calculated based on the simulation results.

  17. Symmetry breaking and polarization of the C. elegans zygote by the polarity protein PAR-2.

    PubMed

    Zonies, Seth; Motegi, Fumio; Hao, Yingsong; Seydoux, Geraldine

    2010-05-01

    Polarization of the C. elegans zygote is initiated by ECT-2-dependent cortical flows, which mobilize the anterior PAR proteins (PAR-3, PAR-6 and PKC-3) away from the future posterior end of the embryo marked by the sperm centrosome. Here, we demonstrate the existence of a second, parallel and redundant pathway that can polarize the zygote in the absence of ECT-2-dependent cortical flows. This second pathway depends on the polarity protein PAR-2. We show that PAR-2 localizes to the cortex nearest the sperm centrosome even in the absence of cortical flows. Once on the cortex, PAR-2 antagonizes PAR-3-dependent recruitment of myosin, creating myosin flows that transport the anterior PAR complex away from PAR-2 in a positive-feedback loop. We propose that polarity in the C. elegans zygote is initiated by redundant ECT-2- and PAR-2-dependent mechanisms that lower PAR-3 levels locally, triggering a positive-feedback loop that polarizes the entire cortex.

  18. Does comorbid alcohol and substance abuse affect electroconvulsive therapy outcome in the treatment of mood disorders?

    PubMed

    Moss, Lori; Vaidya, Nutan

    2014-03-01

    Antidepressant medications remain the principal agents used to treat patients with mood disorders, although 30% to 40% of these patients do not improve. One of the factors associated with poor medication response is alcohol and substance abuse. Persons with mood disorders are at the greatest risk for suicide, and alcoholism is a significant additional risk factor. Electroconvulsive therapy (ECT) is shown to be the most effective treatment for major depression especially when associated with psychosis, catatonia, and suicide intent. However, similar to most antidepressant trials, patients with depression and comorbid alcohol and substance abuse are excluded from ECT efficacy studies. Through a retrospective chart review, we compared response to ECT in patients with mood disorder and comorbid alcohol and drug abuse to those with mood disorder only. From 2004 to 2010, 80 patients with mood disorder received ECT. Fifty of these had comorbid alcohol or drug abuse. Using a 10-item psychopathology scale, we compared pre- and post-ECT symptom severity between the 2 groups. Outcome was determined by measuring a decrease in the pre-ECT and post-ECT score using Wilcoxon rank tests, with statistical significance at P = 0.05. There was no difference between the 2 groups in most demographics, ECT medication, or seizure quality. There was no difference in ECT outcome between those with comorbid alcohol abuse and those without based on percent decrease in pre- and post-ECT symptom scores (abuse: mean [SD], 0.89 [0.2] vs nonabuse: mean [SD], 0.93 [0.16]; Wilcoxon, 1332; P = 0.086). When we compared those who met the criteria for alcohol or drug dependence (19 patients) with those with no abuse, there was a trend for the dependence group to not do as well (dependence: mean [SD], 0.83 [0.25] vs nonabuse: mean [SD], 0.93 [0.16]; Wilcoxon, 405; P = 0.053). Those with combined drug and alcohol abuse (18 patients) did have a significantly worse outcome (combined: mean [SD], 0.82 [0

  19. GIV/Girdin activates Gαi and inhibits Gαs via the same motif

    PubMed Central

    Gupta, Vijay; Bhandari, Deepali; Leyme, Anthony; Aznar, Nicolas; Midde, Krishna K.; Lo, I-Chung; Ear, Jason; Niesman, Ingrid; López-Sánchez, Inmaculada; Blanco-Canosa, Juan Bautista; von Zastrow, Mark; Garcia-Marcos, Mikel; Farquhar, Marilyn G.; Ghosh, Pradipta

    2016-01-01

    We previously showed that guanine nucleotide-binding (G) protein α subunit (Gα)-interacting vesicle-associated protein (GIV), a guanine-nucleotide exchange factor (GEF), transactivates Gα activity-inhibiting polypeptide 1 (Gαi) proteins in response to growth factors, such as EGF, using a short C-terminal motif. Subsequent work demonstrated that GIV also binds Gαs and that inactive Gαs promotes maturation of endosomes and shuts down mitogenic MAPK–ERK1/2 signals from endosomes. However, the mechanism and consequences of dual coupling of GIV to two G proteins, Gαi and Gαs, remained unknown. Here we report that GIV is a bifunctional modulator of G proteins; it serves as a guanine nucleotide dissociation inhibitor (GDI) for Gαs using the same motif that allows it to serve as a GEF for Gαi. Upon EGF stimulation, GIV modulates Gαi and Gαs sequentially: first, a key phosphomodification favors the assembly of GIV–Gαi complexes and activates GIV’s GEF function; then a second phosphomodification terminates GIV’s GEF function, triggers the assembly of GIV–Gαs complexes, and activates GIV’s GDI function. By comparing WT and GIV mutants, we demonstrate that GIV inhibits Gαs activity in cells responding to EGF. Consequently, the cAMP→PKA→cAMP response element-binding protein signaling axis is inhibited, the transit time of EGF receptor through early endosomes are accelerated, mitogenic MAPK–ERK1/2 signals are rapidly terminated, and proliferation is suppressed. These insights define a paradigm in G-protein signaling in which a pleiotropically acting modulator uses the same motif both to activate and to inhibit G proteins. Our findings also illuminate how such modulation of two opposing Gα proteins integrates downstream signals and cellular responses. PMID:27621449

  20. Cost-effectiveness of Electroconvulsive Therapy vs Pharmacotherapy/Psychotherapy for Treatment-Resistant Depression in the United States.

    PubMed

    Ross, Eric L; Zivin, Kara; Maixner, Daniel F

    2018-05-09

    probabilistic sensitivity analyses. Incorporating all input data uncertainty, we estimate a 74% to 78% likelihood that at least 1 of the ECT strategies is cost-effective and a 56% to 58% likelihood that third-line ECT is the optimal strategy. For US patients with treatment-resistant depression, ECT may be an effective and cost-effective treatment option. Although many factors influence the decision to proceed with ECT, these data suggest that, from a health-economic standpoint, ECT should be considered after failure of 2 or more lines of pharmacotherapy/psychotherapy.

  1. Optimal experimental design in an epidermal growth factor receptor signalling and down-regulation model.

    PubMed

    Casey, F P; Baird, D; Feng, Q; Gutenkunst, R N; Waterfall, J J; Myers, C R; Brown, K S; Cerione, R A; Sethna, J P

    2007-05-01

    We apply the methods of optimal experimental design to a differential equation model for epidermal growth factor receptor signalling, trafficking and down-regulation. The model incorporates the role of a recently discovered protein complex made up of the E3 ubiquitin ligase, Cbl, the guanine exchange factor (GEF), Cool-1 (beta -Pix) and the Rho family G protein Cdc42. The complex has been suggested to be important in disrupting receptor down-regulation. We demonstrate that the model interactions can accurately reproduce the experimental observations, that they can be used to make predictions with accompanying uncertainties, and that we can apply ideas of optimal experimental design to suggest new experiments that reduce the uncertainty on unmeasurable components of the system.

  2. Design and operations of a load-tolerant external conjugate-T matching system for the A2 ICRH antennas at JET

    NASA Astrophysics Data System (ADS)

    Monakhov, I.; Graham, M.; Blackman, T.; Dowson, S.; Durodie, F.; Jacquet, P.; Lehmann, J.; Mayoral, M.-L.; Nightingale, M. P. S.; Noble, C.; Sheikh, H.; Vrancken, M.; Walden, A.; Whitehurst, A.; Wooldridge, E.; Contributors, JET-EFDA

    2013-08-01

    A load-tolerant external conjugate-T (ECT) impedance matching system for two A2 ion cyclotron resonance heating (ICRH) antennas was successfully put into operation at JET. The system allows continuous injection of the radio-frequency (RF) power into plasma in the presence of strong antenna loading perturbations caused by edge-localized modes (ELMs). Reliable ECT performance was demonstrated under a variety of antenna loading conditions including H-mode plasmas with radial outer gaps (ROGs) in the range 4-14 cm. The high resilience to ELMs predicted during the circuit simulations was fully confirmed experimentally. Dedicated arc-detection techniques and real-time matching algorithms were developed as a part of the ECT project. The new advanced wave amplitude comparison system has proven highly efficient in detection of arcs both between and during ELMs. The ECT system has allowed the delivery of up to 4 MW of RF power without trips into plasmas with type-I ELMs. Together with the 3 dB system and the ITER-like antenna, the ECT has brought the total RF power coupled to ELMy plasma to over 8 MW, considerably enhancing JET research capabilities. This paper provides an overview of the key design features of the ECT system and summarizes the main experimental results achieved so far.

  3. The C-terminus of the oncoprotein TGAT is necessary for plasma membrane association and efficient RhoA-mediated signaling.

    PubMed

    van Unen, J; Botman, D; Yin, T; Wu, Y I; Hink, M A; Gadella, T W J; Postma, M; Goedhart, J

    2018-06-07

    Rho guanine exchange factors (RhoGEFs) control cellular processes such as migration, adhesion and proliferation. Alternative splicing of the RhoGEF Trio produces TGAT. The RhoGEF TGAT is an oncoprotein with constitutive RhoGEF activity. We investigated whether the subcellular location of TGAT is critical for its RhoGEF activity. Since plasma membrane associated RhoGEFs are particularly effective at activating RhoA, plasma membrane localization of TGAT was examined. To this end, we developed a highly sensitive image analysis method to quantitatively measure plasma membrane association. The method requires a cytoplasmic marker and a plasma membrane marker, which are co-imaged with the tagged protein of interest. Linear unmixing is performed to determine the plasma membrane and cytoplasmic component in the fluorescence signal of protein of interest. The analysis revealed that wild-type TGAT is partially co-localized with the plasma membrane. Strikingly, cysteine TGAT-mutants lacking one or more putative palmitoylation sites in the C-tail, still showed membrane association. In contrast, a truncated variant, lacking the last 15 amino acids, TGAT Δ15 , lost membrane association. We show that membrane localization of TGAT was responsible for high RhoGEF activity by using a RhoA FRET-sensor and by determining F-actin levels. Mutants of TGAT that still maintained membrane association showed similar activity as wild-type TGAT. In contrast, the activity was abrogated for the cytoplasmic TGAT Δ15 variant. Synthetic recruitment of TGAT Δ15 to membranes confirmed that TGAT effectively activates RhoA at the plasma membrane. Together, these results show that membrane association of TGAT is critical for its activity.

  4. TD-60 links RalA GTPase function to the CPC in mitosis

    PubMed Central

    Papini, Diana; Langemeyer, Lars; Abad, Maria A.; Kerr, Alastair; Samejima, Itaru; Eyers, Patrick A.; Jeyaprakash, A. Arockia; Higgins, Jonathan M. G.; Barr, Francis A.; Earnshaw, William C.

    2015-01-01

    TD-60 (also known as RCC2) is a highly conserved protein that structurally resembles the Ran guanine exchange factor (GEF) RCC1, but has not previously been shown to have GEF activity. TD-60 has a typical chromosomal passenger complex (CPC) distribution in mitotic cells, but associates with integrin complexes and is involved in cell motility during interphase. Here we show that TD-60 exhibits GEF activity, in vitro and in cells, for the small GTPase RalA. TD-60 or RalA depletion causes spindle abnormalities in prometaphase associated with abnormal centromeric accumulation of CPC components. TD-60 and RalA apparently work together to contribute to the regulation of kinetochore–microtubule interactions in early mitosis. Importantly, several mitotic phenotypes caused by TD-60 depletion are reverted by the expression of a GTP-locked mutant, RalA (Q72L). The demonstration that a small GTPase participates in the regulation of the CPC reveals a level of mitotic regulation not suspected in previous studies. PMID:26158537

  5. GDP-bound and nucleotide-free intermediates of the guanine nucleotide exchange in the Rab5·Vps9 system.

    PubMed

    Uejima, Tamami; Ihara, Kentaro; Goh, Tatsuaki; Ito, Emi; Sunada, Mariko; Ueda, Takashi; Nakano, Akihiko; Wakatsuki, Soichi

    2010-11-19

    Many GTPases regulate intracellular transport and signaling in eukaryotes. Guanine nucleotide exchange factors (GEFs) activate GTPases by catalyzing the exchange of their GDP for GTP. Here we present crystallographic and biochemical studies of a GEF reaction with four crystal structures of Arabidopsis thaliana ARA7, a plant homolog of Rab5 GTPase, in complex with its GEF, VPS9a, in the nucleotide-free and GDP-bound forms, as well as a complex with aminophosphonic acid-guanylate ester and ARA7·VPS9a(D185N) with GDP. Upon complex formation with ARA7, VPS9 wedges into the interswitch region of ARA7, inhibiting the coordination of Mg(2+) and decreasing the stability of GDP binding. The aspartate finger of VPS9a recognizes GDP β-phosphate directly and pulls the P-loop lysine of ARA7 away from GDP β-phosphate toward switch II to further destabilize GDP for its release during the transition from the GDP-bound to nucleotide-free intermediates in the nucleotide exchange reaction.

  6. SU-G-IeP4-08: Initial Investigations of Up-Converting Nanoparticles (UCNP) for 3D Tissue Imaging in Optical-ECT

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yoon, S; Dewhirst, M; Oldham, M

    Purpose: Near-IR absorptive up-converting nanoparticles (UCNPs) is a novel contrast for optical-ECT that allows auto-fluorescence-free 3D imaging of labeled cells in a matrix of large (∼1cm{sup 3}) unsectioned normal tissue. This has the potential to image small metastases or dormant cells that is difficult with down-converting fluorescing dyes due to auto-fluorescence. The feasibility of imaging UCNP in agarose phantoms and a mouse lung is demonstrated, aided by a 3D-printed optical-ECT stage designed to excite UCNP in a mouse lung. Methods: The UCNP, NaYF{sub 4}:Yb/Er (20/2%), studied in this work up-converts 980nm light to visible light peaking sharply at ∼540nm. Tomore » characterize the UCNP emission as a function of UCNP concentration, cylindrical 2.5%wt agarose phantoms infused with UCNP at concentrations of 25µg/mL and 50µg/mL were exposed to 1.5W 980nm laser coupled to an optical fiber. The fiber was held stably at 1cm above the stage via a custom 3D-printed stage. An optically cleared lung harvested from a BALBc mice was then injected with 100µL of 1mg/mL UCNP solution ex vivo. Tomographic imaging of the UCNP emission in lung was performed. Results: The laser beam tract is visualized within the agarose phantom. A line profile of UCNP emission at 25µg/mL versus 50µg/mL shows that increasing the UCNP concentration increases emission count. UCNPs injected into a cleared mouse lung disperse throughout the respiratory tract, allowing for visualization and 3D reconstruction. Excitation before and after UCNP injection shows the tissue exhibits no auto-fluorescence at 980nm, allowing clear view of the UCNP without any obscuring features such as conventional down-converting fluorescent tags. Conclusion: We confirm that up-conversion in tissue circumvents completely tissue auto-fluorescence, which allowed background-free 3D reconstruction of the UCNP distribution. We also confirm that raising the UCNP concentration increases emission and that UCNPs are

  7. Genome-wide siRNA screen identifies UNC50 as a regulator of Shiga toxin 2 trafficking

    PubMed Central

    Iles, Lakesla R.; Bartholomeusz, Geoffrey

    2017-01-01

    Shiga toxins 1 and 2 (STx1 and STx2) undergo retrograde trafficking to reach the cytosol. Early endosome-to-Golgi transport allows the toxins to evade degradation in lysosomes. Targeting this trafficking step has therapeutic promise, but the mechanism of trafficking for the more potent toxin STx2 is unclear. To identify host factors required for early endosome-to-Golgi trafficking of STx2, we performed a viability-based genome-wide siRNA screen in HeLa cells. 564, 535, and 196 genes were found to be required for toxicity induced by STx1 only, STx2 only, and both toxins, respectively. We focused on validating endosome/Golgi-localized hits specific for STx2 and found that depletion of UNC50 blocked early endosome-to-Golgi trafficking and induced lysosomal degradation of STx2. UNC50 acted by recruiting GBF1, an ADP ribosylation factor–guanine nucleotide exchange factor (ARF-GEF), to the Golgi. These results provide new information about STx2 trafficking mechanisms and may advance efforts to generate therapeutically viable toxin-trafficking inhibitors. PMID:28883040

  8. Possible Association between Serum Matrix Metalloproteinase-9 (MMP-9) Levels and Relapse in Depressed Patients following Electroconvulsive Therapy (ECT)

    PubMed Central

    Shibasaki, Chiyo; Itagaki, Kei; Abe, Hiromi; Kajitani, Naoto; Okada-Tsuchioka, Mami; Takebayashi, Minoru

    2018-01-01

    Abstract Background Matrix metalloproteinases are involved in neuroinflammatory processes, which could underlie depression. Serum levels of MMP-9 and MMP-2 in depressed patients are significantly altered following electroconvulsive therapy, but an association between altered matrix metalloproteinases after successful ECT and possible relapse has yet to be investigated. Methods Serum was obtained twice, before and immediately after a course of electroconvulsive therapy, from 38 depressed patients. Serum was also collected, once, from two groups of age- and gender-matched healthy controls, 40 volunteers in each group. Possible associations between levels of matrix metalloproteinases and relapse during a 1-year follow-up period were analyzed. Results Excluding patients who did not respond to electroconvulsive therapy and patients lost to follow-up, data from 28 patients were evaluated. Eighteen of the patients (64.3%) relapsed within 1 year. In the group that did not relapse, serum levels of MMP-9 were significantly decreased after a course of electroconvulsive therapy, but not in the group that relapsed. No association between MMP-2 and relapse was observed. Conclusion The degree of change in serum MMP-9 change could be associated with relapse following electroconvulsive therapy in depressed patients. PMID:29025075

  9. Ketamine infusions for treatment resistant depression: a series of 28 patients treated weekly or twice weekly in an ECT clinic.

    PubMed

    Diamond, Peter R; Farmery, Andrew D; Atkinson, Stephanie; Haldar, Jag; Williams, Nicola; Cowen, Phil J; Geddes, John R; McShane, Rupert

    2014-06-01

    Ketamine has a rapid antidepressant effect in treatment-resistant depression (TRD). The effects on cognitive function of multiple ketamine infusions and of concurrent antidepressant medication on response rate and duration are not known. Twenty-eight patients with uni- or bipolar TRD were treated over three weeks with either three or six ketamine infusions (0.5 mg/kg over 40 minutes) in the recovery room of a routine ECT clinic. Post-treatment memory assessments were conducted on day 21 (4-7 days after the final infusion). Patients were followed up for six months where possible, with severity of depression and side effects monitored throughout. Eight (29%) patients responded of whom four remitted. Only three (11%) patients had responded within six hours after a single infusion, but in all responders, the response had developed before the third infusion. The duration of response from the final infusion was variable (median 70, range 25-168 days). Discontinuations included two (7%) because of acute adverse reactions during the infusion and five (18%) because of failure to benefit and increasing anxiety. Ketamine was not associated with memory impairment. The ECT clinic was rated suitable by patients and offered appropriate levels of monitoring. This small, open label naturalistic study shows that up to six low dose ketamine infusions can safely be given within an existing NHS clinical structure to patients who continue their antidepressants. The response rate was comparable to that found in RCTs of single doses of ketamine in antidepressant-free patients but took slightly longer to develop. © The Author(s) 2014.

  10. Multifactorial determinants of the neurocognitive effects of electroconvulsive therapy.

    PubMed

    McClintock, Shawn M; Choi, Jimmy; Deng, Zhi-De; Appelbaum, Lawrence G; Krystal, Andrew D; Lisanby, Sarah H

    2014-06-01

    For many patients with neuropsychiatric illnesses, standard psychiatric treatments with mono or combination pharmacotherapy, psychotherapy, and transcranial magnetic stimulation are ineffective. For these patients with treatment-resistant neuropsychiatric illnesses, a main therapeutic option is electroconvulsive therapy (ECT). Decades of research have found ECT to be highly effective; however, it can also result in adverse neurocognitive effects. Specifically, ECT results in disorientation after each session, anterograde amnesia for recently learned information, and retrograde amnesia for previously learned information. Unfortunately, the neurocognitive effects and underlying mechanisms of action of ECT remain poorly understood. The purpose of this paper was to synthesize the multiple moderating and mediating factors that are thought to underlie the neurocognitive effects of ECT into a coherent model. Such factors include demographic and neuropsychological characteristics, neuropsychiatric symptoms, ECT technical parameters, and ECT-associated neurophysiological changes. Future research is warranted to evaluate and test this model, so that these findings may support the development of more refined clinical seizure therapy delivery approaches and efficacious cognitive remediation strategies to improve the use of this important and widely used intervention tool for neuropsychiatric diseases.

  11. Influence of GRIK4 genetic variants on the electroconvulsive therapy response.

    PubMed

    Minelli, Alessandra; Congiu, Chiara; Ventriglia, Mariacarla; Bortolomasi, Marco; Bonvicini, Cristian; Abate, Maria; Sartori, Riccardo; Gainelli, Giulio; Gennarelli, Massimo

    2016-07-28

    Several lines of evidence have shown the involvement of the glutamatergic system in the function of electroconvulsive therapy (ECT). In particular, patients with treatment resistant depression (TRD) and chronic depression have lower levels of glutamate/glutamine than controls, and ECT can reverse this deficit. Genetic factors might contribute to modulating the mechanisms underlying ECT. This study aimed to evaluate the relationship between three polymorphisms (rs1954787, rs4936554 and rs11218030) of the glutamate receptor ionotropic kainate 4 (GRIK4) gene and responsiveness to ECT treatment in a sample of one hundred individuals, TRD or depressive Bipolar Disorder patients resistant to pharmacological treatments. The results revealed that GRIK4 variants were significantly associated with the response to ECT. In particular, we found that patients carrying the G allele of the GRIK4 rs11218030 had a significantly poorer response to ECT (p=2.71×10(-4)), showing five times the risk of relapse after ECT compared to the AA homozygotes. Analogously, patients carrying the GG rs1954787 genotype and rs4936554A allele carriers presented a double risk of lack of response after ECT (p=0.013 and p=0.040, respectively). In conclusion, the current study provides new evidence, indicating that some GRIK4 variants modulate the response to ECT in patients with depression resistant to treatment, suggesting a role for kainate receptor modulation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Cross-Species Analyses Identify the BNIP-2 and Cdc42GAP Homology (BCH) Domain as a Distinct Functional Subclass of the CRAL_TRIO/Sec14 Superfamily

    PubMed Central

    Gupta, Anjali Bansal; Wee, Liang En; Zhou, Yi Ting; Hortsch, Michael; Low, Boon Chuan

    2012-01-01

    The CRAL_TRIO protein domain, which is unique to the Sec14 protein superfamily, binds to a diverse set of small lipophilic ligands. Similar domains are found in a range of different proteins including neurofibromatosis type-1, a Ras GTPase-activating Protein (RasGAP) and Rho guanine nucleotide exchange factors (RhoGEFs). Proteins containing this structural protein domain exhibit a low sequence similarity and ligand specificity while maintaining an overall characteristic three-dimensional structure. We have previously demonstrated that the BNIP-2 and Cdc42GAP Homology (BCH) protein domain, which shares a low sequence homology with the CRAL_TRIO domain, can serve as a regulatory scaffold that binds to Rho, RhoGEFs and RhoGAPs to control various cell signalling processes. In this work, we investigate 175 BCH domain-containing proteins from a wide range of different organisms. A phylogenetic analysis with ∼100 CRAL_TRIO and similar domains from eight representative species indicates a clear distinction of BCH-containing proteins as a novel subclass within the CRAL_TRIO/Sec14 superfamily. BCH-containing proteins contain a hallmark sequence motif R(R/K)h(R/K)(R/K)NL(R/K)xhhhhHPs (‘h’ is large and hydrophobic residue and ‘s’ is small and weekly polar residue) and can be further subdivided into three unique subtypes associated with BNIP-2-N, macro- and RhoGAP-type protein domains. A previously unknown group of genes encoding ‘BCH-only’ domains is also identified in plants and arthropod species. Based on an analysis of their gene-structure and their protein domain context we hypothesize that BCH domain-containing genes evolved through gene duplication, intron insertions and domain swapping events. Furthermore, we explore the point of divergence between BCH and CRAL-TRIO proteins in relation to their ability to bind small GTPases, GAPs and GEFs and lipid ligands. Our study suggests a need for a more extensive analysis of previously uncharacterized BCH,

  13. Index of /data/nccf/com/gens/prod

    Science.gov Websites

    -2018 17:38 - cmce.20180527/ 27-May-2018 05:39 - fens.20180526/ 26-May-2018 17:50 - fens.20180527/ 27 -May-2018 06:20 - gefs.20180520/ 20-May-2018 22:41 - gefs.20180521/ 21-May-2018 22:43 - gefs.20180522 / 22-May-2018 22:43 - gefs.20180523/ 23-May-2018 22:42 - gefs.20180524/ 24-May-2018 22:43 - gefs

  14. Making Visible Teacher Reports of Their Teaching Experiences: The Early Childhood Teacher Experiences Scale

    ERIC Educational Resources Information Center

    Fantuzzo, John; Perlman, Staci; Sproul, Faith; Minney, Ashley; Perry, Marlo A.; Li, Feifei

    2012-01-01

    The study developed multiple independent scales of early childhood teacher experiences (ECTES). ECTES was co-constructed with preschool, kindergarten, and first grade teachers in a large urban school district. Demographic, ECTES, and teaching practices data were collected from 584 teachers. Factor analyses documented three teacher experience…

  15. Influence of the internal wall thickness of electrical capacitance tomography sensors on image quality

    NASA Astrophysics Data System (ADS)

    Liang, Shiguo; Ye, Jiamin; Wang, Haigang; Wu, Meng; Yang, Wuqiang

    2018-03-01

    In the design of electrical capacitance tomography (ECT) sensors, the internal wall thickness can vary with specific applications, and it is a key factor that influences the sensitivity distribution and image quality. This paper will discuss the effect of the wall thickness of ECT sensors on image quality. Three flow patterns are simulated for wall thicknesses of 2.5 mm to 15 mm on eight-electrode ECT sensors. The sensitivity distributions and potential distributions are compared for different wall thicknesses. Linear back-projection and Landweber iteration algorithms are used for image reconstruction. Relative image error and correlation coefficients are used for image evaluation using both simulation and experimental data.

  16. Effects of COMT, DRD2, BDNF, and APOE Genotypic Variation on Treatment Efficacy and Cognitive Side Effects of Electroconvulsive Therapy.

    PubMed

    Bousman, Chad A; Katalinic, Natalie; Martin, Donel M; Smith, Deidre J; Ingram, Anna; Dowling, Nathan; Ng, Chee; Loo, Colleen K

    2015-06-01

    The aim of this study was to explore the main and interaction effects of the COMT Val158Met, DRD2 C957T, BDNF Val66Met, and APOE polymorphisms on treatment efficacy and cognitive side effects of electroconvulsive therapy (ECT). A total of 117 adult inpatients with a diagnosis of major depressive disorder recruited from 3 hospitals were administered the Montgomery-Äsberg Depression Rating Scale and a cognitive battery assessing global cognition, anterograde memory, executive function, speed and concentration, as well as retrograde memory at baseline and after ECT treatment. DRD2 C957T heterozygotes had 3.7 (95% confidence interval, 1.13-12.25; P = 0.032) greater odds of remission compared with CC homozygotes. Among the men, COMT Val/Val carriers had greater depressive symptom reduction compared with Met/Met carriers (Montgomery-Äsberg Depression Rating Scale percentage of reduction, 76% vs 35%; P = 0.020) but not among the women (P = 0.903) after ECT. For cognitive outcomes, an interaction effect on anterograde memory was observed between the DRD2 and BDNF polymorphisms (P = 0.016), in which carriers of the DRD2 TT and BDNF Val/Val genotypes had significantly less decline in anterograde performance than those that carried the TC and Met-allele (P = 0.001) or CC and Met-allele (P = 0.003) genotypes. However, no results withstood correction for multiple comparisons. These observations provide preliminary evidence supporting an association between common functional genotypic variation and ECT efficacy as well as anterograde memory side effects after ECT. Validation of these findings is required before firm conclusions can be made and clinical utility can be assessed.

  17. Far-side geometrical enhancement in surface-enhanced Raman scattering with Ag plasmonic films

    NASA Astrophysics Data System (ADS)

    Perera, M. Nilusha M. N.; Gibbs, W. E. Keith; Juodkazis, Saulius; Stoddart, Paul R.

    2018-01-01

    Surface-enhanced Raman scattering (SERS) is a surface sensitive technique where the large increase in scattering has primarily been attributed to electromagnetic and chemical enhancements. While smaller geometrical enhancements due to thin film interference and cavity resonances have also been reported, an additional enhancement in the SERS signal, referred to as the `far-side geometrical enhancement', occurs when the SERS substrate is excited through an underlying transparent dielectric substrate. Here the far-side geometrically-enhanced SERS signal has been explored experimentally in more detail. Thermally evaporated Ag plasmonic films functionalised with thiophenol were used to study the dependence of the geometrically-enhanced SERS signal on the excitation wavelength, supporting substrate material and excitation angle of incidence. The results were interpreted using a `geometrical enhancement factor' (GEF), defined as the ratio of far-side to near-side SERS signal intensity. The experimental results confirmed that the highest GEFs of 3.2-3.5× are seen closer to the localized surface plasmon resonance peak of the Ag metallic nanostructures. Interestingly, the GEF for Ag plasmonic films deposited on glass and sapphire were the same within the measurement errors, whereas increasing angle of incidence showed a decrease in the GEF. Given this improved understanding of the far-side geometrical SERS enhancement, the potential for further signal amplification and optimisation for practical sensing applications can now be considered, especially for SERS detection modes at the farend of optical fibre probes and through process windows.

  18. Possible Association between Serum Matrix Metalloproteinase-9 (MMP-9) Levels and Relapse in Depressed Patients following Electroconvulsive Therapy (ECT).

    PubMed

    Shibasaki, Chiyo; Itagaki, Kei; Abe, Hiromi; Kajitani, Naoto; Okada-Tsuchioka, Mami; Takebayashi, Minoru

    2018-03-01

    Matrix metalloproteinases are involved in neuroinflammatory processes, which could underlie depression. Serum levels of MMP-9 and MMP-2 in depressed patients are significantly altered following electroconvulsive therapy, but an association between altered matrix metalloproteinases after successful ECT and possible relapse has yet to be investigated. Serum was obtained twice, before and immediately after a course of electroconvulsive therapy, from 38 depressed patients. Serum was also collected, once, from two groups of age- and gender-matched healthy controls, 40 volunteers in each group. Possible associations between levels of matrix metalloproteinases and relapse during a 1-year follow-up period were analyzed. Excluding patients who did not respond to electroconvulsive therapy and patients lost to follow-up, data from 28 patients were evaluated. Eighteen of the patients (64.3%) relapsed within 1 year. In the group that did not relapse, serum levels of MMP-9 were significantly decreased after a course of electroconvulsive therapy, but not in the group that relapsed. No association between MMP-2 and relapse was observed. The degree of change in serum MMP-9 change could be associated with relapse following electroconvulsive therapy in depressed patients. © The Author 2017. Published by Oxford University Press on behalf of CINP.

  19. Multifactorial Determinants of the Neurocognitive Effects of Electroconvulsive Therapy

    PubMed Central

    McClintock, Shawn M.; Choi, Jimmy; Deng, Zhi-De; Appelbaum, Lawrence G.; Krystal, Andrew D.; Lisanby, Sarah H.

    2014-01-01

    For many patients with neuropsychiatric illnesses, standard psychiatric treatments with mono or combination pharmacotherapy, psychotherapy, and transcranial magnetic stimulation are ineffective. For these patients with treatment resistant neuropsychiatric illnesses, a main therapeutic option is electroconvulsive therapy (ECT). Decades of research have found ECT to be highly effective; however, it can also result in adverse neurocognitive effects. Specifically, ECT results in disorientation after each session, anterograde amnesia for recently learned information, and retrograde amnesia for previously learned information. Unfortunately, the neurocognitive effects and underlying mechanisms of action of ECT remain poorly understood. The purpose of this paper is to synthesize the multiple moderating and mediating factors that are thought to underlie the neurocognitive effects of ECT into a coherent model. Such factors include demographic and neuropsychological characteristics, neuropsychiatric symptoms, ECT technical parameters, and ECT associated neurophysiological changes. Future research is warranted to evaluate and test this model, so that these findings may support the development of more refined clinical seizure therapy delivery approaches and efficacious cognitive remediation strategies to improve the utility of this important and widely used intervention tool for neuropsychiatric diseases. PMID:24820942

  20. PDZ Protein Regulation of G Protein-Coupled Receptor Trafficking and Signaling Pathways.

    PubMed

    Dunn, Henry A; Ferguson, Stephen S G

    2015-10-01

    G protein-coupled receptors (GPCRs) contribute to the regulation of every aspect of human physiology and are therapeutic targets for the treatment of numerous diseases. As a consequence, understanding the myriad of mechanisms controlling GPCR signaling and trafficking is essential for the development of new pharmacological strategies for the treatment of human pathologies. Of the many GPCR-interacting proteins, postsynaptic density protein of 95 kilodaltons, disc large, zona occludens-1 (PDZ) domain-containing proteins appear most abundant and have similarly been implicated in disease mechanisms. PDZ proteins play an important role in regulating receptor and channel protein localization within synapses and tight junctions and function to scaffold intracellular signaling protein complexes. In the current study, we review the known functional interactions between PDZ domain-containing proteins and GPCRs and provide insight into the potential mechanisms of action. These PDZ domain-containing proteins include the membrane-associated guanylate-like kinases [postsynaptic density protein of 95 kilodaltons; synapse-associated protein of 97 kilodaltons; postsynaptic density protein of 93 kilodaltons; synapse-associated protein of 102 kilodaltons; discs, large homolog 5; caspase activation and recruitment domain and membrane-associated guanylate-like kinase domain-containing protein 3; membrane protein, palmitoylated 3; calcium/calmodulin-dependent serine protein kinase; membrane-associated guanylate kinase protein (MAGI)-1, MAGI-2, and MAGI-3], Na(+)/H(+) exchanger regulatory factor proteins (NHERFs) (NHERF1, NHERF2, PDZ domain-containing kidney protein 1, and PDZ domain-containing kidney protein 2), Golgi-associated PDZ proteins (Gα-binding protein interacting protein, C-terminus and CFTR-associated ligand), PDZ domain-containing guanine nucleotide exchange factors (GEFs) 1 and 2, regulator of G protein signaling (RGS)-homology-RhoGEFs (PDZ domain-containing RhoGEF and

  1. A non-canonical role for Rgnef in promoting integrin-stimulated focal adhesion kinase activation

    PubMed Central

    Miller, Nichol L. G.; Lawson, Christine; Kleinschmidt, Elizabeth G.; Tancioni, Isabelle; Uryu, Sean; Schlaepfer, David D.

    2013-01-01

    Summary Rgnef (also known as p190RhoGEF or ARHGEF28) is a Rho guanine-nucleotide-exchange factor (GEF) that binds focal adhesion kinase (FAK). FAK is recruited to adhesions and activated by integrin receptors binding to matrix proteins, such as fibronectin (FN). Canonical models place Rgnef downstream of integrin–FAK signaling in regulating Rho GTPase activity and cell movement. Herein, we establish a new, upstream role for Rgnef in enhancing FAK localization to early peripheral adhesions and promoting FAK activation upon FN binding. Rgnef-null mouse embryo fibroblasts (MEFs) exhibit defects in adhesion formation, levels of FAK phosphotyrosine (pY)-397 and FAK localization to peripheral adhesions upon re-plating on FN. Rgnef re-expression rescues these defects, but requires Rgnef–FAK binding. A mutation in the Rgnef pleckstrin homology (PH) domain inhibits adhesion formation, FAK localization, and FAK-Y397 and paxillin-Y118 phosphorylation without disrupting the Rgnef–FAK interaction. A GEF-inactive Rgnef mutant rescues FAK-Y397 phosphorylation and early adhesion localization, but not paxillin-Y118 phosphorylation. This suggests that, downstream of FN binding, paxillin-pY118 requires Rgnef GEF activity through a mechanism distinct from adhesion formation and FAK activation. These results support a scaffolding role for Rgnef in FAK localization and activation at early adhesions in a PH-domain-dependent but GEF-activity-independent manner. PMID:24006257

  2. The integrity of the plant Golgi apparatus depends on cell growth-controlled activity of GNL1.

    PubMed

    Du, Wenyan; Tamura, Kentaro; Stefano, Giovanni; Brandizzi, Federica

    2013-05-01

    Membrane traffic and organelle integrity in the plant secretory pathway depend on ARF-GTPases, which are activated by guanine-nucleotide exchange factors (ARF-GEFs). While maintenance of conserved roles, evolution of unique functions as well as tissue-specific roles have been shown for a handful of plant ARF-GEFs, a fundamental yet unanswered question concerns the extent to which their function overlaps during cell growth. To address this, we have characterized pao, a novel allele of GNOM-like 1 (GNL1), a brefeldin A (BFA)-insensitive ARF-GEF, isolated through a confocal microscopy-based forward genetics screen of the Golgi in Arabidopsis thaliana. Specifically, we have analyzed the dependence of the integrity of trafficking routes and secretory organelles on GNL1 availability during expansion stages of cotyledon epidermal cells, an exquisite model system for vegetative cell growth analyses in intact tissues. We show that Golgi traffic is influenced largely by GNL1 availability at early stages of cotyledon cell expansion but by BFA-sensitive GEFs when cell growth terminates. These data reveal an unanticipated level of complexity in the biology of GNL1 by showing that its cellular roles are correlated with cell growth. These results also indicate that the cell growth stage is an important element weighting into functional analyses of the cellular roles of ARF-GEFs.

  3. Safety considerations for outpatient electroconvulsive therapy.

    PubMed

    Reti, Irving M; Walker, Melinda; Pulia, Kathy; Gallegos, Jesus; Jayaram, Geetha; Vaidya, Punit

    2012-03-01

    As electroconvulsive therapy (ECT) requires general anesthesia and is associated with both cognitive and non-cognitive side effects, careful consideration must be given to the safety aspects of providing ECT on an outpatient basis. Drawing upon published literature and their clinical experience administering outpatient ECT, the authors propose best practices for safely providing ECT to outpatients. They review criteria for selecting patients for outpatient ECT as well as treatment and programmatic issues. The authors highlight the importance of educating referring clinicians as well as patients and their families about factors involved in the safe delivery of ECT for outpatients. Fiscal considerations and the drive toward reduced length of stay are prompting insurers and caregivers to choose outpatient over inpatient ECT. For each patient, such a choice merits a careful analysis of the risks of outpatient ECT, as well as the implementation of measures to ensure patient safety.

  4. The guanine nucleotide exchange factor Ric-8A induces domain separation and Ras domain plasticity in Gαi1

    PubMed Central

    Van Eps, Ned; Thomas, Celestine J.; Hubbell, Wayne L.; Sprang, Stephen R.

    2015-01-01

    Heterotrimeric G proteins are activated by exchange of GDP for GTP at the G protein alpha subunit (Gα), most notably by G protein-coupled transmembrane receptors. Ric-8A is a soluble cytoplasmic protein essential for embryonic development that acts as both a guanine nucleotide exchange factor (GEF) and a chaperone for Gα subunits of the i, q, and 12/13 classes. Previous studies demonstrated that Ric-8A stabilizes a dynamically disordered state of nucleotide-free Gα as the catalytic intermediate for nucleotide exchange, but no information was obtained on the structures involved or the magnitude of the structural fluctuations. In the present study, site-directed spin labeling (SDSL) together with double electron-electron resonance (DEER) spectroscopy is used to provide global distance constraints that identify discrete members of a conformational ensemble in the Gαi1:Ric-8A complex and the magnitude of structural differences between them. In the complex, the helical and Ras-like nucleotide-binding domains of Gαi1 pivot apart to occupy multiple resolved states with displacements as large as 25 Å. The domain displacement appears to be distinct from that observed in Gαs upon binding of Gs to the β2 adrenergic receptor. Moreover, the Ras-like domain exhibits structural plasticity within and around the nucleotide-binding cavity, and the switch I and switch II regions, which are known to adopt different conformations in the GDP- and GTP-bound states of Gα, undergo structural rearrangements. Collectively, the data show that Ric-8A induces a conformationally heterogeneous state of Gαi and provide insight into the mechanism of action of a nonreceptor Gα GEF. PMID:25605908

  5. Global environment facility: Independent evaluation of the pilot phase; Fondo para el medio ambiente mundial: evaluacion independiente de la etapa experimental

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    NONE

    1994-06-01

    This study responds to a request by participants in the Global Environment Facility (GEF) for an independent evaluation of the pilot phase. It profiles the GEF, discusses its policy framework, and reviews project development procedures and the strategies and projects in each of the GEF`s four focal areas. The study concludes that fundamental changes must occur and recommends specific reforms, such as articulating more clearly the GEF`s mandate, objectives, and strategies; addressing deficiencies in meeting its global focus; improving capacities and procedures within implementing agencies for managing the portfolio; and increasing non-government organization (NGO), country and community-level participation.

  6. Global environment facility: Independent evaluation of the pilot phase; Fonds pour l`environnement mondial: evaluation independante de la phase pilote

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    NONE

    1994-12-31

    This study responds to a request by participants in the Global Environment Facility (GEF) for an independent evaluation of the pilot phase. It profiles the GEF, discusses its policy framework, and reviews project development procedures and the strategies and projects in each of the GEF`s four focal areas. The study concludes that fundamental changes must occur and recommends specific reforms, such as articulating more clearly the GEF`s mandate, objectives, and strategies; addressing deficiencies in meeting its global focus; improving capacities and procedures within implementing agencies for managing the portfolio; and increasing non-government organization (NGO), country and community-level participation.

  7. Does electroconvulsive therapy cause epilepsy?

    PubMed

    Ray, Anindya Kumar

    2013-09-01

    Electroconvulsive therapy (ECT) has been mentioned as a risk factor for epilepsy in some texts. This observation is based on isolated case reports and 2 studies done in 1980s. Since 1983, no study was done on this topic. The objective of the current study was to find out the incidence of spontaneous seizures after ECT. The study was done in Central Institute of Psychiatry, India. It was a retrospective cohort study where files of the patients receiving unmodified ECT during 1990 to 1995 were reviewed over approximately the next 10 years. Patients having the risk factors for spontaneous seizures like past and family history of seizure, substance abuse, and organicity were excluded from the study group. For minimizing the confounding effect of concurrent psychotropic drugs, an age-, sex-, and diagnosis-matched control group was selected. This group consisted of patients admitted during the same time and treated with similar drugs but no ECT. No report of spontaneous seizure was found in the study group of 619 patients. One patient who was excluded from the study group due to suspected neurosyphilis developed recurrent seizures 1 month after ECT. Two patients in the control group had single occasion convulsion with no further recurrence even with continuation of similar drugs. Electroconvulsive therapy has not been found to cause epilepsy. Patient's underlying organic condition may influence development of seizures.

  8. The Clonic Phase of Seizures in Patients Treated with Electroconvulsive Therapy is Related to Age and Stimulus Intensity.

    PubMed

    Wang, Chao-Chih; Lin, Ching-Hung; Chiu, Yao-Chu; Tseng, Chih-Chieh

    2013-01-01

    Electroconvulsive therapy (ECT) is effective in the treatment of major depressive disorder and schizophrenia in patients who are drug-naïve or less-receptive to antipsychotic drugs. Several studies have discussed the correlation between patient characteristics, input-current volume, and seizure duration. According to the present principle of ECT guidelines, the therapeutic effect of ECT mostly correlates with seizure duration. As the tonic phase is different from the clonic phase with respect to brain function and activity, it is informative to analyze both the tonic and clonic phases. Thus, this study sought to clarify the relationship between the features of the two phases, and to re-examine and refine guidelines regarding ECT treatment. ECT-course data from 44 schizophrenia or bipolar I patients were recollected, including the number of treatments that they had received, their gender, age, and the association of these characteristics with motor seizure duration was analyzed. A two-factor correlation was employed to test the relationship between each of the two factors. The post-analysis results indicate that seizure duration and age are significantly correlated. Older patients had relatively short seizure durations after ECT-treatment. Notably, a negative correlation was only found between age and the clonic phase of the seizure, not between age and the tonic phase. Furthermore, this study also found an inverse relationship between ECT-intensity and the clonic phase, but not between ECT-intensity and the tonic phase. This study demonstrated that age and ECT-intensity are negatively correlated with seizure duration, particularly in the clonic phase. The present observations are not fully consistent with the basic guidelines of the APA-ECT practical manual. Accordingly, the predictions regarding the therapeutic effect of ECT can be based on both the seizure duration and the clonic phase.

  9. Electroconvulsive therapy and subsequent epilepsy in patients with affective disorders: A register-based Danish cohort study.

    PubMed

    Bøg, Fie Krossdal; Jørgensen, Martin Balslev; Andersen, Zorana Jovanovic; Osler, Merete

    It has been suggested that Electroconvulsive Therapy (ECT) might increase the risk of epilepsy but the few patient studies with retrospective data from medical records do not support the hypothesis. The aim of this study was to examine the relationship between ECT and subsequent incident epilepsy in patients with affective disorder. We also explored whether any association varied with number of ECTs and time since last treatment. All 169,457 patients with first hospital contact for an affective disorder between January 2005 and December 2015 were identified in the Danish National Patient Registry and followed for incident epilepsy from January 2005 until November 2016. The association between ECT and epilepsy was examined using Cox proportional hazard regression with adjustment for gender, age, educational level, comorbid schizophrenia, previous stroke and antidepressant and antipsychotic medication use. A total of 5875 patients had at least one ECT and 1873 patients developed epilepsy (Incidence rate: 213 pr. 100,000 person years) during the follow-up of mean 5 years. In patients below age 40 years, ECT was associated with a higher rate of epilepsy after adjustment for covariables (Hazard Ratio (HR) = 1.84; 95% Confidence Intervals (CI) = [1.24-2.74]). In patients aged 41-60 years ECT was not associated with epilepsy, while for those above 60 treated with ECT the rate was lower (HR = 0.57; (95% CI = [0.37-0.89]). In patients with affective disorders, we found a weak positive association between ECT and subsequent diagnosis of epilepsy in those younger than 40 years, and a weak negative association in patients older than 60 years. The associations might be subject to residual confounding from risk factors related to ECT. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Predictors of readmission after successful electroconvulsive therapy for depression: a chart review study.

    PubMed

    Uchida, Takahito; Kishimoto, Taishiro; Koreki, Akihiro; Nakao, Shigetsugu; Owada, Ai; Koizumi, Teruki; Saito, Atsuyuki; Sato, Minako; Sawada, Shinya; Matsuzaki, Ryuta; Petrides, Georgios; Mimura, Masaru

    2016-11-01

    The study aimed to identify the predictors for readmission after a successful electroconvulsive therapy (ECT) course. Medical charts of patients who received ECT for major depressive episodes were reviewed. Patients' demographic characteristics and treatment parameters, such as ECT charge, seizure duration, the number of ECT sessions and pharmacotherapy, were extracted. We compared differences between those who were readmitted after successful ECT within 6 and 12 months, versus those not readmitted. We also conducted a multivariate logistic regression analysis to identify the predictors for readmission. Out of 51 patients who were discharged after ECT, 27 patients met the inclusion criteria and were included in the analysis. Eight patients were readmitted within 6 months after discharge, and four more patients were readmitted during the next 6-month follow up. Comparing patients who were and were not readmitted, we found no significant differences between groups, including ECT parameters such as the number of ECT sessions, average charge and final charge. No predictors for readmission were found through multivariate analysis. Although patients who require higher ECT charge and more sessions seem to be prone to readmission, our dataset suggested that none of these types of ECT parameters were risk factors for readmission.

  11. Comparison of electric field strength and spatial distribution of electroconvulsive therapy and magnetic seizure therapy in a realistic human head model

    PubMed Central

    Lee, Won Hee; Lisanby, Sarah H.; Laine, Andrew F.; Peterchev, Angel V.

    2017-01-01

    Background This study examines the strength and spatial distribution of the electric field induced in the brain by electroconvulsive therapy (ECT) and magnetic seizure therapy (MST). Methods The electric field induced by standard (bilateral, right unilateral, and bifrontal) and experimental (focal electrically administered seizure therapy and frontomedial) ECT electrode configurations as well as a circular MST coil configuration was simulated in an anatomically realistic finite element model of the human head. Maps of the electric field strength relative to an estimated neural activation threshold were used to evaluate the stimulation strength and focality in specific brain regions of interest for these ECT and MST paradigms and various stimulus current amplitudes. Results The standard ECT configurations and current amplitude of 800–900 mA produced the strongest overall stimulation with median of 1.8–2.9 times neural activation threshold and more than 94% of the brain volume stimulated at suprathreshold level. All standard ECT electrode placements exposed the hippocampi to suprathreshold electric field, although there were differences across modalities with bilateral and right unilateral producing respectively the strongest and weakest hippocampal stimulation. MST stimulation is up to 9 times weaker compared to conventional ECT, resulting in direct activation of only 21% of the brain. Reducing the stimulus current amplitude can make ECT as focal as MST. Conclusions The relative differences in electric field strength may be a contributing factor for the cognitive sparing observed with right unilateral compared to bilateral ECT, and MST compared to right unilateral ECT. These simulations could help understand the mechanisms of seizure therapies and develop interventions with superior risk/benefit ratio. PMID:27318858

  12. In Candida albicans hyphae, Sec2p is physically associated with SEC2 mRNA on secretory vesicles.

    PubMed

    Caballero-Lima, David; Hautbergue, Guillaume M; Wilson, Stuart A; Sudbery, Peter E

    2014-11-01

    Candida albicans hyphae grow in a highly polarized fashion from their tips. This polarized growth requires the continuous delivery of secretory vesicles to the tip region. Vesicle delivery depends on Sec2p, the Guanine Exchange Factor (GEF) for the Rab GTPase Sec4p. GTP bound Sec4p is required for the transit of secretory vesicles from the trans-Golgi to sites of polarized growth. We previously showed that phosphorylation of Sec2p at residue S584 was necessary for Sec2p to support hyphal, but not yeast growth. Here we show that on secretory vesicles SEC2 mRNA is physically associated with Sec2p. Moreover, we show that the phosphorylation of S584 allows SEC2 mRNA to dissociate from Sec2p and we speculate that this is necessary for Sec2p function and/or translation. During hyphal extension, the growing tip may be separated from the nucleus by up to 15 μm. Transport of SEC2 mRNA on secretory vesicles to the tip localizes SEC2 translation to tip allowing a sufficient accumulation of this key protein at the site of polarized growth. © 2014 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.

  13. Electric field strength and focality in electroconvulsive therapy and magnetic seizure therapy: a finite element simulation study

    NASA Astrophysics Data System (ADS)

    Deng, Zhi-De; Lisanby, Sarah H.; Peterchev, Angel V.

    2011-02-01

    We present the first computational study comparing the electric field induced by various electroconvulsive therapy (ECT) and magnetic seizure therapy (MST) paradigms. Four ECT electrode configurations (bilateral, bifrontal, right unilateral, and focal electrically administered seizure therapy) and three MST coil configurations (circular, cap, and double cone) were modeled. The model incorporated a modality-specific neural activation threshold. ECT (0.3 ms pulse width) and MST induced the maximum electric field of 2.1-2.5 V cm-1 and 1.1-2.2 V cm-1 in the brain, corresponding to 6.2-7.2 times and 1.2-2.3 times the neural activation threshold, respectively. The MST electric field is more confined to the superficial cortex compared to ECT. The brain volume stimulated was much larger with ECT (up to 100%) than with MST (up to 8.2%). MST with the double-cone coil was the most focal, and bilateral ECT was the least focal. Our results suggest a possible biophysical explanation of the reduced side effects of MST compared to ECT. Our results also indicate that the conventional ECT pulse amplitude (800-900 mA) is much higher than necessary for seizure induction. Reducing the ECT pulse amplitude should be explored as a potential means of diminishing side effects.

  14. Electric field strength and focality in electroconvulsive therapy and magnetic seizure therapy: A finite element simulation study

    PubMed Central

    Deng, Zhi-De; Lisanby, Sarah H.; Peterchev, Angel V.

    2014-01-01

    We present the first computational study comparing the electric field induced by various electroconvulsive therapy (ECT) and magnetic seizure therapy (MST) paradigms. Four ECT electrode configurations (bilateral, bifrontal, right unilateral, and focal electrically administered seizure therapy) and three MST coil configurations (circular, cap, and double cone) were modeled. The model incorporated a modality-specific neural activation threshold. ECT (0.3 ms pulse width) and MST induced maximum electric field in the brain of 2.1–2.5 V/cm and 1.1–2.2 V/cm, corresponding to 6.2–7.2 times and 1.22.3 times the neural activation threshold, respectively. The MST electric field is more confined to the superficial cortex compared to ECT. The brain volume stimulated was much higher with ECT (up to 100%) than MST (up to 8.2%). MST with the double cone coil was the most focal and bilateral ECT was the least focal. Our results suggest a possible biophysical explanation of the reduced side effects of MST compared to ECT. Our results also indicate that the conventional ECT pulse amplitude (800–900 mA) is much higher than necessary for seizure induction. Reducing the ECT pulse amplitude should be explored as a potential means of diminishing side effects. PMID:21248385

  15. Direct recovery of regional tracer kinetics from temporally inconsistent dynamic ECT projections using dimension-reduced time-activity basis

    NASA Astrophysics Data System (ADS)

    Maltz, Jonathan S.

    2000-11-01

    We present an algorithm of reduced computational cost which is able to estimate kinetic model parameters directly from dynamic ECT sinograms made up of temporally inconsistent projections. The algorithm exploits the extreme degree of parameter redundancy inherent in linear combinations of the exponential functions which represent the modes of first-order compartmental systems. The singular value decomposition is employed to find a small set of orthogonal functions, the linear combinations of which are able to accurately represent all modes within the physiologically anticipated range in a given study. The reduced-dimension basis is formed as the convolution of this orthogonal set with a measured input function. The Moore-Penrose pseudoinverse is used to find coefficients of this basis. Algorithm performance is evaluated at realistic count rates using MCAT phantom and clinical 99mTc-teboroxime myocardial study data. Phantom data are modelled as originating from a Poisson process. For estimates recovered from a single slice projection set containing 2.5×105 total counts, recovered tissue responses compare favourably with those obtained using more computationally intensive methods. The corresponding kinetic parameter estimates (coefficients of the new basis) exhibit negligible bias, while parameter variances are low, falling within 30% of the Cramér-Rao lower bound.

  16. Role of Abl kinase and the Wave2 signaling complex in HIV-1 entry at a post-hemifusion step.

    PubMed

    Harmon, Brooke; Campbell, Nancy; Ratner, Lee

    2010-06-17

    Entry of human immunodeficiency virus type 1 (HIV-1) commences with binding of the envelope glycoprotein (Env) to the receptor CD4, and one of two coreceptors, CXCR4 or CCR5. Env-mediated signaling through coreceptor results in Galphaq-mediated Rac activation and actin cytoskeleton rearrangements necessary for fusion. Guanine nucleotide exchange factors (GEFs) activate Rac and regulate its downstream protein effectors. In this study we show that Env-induced Rac activation is mediated by the Rac GEF Tiam-1, which associates with the adaptor protein IRSp53 to link Rac to the Wave2 complex. Rac and the tyrosine kinase Abl then activate the Wave2 complex and promote Arp2/3-dependent actin polymerization. Env-mediated cell-cell fusion, virus-cell fusion and HIV-1 infection are dependent on Tiam-1, Abl, IRSp53, Wave2, and Arp3 as shown by attenuation of fusion and infection in cells expressing siRNA targeted to these signaling components. HIV-1 Env-dependent cell-cell fusion, virus-cell fusion and infection were also inhibited by Abl kinase inhibitors, imatinib, nilotinib, and dasatinib. Treatment of cells with Abl kinase inhibitors did not affect cell viability or surface expression of CD4 and CCR5. Similar results with inhibitors and siRNAs were obtained when Env-dependent cell-cell fusion, virus-cell fusion or infection was measured, and when cell lines or primary cells were the target. Using membrane curving agents and fluorescence microscopy, we showed that inhibition of Abl kinase activity arrests fusion at the hemifusion (lipid mixing) step, suggesting a role for Abl-mediated actin remodeling in pore formation and expansion. These results suggest a potential utility of Abl kinase inhibitors to treat HIV-1 infected patients.

  17. Reducing Falls After Electroconvulsive Therapy: A Quality Improvement Project.

    PubMed

    Brown, Allana Marie

    2017-07-01

    Falls after electroconvulsive therapy (ECT) in patients 60 and older have been long recognized as a major clinical care issue across many mental health care settings. The evidence base for fall prevention strategies after receiving ECT is sparse. The risk factors for falls after ECT are vast and complex in nature, especially considering existing comorbid medical conditions. The dearth of research in guiding practitioners on fall reduction interventions for this patient population illuminates a gap in mental health care quality and safety. The purpose of the current nurse-led quality improvement project was to reduce falls in patients undergoing ECT by enhancing safety measures through education and a post-ECT treatment protocol. The project did not prove to be as efficacious as anticipated as measured by fall rate outcomes. Several factors that may account for the project's findings are discussed. [Journal of Psychosocial Nursing and Mental Health Services, 55(7), 20-29.]. Copyright 2017, SLACK Incorporated.

  18. Machineries regulating the activity of the small GTPase Arf6 in cancer cells are potential targets for developing innovative anti-cancer drugs.

    PubMed

    Yamauchi, Yohei; Miura, Yuki; Kanaho, Yasunori

    2017-01-01

    The Small GTPase ADP-ribosylation factor 6 (Arf6) functions as the molecular switch in cellular signaling pathways by cycling between GDP-bound inactive and GTP-bound active form, which is precisely regulated by two regulators, guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Numerous studies have shown that these machineries play critical roles in tumor angiogenesis/growth and cancer cell invasion/metastasis through regulating the cycling of Arf6. Here, we summarize accumulating knowledge for involvement of Arf6 GEFs/GAPs and small molecule inhibitors of Arf6 signaling/cycling in cancer progression, and discuss possible strategies for developing innovative anti-cancer drugs targeting Arf6 signaling/cycling. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Evidence for the Involvement of Lfc and Tctex-1 in Axon Formation

    PubMed Central

    Conde, Cecilia; Arias, Cristina; Robin, Maria; Li, Aiqun; Saito, Masaki; Chuang, Jen-Zen; Nairn, Angus C.; Sung, Ching-Hwa; Cáceres, Alfredo

    2013-01-01

    RhoA and Rac play key and opposite roles during neuronal polarization. We now show that Lfc, a guanosine nucleotide exchange factor (GEF), localizes to the Golgi apparatus and growth cones of developing neurons and negatively regulates neurite sprouting and axon formation through a Rho signaling pathway. Tctex-1, a dynein light chain implicated in axon outgrowth by modulating actin dynamics and Rac activity, colocalizes and physically interacts with Lfc, thus inhibiting its GEF activity, decreasing Rho-GTP levels, and functionally antagonizing Lfc during neurite formation. PMID:20463241

  20. The G Protein α Chaperone Ric-8 as a Potential Therapeutic Target

    PubMed Central

    Papasergi, Makaía M.; Patel, Bharti R.

    2015-01-01

    Resistance to inhibitors of cholinesterase (Ric-8)A and Ric-8B are essential genes that encode positive regulators of heterotrimeric G protein α subunits. Controversy persists surrounding the precise way(s) that Ric-8 proteins affect G protein biology and signaling. Ric-8 proteins chaperone nucleotide-free Gα-subunit states during biosynthetic protein folding prior to G protein heterotrimer assembly. In organisms spanning the evolutionary window of Ric-8 expression, experimental perturbation of Ric-8 genes results in reduced functional abundances of G proteins because G protein α subunits are misfolded and degraded rapidly. Ric-8 proteins also act as Gα-subunit guanine nucleotide exchange factors (GEFs) in vitro. However, Ric-8 GEF activity could strictly be an in vitro phenomenon stemming from the ability of Ric-8 to induce partial Gα unfolding, thereby enhancing GDP release. Ric-8 GEF activity clearly differs from the GEF activity of G protein–coupled receptors (GPCRs). G protein βγ is inhibitory to Ric-8 action but obligate for receptors. It remains an open question whether Ric-8 has dual functions in cells and regulates G proteins as both a molecular chaperone and GEF. Clearly, Ric-8 has a profound influence on heterotrimeric G protein function. For this reason, we propose that Ric-8 proteins are as yet untested therapeutic targets in which pharmacological inhibition of the Ric-8/Gα protein–protein interface could serve to attenuate the effects of disease-causing G proteins (constitutively active mutants) and/or GPCR signaling. This minireview will chronicle the understanding of Ric-8 function, provide a comparative discussion of the Ric-8 molecular chaperoning and GEF activities, and support the case for why Ric-8 proteins should be considered potential targets for development of new therapies. PMID:25319541

  1. A prospective comparative study of interaction between lithium and modified electroconvulsive therapy.

    PubMed

    Thirthalli, Jagadisha; Harish, Thippeswamy; Gangadhar, Bangalore N

    2011-03-01

    To compare patients on lithium and those not on lithium with regard to adverse effects while receiving ECT. Inpatients with schizophrenia, non-organic psychosis, mania and depression, who were prescribed ECTs either on (n=27) or not (n=28) on lithium were studied. Clinicians blind to lithium-status recorded seizure parameters, interaction with succinyl choline, cardiovascular response, recovery from ECT and immediate post-ECT complications. The lithium group showed no significant difference in terms of seizure variables, apnea time, and recovery from anaesthesia when compared to the non-lithium group. Average maximum heart rate, average maximum systolic blood pressure and average maximum rate pressure product were significantly lower in patients who had combined lithium and ECT. In lithium patients the average time to post-ECT recovery was directly correlated with serum lithium level. Though concurrent lithium is by and large safe during ECT, it benefits to maintain serum lithium level at lower end of therapeutic range. However, the findings can be applied to relatively young patients with no risk factors for ECT-complications.

  2. Vav family exchange factors: an integrated regulatory and functional view

    PubMed Central

    Bustelo, Xosé R

    2014-01-01

    The Vav family is a group of tyrosine phosphorylation-regulated signal transduction molecules hierarchically located downstream of protein tyrosine kinases. The main function of these proteins is to work as guanosine nucleotide exchange factors (GEFs) for members of the Rho GTPase family. In addition, they can exhibit a variety of catalysis-independent roles in specific signaling contexts. Vav proteins play essential signaling roles for both the development and/or effector functions of a large variety of cell lineages, including those belonging to the immune, nervous, and cardiovascular systems. They also contribute to pathological states such as cancer, immune-related dysfunctions, and atherosclerosis. Here, I will provide an integrated view about the evolution, regulation, and effector properties of these signaling molecules. In addition, I will discuss the pros and cons for their potential consideration as therapeutic targets. PMID:25483299

  3. In-hospital mortality among electroconvulsive therapy recipients: A 17-year nationwide population-based retrospective study.

    PubMed

    Liang, C-S; Chung, C-H; Tsai, C-K; Chien, W-C

    2017-05-01

    Electroconvulsive therapy (ECT) remains irreplaceable in the treatment of several psychiatric conditions. However, evidence derived using data from a national database to support its safety is limited. The aim of this study was to investigate in-hospital mortality among patients with psychiatric conditions treated with and without ECT. Using data from the Taiwan National Health Insurance Research Database from 1997 to 2013, we identified 828,899 inpatients with psychiatric conditions, among whom 0.19% (n=1571) were treated with ECT. We found that ECT recipients were more frequently women, were younger and physically healthier, lived in more urbanized areas, were treated in medical centers, and had longer hospital stays. ECT recipients had lower odds of in-hospital mortality than did those who did not receive ECT. Moreover, no factor was identified as being able to predict mortality in patients who underwent ECT. Among all patients, ECT was not associated with in-hospital mortality after controlling for potential confounders. ECT was indicated to be safe and did not increase the odds of in-hospital mortality. However, ECT appeared to be administered only on physically healthy but psychiatrically compromised patients, a pattern that is in opposition with the scientific evidence supporting its safety. Moreover, our data suggest that ECT is still used as a treatment of last resort in the era of modern psychiatry. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  4. Discovery of Aminopiperidine Indoles That Activate the Guanine Nucleotide Exchange Factor SOS1 and Modulate RAS Signaling.

    PubMed

    Abbott, Jason R; Hodges, Timothy R; Daniels, R Nathan; Patel, Pratiq A; Kennedy, Jack Phillip; Howes, Jennifer E; Akan, Denis T; Burns, Michael C; Sai, Jiqing; Sobolik, Tammy; Beesetty, Yugandhar; Lee, Taekyu; Rossanese, Olivia W; Phan, Jason; Waterson, Alex G; Fesik, Stephen W

    2018-06-01

    Deregulated RAS activity, often the result of mutation, is implicated in approximately 30% of all human cancers. Despite this statistic, no clinically successful treatment for RAS-driven tumors has yet been developed. One approach for modulating RAS activity is to target and affect the activity of proteins that interact with RAS, such as the guanine nucleotide exchange factor (GEF) son of sevenless homologue 1 (SOS1). Here, we report on structure-activity relationships (SAR) in an indole series of compounds. Using structure-based design, we systematically explored substitution patterns on the indole nucleus, the pendant amino acid moiety, and the linker unit that connects these two fragments. Best-in-class compounds activate the nucleotide exchange process at sub-micromolar concentrations in vitro, increase levels of active RAS-GTP in HeLa cells, and elicit signaling changes in the mitogen-activated protein kinase/extracellular regulated kinase (MAPK/ERK) pathway, resulting in a decrease in pERK1/2 T202/Y204 protein levels at higher compound concentrations.

  5. Treatment of Adults With Treatment-Resistant Depression: Electroconvulsive Therapy Plus Antidepressant or Electroconvulsive Therapy Alone? Evidence From an Indirect Comparison Meta-Analysis

    PubMed Central

    Song, Guo-Min; Tian, Xu; Shuai, Ting; Yi, Li-Juan; Zeng, Zi; Liu, Shuang; Zhou, Jian-Guo; Wang, Yan

    2015-01-01

    Abstract Electroconvulsive therapy (ECT) and antidepressant are the effective treatment alternatives for patients with treatment-resistant depression (TRD); however, the effects and safety of the ECT plus antidepressant relative to ECT alone remain controversial. We decide to assess the potential of ECT plus antidepressant compared with ECT alone by undertaking an indirect comparison meta-analysis. Databases from PubMed, ISI Web of Science, CENTRAL, Clinicaltrials.gov, EMBASE, CBM (China Biomediccal Literatures Database), and CNKI (China National Knowledge Infrastructure) were searched for relevant studies through November 21, 2014. Literature was screened, data were extracted and methodological quality of the eligible trial was assessed by 2 independent reviewers accordingly. Then, head-to-head and indirect comparison meta-analyses were carried out. A total of 17 studies which including 13 studies regarding ECT plus antidepressant versus antidepressant alone and 4 studies concerning ECT versus antidepressant alone containing a total of 1098 patients were incorporated into this meta-analysis. The head-to-head comparison suggested that response rate can be improved in the ECT plus antidepressant (RR, 1.82; 95% CI, 1.55–2.14) and ECT alone group (RR, 2.24, 95% CI, 1.51–3.33) compared with antidepressant alone, respectively; adverse complications including memory deterioration and somatization were not significantly increased except incidence of memory deterioration in ECT plus antidepressant in the 4th weeks after treatment (RR, 0.09, 95% CI, 0.02–0.49). Indirect comparison meta-analysis showed that no significant differences were detected in response rate and memory deterioration between ECT plus antidepressant and ECT alone. However, ECT plus antidepressant increased the incidence of memory deterioration relative to ECT alone. With present evidence, the regime of ECT plus antidepressant should not be preferentially recommended to treat the patients with TRD

  6. Increased BDNF levels after electroconvulsive therapy in patients with major depressive disorder: A meta-analysis study.

    PubMed

    Rocha, Renan Boeira; Dondossola, Eduardo Ronconi; Grande, Antônio José; Colonetti, Tamy; Ceretta, Luciane Bisognin; Passos, Ives C; Quevedo, Joao; da Rosa, Maria Inês

    2016-12-01

    We performed a systematic review and meta-analysis to estimate brain-derived neurotrophic factor (BDNF) level in patients with major depressive disorder (MDD) after electroconvulsive therapy (ECT). A comprehensive search of the Cochrane Library, MEDLINE, LILACS, Grey literature, and EMBASE was performed for papers published from January 1990 to April 2016. The following key terms were searched: "major depressive disorder", "unipolar depression", "brain-derived neurotrophic factor", and "electroconvulsive therapy". A total of 252 citations were identified by the search strategy, and nine studies met the inclusion criteria of the meta-analysis. BDNF levels were increased among patients with MDD after ECT (P value = 0.006). The standardized mean difference was 0.56 (95% CI: 0.17-0.96). Additionally, we found significant heterogeneity between studies (I 2  = 73%). Our findings suggest a potential role of BDNF as a marker of treatment response after ECT in patients with MDD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Cell division requires a direct link between microtubule-bound RacGAP and Anillin in the contractile ring.

    PubMed

    Gregory, Stephen L; Ebrahimi, Saman; Milverton, Joanne; Jones, Whitney M; Bejsovec, Amy; Saint, Robert

    2008-01-08

    The mitotic microtubule array plays two primary roles in cell division. It acts as a scaffold for the congression and separation of chromosomes, and it specifies and maintains the contractile-ring position. The current model for initiation of Drosophila and mammalian cytokinesis [1-5] postulates that equatorial localization of a RhoGEF (Pbl/Ect2) by a microtubule-associated motor protein complex creates a band of activated RhoA [6], which subsequently recruits contractile-ring components such as actin, myosin, and Anillin [1-3]. Equatorial microtubules are essential for continued constriction, but how they interact with the contractile apparatus is unknown. Here, we report the first direct molecular link between the microtubule spindle and the actomyosin contractile ring. We find that the spindle-associated component, RacGAP50C, which specifies the site of cleavage [1-5], interacts directly with Anillin, an actin and myosin binding protein found in the contractile ring [7-10]. Both proteins depend on this interaction for their localization. In the absence of Anillin, the spindle-associated RacGAP loses its association with the equatorial cortex, and cytokinesis fails. These results account for the long-observed dependence of cytokinesis on the continual presence of microtubules at the cortex.

  8. Improving medium-range and seasonal hydroclimate forecasts in the southeast USA

    NASA Astrophysics Data System (ADS)

    Tian, Di

    Accurate hydro-climate forecasts are important for decision making by water managers, agricultural producers, and other stake holders. Numerical weather prediction models and general circulation models may have potential for improving hydro-climate forecasts at different scales. In this study, forecast analogs of the Global Forecast System (GFS) and Global Ensemble Forecast System (GEFS) based on different approaches were evaluated for medium-range reference evapotranspiration (ETo), irrigation scheduling, and urban water demand forecasts in the southeast United States; the Climate Forecast System version 2 (CFSv2) and the North American national multi-model ensemble (NMME) were statistically downscaled for seasonal forecasts of ETo, precipitation (P) and 2-m temperature (T2M) at the regional level. The GFS mean temperature (Tmean), relative humidity, and wind speed (Wind) reforecasts combined with the climatology of Reanalysis 2 solar radiation (Rs) produced higher skill than using the direct GFS output only. Constructed analogs showed slightly higher skill than natural analogs for deterministic forecasts. Both irrigation scheduling driven by the GEFS-based ETo forecasts and GEFS-based ETo forecast skill were generally positive up to one week throughout the year. The GEFS improved ETo forecast skill compared to the GFS. The GEFS-based analog forecasts for the input variables of an operational urban water demand model were skillful when applied in the Tampa Bay area. The modified operational models driven by GEFS analog forecasts showed higher forecast skill than the operational model based on persistence. The results for CFSv2 seasonal forecasts showed maximum temperature (Tmax) and Rs had the greatest influence on ETo. The downscaled Tmax showed the highest predictability, followed by Tmean, Tmin, Rs, and Wind. The CFSv2 model could better predict ETo in cold seasons during El Nino Southern Oscillation (ENSO) events only when the forecast initial condition was in

  9. Factor Structure and Validity of Paper-and-Pencil Measures of Mental Speed: Evidence for a Higher-Order Model?

    ERIC Educational Resources Information Center

    Danthiir, Vanessa; Wilhelm, Oliver; Schulze, Ralf; Roberts, Richard D.

    2005-01-01

    This study explored the structure of elementary cognitive tasks (ECTs) and relations between the corresponding construct(s) with processing speed (Gs) and fluid intelligence (Gf). Participants (N=321) completed 14 ECTs, 3 Gs, and 6 Gf marker tests, all administered in paper-and-pencil format to reduce potential confounds evident when tasks are…

  10. Episodic Visual Learning/Memory and Attentional Flexibility in Patients With Major Depressive Disorder After Clinically Effective Electroconvulsive Therapy.

    PubMed

    Kalogerakou, Stamatina; Oulis, Panagiotis; Anyfandi, Eleni; Konstantakopoulos, George; Papakosta, Vasiliki-Maria; Kontis, Dimitrios; Theochari, Eirini; Angelopoulos, Elias; Zervas, Ioannis M; Mellon, Robert C; Papageorgiou, Charalambos C; Tsaltas, Eleftheria

    2015-12-01

    This study is a follow-up of a previous one reporting that the neuropsychological profile of pharmacoresistant patients with major depressive disorder referred for electroconvulsive therapy (ECT, ECT group) contrasted with that of their pharmacorespondent counterparts (NECT group). The NECT group exhibited severe visuospatial memory and minor executive deficits; the ECT group presented the reverse pattern. In that same ECT group, the current follow-up study examined the effects of clinically effective ECT on both cognitive domains 2 months later. Fifteen ECT patients were administered Hamilton Depression (HAMD-24), Hamilton Anxiety (HAMA), Mini-Mental State Examination Scales and 5 tests of Cambridge Neuropsychological Test Automated Battery at intake (pre-ECT), end of ECT course (post-ECT), and 2 months thereafter (follow-up). Electroconvulsive therapy was effective in relieving clinical depression. After a post-ECT decline, the patients exhibited significant improvement in both Cambridge Neuropsychological Test Automated Battery, paired associate learning, and Stockings of Cambridge. By contrast, their major pre-ECT deficit in intra/extradimensional set shifting remained virtually unaffected. Our findings suggest that attentional flexibility deficits may constitute a neuropsychological trait-like feature of pharmacoresistant, ECT-referred major depressive disorder patients. However, this deficit does not seem generalized, given patient improvement in episodic visual learning/memory and some indication of improvement in spatial planning after ECT.

  11. Neuropeptide-stimulated cell migration in prostate cancer cells is mediated by RhoA kinase signaling and inhibited by neutral endopeptidase.

    PubMed

    Zheng, R; Iwase, A; Shen, R; Goodman, O B; Sugimoto, N; Takuwa, Y; Lerner, D J; Nanus, D M

    2006-09-28

    The neuropeptides bombesin and endothelin-1 stimulate prostate cancer (PC) cell migration and invasion (J Clin Invest, 2000; 106: 1399-1407). The intracellular signaling pathways that direct this cell movement are not well delineated. The monomeric GTPase RhoA is required for migration in several cell types including neutrophils, monocytes and fibroblasts. We demonstrate that bombesin-stimulated PC cell migration occurs via the heterotrimeric G-protein-coupled receptors (G-protein) G alpha 13 subunit leading to activation of RhoA, and Rho-associated coiled-coil forming protein kinase (ROCK). Using siRNA to suppress expression of the three known G-protein alpha-subunit-associated RhoA guanine nucleotide exchange factors (GEFs), we also show that two of these RhoA GEFs, PDZ-RhoGEF and leukemia-associated RhoGEF (LARG), link bombesin receptors to RhoA in a non-redundant manner in PC cells. We next show that focal adhesion kinase, which activates PDZ-RhoGEF and LARG, is required for bombesin-stimulated RhoA activation. Neutral endopeptidase (NEP) is expressed on normal prostate epithelium whereas loss of NEP expression contributes to PC progression. We also demonstrate that NEP inhibits neuropeptide activation of RhoA. Together, these results establish a contiguous signaling pathway from the bombesin receptor to ROCK in PC cells, and they implicate NEP as a major regulator of neuropeptide-stimulated RhoA in these cells. This work also identifies members of this signaling pathway as potential targets for rational pharmacologic manipulation of neuropeptide-stimulated migration of PC cells.

  12. The mortality rate of electroconvulsive therapy: a systematic review and pooled analysis.

    PubMed

    Tørring, N; Sanghani, S N; Petrides, G; Kellner, C H; Østergaard, S D

    2017-05-01

    Electroconvulsive therapy (ECT) remains underutilized because of fears of cognitive and medical risks, including the risk of death. In this study, we aimed to assess the mortality rate of ECT by means of a systematic review and pooled analysis. The study was conducted in adherence with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The ECT-related mortality rate was calculated as the total number of ECT-related deaths reported in the included studies divided by the total number of ECT treatments. Fifteen studies with data from 32 countries reporting on a total of 766 180 ECT treatments met the inclusion criteria. Sixteen cases of ECT-related death were reported in the included studies yielding an ECT-related mortality rate of 2.1 per 100 000 treatments (95% CI: 1.2-3.4). In the nine studies that were published after 2001 (covering 414 747 treatments), there was only one reported ECT-related death. The ECT-related mortality rate was estimated at 2.1 per 100 000 treatments. In comparison, a recent analysis of the mortality of general anesthesia in relation to surgical procedures reported a mortality rate of 3.4 per 100 000. Our findings document that death caused by ECT is an extremely rare event. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Pulmonary edema after electroconvulsive therapy in a patient treated for long-standing asthma with a beta2 stimulant.

    PubMed

    Hatta, Kotaro; Kitajima, Akiyoshi; Ito, Masanobu; Usui, Chie; Arai, Heii

    2007-03-01

    A 68-year-old man was scheduled to receive 8 treatments of electroconvulsive therapy (ECT) for severe depression. He was being treated for long-standing asthma with a beta2 stimulant, clenbuterol hydrochloride, and had experienced no asthma attack for 9 years. Although he experienced no adverse consequence in his 7 treatments, pulmonary edema ensued from his eighth treatment despite no change in anesthesia and in the technical parameters of ECT. He was treated with oxygen and intravenous hydrocortisone, after which he quickly recovered. Transient eosinophilia was observed, but clinical symptoms of asthma did not appear. Although the association between pulmonary edema and well-controlled asthma was unclear, thiopental as induction of anesthesia or esmolol as poststimulus delivery might have played a role in the event. There may be a possibility of pulmonary edema even after several uneventful ECT treatments in a patient with asthma.

  14. Electroconvulsive therapy and aerobic exercise training increased BDNF and ameliorated depressive symptoms in patients suffering from treatment-resistant major depressive disorder.

    PubMed

    Salehi, Iraj; Hosseini, Seyed Mohammad; Haghighi, Mohammad; Jahangard, Leila; Bajoghli, Hafez; Gerber, Markus; Pühse, Uwe; Kirov, Roumen; Holsboer-Trachsler, Edith; Brand, Serge

    2014-10-01

    To treat patients suffering from treatment-resistant major depressive disorder (TR-MDD), research has focused on electroconvulsive therapy (ECT) and aerobic exercise training (AET). Brain derived neurotrophic factor (BDNF) seems to be key in MDD. The aims of the present study were therefore two-fold, to investigate in a three-arm interventional study the differential effects of ECT, ECT plus AET, and AET alone in patients suffering from TR-MDD on 1. depressive symptoms and 2. 60 patients with TR-MDD (mean age: 31 years; 31.6% female patients) were randomly assigned either to the ECT, ECT + AET, or AET condition. The AET condition consisted of treadmill exercise for 30 min, three times a week. Both depression severity and BDNF levels were assessed at baseline and 4 weeks later. All patients were further treated with an SSRI standard medication. BDNF levels increased over time in all three study conditions. After completion of the intervention program, the ECT group showed significantly higher BDNF levels compared to the ECT + AET and the AET conditions. Depressive symptoms decreased in all three conditions over time. The combination of ECT + AET led to a significantly greater decrease than in either the ECT or AET alone conditions. BDNF levels were not associated with symptoms of depression. The pattern of results suggests that ECT, AET and particularly their combination are promising directions for treatment patients suffering from TR-MDD, and that it remains unclear to what extent BDNF is key and a reliable biomarker for TR-MDD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Analysis of the hygrothermal effects and parametric study of the edge crack torsion (ECT) mode 3 test layups

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, J.; O`Brien, T.K.

    1997-12-31

    A shear deformation theory including residual thermal and moisture effects is developed for the analysis of either symmetric or asymmetric laminates with midplane edge delamination under torsional loading. The theory is based on an assumed displacement field that includes shear deformation. The governing equations and boundary conditions are obtained from the principle of virtual work. The analysis of the [90/({+-}45){sub n}/({+-}45){sub n}/90]{sub s} edge crack torsion (ECT) Mode 3 test layup indicates that thee are no hygrothermal effects on the Mode 3 strain energy release rate because the laminate, and both sublaminates above and below the delamination, are symmetric layups.more » A further parametric study reveals that some other layups can have negligible hygrothermal effects even when the sublaminates above and below the delamination are not symmetric about their own midplanes. However, these layups may suffer from distortion after the curing process. Another interesting set of layups investigated is a class of antisymmetric laminates with [{+-}({theta}/{theta} {minus} 90){sub 2}/{theta}]{sub n} layups. It is observed that when n takes on even numbers (2 and 4), both hygrothermal and Mode 1 effects can be neglected. From this point of view, these layups provide a way to determine the Mode 3 toughness between two dissimilar layers. However, when n takes on odd numbers (1 and 3), both hygrothermal and Mode 1 effects may be strong in these layups. In particular, when {theta} equals 45{degree}, the layups are free from both hygrothermal and Mode 1 effects irrespective of n.« less

  16. An m6A-YTH Module Controls Developmental Timing and Morphogenesis in Arabidopsis.

    PubMed

    Arribas-Hernández, Laura; Bressendorff, Simon; Hansen, Mathias Henning; Poulsen, Christian; Erdmann, Susanne; Brodersen, Peter

    2018-04-11

    Methylation of N6-adenosine (m6A) in mRNA is an important post-transcriptional gene regulatory mechanism in eukaryotes. m6A provides a binding site for effector proteins ("readers") that influence pre-mRNA splicing, mRNA degradation or translational efficiency. YT521-B homology (YTH) domain proteins are important m6A readers with established functions in animals. Plants contain more YTH domain proteins than other eukaryotes, but their biological importance remains unknown. Here, we show that the cytoplasmic Arabidopsis thaliana YTH domain proteins EVOLUTIONARILY CONSERVED C-TERMINAL REGION2/3 (ECT2/3) are required for the correct timing of leaf formation and for normal leaf morphology. These functions depend fully on intact m6A binding sites of ECT2 and ECT3, indicating that they function as m6A readers. Mutation of the close ECT2 homolog, ECT4, enhances the delayed leaf emergence and leaf morphology defects of ect2/ect3 mutants, and all three ECT proteins are expressed at leaf formation sites in the shoot apex of young seedlings and in the division zone of developing leaves. ECT2 and ECT3 are also highly expressed at early stages of trichome development and are required for trichome morphology, as previously reported for m6A itself. Overall, our study establishes the relevance of a cytoplasmic m6A-YTH regulatory module in the timing and execution of plant organogenesis. © 2018 American Society of Plant Biologists. All rights reserved.

  17. Continuation and Maintenance Electroconvulsive Therapy for Mood Disorders: Review of the Literature

    PubMed Central

    Petrides, Georgios; Tobias, Kristen G.; Kellner, Charles H.; Rudorfer, Matthew V.

    2011-01-01

    Background Electroconvulsive therapy (ECT) is a highly effective treatment for mood disorders. Continuation ECT (C-ECT) and maintenance ECT (M-ECT) are required for many patients suffering from severe and recurrent forms of mood disorders. This is a review of the literature regarding C- and M-ECT. Methods We conducted a computerized search using the words continuation ECT, maintenance ECT, depression, mania, bipolar disorder and mood disorders. We report on all articles published in the English language from 1998 to 2009. Results We identified 32 reports. There were 24 case reports and retrospective reviews on 284 patients. Two of these reports included comparison groups, and 1 had a prospective follow-up in a subset of subjects. There were 6 prospective naturalistic studies and 2 randomized controlled trials. Conclusions C-ECT and M-ECT are valuable treatment modalities to prevent relapse and recurrence of mood disorders in patients who have responded to an index course of ECT. C-ECT and M-ECT are underused and insufficiently studied despite positive clinical experience of more than 70 years. Studies which are currently under way should allow more definitive recommendations regarding the choice, frequency and duration of C-ECT and M-ECT following acute ECT. PMID:21811083

  18. [Virulence determinant of Chromobacterium violaceum].

    PubMed

    Miki, Tsuyoshi

    2014-01-01

    Chromobacterium violaceum is a Gram-negative bacterium that infects humans and animals with fatal sepsis. The infection with C. violaceum is rare in case of those who are healthy, but once established, C. violaceum causes sever disease accompanied by abscess formation in the lungs, liver and spleen. Furthermore, C. violaceum is resistant to a broad range of antibiotics, which in some cases renders the antimicrobial therapy for this infection difficult. Thus, the infection with C. violaceum displays high mortality rates unless initial proper antimicrobial therapy. In contrast, the infection mechanism had completely remained unknown. To this end, we have tried to identify virulence factors-associated with C. violaceum infection. Two distinct type III secretion systems (TTSSs) were thought to be one of the most important virulence factors, which are encoded by Chromobacterium pathogenicity island 1/1a and 2 (Cpi-1/-1a and -2) respectively. Our results have shown that Cpi-1/-1a-encoded TTSS, but not Cpi-2, is indispensable for the virulence in a mouse infection model. C. violaceum caused fulminant hepatitis in a Cpi-1/-1a-encoded TTSS-dependent manner. We next have identified 16 novel effectors secreted from Cpi-1/-1a-encoded TTS machinery. From these effectors, we found that CopE (Chromobacterium outer protein E) has similarities to a guanine nucleotide exchange factor (GEF) for Rho GTPases. CopE acts as GEF for Rac1 and Cdc42, leading to induction of actin cytoskeletal rearrangement. Interestingly, C. violaceum invades cultured human epithelial cells in a CopE-dependent manner. Finally, an inactivation of CopE by disruption of copE gene or amino acid point mutation leading to loss of GEF activity attenuates significantly the mouse virulence of C. violaceum. These results suggest that Cpi-1/-1a-encoded TTSS is a major virulence determinant for C. violaceum infection, and that CopE contributes to the virulence in part of this pathogen.

  19. A critical examination of bifrontal electroconvulsive therapy: clinical efficacy, cognitive side effects, and directions for future research.

    PubMed

    Crowley, Kevin; Pickle, Jody; Dale, Roman; Fattal, Omar

    2008-12-01

    Bifrontal (BF) electroconvulsive therapy (ECT), although researched less extensively than bitemporal (BT) or right unilateral (RUL) ECT, has been suggested to be comparable to the other 2 electrode placements with respect to clinical efficacy while resulting in less cognitive impairment than BT ECT. Imaging studies have indicated that seizures induced by BF ECT affect the brain differently than BT or RUL ECT, in that BF ECT increases cerebral blood flow in the frontal lobes more intensely than either of the other 2 placements. Therefore, it is possible that the cognitive impairment manifested after a course of BF ECT could also be different than the impairment seen with BT and RUL ECT. Research conducted on cognitive impairment from BF ECT to date has been inadequate due to the use of nonspecific cognitive measures (such as the Mini-Mental Status Examination) or an inordinate focus on memory functioning (which is believed to be mostly subsumed in the temporal lobes). Because BF ECT increases cerebral blood flow in the frontal lobes more intensely than either of the other placements, research must instead focus on investigating the possible effects of BF ECT on executive functioning, which is believed to be subsumed in the frontal lobes. This is especially important because of the established relationship between executive dysfunction and depression and also because of the increasing popularity of BF ECT.

  20. Kelch-like ECH-associated Protein 1-dependent Nuclear Factor-E2-related Factor 2 Activation in Relation to Antioxidation Induced by Sevoflurane Preconditioning.

    PubMed

    Cai, Min; Tong, Li; Dong, Beibei; Hou, Wugang; Shi, Likai; Dong, Hailong

    2017-03-01

    The authors have reported that antioxidative effects play a crucial role in the volatile anesthetic-induced neuroprotection. Accumulated evidence shows that endogenous antioxidation could be up-regulated by nuclear factor-E2-related factor 2 through multiple pathways. However, whether nuclear factor-E2-related factor 2 activation is modulated by sevoflurane preconditioning and, if so, what is the signaling cascade underlying upstream of this activation are still unknown. Sevoflurane preconditioning in mice was performed with sevoflurane (2.5%) 1 h per day for five consecutive days. Focal cerebral ischemia/reperfusion injury was induced by middle cerebral artery occlusion. Expression of nuclear factor-E2-related factor 2, kelch-like ECH-associated protein 1, manganese superoxide dismutase, thioredoxin-1, and nicotinamide adenine dinucleotide phosphate quinolone oxidoreductase-1 was detected (n = 6). The antioxidant activities and oxidative product expression were also examined. To determine the role of kelch-like ECH-associated protein 1 inhibition-dependent nuclear factor-E2-related factor 2 activation in sevoflurane preconditioning-induced neuroprotection, the kelch-like ECH-associated protein 1-nuclear factor-E2-related factor 2 signal was modulated by nuclear factor-E2-related factor 2 knockout, kelch-like ECH-associated protein 1 overexpression lentivirus, and kelch-like ECH-associated protein 1 deficiency small interfering RNA (n = 8). The infarct volume, neurologic scores, and cellular apoptosis were assessed. Sevoflurane preconditioning elicited neuroprotection and increased nuclear factor-E2-related factor 2 nuclear translocation, which in turn up-regulated endogenous antioxidation and reduced oxidative injury. Sevoflurane preconditioning reduced kelch-like ECH-associated protein 1 expression. Nuclear factor-E2-related factor 2 ablation abolished neuroprotection and reversed sevoflurane preconditioning by mediating the up-regulation of antioxidants. Kelch

  1. Knowledge and Attitude of Patients with Psychiatric Disorders and their Relatives Toward Electroconvulsive Therapy

    PubMed Central

    Dan, Amitava; Grover, Sandeep; Chakrabarti, Subho

    2014-01-01

    Objective: Knowledge and attitude regarding electroconvulsive therapy (ECT) is one of the important parameters for acceptance of ECT as a safe and effective treatment option. Several factors shape the knowledge and attitude of general people such as previous experience of ECT, sources of their information about ECT and prevailing myths about ECT. The present study attempted to examine the knowledge and attitude concerning ECT among patients with psychiatric disorders and their relatives. Materials and Methods: Knowledge and attitudes regarding ECT were assessed using the Bengali version of the ECT knowledge and attitude questionnaires, between 100 clinically stable patients with mental illnesses and their healthy relatives. Results: Majority of the patients and relatives were unaware of the basic facts about ECT. Relatives were somewhat better informed and more positive about ECT than patients, but the differences between the two groups were not significant. Previous experience of ECT did not have any major impact in knowledge and attitude in both patients and relative groups. Patients obtained information, mostly from media (44%), doctors (23%), and from personal experiences (13%). On the other hand, relatives obtained information almost equally from media (26%), doctors (27%), and experience of friends or relatives (28%). No significant difference was observed in knowledge and attitude in patients who had obtained their facts from doctors (n=23) and from other sources (n=77). Among relatives, those who had obtained their information from doctors (n=27) were better informed than those who had obtained so from other sources (n=73). Conclusions: Since patients and relatives have poor knowledge and negative attitude toward ECT, medical professionals should impart proper information about ECT to patients and relatives to increase the acceptability of this treatment. PMID:25035549

  2. Interactions between the bud emergence proteins Bem1p and Bem2p and Rho-type GTPases in yeast.

    PubMed

    Peterson, J; Zheng, Y; Bender, L; Myers, A; Cerione, R; Bender, A

    1994-12-01

    The SH3 domain-containing protein Bem1p is needed for normal bud emergence and mating projection formation, two processes that require asymmetric reorganizations of the cortical cytoskeleton in Saccharomyces cerevisiae. To identify proteins that functionally and/or physically interact with Bem1p, we screened for mutations that display synthetic lethality with a mutant allele of the BEM1 gene and for genes whose products display two-hybrid interactions with the Bem1 protein. CDC24, which is required for bud emergence and encodes a GEF (guanine-nucleotide exchange factor) for the essential Rho-type GTPase Cdc42p, was identified during both screens. The COOH-terminal 75 amino acids of Cdc24p, outside of the GEF domain, can interact with a portion of Bem1p that lacks both SH3 domains. Bacterially expressed Cdc24p and Bem1p bind to each other in vitro, indicating that no other yeast proteins are required for this interaction. The most frequently identified gene that arose from the bem1 synthetic-lethal screen was the bud-emergence gene BEM2 (Bender and Pringle. 1991. Mol. Cell Biol. 11:1295-1395), which is allelic with IPL2 (increase in ploidy; Chan and Botstein, 1993. Genetics. 135:677-691). Here we show that Bem2p contains a GAP (GTPase-activating protein) domain for Rho-type GTPases, and that this portion of Bem2p can stimulate in vitro the GTPase activity of Rho1p, a second essential yeast Rho-type GTPase. Cells deleted for BEM2 become large and multinucleate. These and other genetic, two-hybrid, biochemical, and phenotypic data suggest that multiple Rho-type GTPases control the reorganization of the cortical cytoskeleton in yeast and that the functions of these GTPases are tightly coupled. Also, these findings raise the possibility that Bem1p may regulate or be a target of action of one or more of these GTPases.

  3. Interactions between the bud emergence proteins Bem1p and Bem2p and Rho- type GTPases in yeast

    PubMed Central

    1994-01-01

    The SH3 domain-containing protein Bem1p is needed for normal bud emergence and mating projection formation, two processes that require asymmetric reorganizations of the cortical cytoskeleton in Saccharomyces cerevisiae. To identify proteins that functionally and/or physically interact with Bem1p, we screened for mutations that display synthetic lethality with a mutant allele of the BEM1 gene and for genes whose products display two-hybrid interactions with the Bem1 protein. CDC24, which is required for bud emergence and encodes a GEF (guanine- nucleotide exchange factor) for the essential Rho-type GTPase Cdc42p, was identified during both screens. The COOH-terminal 75 amino acids of Cdc24p, outside of the GEF domain, can interact with a portion of Bem1p that lacks both SH3 domains. Bacterially expressed Cdc24p and Bem1p bind to each other in vitro, indicating that no other yeast proteins are required for this interaction. The most frequently identified gene that arose from the bem1 synthetic-lethal screen was the bud-emergence gene BEM2 (Bender and Pringle. 1991. Mol. Cell Biol. 11:1295-1395), which is allelic with IPL2 (increase in ploidy; Chan and Botstein, 1993. Genetics. 135:677-691). Here we show that Bem2p contains a GAP (GTPase-activating protein) domain for Rho-type GTPases, and that this portion of Bem2p can stimulate in vitro the GTPase activity of Rho1p, a second essential yeast Rho-type GTPase. Cells deleted for BEM2 become large and multinucleate. These and other genetic, two-hybrid, biochemical, and phenotypic data suggest that multiple Rho-type GTPases control the reorganization of the cortical cytoskeleton in yeast and that the functions of these GTPases are tightly coupled. Also, these findings raise the possibility that Bem1p may regulate or be a target of action of one or more of these GTPases. PMID:7962098

  4. Synergistic antitumor effect between gefitinib and fractionated irradiation in anaplastic oligodendrogliomas cannot be predicted by the Egfr signaling activity.

    PubMed

    Pinel, Sophie; Mriouah, Jihane; Vandamme, Marc; Chateau, Alicia; Plénat, François; Guérin, Eric; Taillandier, Luc; Bernier-Chastagner, Valérie; Merlin, Jean-Louis; Chastagner, Pascal

    2013-01-01

    In high-grade gliomas, the identification of patients that could benefit from EGFR inhibitors remains a challenge, hindering the use of these agents. Using xenografts models, we evaluated the antitumor effect of the combined treatment "gefitinib + radiotherapy" and aimed to identify the profile of responsive tumors. Expression of phosphorylated proteins involved in the EGFR-dependent signaling pathways was analyzed in 10 glioma models. We focused on three models of anaplastic oligodendrogliomas (TCG2, TCG3 and TCG4) harboring high levels of phospho-EGFR, phospho-AKT and phospho-MEK1. They were treated with gefitinib (GEF 75 mg/kg/day x 5 days/week, for 2 weeks) and/or fractionated radiotherapy (RT: 5x2Gy/week for 2 weeks). Our results showed that GEF and/or RT induced significant tumor growth delays. However, only the TCG3 xenografts were highly responsive to the combination GEF+RT, with ∼50% of tumor cure. Phosphoproteins analysis five days after treatment onset demonstrated in TCG3 xenografts, but not in TCG2 model, that the EGFR-dependent pathways were inhibited after GEF treatment. Moreover, TCG3-bearing mice receiving GEF monotherapy exhibited a transient beneficial therapeutic response, rapidly followed by tumor regrowth, along with a major vascular remodeling. Taken together, our data evoked an "EGFR-addictive" behavior for TCG3 tumors. This study confirms that combination of gefitinib with fractionated irradiation could be a potent therapeutic strategy for anaplastic oligodendrogliomas harboring EGFR abnormalities but this treatment seems mainly beneficial for "EGFR-addictive" tumors. Unfortunately, neither the usual molecular markers (EGFR amplification, PTEN loss) nor the basal overexpression of phosphoproteins were useful to distinguish this responsive tumor. Evaluating the impact of TKIs on the EGFR-dependent pathways during the treatment might be more relevant, and requires further validation.

  5. Low medical morbidity and mortality after acute courses of electroconvulsive therapy in a population-based sample.

    PubMed

    Blumberger, D M; Seitz, D P; Herrmann, N; Kirkham, J G; Ng, R; Reimer, C; Kurdyak, P; Gruneir, A; Rapoport, M J; Daskalakis, Z J; Mulsant, B H; Vigod, S N

    2017-12-01

    To determine event rates for specific medical events and mortality among individuals receiving electroconvulsive therapy (ECT). Population-based cohort study using health administrative data of acute ECT treatments delivered in Ontario, Canada, from 2003 to 2011. We measured the following medical event rates, per 10 000 ECT treatments, up to 7 and 30 days post-treatment: stroke, seizure, acute myocardial infarction, arrhythmia, pneumonia, pulmonary embolus, deep vein thrombosis, gastrointestinal bleeding, falls, hip fracture, and mortality. A total of 135 831 ECT treatments were delivered to 8810 unique patients. Overall medical event rates were 9.1 and 16.8 per 10 000 ECT treatments respectively. The most common medical events were falls (2.7 and 5.5 per 10 000 ECT treatments) and pneumonia (1.8 and 3.8 per 10 000 ECT treatments). Fewer than six deaths occurred on the day of an ECT treatment. This corresponded to a mortality rate of less than 0.4 per 10 000 treatments. Deaths within 7 and 30 days of an ECT treatment, excluding deaths due to external causes (e.g., accidental and intentional causes of death), were 1.0 and 2.4 per 10 000 ECT treatments respectively. Morbidity and mortality events after ECT treatments were relatively low, supporting ECT as a low-risk medical procedure. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Trends in use of electroconvulsive therapy in South London from 1949 to 2006.

    PubMed

    Lambe, Sinéad; Mogg, Andrew; Eranti, Savitha; Pluck, Graham; Hastilow, Sarah; McLoughlin, Declan M

    2014-12-01

    Electroconvulsive therapy (ECT) remains the most acutely effective treatment for severe depression, but its use has declined since its introduction more than 70 years ago. To provide some historical perspective on changes in ECT practice, the objective of the present study was to identify trends in ECT practice in selected teaching hospitals in South London, UK, between 1949 and 2006. Annual rates of ECT for 1949-1970 were estimated from the contemporary hospital reports of the Maudsley and Bethlem Royal hospitals in South London, UK. Case notes were also retrospectively reviewed to calculate annual rates of ECT administration and extract demographic and clinical information for approximately every 5 years between 1987 and 2006. The annual rate of ECT peaked at 35% of total admission in 1956 and declined gradually thereafter to 10.8% by 1970 and fell below 2.2% from 1991 onward. Depressed and female patients were more likely to receive ECT. Compared to previous years, patients were more severely ill and treatment resistant in 2006, whereas ethnic minorities made up 30% of patients receiving ECT compared to approximately 14% in the preceding years. Currently, ECT seems to be provided increasingly late in more severe illness episodes. The ethnicity of patients receiving ECT in South London may be becoming more representative of the background population, but ECT is being used relatively more frequently for nonaffective disorders in ethnic minorities.

  7. [Exon-dependent Subgroup-analysis of the Non-interventional REASON-Study: PFS and OS in EGFR-mutated NSCLC Patients Treated with Gefitinib or Chemotherapy].

    PubMed

    Schuette, W; Dietel, M; Thomas, M; Eberhardt, W; Griesinger, F; Zirrgiebel, U; Radke, S; Schirmacher, P

    2016-08-01

    To analyze the influence of the localization of mutations in the epidermal growth factor receptor (EGFR) gene on progression-free (PFS) and overall survival (OS) in patients (pts) with locally advanced or metastatic non-small cell lung cancer (NSCLC) treated with gefitinib (gef) or chemotherapy (CT) under real world conditions within the REASON study. Subgroups of pts with mutations in exon 19 (n = 141), 18/20 (n = 43), and 21 (n = 104) were analyzed for PFS and OS according to gef or CT treatment and compared using the log-rank test. Pts with mutations in exon 19 and 18/20 treated with gef as first line therapy showed increased PFS and OS compared to CT. This increase was statistically significant in pts with exon 19 mutation (11.3 vs. 6.5 months), but was not found in pts with exon 21 mutation (9.1 vs. 9.3 months). Also, OS was significantly increased in patients with mutation in exon 19 treated with gef ever over all treatment lines compared to CT (21.8 vs. 10.6 months), whereas this was not found in pts with mutation in exon 21 (14.1 vs. 13.9 months). Localization and nature of EGFR mutations influences gefitinib treatment outcomes under routine conditions and should therefore be analyzed in detail. © Georg Thieme Verlag KG Stuttgart · New York.

  8. Pseudocholinesterase levels in patients under electroconvulsive therapy

    PubMed Central

    Küçükosman, Gamze; Pişkin, Özcan; Hancı, Volkan; Okyay, Rahşan D.; Ayoğlu, Hilal; Yurtlu, Bülent S.; Akın, Mehmet; Turan, Işıl

    2018-01-01

    Objectives: In this study, we aimed to retrospectively assess the correlation of pseudocholinesterase (PChE) levels with age, gender, body weight and diagnosed psychiatric diseases in electroconvulsive therapy (ECT) cases. Methods: This retrospective study was conducted at Bülent Ecevit University Hospital, Zonguldak, Turkey, between 2007 and 2011. In the study, 193 ECT case files were retrospectively scanned to evaluate PChE values before ECT and other file information. Results: There was no difference between gender in terms of PChE levels. Correlation analysis determined a weakly positive correlation between age (p=0.013; correlation coefficient [cc]: 0.178) and body weight (p<0.001; cc: 0.273) and PChE levels. No correlation was found between age, gender, weight or psychiatric diagnosis, and PChE levels. Conclusion: Neuromuscular blockage is a significant factor that increases patient safety, while increasing the efficacy of ECT. In choosing muscle relaxant agents, both patient factors and the pharmacological properties of the neuromuscular blocker should be considered. We think that in situations with delayed recovery of ECT cases without identified PChE levels, low PChE levels must be considered. PMID:29332117

  9. Pseudocholinesterase levels in patients under electroconvulsive therapy.

    PubMed

    Küçükosman, Gamze; Pişkin, Özcan; Hancı, Volkan; Okyay, Rahşan D; Ayoğlu, Hilal; Yurtlu, Bülent S; Akın, Mehmet; Turan, Işıl Ö

    2018-01-01

    In this study, we aimed to retrospectively assess the correlation of pseudocholinesterase (PChE) levels with age, gender, body weight and diagnosed psychiatric diseases in electroconvulsive therapy (ECT) cases. Methods: This retrospective study was conducted at Bülent Ecevit University Hospital, Zonguldak, Turkey, between 2007 and 2011. In the study, 193 ECT case files were retrospectively scanned to evaluate PChE values before ECT and other file information.  Results: There was no difference between gender in terms of PChE levels. Correlation analysis determined a weakly positive correlation between age (p=0.013; correlation coefficient [cc]: 0.178) and body weight (p less than 0.001; cc: 0.273) and PChE levels. No correlation was found between age, gender, weight or psychiatric diagnosis, and PChE levels.  Conclusion: Neuromuscular blockage is a significant factor that increases patient safety, while increasing the efficacy of ECT. In choosing muscle relaxant agents, both patient factors and the pharmacological properties of the neuromuscular blocker should be considered. We think that in situations with delayed recovery of ECT cases without identified PChE levels, low PChE levels must be considered.

  10. The Guanine Nucleotide Exchange Factor Tiam1 Affects Neuronal Morphology; Opposing Roles for the Small GTPases Rac and Rho

    PubMed Central

    van Leeuwen, Frank N.; Kain, Hendrie E.T.; van der Kammen, Rob A.; Michiels, Frits; Kranenburg, Onno W.; Collard, John G.

    1997-01-01

    The invasion-inducing T-lymphoma invasion and metastasis 1 (Tiam1) protein functions as a guanine nucleotide exchange factor (GEF) for the small GTPase Rac1. Differentiation-dependent expression of Tiam1 in the developing brain suggests a role for this GEF and its effector Rac1 in the control of neuronal morphology. Here we show that overexpression of Tiam1 induces cell spreading and affects neurite outgrowth in N1E-115 neuroblastoma cells. These effects are Rac-dependent and strongly promoted by laminin. Overexpression of Tiam1 recruits the α6β1 integrin, a laminin receptor, to specific adhesive contacts at the cell periphery, which are different from focal contacts. Cells overexpressing Tiam1 no longer respond to lysophosphatidic acid– induced neurite retraction and cell rounding, processes mediated by Rho, suggesting that Tiam1-induced activation of Rac antagonizes Rho signaling. This inhibition can be overcome by coexpression of constitutively active RhoA, which may indicate that regulation occurs at the level of Rho or upstream. Conversely, neurite formation induced by Tiam1 or Rac1 is further promoted by inactivating Rho. These results demonstrate that Rac- and Rho-mediated pathways oppose each other during neurite formation and that a balance between these pathways determines neuronal morphology. Furthermore, our data underscore the potential role of Tiam1 as a specific regulator of Rac during neurite formation and illustrate the importance of reciprocal interactions between the cytoskeleton and the extracellular matrix during this process. PMID:9348295

  11. Electroconvulsive Therapy Practice in Spain: A National Survey.

    PubMed

    Vera, Ignacio; Sanz-Fuentenebro, Javier; Urretavizcaya, Mikel; Verdura, Ernesto; Soria, Virginia; Martínez-Amorós, Erika; Bernardo, Miquel

    2016-03-01

    The use of electroconvulsive therapy (ECT) in Spain has not been systematically evaluated since 2000 to 2001. The aim of this study is to assess the current use of ECT in Spain. A cross-sectional survey was conducted covering every psychiatric unit in Spain as of December 31, 2012. About 93.2% of the centers answered the questionnaire. About 54.9% of the psychiatric units applied ECT at a rate of 0.66 patients per 10,000 inhabitants. Wide variations existed among the different autonomous communities and provinces. Written informed consent was obtained in all the facilities. About 38.2% of ECT-treated patients were 65 years or older. About 55.7% were women. Depressive episodes were the main indication for ECT (80.2%). All the facilities applied modified ECT. No sine wave current devices are currently used in Spain. Bifrontotemporal ECT was elective in 85% of the hospitals, bifrontal in 13.3%, and unilateral in 1.8%. Stimulus titration methods were elective in 8.6% of the centers. The decision to end ECT relied on the psychiatrist's clinical impression in 89.4% of the centers and on rating scales in 10.6%. The ECT training was mandatory in 56.5% of the centers. The ECT practice has significantly improved in Spain in recent years. Overall, Spanish facilities seem to comply with established clinical guidelines; however, specific concerns were identified, meaning there is still further scope for improvement.

  12. Using "CONNected objECT (CONNECT)" Algorithm to Explore Intense Global Water Vapor Transport to Investigate Impacts of Climate Variability and Change

    NASA Astrophysics Data System (ADS)

    Kawzenuk, B.; Sellars, S. L.; Nguyen, P.; Ralph, F. M.; Sorooshian, S.

    2017-12-01

    The CONNected objECT (CONNECT) algorithm is applied to Integrated Water Vapor Transport (IVT) data from the NASA's Modern-Era Retrospective Analysis for Research and Applications - Version 2 reanalysis product for the period 1980 to 2016 to study water vapor transport globally. The algorithm generates life-cycle records as statistical objects for the time and space location of the evolving strong vapor transport events. Global statistics are presented and used to investigate how climate variability impacts the events' location and frequency. Results show distinct water vapor object frequency and seasonal peaks during NH and SH Winter. Moreover, a positive linear trend in the annual number of objects is reported, increasing by 3.58 objects year-over-year (with 95% confidence, +/- 1.39). In addition, we show five distinct regions where these events typically exist (southeastern United States, eastern China, South Pacific south of 25°S, eastern South America and off the southern tip of South Africa), and where they rarely exist (eastern South Pacific Ocean and central southern Atlantic Ocean between 5°N-25°S). In addition, the event frequency and geographical location are also shown to be related to the Arctic Oscillation, Pacific North American Pattern, and the Quasi-Biennial Oscillation.

  13. Bitemporal v. high-dose right unilateral electroconvulsive therapy for depression: a systematic review and meta-analysis of randomized controlled trials.

    PubMed

    Kolshus, E; Jelovac, A; McLoughlin, D M

    2017-02-01

    Brief-pulse electroconvulsive therapy (ECT) is the most acutely effective treatment for severe depression though concerns persist about cognitive side-effects. While bitemporal electrode placement is the most commonly used form worldwide, right unilateral ECT causes less cognitive side-effects though historically it has been deemed less effective. Several randomized trials have now compared high-dose (>5× seizure threshold) unilateral ECT with moderate-dose (1.0-2.5× seizure threshold) bitemporal ECT to investigate if it is as effective as bitemporal ECT but still has less cognitive side-effects. We aimed to systematically review these trials and meta-analyse clinical and cognitive outcomes where appropriate. We searched PubMed, PsycINFO, Web of Science, Cochrane Library and EMBASE for randomized trials comparing these forms of ECT using the terms 'electroconvulsive' OR 'electroshock' AND 'trial'. Seven trials (n = 792) met inclusion criteria. Bitemporal ECT did not differ from high-dose unilateral ECT on depression rating change scores [Hedges's g = -0.03, 95% confidence interval (CI) -0.17 to 0.11], remission (RR 1.06, 95% CI 0.93-1.20), or relapse at 12 months (RR 1.42, 95% CI 0.90-2.23). There was an advantage for unilateral ECT on reorientation time after individual ECT sessions (mean difference in minutes = -8.28, 95% CI -12.86 to -3.70) and retrograde autobiographical memory (Hedges's g = -0.46, 95% CI -0.87 to -0.04) after completing an ECT course. There were no differences for general cognition, category fluency and delayed visual and verbal memory. High-dose unilateral ECT does not differ from moderate-dose bitemporal ECT in antidepressant efficacy but has some cognitive advantages.

  14. Targeted Sos1 deletion reveals its critical role in early T-cell development

    PubMed Central

    Kortum, Robert L.; Sommers, Connie L.; Alexander, Clayton P.; Pinski, John M.; Li, Wenmei; Grinberg, Alex; Lee, Jan; Love, Paul E.; Samelson, Lawrence E.

    2011-01-01

    Activation of the small G protein Ras is required for thymocyte differentiation. In thymocytes, Ras is activated by the Ras guanine exchange factors (RasGEFs) Sos1, Sos2, and RasGRP1. We report the development of a floxed allele of sos1 to assess the role of Sos1 during thymocyte development. Sos1 was required for pre–T-cell receptor (pre-TCR)– but not TCR-stimulated developmental signals. Sos1 deletion led to a partial block at the DN-to-DP transition. Sos1-deficient thymocytes showed reduced pre-TCR–stimulated proliferation, differentiation, and ERK phosphorylation. In contrast, TCR-stimulated positive selection, and negative selection under strong stimulatory conditions, remained intact in Sos1-deficient mice. Comparison of RasGEF expression at different developmental stages showed that relative to Sos2 and RasGRP1, Sos1 is most abundant in DN thymocytes, but least abundant in DP thymocytes. These data reveal that Sos1 is uniquely positioned to affect signal transduction early in thymocyte development. PMID:21746917

  15. Gain-of-function SOS1 mutations cause a distinctive form of noonansyndrome

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tartaglia, Marco; Pennacchio, Len A.; Zhao, Chen

    2006-09-01

    Noonan syndrome (NS) is a developmental disordercharacterized by short stature, facial dysmorphia, congenital heartdefects and skeletal anomalies1. Increased RAS-mitogenactivated proteinkinase (MAPK) signaling due to PTPN11 and KRAS mutations cause 50 percentof NS2-6. Here, we report that 22 of 129 NS patients without PTPN11 orKRAS mutation (17 percent) have missense mutations in SOS1, which encodesa RAS-specific guanine nucleotide exchange factor (GEF). SOS1 mutationscluster at residues implicated in the maintenance of SOS1 in itsautoinhibited form and ectopic expression of two NS-associated mutantsinduced enhanced RAS activation. The phenotype associated with SOS1defects is distinctive, although within NS spectrum, with a highprevalence of ectodermal abnormalitiesmore » but generally normal developmentand linear growth. Our findings implicate for the first timegain-of-function mutations in a RAS GEF in inherited disease and define anew mechanism by which upregulation of the RAS pathway can profoundlychange human development.« less

  16. Mechanism of SOS PR-domain autoinhibition revealed by single-molecule assays on native protein from lysate

    PubMed Central

    Lee, Young Kwang; Low-Nam, Shalini T.; Chung, Jean K.; Hansen, Scott D.; Lam, Hiu Yue Monatrice; Alvarez, Steven; Groves, Jay T.

    2017-01-01

    The guanine nucleotide exchange factor (GEF) Son of Sevenless (SOS) plays a critical role in signal transduction by activating Ras. Here we introduce a single-molecule assay in which individual SOS molecules are captured from raw cell lysate using Ras-functionalized supported membrane microarrays. This enables characterization of the full-length SOS protein, which has not previously been studied in reconstitution due to difficulties in purification. Our measurements on the full-length protein reveal a distinct role of the C-terminal proline-rich (PR) domain to obstruct the engagement of allosteric Ras independently of the well-known N-terminal domain autoinhibition. This inhibitory role of the PR domain limits Grb2-independent recruitment of SOS to the membrane through binding of Ras·GTP in the SOS allosteric binding site. More generally, this assay strategy enables characterization of the functional behaviour of GEFs with single-molecule precision but without the need for purification. PMID:28452363

  17. Mechanism of SOS PR-domain autoinhibition revealed by single-molecule assays on native protein from lysate.

    PubMed

    Lee, Young Kwang; Low-Nam, Shalini T; Chung, Jean K; Hansen, Scott D; Lam, Hiu Yue Monatrice; Alvarez, Steven; Groves, Jay T

    2017-04-28

    The guanine nucleotide exchange factor (GEF) Son of Sevenless (SOS) plays a critical role in signal transduction by activating Ras. Here we introduce a single-molecule assay in which individual SOS molecules are captured from raw cell lysate using Ras-functionalized supported membrane microarrays. This enables characterization of the full-length SOS protein, which has not previously been studied in reconstitution due to difficulties in purification. Our measurements on the full-length protein reveal a distinct role of the C-terminal proline-rich (PR) domain to obstruct the engagement of allosteric Ras independently of the well-known N-terminal domain autoinhibition. This inhibitory role of the PR domain limits Grb2-independent recruitment of SOS to the membrane through binding of Ras·GTP in the SOS allosteric binding site. More generally, this assay strategy enables characterization of the functional behaviour of GEFs with single-molecule precision but without the need for purification.

  18. An astral simulacrum of the central spindle accounts for normal, spindle-less, and anucleate cytokinesis in echinoderm embryos

    PubMed Central

    Su, Kuan-Chung; Bement, William M.; Petronczki, Mark; von Dassow, George

    2014-01-01

    Cytokinesis in animal cells depends on spindle-derived spatial cues that culminate in Rho activation, and thereby actomyosin assembly, in a narrow equatorial band. Although the nature, origin, and variety of such cues have long been obscure, one component is certainly the Rho activator Ect2. Here we describe the behavior and function of Ect2 in echinoderm embryos, showing that Ect2 migrates from spindle midzone to astral microtubules in anaphase and that Ect2 shapes the pattern of Rho activation in incipient furrows. Our key finding is that Ect2 and its binding partner Cyk4 accumulate not only at normal furrows, but also at furrows that form in the absence of associated spindle, midzone, or chromosomes. In all these cases, the cell assembles essentially the same cytokinetic signaling ensemble—opposed astral microtubules decorated with Ect2 and Cyk4. We conclude that if multiple signals contribute to furrow induction in echinoderm embryos, they likely converge on the same signaling ensemble on an analogous cytoskeletal scaffold. PMID:25298401

  19. Subjective Memory Immediately Following Electroconvulsive Therapy.

    PubMed

    Brus, Ole; Nordanskog, Pia; Båve, Ullvi; Cao, Yang; Hammar, Åsa; Landén, Mikael; Lundberg, Johan; Nordenskjöld, Axel

    2017-06-01

    The aims of the present study were to describe the short-term rate of subjective memory worsening (SMW) and identify factors of importance for SMW in a large clinical sample treated for depression with electroconvulsive therapy (ECT). This register-based study included 1212 patients from the Swedish National Quality Register for ECT. Subjective memory worsening was defined as a 2-point worsening on the memory item of the Comprehensive Psychopathological Rating Scale from before to within 1 week after treatment. Associations between patient characteristics and treatment factors were examined using logistic regression. Subjective memory worsening was experienced in 26%. It was more common in women than in men (31% vs 18%; P < 0.001) and more common in patients aged 18 to 39 years than in patients 65 years or older (32% vs 22%; P = 0.008). Patients with less subjective memory disturbances before ECT had a greater risk of SMW. Patients in remission after ECT had a lower risk of SMW. A brief pulse width stimulus gave higher risk of SMW compared with ultrabrief pulse (odds ratio, 1.61; 95% confidence interval, 1.05-2.47). Subjective memory worsening is reported by a minority of patients. However, young women are at risk of experiencing SMW. Ultrabrief pulse width stimulus could be considered for patients treated with unilateral electrode placement who experience SMW. Each patient should be monitored with regard to symptoms and adverse effects, and treatment should be adjusted on an individual basis to maximize the clinical effect and with efforts to minimize the cognitive adverse effects.

  20. Coupling of the Matched Gravity and Electromagnetic Fields of the Sun with Jupiter and its Moons Together in Nearest Portion of Jupiter's Orbit to the Sun as the Main Cause of the Peak of Approximately 11 Yearly Solar Cycles and Hazards from Solar Storms

    NASA Astrophysics Data System (ADS)

    Gholibeigian, Kazem; Gholibeigian, Hassan

    2016-04-01

    On March 13, 1989 the entire province of Quebec Blackout by solar storm during solar cycle 22. The solar storm of 1859, also known as the Carrington event, was a powerful geomagnetic solar storm during solar cycle 10. The solar storm of 2012 during solar cycle 24 was of similar magnitude, but it passed Earth's orbit without striking the plane. All of these solar storms occurred in the peak of 11 yearly solar cycles. In this way, the White House in its project which is focusing on hazards from solar system, in a new strategy and action plan to increase protection from damaging solar emissions, should focus on coupling of the matched Gravity and Electromagnetic Fields)GEFs) of the Sun with Jupiter and its moons together. On the other hand, in solar system, the Jupiter's gravity has largest effect to the Sun's core and its dislocation, because the gravity force between the Jupiter and the Sun is 11.834 times, In addition overlapping of the solar cycles with the Jupiter's orbit period is 11.856 years. These observable factors lead us to the effect of the Jupiter and Sun gravity fields coupling as the main cause of the approximately 11 years duration for solar cycles. Its peak in each cycle is when the Jupiter is in nearest portion to the Sun in its orbit. In this way, the other planets in their coupling with Sun help to the variations and strengthening solar cycles. [Gholibeigian, 7/24/2015http://adsabs.harvard.edu/abs/2014EGU]. In other words, the both matched GEFs are generating by the large scale forced convection system inside the stars and planets [Gholibeigian et. al, AGU Fall Meeting 2015]. These two fields are couple and strengthening each other. The Jupiter with its 67 moons generate the largest coupled and matched GEFs in its core and consequently strongest effect on the Sun's core. Generation and coupling of the Jupiter's GEFs with its moons like Europa, Io and Ganymede make this planet of thousands of times brighter and many times bigger than Earth as the

  1. Improvement of cycloid psychosis following electroconvulsive therapy.

    PubMed

    Holm, Jonas; Brus, Ole; Båve, Ullvi; Landen, Mikael; Lundberg, Johan; Nordanskog, Pia; von Knorring, Lars; Nordenskjöld, Axel

    2017-08-01

    The treatment of choice for cycloid psychosis has traditionally been electroconvulsive therapy (ECT), but there is a lack of studies on its effectiveness. The primary aim of this register study was to determine the rates of remission and response after ECT for cycloid psychosis. The secondary aim was to examine possible predictors of outcome. Data were obtained from the National Quality Register for ECT in Sweden. The study population was patients (n = 42) who received ECT for acute polymorphic psychotic disorder without symptoms of schizophrenia or for cycloid psychosis between 2011-2015 in 13 hospitals. Remission and response rates were calculated using Clinical Global Impression-Severity (CGI-S) and -Improvement scores, respectively. Variables with possible predictive value were tested using Chi-square and Fisher's exact test. The response rate was 90.5%. The remission rate was 45.2%. Of 42 patients, 40 improved their CGI-S score after ECT (p < 0.001). The mean number of ECT treatments was 2.5 for non-responders and 7.0 for responders (p = 0.010). The mean number of ECT treatments did not differ significantly between remitters and non-remitters (7.2 vs 6.1, p = 0.31). None of the other investigated potential predictors was statistically significantly associated with outcome. ECT is an effective treatment for cycloid psychosis. Future studies need to compare the outcome of ECT to that of other treatment strategies. The high response rate with ECT indicates that cycloid psychosis is a clinically useful diagnosis.

  2. Electroconvulsive Therapy in the Treatment of Mood Disorders: One-Year Follow-up.

    PubMed

    Çakir, Sibel; Çağlar, Nuran

    2017-09-01

    Electroconvulsive therapy (ECT) is known to be an effective option in the treatment of mood disorders, especially resistant depression. However, the remission achieved by ECT was reported to be not long lasting enough. The aim of the present study was to investigate the relapse/recurrence rates and associated risk factors during the first year after ECT in patients diagnosed with mood disorders. In a naturalistic observation, patients diagnosed with unipolar depressive disorder or a depressive episode of bipolar disorder and who had achieved remission by ECT were followed up for at least one year. The patients were evaluated with structured interviews during the follow-up period. The relapse/recurrence rates were the primary outcome measurements, while hospitalization and suicide attempts were the secondary outcome measurements. The remitted and non-remitted patients were compared regarding the clinical features, ECT, and pharmacological variables. Fifty of 62 patients who had achieved remission with ECT completed the one year follow-up period. Thirty-three patients (66%) had relapse/recurrence, while 17 (34%) patients remained in remission. The relapse rates were similar in patients with unipolar depression and bipolar disorders. The mean number of ECT sessions was higher in relapsed patients with bipolar disorders. Multiple episodes were more frequent in non-remitted patients with unipolar depression. Comorbid psychiatric diagnosis was higher in non-remitted patients with unipolar and bipolar disorders. The relapse/recurrence rate was found to be fairly high in the first year of follow-up in patients who had achieved remission with ECT. ECT decisions should be made carefully in patients with comorbid psychiatric diagnosis and multiple episodes as these are more risky. The ECT application procedure and successive maintenance treatment (maintenance ECT, pharmacotherapy, and psychotherapy) should be planned to sustain the remission for patients with mood disorders

  3. Electroconvulsive Therapy - What Do Patients Think Of Their Treatment?

    PubMed

    Maguire, S; Rea, S M; Convery, P

    2016-09-01

    The Regulation and Quality Improvement Authority (RQIA) monitors the administration of electroconvulsive therapy (ECT) in Northern Ireland (NI). As part of their inspection methodology RQIA wished to include feedback from ECT patients. The aim of this report is to summarise the opinions of ECT patients over a 1-year period and to compare their feedback about treatment with the standards of best practice, as defined by the Electroconvulsive Therapy Accreditation Service (ECTAS). RQIA was granted permission to use the ECTAS patient questionnaire. The questionnaire was distributed to all the ECT clinics in NI and staff were requested to give them to patients who had received a course of ECT. A total of 42 individuals returned questionnaires, 24 females (57.1%) and 18 (42.9%) males. The response rate was 26%. Almost half of respondents were detained under the Mental Health (Northern Ireland) Order 1986 (n=19, 45.2%), with one third receiving ECT as a day patient (n=14, 33.3%). Respondents reported having detailed information about ECT, with ECTAS standards 4.2 and 4.3 being affirmed in over 80% of cases. Eighty percent of respondents (n=34) believed they benefited from ECT. The results are mainly favourable towards ECT. The majority felt they benefited from treatment.

  4. Early Career Teachers' Perceptions and Experiences of Leadership Development: Balancing Structure and Agency in Contrasting School Contexts

    ERIC Educational Resources Information Center

    Woodhouse, Joan; Pedder, David

    2017-01-01

    Drawing on the findings of a three-year, longitudinal study investigating early career teachers' (ECTs) experiences and perceptions of leadership development in English secondary schools, this paper highlights, from the perspectives of ECTs, some of the factors that support and facilitate leadership development during the first few years of the…

  5. Analytical investigation of the hygrothermal effects and parametric study of the Edge Crack Torsion (ECT) mode 3 test lay-ups

    NASA Technical Reports Server (NTRS)

    Li, Jian; Obrien, T. Kevin

    1995-01-01

    A shear deformation theory including residual thermal and moisture effects is developed for the analysis of either symmetric or unsymmetric laminates with mid-plane edge delamination under torsion loading. The theory is based on an assumed displacement field which includes shear deformation. The governing equations and boundary conditions are obtained from the principle of virtual work. The analysis of the (90/(+/- 45)(n)/(-/+ 45)(n)/90)(s) ECT mode 3 test lay-up indicates that there are no hygrothermal effects on the mode 3 strain energy release rate because the laminate, and both sublaminates above and below the delamination, are symmetric lay-ups. A further parametric study reveals that some other lay-ups can have negligible hygrothermal effects even when the sublaminates above and below the delamination are not symmetric about their own mid-planes. However, these lay-ups may suffer from distortion after the curing process. Another Interesting set of lay-ups investigated is a class of antisymmetric laminates with (+/-(theta/(theta -90)(2)/theta))(n) lay-ups. It is observed that when n takes on even numbers (2 and 4), both hygrothermal and mode 1 effects can be neglected. From this point of view, these lay-ups provide a way to determine the mode 3 toughness between two dissimilar layers. However, when n takes on odd numbers (1 and 3), both hygrothermal and mode 1 effects may be strong in these lay-ups. In particular, when theta equals 45 deg, the lay-ups are free from both hygrothermal and mode 1 effects irrespective of n.

  6. 16 CFR 1105.2 - Factors.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Factors. 1105.2 Section 1105.2 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS CONTRIBUTIONS TO COSTS OF PARTICIPANTS IN DEVELOPMENT OF CONSUMER PRODUCT SAFETY STANDARDS § 1105.2 Factors. The Commission...

  7. GNOM regulates root hydrotropism and phototropism independently of PIN-mediated auxin transport.

    PubMed

    Moriwaki, Teppei; Miyazawa, Yutaka; Fujii, Nobuharu; Takahashi, Hideyuki

    2014-02-01

    Plant roots exhibit tropisms in response to gravity, unilateral light and moisture gradients. During gravitropism, an auxin gradient is established by PIN auxin transporters, leading to asymmetric growth. GNOM, a guanine nucleotide exchange factor of ARF GTPase (ARF-GEF), regulates PIN localization by regulating subcellular trafficking of PINs. Therefore, GNOM is important for gravitropism. We previously isolated mizu-kussei2 (miz2), which lacks hydrotropic responses; MIZ2 is allelic to GNOM. Since PIN proteins are not required for root hydrotropism in Arabidopsis, the role of GNOM in root hydrotropism should differ from that in gravitropism. To examine this possibility, we conducted genetic analysis of gnom(miz2) and gnom trans-heterozygotes. The mutant gnom(miz2), which lacks hydrotropic responses, was partially recovered by gnom(emb30-1), which lacks GEF activity, but not by gnom(B4049), which lacks heterotypic domain interactions. Furthermore, the phototropic response of gnom trans-heterozygotes differed from that of the pin2 mutant allele eir1-1. Moreover, defects in the polarities of PIN2 and auxin distribution in a severe gnom mutant were recovered by gnom(miz2). Therefore, an unknown GNOM-mediated vesicle trafficking system may mediate root hydrotropism and phototropism independently of PIN trafficking. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Therapeutic and prophylactic utility of the memory-enhancing drug donepezil hydrochloride on cognition of patients undergoing electroconvulsive therapy: a randomized controlled trial.

    PubMed

    Prakash, Jyoti; Kotwal, Atul; Prabhu, Hra

    2006-09-01

    Substantial progress has been made in identifying how the treatment parameters used in electroconvulsive therapy (ECT) impact its cognitive side effects. However, there is limited information regarding the role of memory enhancers in post-ECT cognitive disturbances. We evaluated the therapeutic and prophylactic efficacy of the memory-enhancing drug donepezil hydrochloride on cognition of patients undergoing ECT. A triple blind (the study subjects, clinician assessing the cognition, and the data analyst were unaware of subject allocation for trial assessment) randomized controlled trial was carried out in a General Hospital Psychiatry Unit. Subjects were randomized into 2 groups. One group received ECT with placebo, whereas the other group received ECT and donepezil (a memory-enhancing drug). Study participants were assessed in post-ECT period to analyze cognitive deficits and to compare the differences in 2 groups, as regards recovery of various aspects of cognition. The post-ECT recovery of various components of cognition was more rapid in patients using donepezil as compared to those not given donepezil (P < 0.05). This significant improvement in recovery time among patients receiving donepezil bears therapeutic implication in immediate post-ECT cognitive deficits.

  9. Electroconvulsive Therapy for Treatment of Major Depression in a 100-Year-Old Patient with Severe Aortic Stenosis: A 5-year follow up report

    PubMed Central

    O'Reardon, John P.; Cristancho, Mario A.; Ryley, Barbara; Patel, Kajal R.; Haber, Howard L.

    2011-01-01

    Although there is no specific age cut-off for ECT and no absolute contraindication to its use, very old age as well as the presence of cardiac conditions such as aortic stenosis are factors that may negatively impact the clinician's decision to administer ECT in the individual case. We report our follow-up of a 100 year old female with severe aortic stenosis who has now received ECT safely for a period of 5 years. No cardiac complications have emerged during this period. Her prior unipolar depressive episode with catatonic features remains in remission with a single prophylactic ECT session every 3 months. We have observed from our experience with this unique case that periodic multidisciplinary re-evaluation of the evolving risk-benefit profile of ECT is essential along with the inclusion of family members in this dialogue. Our patient course illustrates that neither advanced age nor severe aortic stenosis are absolute contraindications to ECT even over an extended period of time. Each case needs to be evaluated on its merits. To our knowledge, this case represents the oldest patient in the literature where ECT has been administered safely for such an extended period in the setting of severe aortic stenosis. PMID:21865959

  10. Role of Nuclear Factor Erythroid 2-Related Factor 2 in Diabetic Nephropathy

    PubMed Central

    Min, Xu; Xu, Xiaohong

    2017-01-01

    Diabetic nephropathy (DN) is manifested as increased urinary protein level, decreased glomerular filtration rate, and final renal dysfunction. DN is the leading cause of end-stage renal disease worldwide and causes a huge societal healthcare burden. Since satisfied treatments are still limited, exploring new strategies for the treatment of this disease is urgently needed. Oxidative stress takes part in the initiation and development of DN. In addition, nuclear factor erythroid 2-related factor 2 (Nrf2) plays a key role in the cellular response to oxidative stress. Thus, activation of Nrf2 seems to be a new choice for the treatment of DN. In current review, we discussed and summarized the therapeutic effects of Nrf2 activation on DN from both basic and clinical studies. PMID:28512642

  11. Strategies to minimize cognitive side effects with ECT: aspects of ECT technique.

    PubMed

    Prudic, Joan

    2008-03-01

    The adverse cognitive effects of electroconvulsive therapy are important limitations in the use of this treatment that continues to be a significant therapeutic strategy after 7 decades of use. Among the approaches to mitigation of these side effects are considerations involving the prescription and manipulation of the electrical stimulus itself. The impact of the following electrical factors on the cognitive outcomes of electroconvulsive therapy are surveyed: efficiency of the stimulus as expressed in electrical waveform; targeting of the stimulus, the major concept underlying electrode placement; stimulus dosing; and frequency and number of treatments. The current state of development of knowledge in these areas is summarized, and methods to achieve the best cognitive outcomes without sacrificing clinical efficacy are discussed. Future trends in the further optimization of the electrical stimulus are briefly mentioned.

  12. A Model for Direction Sensing in Dictyostelium discoideum: Ras Activity and Symmetry Breaking Driven by a Gβγ-Mediated, Gα2-Ric8 -- Dependent Signal Transduction Network

    PubMed Central

    Cheng, Yougan; Othmer, Hans

    2016-01-01

    Chemotaxis is a dynamic cellular process, comprised of direction sensing, polarization and locomotion, that leads to the directed movement of eukaryotic cells along extracellular gradients. As a primary step in the response of an individual cell to a spatial stimulus, direction sensing has attracted numerous theoretical treatments aimed at explaining experimental observations in a variety of cell types. Here we propose a new model of direction sensing based on experiments using Dictyostelium discoideum (Dicty). The model is built around a reaction-diffusion-translocation system that involves three main component processes: a signal detection step based on G-protein-coupled receptors (GPCR) for cyclic AMP (cAMP), a transduction step based on a heterotrimetic G protein Gα2βγ, and an activation step of a monomeric G-protein Ras. The model can predict the experimentally-observed response of cells treated with latrunculin A, which removes feedback from downstream processes, under a variety of stimulus protocols. We show that Gα2βγ cycling modulated by Ric8, a nonreceptor guanine exchange factor for Gα2 in Dicty, drives multiple phases of Ras activation and leads to direction sensing and signal amplification in cAMP gradients. The model predicts that both Gα2 and Gβγ are essential for direction sensing, in that membrane-localized Gα2*, the activated GTP-bearing form of Gα2, leads to asymmetrical recruitment of RasGEF and Ric8, while globally-diffusing Gβγ mediates their activation. We show that the predicted response at the level of Ras activation encodes sufficient ‘memory’ to eliminate the ‘back-of-the wave’ problem, and the effects of diffusion and cell shape on direction sensing are also investigated. In contrast with existing LEGI models of chemotaxis, the results do not require a disparity between the diffusion coefficients of the Ras activator GEF and the Ras inhibitor GAP. Since the signal pathways we study are highly conserved between Dicty

  13. Protocolized hyperventilation enhances electroconvulsive therapy.

    PubMed

    de Arriba-Arnau, Aida; Dalmau, Antonia; Soria, Virginia; Salvat-Pujol, Neus; Ribes, Carmina; Sánchez-Allueva, Ana; Menchón, José Manuel; Urretavizcaya, Mikel

    2017-08-01

    Hyperventilation is recommended in electroconvulsive therapy (ECT) to enhance seizures and to increase patients' safety. However, more evidence is needed regarding its effects and the optimum method of application. This prospective study involving 21 subjects compared two procedures, protocolized hyperventilation (PHV) and hyperventilation as usual (HVau), applied to the same patient in two consecutive sessions. Transcutaneous partial pressure of carbon dioxide (TcPCO 2 ) was measured throughout all sessions. Ventilation parameters, hemodynamic measures, seizure characteristics, and side effects were also explored. PHV resulted in lower TcPCO 2 after hyperventilation (p=.008) and over the whole session (p=.035). The lowest TcPCO 2 was achieved after voluntary hyperventilation. Changes in TcPCO 2 from baseline showed differences between HVau and PHV at each session time-point (all p<.05). Between- and within-subjects factors were statistically significant in a general linear model. Seizure duration was greater in PHV sessions (p=.028), without differences in other seizure quality parameters or adverse effects. Correlations were found between hypocapnia induction and seizure quality indexes. Secondary outcomes could be underpowered. PHV produces hypocapnia before the stimulus, modifies patients' TcPCO 2 values throughout the ECT session and lengthens seizure duration. Voluntary hyperventilation is the most important part of the PHV procedure with respect to achieving hypocapnia. A specific ventilation approach, CO 2 quantification and monitoring may be advisable in ECT. PHV is easy to apply in daily clinical practice and does not imply added costs. Ventilation management has promising effects in terms of optimizing ECT technique. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Rasfonin, a novel 2-pyrone derivative, induces ras-mutated Panc-1 pancreatic tumor cell death in nude mice.

    PubMed

    Xiao, Z; Li, L; Li, Y; Zhou, W; Cheng, J; Liu, F; Zheng, P; Zhang, Y; Che, Y

    2014-05-22

    Rasfonin is a novel 2-pyrone derivative reported to induce apoptosis in ras-dependent cells. In this study, its effects on ras-mutated pancreatic cancer cells were investigated in vitro and in vivo. Two human pancreatic cancer cell lines Panc-1 (mutated K-ras) and BxPC-3 (wild-type K-ras) were selected to test the effects of rasfonin on cell proliferation, clone formation, migration and invasion in vitro. Immunoblotting was used to detect the expressions of EGFR-Ras-Raf-MEK-ERK signaling pathway proteins. Ras activity was measured using a pull-down ELISA kit and guanine exchange factor (GEF)/GTPase-activating proteins (GAP) activity was measured by [(3)H]-GDP radiometric ligand binding. For an in vivo study, CD1 nude mice bearing Panc-1 cells were treated with rasfonin or Salirasib (FTS). We found that rasfonin suppressed proliferation more strongly in Panc-1 cells (IC50=5.5 μM) than BxPC-3 cells (IC50=10 μM) in vitro. Clone formation, migration and invasion by Panc-1 cells were also reduced by rasfonin. Rasfonin had little effect on the farnesylation of Ras, but it strongly downregulated Ras activity and consequently phosphorylation of c-Raf/MEK/ERK. Further experiments indicated that rasfonin reduced Son of sevenless (Sos1) expression but did not alter GEF and GAP activities. The in vivo experiments also revealed that rasfonin (30 mg/kg) delayed the growth of xenograft tumors originating from Panc-1 cells. Tumor weight was ultimately decreased after 20 days of treatment of rasfonin. Rasfonin is a robust inhibitor of pancreatic cancers with the K-ras mutation. The reduction of Sos1 expression and the consequently depressed Ras-MAPK activity could be important in its anticancer activity.

  15. Rasfonin, a novel 2-pyrone derivative, induces ras-mutated Panc-1 pancreatic tumor cell death in nude mice

    PubMed Central

    Xiao, Z; Li, L; Li, Y; Zhou, W; Cheng, J; Liu, F; Zheng, P; Zhang, Y; Che, Y

    2014-01-01

    Rasfonin is a novel 2-pyrone derivative reported to induce apoptosis in ras-dependent cells. In this study, its effects on ras-mutated pancreatic cancer cells were investigated in vitro and in vivo. Two human pancreatic cancer cell lines Panc-1 (mutated K-ras) and BxPC-3 (wild-type K-ras) were selected to test the effects of rasfonin on cell proliferation, clone formation, migration and invasion in vitro. Immunoblotting was used to detect the expressions of EGFR–Ras–Raf–MEK–ERK signaling pathway proteins. Ras activity was measured using a pull-down ELISA kit and guanine exchange factor (GEF)/GTPase-activating proteins (GAP) activity was measured by [3H]-GDP radiometric ligand binding. For an in vivo study, CD1 nude mice bearing Panc-1 cells were treated with rasfonin or Salirasib (FTS). We found that rasfonin suppressed proliferation more strongly in Panc-1 cells (IC50=5.5 μM) than BxPC-3 cells (IC50=10 μM) in vitro. Clone formation, migration and invasion by Panc-1 cells were also reduced by rasfonin. Rasfonin had little effect on the farnesylation of Ras, but it strongly downregulated Ras activity and consequently phosphorylation of c-Raf/MEK/ERK. Further experiments indicated that rasfonin reduced Son of sevenless (Sos1) expression but did not alter GEF and GAP activities. The in vivo experiments also revealed that rasfonin (30 mg/kg) delayed the growth of xenograft tumors originating from Panc-1 cells. Tumor weight was ultimately decreased after 20 days of treatment of rasfonin. Rasfonin is a robust inhibitor of pancreatic cancers with the K-ras mutation. The reduction of Sos1 expression and the consequently depressed Ras–MAPK activity could be important in its anticancer activity. PMID:24853419

  16. Electroconvulsive Therapy for Agitation in Schizophrenia: Metaanalysis of Randomized Controlled Trials.

    PubMed

    Gu, Xiaojing; Zheng, Wei; Guo, Tong; Ungvari, Gabor S; Chiu, Helen F K; Cao, Xiaolan; D'Arcy, Carl; Meng, Xiangfei; Ning, Yuping; Xiang, Yutao

    2017-02-25

    Agitation poses a significant challenge in the treatment of schizophrenia. Electroconvulsive therapy (ECT) is a fast, effective and safe treatment for a variety of psychiatric disorders, but no meta-analysis of ECT treatment for agitation in schizophrenia has yet been reported. To systematically evaluate the efficacy and safety of ECT alone or ECT-antipsychotics (APs) combination for agitation in schizophrenia. Systematic literature search of randomized controlled trials (RCTs) was performed. Two independent evaluators selected studies, extracted data about outcomes and safety with available data, conducted quality assessment and data synthesis. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) was used to judge the level of the overall evidence of main outcomes. Seven RCTs from China, including ECT alone (4 RCTs with 5 treatment arms, n=240) and ECT-APs combination (3 RCTs, n=240), were identified. Participants in the studies were on average 34.3(4.5) years of age and lasted an average of 4.3(3.1) weeks of treatment duration. All 7 RCTs were non-blinded, and were rated as low quality based on Jadad scale. Meta-analysis of the pooled sample found no significant difference in the improvement of the agitation sub-score of the Positive and Negative Syndrome Scale (PANSS) when ECT alone (weighted mean difference=-0.90, (95% confidence interval (CI): -2.91, 1.11), p=0.38) or ECT-APs combination (WMD=-1.34, (95%CI: -4.07, 1.39), p=0.33) compared with APs monotherapy. However, ECT alone was superior to APs monotherapy regarding PANSS total score (WMD=-7.13, I 2 =0%, p =0.004) and its excitement sub-score (WMD=-1.97, p <0.0001) as well as the PANSS total score at 14 days (WMD=-7.13, I 2 =0%, p =0.004) and its excitement sub-score at 7 and 14 days (WMD=-1.97 to -1.92, p =0.002 to 0.0001) after ECT. The ECT-APs combination was superior to APs monotherapy with respect to the PANSS total score at treatment endpoint (WMD=-10.40, p=0.03) and 7 days

  17. Genetic analysis and CRISPR typing of Salmonella enterica serovar Enteritidis from different sources revealed potential transmission from poultry and pig to human.

    PubMed

    Li, Qiuchun; Wang, Xin; Yin, Kequan; Hu, Yachen; Xu, Haiyan; Xie, Xiaolei; Xu, Lijuan; Fei, Xiao; Chen, Xiang; Jiao, Xinan

    2018-02-02

    Salmonella enterica serovar Enteritidis (S. Enteritidis) is one of the most prevalent serotypes in Salmonella isolated from poultry and the most commonly reported cause of human salmonellosis. In this study, we aimed to assess the genetic diversity of 329 S. Enteritidis strains isolated from different sources from 2009 to 2016 in China. Clustered regularly interspaced short palindromic repeat (CRISPR) typing was used to characterize these 262 chicken clinical isolates, 38 human isolates, 18 pig isolates, six duck isolates, three goose isolates and two isolates of unknown source. A total of 18 Enteritidis CRISPR types (ECTs) were identified, with ECT2, ECT8 and ECT4 as the top three ECTs. CRISPR typing identified ECT2 as the most prevalent ECT, which accounted for 41% of S. Enteritidis strains from all the sources except duck. ECT9 and ECT13 were identified in both pig and human isolates and revealed potential transmission from pig to human. A cluster analysis distributed 18 ECTs, including the top three ECTs, into four lineages with LI as the predominant lineage. Forty-eight out of 329 isolates were subjected to whole genome sequence typing, which divided them into four clusters, with Cluster I as the predominant cluster. Cluster I included 92% (34/37) of strains located in LI identified from the CRISPR typing, confirming the good correspondence between both typing methods. In addition, the CRISPR typing also revealed the close relationship between ECTs and isolated areas, confirming that CRISPR spacers might be obtained by bacteria from the unique phage or plasmid pools in the environment. However, further analysis is needed to determine the function of CRISPR-Cas systems in Salmonella and the relationship between spacers and the environment. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. EFFICACY AND LONG-TERM CLINICAL OUTCOME OF COMORBID POSTTRAUMATIC STRESS DISORDER AND MAJOR DEPRESSIVE DISORDER AFTER ELECTROCONVULSIVE THERAPY.

    PubMed

    Ahmadi, Naser; Moss, Lori; Simon, Edwin; Nemeroff, Charles B; Atre-Vaidya, Nutan

    2016-07-01

    Many patients fulfill criteria for both posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). Electroconvulsive therapy (ECT) is generally acknowledged to be the most-effective treatment for refractory MDD. This study investigated the efficacy of ECT on long-term clinical outcome of comorbid PTSD and MDD. This retrospective nested matched case-control study is inclusive of 22,164 subjects [3,485 with comorbid MDD and PTSD (92 with ECT and 3,393 without ECT) and 18,679 without MDD and PTSD]. Using the clinical global impression scale (CGI) to assess efficacy, more-robust improvement of PTSD and MDD symptoms was observed with ECT (90%), compared to antidepressant-treatment alone(50%) (P = 0.001). During the median of 8 years of follow-up, the death-rate was 8% in subjects without PTSD and MDD, 9.7% in PTSD and MDD treated with ECT and 18% in PTSD and MDD without ECT (P < 0.05). The suicide-rate was 2.2 and 5.9% in PTSD and MDD with and without ECT-treatment, respectively (P < 0.05). Survival-analyses revealed that the relative-risk of cardiovascular and all-cause mortality is not significantly different in patients with comorbid MDD and PTSD treated with ECT, compared to a matched-cohort without PTSD and MDD (P > 0.05). The relative risk of suicidality, all-cause, and cardiovascular mortality was reduced 64, 65, and 46% in MDD and PTSD patients treated with ECT, compared to those without ECT (P < 0.05). ECT is associated with a significant reduction of symptoms of PTSD and MDD, as well as reduction in risk of suicidality, cardiovascular, and all-cause mortality in MDD and PTSD, an effect more robust than antidepressant-therapy alone. © 2015 Wiley Periodicals, Inc.

  19. Activation of Rab GTPase Sec4 by its GEF Sec2 is required for prospore membrane formation during sporulation in yeast Saccharomyces cerevisiae.

    PubMed

    Suda, Yasuyuki; Tachikawa, Hiroyuki; Inoue, Ichiro; Kurita, Tomokazu; Saito, Chieko; Kurokawa, Kazuo; Nakano, Akihiko; Irie, Kenji

    2018-02-01

    Sec2 activates Sec4 Rab GTPase as a guanine nucleotide exchange factor for the recruitment of downstream effectors to facilitate tethering and fusion of post-Golgi vesicles at the plasma membrane. During the meiosis and sporulation of budding yeast, post-Golgi vesicles are transported to and fused at the spindle pole body (SPB) to form a de novo membrane, called the prospore membrane. Previous studies have revealed the role of the SPB outer surface called the meiotic outer plaque (MOP) in docking and fusion of post-Golgi vesicles. However, the upstream molecular machinery for post-Golgi vesicular fusion that facilitates prospore membrane formation remains enigmatic. Here, we demonstrate that the GTP exchange factor for Sec4, Sec2, participates in the formation of the prospore membrane. A conditional mutant in which the SEC2 expression is shut off during sporulation showed sporulation defects. Inactivation of Sec2 caused Sec4 targeting defects along the prospore membranes, thereby causing insufficient targeting of downstream effectors and cargo proteins to the prospore membrane. These results suggest that the activation of Sec4 by Sec2 is required for the efficient supply of post-Golgi vesicles to the prospore membrane and thus for prospore membrane formation/extension and subsequent deposition of spore wall materials. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Solo/Trio8, a membrane-associated short isoform of Trio, modulates endosome dynamics and neurite elongation.

    PubMed

    Sun, Ying-Jie; Nishikawa, Kaori; Yuda, Hideki; Wang, Yu-Lai; Osaka, Hitoshi; Fukazawa, Nobuna; Naito, Akira; Kudo, Yoshihisa; Wada, Keiji; Aoki, Shunsuke

    2006-09-01

    With DNA microarrays, we identified a gene, termed Solo, that is downregulated in the cerebellum of Purkinje cell degeneration mutant mice. Solo is a mouse homologue of rat Trio8-one of multiple Trio isoforms recently identified in rat brain. Solo/Trio8 contains N-terminal sec14-like and spectrin-like repeat domains followed by a single guanine nucleotide exchange factor 1 (GEF1) domain, but it lacks the C-terminal GEF2, immunoglobulin-like, and kinase domains that are typical of Trio. Solo/Trio8 is predominantly expressed in Purkinje neurons of the mouse brain, and expression begins following birth and increases during Purkinje neuron maturation. We identified a novel C-terminal membrane-anchoring domain in Solo/Trio8 that is required for enhanced green fluorescent protein-Solo/Trio8 localization to early endosomes (positive for both early-endosome antigen 1 [EEA1] and Rab5) in COS-7 cells and primary cultured neurons. Solo/Trio8 overexpression in COS-7 cells augmented the EEA1-positive early-endosome pool, and this effect was abolished via mutation and inactivation of the GEF domain or deletion of the C-terminal membrane-anchoring domain. Moreover, primary cultured neurons transfected with Solo/Trio8 showed increased neurite elongation that was dependent on these domains. These results suggest that Solo/Trio8 acts as an early-endosome-specific upstream activator of Rho family GTPases for neurite elongation of developing Purkinje neurons.

  1. Convex foundations for generalized MaxEnt models

    NASA Astrophysics Data System (ADS)

    Frongillo, Rafael; Reid, Mark D.

    2014-12-01

    We present an approach to maximum entropy models that highlights the convex geometry and duality of generalized exponential families (GEFs) and their connection to Bregman divergences. Using our framework, we are able to resolve a puzzling aspect of the bijection of Banerjee and coauthors between classical exponential families and what they call regular Bregman divergences. Their regularity condition rules out all but Bregman divergences generated from log-convex generators. We recover their bijection and show that a much broader class of divergences correspond to GEFs via two key observations: 1) Like classical exponential families, GEFs have a "cumulant" C whose subdifferential contains the mean: Eo˜pθ[φ(o)]∈∂C(θ) ; 2) Generalized relative entropy is a C-Bregman divergence between parameters: DF(pθ,pθ')= D C(θ,θ') , where DF becomes the KL divergence for F = -H. We also show that every incomplete market with cost function C can be expressed as a complete market, where the prices are constrained to be a GEF with cumulant C. This provides an entirely new interpretation of prediction markets, relating their design back to the principle of maximum entropy.

  2. Nonconvulsive Status Epilepticus After Electroconvulsive Therapy: A Review of Literature.

    PubMed

    Aftab, Awais; VanDercar, Ashley; Alkhachroum, Ayham; LaGrotta, Christine; Gao, Keming

    The clinical presentation and risk factors of nonconvulsive status epilepticus (NCSE) in the context of electroconvulsive therapy (ECT) are poorly understood, and guidance regarding diagnosis and management remains scarce. In this article, we identify case reports of ECT-induced NCSE from literature, and discuss the presentation, diagnosis, and management of these cases in the context of what is known about NCSE from the neurology literature. A literature search on PubMed for case reports of NCSE after ECT. We identified 13 cases for this review. Diagnosis in all cases was based on clinical features and electroencephalogram (EEG) findings. Clinical presentation was altered mental status or unresponsiveness, with subtle motor phenomena in some cases. All cases had nonspecific risk factors that have been associated with prolonged seizures and convulsions, such as recent discontinuation/reduction of benzodiazepines or anticonvulsants, and concurrent use of antipsychotics and antidepressants. All patients were treated with either benzodiazepines or antiepileptic agents. Outcomes in these post-ECT NCSE cases were generally favorable. Although rare, post-ECT NCSE should be kept in mind by physicians when confusion or unresponsiveness develops and continues after ECT; multilead EEG is gold standard for diagnosis. An intravenous (IV) antiepileptic drug (AED) challenge can help clarify the diagnosis. Initial treatment is recommended with IV benzodiazepines, with a repeat dose if necessary. If seizures persist, IV AEDs are warranted. NCSE refractory to this treatment should be treated with a scheduled IV or oral AED. Serial multilead EEGs should be used to monitor resolution of symptoms. NCSE after ECT is a rare but recognizable clinical event. A high clinical suspicion and low threshold for EEG is necessary for prompt diagnosis. Copyright © 2018 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

  3. Electroconvulsive therapy for schizophrenia.

    PubMed

    Tharyan, P; Adams, C E

    2005-04-18

    substantial (I-squared 48.5%). There was a suggestion that ECT resulted in less relapses in the short term than sham ECT (n=47, 2 RCTs, RR fixed 0.26 CI 0.03 to 2.2), and a greater likelihood of being discharged from hospital (n=98, 1 RCT, RR fixed 0.59, CI 0.34 to 1.01). There is no evidence that this early advantage for ECT is maintained over the medium to long term. People treated with ECT did not drop out of treatment earlier than those treated with sham ECT (n=495, 14 RCTs, RR fixed 0.71 CI 0.33 to 1.52, I-squared 0%). Very limited data indicated that visual memory might decline after ECT compared with sham ECT (n=24, 1 RCT, WMD -14.0 CI -23 to -5); the results of verbal memory tests were equivocal. When ECT is directly compared with antipsychotic drug treatments (total n=443, 10 RCTs) results favour the medication group (n=175, 3 RCTs, RR fixed 'not improved at the end of ECT course' 2.18 CI 1.31 to 3.63). Limited evidence suggests that ECT combined with antipsychotic drugs results in greater improvement in mental state (n= 40, 1 RCT, WMD, Brief Psychiatric Rating Scale -3.9 CI - 2.28 to -5.52) than with antipsychotic drugs alone. One small study suggested more memory impairment after a course of ECT combined with antipsychotics than with antipsychotics alone (n=20, MD serial numbers and picture recall -4.90 CI -0.78 to -9.02), though this proved transient. When continuation ECT was added to antipsychotic drugs, the combination was superior to the use of antipsychotics alone (n=30, WMD Global Assessment of Functioning 19.06 CI 9.65 to 28.47), or CECT alone (n=30, WMD -20.30 CI -11.48 to -29.12). Unilateral and bilateral ECT were equally effective in terms of global improvement (n=78, 2 RCTs, RR fixed 'not improved at end of course of ECT' 0.79 CI 0.45 to 1.39). One trial showed a significant advantage for 20 treatments over 12 treatments for numbers globally improved at the end of the ECT course (n=43, RR fixed 2.53 CI 1.13 to 5.66). The evidence in this review suggests

  4. Virtual photon emission from a quark-gluon plasma

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Suryanarayana, S. V.

    We present phenomenological formulas for virtual photon emission rates from a thermalized quark-gluon plasma (QGP) that include bremsstrahlung and annihilation with scattering (AWS) mechanisms along with the Landau-Pomeranchuk-Migdal (LPM) effects. For this purpose we follow the approach of generalized emission functions (GEF) for virtual photon emission, we showed earlier for a fixed temperature and strong coupling constant. In the present work, we extend the LPM calculations for several temperatures and strong coupling strengths, photon energies (q{sub 0}), photon mass (Q{sup 2}), and quark energies (p{sub 0}). We generalize the dynamical scaling variables, x{sub T},x{sub L}, for bremsstrahlung and AWS processesmore » that are now functions of variables p{sub 0},q{sub 0},Q{sup 2},T,{alpha}{sub s}. The GEF introduced earlier, g{sub T}{sup b},g{sub T}{sup a},g{sub L}{sup b},g{sub L}{sup a}, are also generalized for any temperatures and coupling strengths. From this, the imaginary part of the photon polarization tensor as a function of photon mass and energy has been calculated as a one-dimensional integral over these GEF and parton distribution functions in the plasma. By fitting these polarization tensors obtained from GEF method, we obtained a phenomenological formula for virtual photon emission rates as a function of (q{sub 0},Q{sup 2},T,{alpha}{sub s}) that includes bremsstrahlung and AWS mechanisms with LPM effects.« less

  5. A new early cognitive screening measure to detect cognitive side-effects of electroconvulsive therapy?

    PubMed

    Martin, Donel M; Katalinic, Natalie; Ingram, Anna; Schweitzer, Isaac; Smith, Deidre J; Hadzi-Pavlovic, Dusan; Loo, Colleen K

    2013-12-01

    Cognitive side-effects from electroconvulsive therapy (ECT) can be distressing for patients and early detection may have an important role in guiding treatment decisions over the ECT course. This prospective study examined the utility of an early cognitive screening battery for predicting cognitive side-effects which develop later in the ECT course. The screening battery, together with the Mini Mental Status Examination (MMSE), was administered to 123 patients at baseline and after 3 ECT treatments. A more detailed cognitive battery was administered at baseline, after six treatments (post ECT 6) and after the last ECT treatment (post treatment) to assess cognitive side-effects across several domains: global cognition, anterograde memory, executive function, speed and concentration, and retrograde memory. Multivariate analyses examined the predictive utility of change on items from the screening battery for later cognitive changes at post ECT 6 and post treatment. Results showed that changes on a combination of items from the screening battery were predictive of later cognitive changes at post treatment, particularly for anterograde memory (p < 0.01), after controlling for patient and treatment factors. Change on the MMSE predicted cognitive changes at post ECT 6 but not at post treatment. A scoring method for the new screening battery was tested for discriminative ability in a sub-sample of patients. This study provides preliminary evidence that a simple and easy-to-administer measure may potentially be used to help guide clinical treatment decisions to optimise efficacy and cognitive outcomes. Further development of this measure and validation in a more representative ECT clinical population is required. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Electroconvulsive therapy practice in Ukraine.

    PubMed

    Olekseev, Aleksey; Ungvari, Gabor S; Gazdag, Gábor

    2014-09-01

    Patterns of electroconvulsive therapy (ECT) use have recently been extensively surveyed in Central-Eastern Europe. However, data from post-USSR countries are limited. This study aimed to survey ECT practice in Ukraine. All psychiatric services in Ukraine were identified and contacted to obtain information on the use of ECT in 2011 using a 22-item questionnaire. Of the 146 psychiatric inpatient facilities, only 5 confirmed that they performed ECT in 2011. Three other services also performed ECT but refused to provide further information. In the only private psychiatric institute where ECT was offered, 14.28% of inpatients received this treatment in 2011, whereas the corresponding figure in the 6 public psychiatric facilities was a mere 0.4%. Three centers used unmodified ECT, and only 2 centers had equipment that monitored electroencephalogram. In 7 services, in line with international recommendations, affective disorders were the first indications for ECT in Ukraine, whereas uncommon indications such as anorexia or Parkinsonism were also reported. This was the first survey of ECT practice conducted in Ukraine. The provision of ECT in only 8 centers is clearly insufficient for a large country such as Ukraine, which is reflected in the low rate of inpatients treated with ECT. The very limited availability of this effective treatment modality should be addressed by the Ukrainian health authorities.

  7. Prediction of Individual Response to Electroconvulsive Therapy via Machine Learning on Structural Magnetic Resonance Imaging Data.

    PubMed

    Redlich, Ronny; Opel, Nils; Grotegerd, Dominik; Dohm, Katharina; Zaremba, Dario; Bürger, Christian; Münker, Sandra; Mühlmann, Lisa; Wahl, Patricia; Heindel, Walter; Arolt, Volker; Alferink, Judith; Zwanzger, Peter; Zavorotnyy, Maxim; Kugel, Harald; Dannlowski, Udo

    2016-06-01

    Electroconvulsive therapy (ECT) is one of the most effective treatments for severe depression. However, biomarkers that accurately predict a response to ECT remain unidentified. To investigate whether certain factors identified by structural magnetic resonance imaging (MRI) techniques are able to predict ECT response. In this nonrandomized prospective study, gray matter structure was assessed twice at approximately 6 weeks apart using 3-T MRI and voxel-based morphometry. Patients were recruited through the inpatient service of the Department of Psychiatry, University of Muenster, from March 11, 2010, to March 27, 2015. Two patient groups with acute major depressive disorder were included. One group received an ECT series in addition to antidepressants (n = 24); a comparison sample was treated solely with antidepressants (n = 23). Both groups were compared with a sample of healthy control participants (n = 21). Binary pattern classification was used to predict ECT response by structural MRI that was performed before treatment. In addition, univariate analysis was conducted to predict reduction of the Hamilton Depression Rating Scale score by pretreatment gray matter volumes and to investigate ECT-related structural changes. One participant in the ECT sample was excluded from the analysis, leaving 67 participants (27 men and 40 women; mean [SD] age, 43.7 [10.6] years). The binary pattern classification yielded a successful prediction of ECT response, with accuracy rates of 78.3% (18 of 23 patients in the ECT sample) and sensitivity rates of 100% (13 of 13 who responded to ECT). Furthermore, a support vector regression yielded a significant prediction of relative reduction in the Hamilton Depression Rating Scale score. The principal findings of the univariate model indicated a positive association between pretreatment subgenual cingulate volume and individual ECT response (Montreal Neurological Institute [MNI] coordinates x = 8, y = 21, z = -18

  8. Effects of small-dose dexmedetomidine on hyperdynamic responses to electroconvulsive therapy.

    PubMed

    Li, Xiang; Tan, Fang; Jian, Chao-Jun; Guo, Na; Zhong, Zhi-Yong; Hei, Zi-Qing; Zhou, Shao-Li

    2017-08-01

    Acute hemodynamic responses to electroconvulsive therapy (ECT) may increase the risk of cardiovascular complications in vulnerable patients. The aim of the current study was to assess the effect of small-dose dexmedetomidine on hyperdynamic responses to ECT. Seventy-eight patients were enrolled and randomly allocated to receive either 0.2 μg/kg dexmedetomidine (Dex group, n = 39) or saline (Control group, n = 39) prior to ECT. Heart rate (HR) and mean arterial pressure (MAP) were recorded immediately after the administration of dexmedetomidine (T1), and 0, 1, 3, 5 and 10 min after the electrical stimuli ended (T2, T3, T4, T5 and T6). In addition, the peak HR after ECT, seizure duration, recovery time, and incidence rates of post-ECT adverse effects (agitation, headache and nausea) were also recorded. HR and MAP in the Dex group were significantly lower than those in the Control group from T2 to T5. In addition, peak HR was significantly lower in the Dex group compared with that in the Control group. Seizure length and time to spontaneous breathing, eye opening, and obeying commands in the Dex group were similar to those in the Control group. The incidence rates of post-ECT agitation and headache in the Dex group were significantly lower than that in the Control group. The administration of 0.2 μg/kg dexmedetomidine to patients receiving ECT leads to a significant reduction in HR, MAP, and peak HR responses to ECT without altering seizure duration or delaying recovery. Furthermore, dexmedetomidine effectively reduced the incidence rates of post-ECT adverse effects such as agitation and headache. Copyright © 2017. Published by Elsevier Taiwan LLC.

  9. Myosin IIA/IIB restrict adhesive and protrusive signaling to generate front-back polarity in migrating cells.

    PubMed

    Vicente-Manzanares, Miguel; Newell-Litwa, Karen; Bachir, Alexia I; Whitmore, Leanna A; Horwitz, Alan Rick

    2011-04-18

    Migratory front-back polarity emerges from the cooperative effect of myosin IIA (MIIA) and IIB (MIIB) on adhesive signaling. We demonstrate here that, during polarization, MIIA and MIIB coordinately promote localized actomyosin bundling, which generates large, stable adhesions that do not signal to Rac and thereby form the cell rear. MIIA formed dynamic actomyosin proto-bundles that mark the cell rear during spreading; it also bound to actin filament bundles associated with initial adhesion maturation in protrusions. Subsequent incorporation of MIIB stabilized the adhesions and actomyosin filaments with which it associated and formed a stable, extended rear. These adhesions did not turn over and no longer signal to Rac. Microtubules fine-tuned the polarity by positioning the front opposite the MIIA/MIIB-specified rear. Decreased Rac signaling in the vicinity of the MIIA/MIIB-stabilized proto-bundles and adhesions was accompanied by the loss of Rac guanine nucleotide exchange factor (GEFs), like βPIX and DOCK180, and by inhibited phosphorylation of key residues on adhesion proteins that recruit and activate Rac GEFs. These observations lead to a model for front-back polarity through local GEF depletion.

  10. Electroconvulsive Therapy Use in Youth in the Province of Quebec.

    PubMed

    Loiseau, Annie; Harrisson, Marie-Claude; Beaudry, Vincent; Patry, Simon

    2017-01-01

    Electroconvulsive therapy's (ECT) safety and tolerability is well-established in the treatment of severe psychiatric disorders in adults, but has been less studied in youth. The aim of the present study was to describe the use of ECT in youth in Quebec City and obtain Child and Adolescent Psychiatrists' (CAP) perceptions in the province of Quebec. The authors reviewed charts of minors who received ECT treatment in the Quebec City metropolitan area between 1995 and 2014 (part 1). Data was also collected on CAP perceptions and experience of ECT use in youth by means of a survey (part 2). Part 1 included four girls and two boys, aged between 15 and 17. The main diagnoses were: mood disorders and schizoaffective disorder. Patients received between four and twelve ECT sessions. Five patients responded to treatment, whereas one did not. Treatment and side effects are presented. For part 2, 53 CAP answered the survey. Forty-eight (91%) thought ECT is a good treatment option after failure of other therapeutic modalities and 12 (23%) had prescribed it. All respondents wished to receive additional training regarding ECT use in youth. Our results are consistent with the notion that ECT use in youth with a refractory and complex disease is a safe and effective treatment, although rarely used. The majority of psychiatrists treating children and adolescents in Quebec favor ECT when all available therapeutic modalities have failed, but wished they had more training regarding its use.

  11. The practice of electroconvulsive therapy in Greece.

    PubMed

    Kaliora, Styliani C; Braga, Raphael J; Petrides, Georgios; Chatzimanolis, John; Papadimitriou, George N; Zervas, Iannis M

    2013-09-01

    To describe the practice of electroconvulsive therapy (ECT) in Greece. A survey was conducted during the academic year 2008-2009. Electroconvulsive therapy use was investigated for 2007. All civilian institutions providing inpatient care were included. Centers that provided ECT completed a 57-item questionnaire. Centers that did not offer ECT completed a 13-item questionnaire. Fifty-five (82.1%) of 67 institutions responded. Electroconvulsive therapy was offered in 18 hospitals. Only 2 of 10 university hospitals offered ECT. Overall, 137 patients were treated with 1271 sessions in 2007. Only 1.47% discontinued treatment owing to adverse events. There were no deaths. Schizophrenia was the most common diagnosis (41.3%) among those receiving ECT, followed by major depression (28.9%), bipolar depression (9.1%), catatonia (4.1%), suicidal ideation (3.3%), and schizoaffective disorder (2.5%). Physicians considered major depression (93.8%), catatonia (86.5%), schizophrenia (56.3%), and mania (50%) the most appropriate indications. Written informed consent was required in 77.8% of the institutions, whereas the rest required verbal consent. Bilateral ECT was the preferred electrode placement (88.9%). Modified ECT was used exclusively. Propofol was the preferred anesthetic (44.4%), followed by thiopental (38.9%). Seven (38.9%) of 18 hospitals used a fixed stimulus dose at first treatment. Five (27.8%) of 18 hospitals used the half-age method. Continuation/maintenance ECT was used in 33.3% of the hospitals. Outpatient ECT was seldom used. Lack of training, difficult access to anesthesiology, billing issues, and stigma were cited as the main impediments to the practice of ECT. Electroconvulsive therapy is practiced in moderate numbers in Greece and almost exclusively on an inpatient basis. Lack of training and lack of availability of anesthesiologists were cited as the most common obstacles to providing ECT.

  12. Response to Electroconvulsive Therapy in Patients With Autism Spectrum Disorder and Intractable Challenging Behaviors Associated With Symptoms of Catatonia.

    PubMed

    Sajith, Sreedharan Geetha; Liew, Siew Fai; Tor, Phern Chern

    2017-03-01

    There are several reports of electroconvulsive therapy (ECT) used in autism spectrum disorder (ASD) in the context of catatonic symptoms. We describe response to ECT in two adults with ASD and intellectual disability with intractable aggression and self-injurious behaviors associated with catatonic symptoms who had not responded to standard interventions. Unilateral ECT at a frequency of 3 times a week was given followed by weekly maintenance ECT. Patients' catatonic symptoms included episodes of agitation and echophenomena. Electroconvulsive therapy resulted in significant improvement in their behavior problems but 1 patient relapsed when the ECT was discontinued or frequency of treatment reduced. The second patient required 2 courses of ECT before improvement which was maintained on weekly ECT. Electroconvulsive therapy could be a potentially beneficial intervention in patients with ASD and severe challenging behaviors associated with catatonic symptoms including agitated or excited forms of catatonia.

  13. Relapse following successful electroconvulsive therapy for major depression: a meta-analysis.

    PubMed

    Jelovac, Ana; Kolshus, Erik; McLoughlin, Declan M

    2013-11-01

    High rates of early relapse following electroconvulsive therapy (ECT) are typically reported in the literature. Current treatment guidelines offer little information to clinicians on the optimal nature of maintenance therapy following ECT. The aim of this study was to provide a systematic overview of the existing evidence regarding post-ECT relapse. A keyword search of electronic databases was performed for studies appearing in the peer-reviewed literature before January 2013 reporting on relapse rates in responders to an acute course of ECT administered for a major depressive episode. Meta-analyses were performed where appropriate. Thirty-two studies with up to 2 years' duration of follow-up were included. In modern era studies of continuation pharmacotherapy, 51.1% (95% CI=44.7-57.4%) of patients relapsed by 12 months following successful initial treatment with ECT, with the majority (37.7%, 95% CI=30.7-45.2%) relapsing within the first 6 months. The 6-month relapse rate was similar in patients treated with continuation ECT (37.2%, 95% CI=23.4-53.5%). In randomized controlled trials, antidepressant medication halved the risk of relapse compared with placebo in the first 6 months (risk ratio=0.49, 95% CI=0.39-0.62, p<0.0001, number needed to treat=3.3). Despite continuation therapy, the risk of relapse within the first year following ECT is substantial, with the period of greatest risk being the first 6 months. The largest evidence base for efficacy in post-ECT relapse prevention exists for tricyclic antidepressants. Published evidence is limited or non-existent for commonly used newer antidepressants or popular augmentation strategies. Maintenance of well-being following successful ECT needs to be improved.

  14. Ketamine as the anaesthetic for electroconvulsive therapy: the KANECT randomised controlled trial

    PubMed Central

    Fernie, Gordon; Currie, James; Perrin, Jennifer S.; Stewart, Caroline A.; Anderson, Virginica; Bennett, Daniel M.; Hay, Steven; Reid, Ian C.

    2017-01-01

    Background Ketamine has recently become an agent of interest as an acute treatment for severe depression and as the anaesthetic for electroconvulsive therapy (ECT). Subanaesthetic doses result in an acute reduction in depression severity while evidence is equivocal for this antidepressant effect with anaesthetic or adjuvant doses. Recent systematic reviews call for high-quality evidence from further randomised controlled trials (RCTs). Aims To establish if ketamine as the anaesthetic for ECT results in fewer ECT treatments, improvements in depression severity ratings and less memory impairment than the standard anaesthetic. Method Double-blind, parallel-design, RCT of intravenous ketamine (up to 2 mg/kg) with an active comparator, intravenous propofol (up to 2.5 mg/kg), as the anaesthetic for ECT in patients receiving ECT for major depression on an informal basis. (Trial registration: European Clinical Trials Database (EudraCT): 2011-000396-14 and clinicalTrials.gov: NCT01306760.) Results No significant differences were found on any outcome measure during, at the end of or 1 month following the ECT course. Conclusions Ketamine as an anaesthetic does not enhance the efficacy of ECT. PMID:28254962

  15. Autism-Like Behavior in BTBR Mice Is Improved by Electroconvulsive Therapy.

    PubMed

    Hagen, Eunice; Shprung, Dana; Minakova, Elena; Washington, James; Kumar, Udaya; Shin, Don; Sankar, Raman; Mazarati, Andrey

    2015-07-01

    Autism is a developmental disorder characterized by impairments in social and communication abilities, as well as by restricted and repetitive behaviors. Incidence of autism is higher than earlier estimates, and treatments have limited efficacy and are costly. Limited clinical and experimental evidence suggest that patients with autism may benefit from electroconvulsive therapy (ECT). We examined the therapeutic potential of ECT in BTBR T+ tf/j mice, which represent a validated model of autism. A series of 13 electroconvulsive shocks (ECS) delivered twice a day over 7 days reversed core autism-like behavioral abnormalities-impaired sociability, social novelty, and repetitive behavior-when the animals were tested 24 h after the last ECS. The effect lasted up to 2 weeks after ECT. Neither single ECS nor a series of 6 ECS modified animals' behavior. Chronic infusion into the lateral brain ventricle of a preferential oxytocin receptor blocker (2S)-2-Amino-N-[(1S,2S,4R)-7,7-dimethyl-1-[[[4-(2-methylphenyl)-1-piperazinyl]sulfonyl]methyl]bicyclo[2.2.1]hept-2-yl]-4-(methylsulfonyl)butanamide hydrochloride abolished ECT-induced improvement of sociability and mitigated improvement of social novelty but did not affect ECT-induced reversal of repetitive behavior. These proof-of-principle experiments suggest that ECT may, indeed, be useful in the treatment of autism, and that its therapeutic effects may be mediated, in part, by central oxytocin signaling.

  16. Thrombin Promotes Sustained Signaling and Inflammatory Gene Expression through the CDC25 and Ras-associating Domains of Phospholipase Cϵ*

    PubMed Central

    Dusaban, Stephanie S.; Kunkel, Maya T.; Smrcka, Alan V.; Brown, Joan Heller

    2015-01-01

    Phospholipase C-epsilon (PLCϵ) plays a critical role in G-protein-coupled receptor-mediated inflammation. In addition to its ability to generate the second messengers inositol 1,4,5-trisphosphate and diacylglycerol, PLCϵ, unlike the other phospholipase C family members, is activated in a sustained manner. We hypothesized that the ability of PLCϵ to function as a guanine nucleotide exchange factor (GEF) for Rap1 supports sustained downstream signaling via feedback of Rap1 to the enzyme Ras-associating (RA2) domain. Using gene deletion and adenoviral rescue, we demonstrate that both the GEF (CDC25 homology domain) and RA2 domains of PLCϵ are required for long term protein kinase D (PKD) activation and subsequent induction of inflammatory genes. PLCϵ localization is largely intracellular and its compartmentalization could contribute to its sustained activation. Here we show that localization of PLCϵ to the Golgi is required for activation of PKD in this compartment as well as for subsequent induction of inflammatory genes. These data provide a molecular mechanism by which PLCϵ mediates sustained signaling and by which astrocytes mediate pathophysiological inflammatory responses. PMID:26350460

  17. Cognitive training to improve memory in individuals undergoing electroconvulsive therapy: Negative findings.

    PubMed

    Choi, Jimmy; Wang, Yuanjia; Feng, Tianshu; Prudic, Joan

    2017-09-01

    Although electroconvulsive therapy (ECT) remains the most effective treatment for severe depression, some patients report persistent memory problems following ECT that impact their quality of life and their willingness to consent to further ECT. While cognitive training has been shown to improve memory performance in various conditions, this approach has never been applied to help patients regain their memory after ECT. In a double-blind study, we tested the efficacy of a new cognitive training program called Memory Training for ECT (Mem-ECT), specifically designed to target anterograde and retrograde memory that can be compromised following ECT. Fifty-nine patients with treatment-resistant depression scheduled to undergo ultra-brief right unilateral ECT were randomly assigned to either: (a) Mem-ECT, (b) active control comprised of nonspecific mental stimulation, or (c) treatment as usual. Participants were evaluated within one week prior to the start of ECT and then again within 2 weeks following the last ECT session. All three groups improved in global function, quality of life, depression, and self-reported memory abilities without significant group differences. While there was a decline in verbal delayed recall and mental status, there was no decline in general retrograde memory or autobiographical memory in any of the groups, with no significant memory or clinical benefit for the Mem-ECT or active control conditions compared to treatment as usual. While we report negative findings, these results continue to promote the much needed discussion on developing effective strategies to minimize the adverse memory side effects of ECT, in hopes it will make ECT a better and more easily tolerated treatment for patients with severe depression who need this therapeutic option. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Ultrafast Self-Crystallization of High-External-Quantum-Efficient Fluoride Phosphors for Warm White Light-Emitting Diodes.

    PubMed

    Zhou, Wenli; Fang, Mu-Huai; Lian, Shixun; Liu, Ru-Shi

    2018-05-30

    In this study, we used HF (as good solvent) to dissolve K 2 GeF 6 and K 2 MnF 6 and added ethanol (as poor solvent) to cause ultrafast self-crystallization of K 2 GeF 6 :Mn 4+ crystals, which had an unprecedentedly high external quantum efficiency that reached 73%. By using the red phosphor, we achieved a high-quality warm white light-emitting diode with color-rendering index of R a = 94, R9 = 95, luminous efficacy of 150 lm W -1 , and correlated color temperature at 3652 K. Furthermore, the good-poor solvent strategy can be used to fast synthesize other fluorides.

  19. Influence of electrocautery-induced electromagnetic interference on quantitative electroencephalographic monitoring of hypnosis during general anesthesia: comparison between the ADMS® and the BIS VISTATM.

    PubMed

    Kim, Dae-Hee; Yoo, Ji-Young; Kim, Jong-Yeop; Ahn, Soo-Hwan; Kim, Seongsu; Min, Sang-Kee

    2018-04-24

    Hypnosis monitors analyze small-amplitude electrical signals transmitted from the brain that could be exposed to the electromagnetic field that occurs around the body during electrocautery (ECT). We investigated the influence of ECT on hypnosis monitoring during anesthesia. We simultaneously monitored BIS and uCON during 50 gynecologic oncology surgeries. During the episodes of ECT, we compared the absolute difference (a-Diff) between the baseline index and the most deviated index after ECT over either 30-60 s (ECT30-60) or more than 60 s (ECT > 60) between the monitors. We also investigated the bias and the limits of agreement between the monitors. Between the two monitors, the a-Diff of ECT30-60 was 1.4 ± 1.1 for the BIS, which was significantly greater than 0.6 ± 0.9 for the uCON (P = 0.003), and the a-Diff of ECT > 60 was 16.5 ± 8.2 for the BIS, which was also significantly greater than 1.4 ± 1.3 for uCON (P < 0.001). The intra-monitor index differences showed that the BIS during ECT > 60 was significantly greater than that during ECT30-60 (P < 0.001), but the uCON showed no significant difference between ECT30-60 and ECT > 60 (P = 0.056). The estimated bias between the monitors was 6.3 ± 9.8 and 95% limits agreement was -12.3 to 25.0. Prolonged ECT intervention might lead to spurious estimations of quantitative EEG indexes. Therefore, hypnosis should be clinically assessed in combination with scrutinized judgment of relevant clinical symptoms and signs for hypnosis.

  20. Maintenance Electroconvulsive Therapy in Severe Bipolar Disorder: A Retrospective Chart Review.

    PubMed

    Santos Pina, Laura; Bouckaert, Filip; Obbels, Jasmien; Wampers, Martien; Simons, Wim; Wyckaert, Sabien; Sienaert, Pascal

    2016-03-01

    The aim of this study was to evaluate the effectiveness of continuation and maintenance electroconvulsive therapy (C/M-ECT) in patients with bipolar or schizoaffective disorder. We reviewed the charts of all patients diagnosed with a bipolar or schizoaffective disorder treated with C/M-ECT from August 2009 until December 2013. We gathered demographic data and treatment variables (electrode placement, stimulus dose, and concomitant use of medication; number of C/M-ECT sessions; and number of new ECT courses). Primary outcome measure was the number of hospitalization days during C/M-ECT as compared with an equal period before starting the index course. Twenty women (64.5%) and 11 men (35.5%) with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition bipolar disorder (n = 22, 71%) or schizoaffective disorder (n = 9, 29%) received C/M-ECT. The mean (SD) age was 51.23 (14.86; range, 28-74) years. Before the start of the index ECT, patients had a mean of 290 hospitalization days (248.4 days, full hospitalization; 41.6 days, partial hospitalization), whereas during C/M-ECT, they had a mean of 214.7 hospitalization days (85.4 days, full hospitalization; 129.3 days, partial hospitalization). The number of readmissions before ECT was 2.13, whereas during C/M-ECT, it decreased to 1.48. Only the decrease in number of full hospitalization days was significant. Most patients (n = 23, 74.19%) needed an acute course of ECT during M-ECT. Maintenance ECT seems to significantly reduce the number of full hospitalization days in patients with severe bipolar or schizoaffective disorder.

  1. Identifying Recipients of Electroconvulsive Therapy: Data From Privately Insured Americans.

    PubMed

    Wilkinson, Samuel T; Agbese, Edeanya; Leslie, Douglas L; Rosenheck, Robert A

    2018-05-01

    Despite the effectiveness of electroconvulsive therapy (ECT), limited epidemiologic research has been conducted to identify rates of ECT use and characteristics of patients who receive ECT. Sociodemographic and clinical characteristics associated with ECT use were examined among patients with mood disorders in the MarketScan commercial insurance claims database. Among individuals with major depressive disorder or bipolar disorder, sociodemographic and clinical characteristics of those who received ECT and those who did not were compared by using bivariate effect size comparisons and multivariate logistic regression. Among unique individuals in the 2014 MarketScan database (N=47,258,528), the ECT utilization rate was 5.56 ECT patients per 100,000 in the population. Of the 969,277 patients with a mood disorder, 2,471 (.25%) received ECT. Those who received ECT had substantially higher rates of additional comorbid psychiatric disorders (risk ratio [RR]=5.70 for any additional psychiatric disorder), numbers of prescription fills for any psychotropic medication (Cohen's d=.77), rates of any substance use disorder (RR=1.97), and total outpatient psychotherapy visits (Cohen's d=.49). The proportion of patients with a mood disorder who received ECT in the West (.19%) was substantially lower than in other U.S. regions (.28%). This difference was almost entirely accounted for by one western state comprising 59.1% of patients in that region. Use of ECT is exceptionally uncommon and limited to patients with extensive multimorbidity and high levels of service use. ECT utilization is most limited in areas of the country where regulatory restrictions are greatest.

  2. Electroconvulsive Therapy and All-Cause Mortality in Texas, 1998-2013.

    PubMed

    Dennis, Nora M; Dennis, Paul A; Shafer, Alan; Weiner, Richard D; Husain, Mustafa M

    2017-03-01

    Electroconvulsive therapy (ECT) remains an effective treatment for major depressive disorder. Since 1995, Texas has maintained an ECT database including patient diagnoses and outcomes, and reporting any deaths within 14 days of receiving an ECT treatment, encompassing a total of 166,711 ECT treatments administered in Texas over the previously unreported period of 1998 to 2013. Descriptive analysis summarized information on deaths reported during the 16-year period-cause of death, type of treatment (index or maintenance) and patient demographics. Multiple logistic regression of death incidence by treatment session was performed to determine whether patient age, sex, race, diagnosis, or year of treatment was associated with death after ECT. Of those deaths occurring within 1 day of an ECT treatment, the death rate was 2.4 per 100,000 treatments. Looking at all deaths within 14 days of an ECT treatment, the death rate increased to 18 per 100,000 treatments but included all deaths regardless of likelihood of causal association with ECT, for example, accidents and suicides, the latter a leading cause of death among individuals with severe major depression or other disorders for which ECT is indicated. Death rate increased significantly with increasing patient age (P = 0.001) and male sex (P = 0.009), and there was a nonsignificant trend toward increased death amongst patients with bipolar disorder or schizophrenia (P = 0.058) versus depression. Our data indicate that ECT is in general a safe procedure with respect to the likelihood of immediate death. Suicide remains a significant risk in ECT patients, despite evidence that ECT reduces suicidal ideation.

  3. Pregnancy and Electroconvulsive Therapy: A Multidisciplinary Approach.

    PubMed

    Ray-Griffith, Shona L; Coker, Jessica L; Rabie, Nader; Eads, Lou Ann; Golden, Kimberly J; Stowe, Zachary N

    2016-06-01

    To scrutinize a series of pregnant women treated with electroconvulsive therapy (ECT) at a tertiary treatment center and combine these data with a literature review to refine the treatment guidelines for ECT during pregnancy. A retrospective chart review of mentally ill pregnant patients treated with ECT since the establishment of a formal women's mental health program. A total of 8 pregnant women treated with ECT were identified from January 2012 to August 2014. Information was extracted from the medical records of a total of 30 ECT treatments across this group. Subjects received an average of 3.75 ECT treatments (range, 1-7). All women were diagnosed as having a mood disorder (either unipolar or bipolar), and 5 of the 8 women had suicidal ideation. The treatment team for ECT was consistent across all treatments. Two women experienced significant complications after the initial treatment: 1) an acute episode of complete heart block; and 2) acute onset of mania after ECT. Obstetrical complications included 2 women with preterm delivery-one secondary to premature rupture of membranes. No other complications or adverse outcomes were recorded. The 5 women with suicidal ideation had symptom resolution, and significant symptom improvement was noted in 6 of the 8 women. Electroconvulsive therapy is a safe and effective treatment during pregnancy and of particular benefit in the acute treatment of suicidal ideation.

  4. Improvement in verbal memory performance in depressed in-patients after treatment with electroconvulsive therapy.

    PubMed

    Biedermann, S V; Bumb, J M; Demirakca, T; Ende, G; Sartorius, A

    2016-12-01

    Electroconvulsive therapy (ECT) is a highly effective and well-tolerated therapy for severe and treatment-resistant depression. Cognitive side-effects are still feared by some patients and clinicians. Importantly, cognitive impairments are among the most disabling symptoms of depression itself. Patients suffering from a severe episode of depression were treated with either ECT or treatment as usual (TAU) in an in-patient setting. Matched healthy participants served as controls (HC). Verbal memory was tested with the California Verbal Learning Test (CVLT) before the specific treatment started (ECT = 15, TAU = 16, HC = 31) and 2 months after the last ECT session or 2 months after discharge respectively. Before the specific treatment started, depressed patients performed substantially worse compared with HC in total, short- and long-delay recall in the CVLT, while the ECT group showed the worst performance. More severely depressed patients showed worse performances in these measures. Intriguingly, verbal memory showed a significant improvement in ECT-treated patients, but not in the other groups. No differences between the groups were found at follow-up. Contrary to the widely feared assumption that ECT has long-term impact on memory functions, we found evidence that ECT is superior to TAU in improving verbal memory in depressed patients. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Oxidative stress-induced miR-27a targets the redox gene nuclear factor erythroid 2-related factor 2 in diabetic embryopathy.

    PubMed

    Zhao, Yang; Dong, Daoyin; Reece, E Albert; Wang, Ashley R; Yang, Peixin

    2018-01-01

    Maternal diabetes induces neural tube defects, and oxidative stress is a causal factor for maternal diabetes-induced neural tube defects. The redox gene nuclear factor erythroid 2-related factor 2 is the master regulator of the cellular antioxidant system. In this study, we aimed to determine whether maternal diabetes inhibits nuclear factor erythroid 2-related factor 2 expression and nuclear factor erythroid 2-related factor 2-controlled antioxidant genes through the redox-sensitive miR-27a. We used a well-established type 1 diabetic embryopathy mouse model induced by streptozotocin for our in vivo studies. Embryos at embryonic day 8.5 were harvested for analysis of nuclear factor erythroid 2-related factor 2, nuclear factor erythroid 2-related factor 2-controlled antioxidant genes, and miR-27a expression. To determine if mitigating oxidative stress inhibits the increase of miR-27a and the decrease of nuclear factor erythroid 2-related factor 2 expression, we induced diabetic embryopathy in superoxide dismutase 2 (mitochondrial-associated antioxidant gene)-overexpressing mice. This model exhibits reduced mitochondria reactive oxygen species even in the presence of hyperglycemia. To investigate the causal relationship between miR-27a and nuclear factor erythroid 2-related factor 2 in vitro, we examined C17.2 neural stem cells under normal and high-glucose conditions. We observed that the messenger RNA and protein levels of nuclear factor erythroid 2-related factor 2 were significantly decreased in embryos on embryonic day 8.5 from diabetic dams compared to those from nondiabetic dams. High-glucose also significantly decreased nuclear factor erythroid 2-related factor 2 expression in a dose- and time-dependent manner in cultured neural stem cells. Our data revealed that miR-27a was up-regulated in embryos on embryonic day 8.5 exposed to diabetes, and that high glucose increased miR-27a levels in a dose- and time-dependent manner in cultured neural stem cells. In

  6. The validity of using an electrocutaneous device for pain assessment in patients with cervical radiculopathy.

    PubMed

    Abbott, Allan; Ghasemi-Kafash, Elaheh; Dedering, Åsa

    2014-10-01

    The purpose of this study was to evaluate the validity and preference for assessing pain magnitude with electrocutaneous testing (ECT) compared to the visual analogue scale (VAS) and Borg CR10 scale in men and women with cervical radiculopathy of varying sensory phenotypes. An additional purpose was to investigate ECT sensory and pain thresholds in men and women with cervical radiculopathy of varying sensory phenotypes. This is a cross-sectional study of 34 patients with cervical radiculopathy. Scatterplots and linear regression were used to investigate bivariate relationships between ECT, VAS and Borg CR10 methods of pain magnitude measurement as well as ECT sensory and pain thresholds. The use of the ECT pain magnitude matching paradigm for patients with cervical radiculopathy with normal sensory phenotype shows good linear association with arm pain VAS (R(2) = 0.39), neck pain VAS (R(2) = 0.38), arm pain Borg CR10 scale (R(2) = 0.50) and neck pain Borg CR10 scale (R(2) = 0.49) suggesting acceptable validity of the procedure. For patients with hypoesthesia and hyperesthesia sensory phenotypes, the ECT pain magnitude matching paradigm does not show adequate linear association with rating scale methods rendering the validity of the procedure as doubtful. ECT for sensory and pain threshold investigation, however, provides a method to objectively assess global sensory function in conjunction with sensory receptor specific bedside examination measures.

  7. Electroconvulsive Therapy Use in Youth in the Province of Quebec

    PubMed Central

    Loiseau, Annie; Harrisson, Marie-Claude; Beaudry, Vincent; Patry, Simon

    2017-01-01

    Objectives Electroconvulsive therapy’s (ECT) safety and tolerability is well-established in the treatment of severe psychiatric disorders in adults, but has been less studied in youth. The aim of the present study was to describe the use of ECT in youth in Quebec City and obtain Child and Adolescent Psychiatrists’ (CAP) perceptions in the province of Quebec. Methods The authors reviewed charts of minors who received ECT treatment in the Quebec City metropolitan area between 1995 and 2014 (part 1). Data was also collected on CAP perceptions and experience of ECT use in youth by means of a survey (part 2). Results Part 1 included four girls and two boys, aged between 15 and 17. The main diagnoses were: mood disorders and schizoaffective disorder. Patients received between four and twelve ECT sessions. Five patients responded to treatment, whereas one did not. Treatment and side effects are presented. For part 2, 53 CAP answered the survey. Forty-eight (91%) thought ECT is a good treatment option after failure of other therapeutic modalities and 12 (23%) had prescribed it. All respondents wished to receive additional training regarding ECT use in youth. Conclusion Our results are consistent with the notion that ECT use in youth with a refractory and complex disease is a safe and effective treatment, although rarely used. The majority of psychiatrists treating children and adolescents in Quebec favor ECT when all available therapeutic modalities have failed, but wished they had more training regarding its use. PMID:28331498

  8. Electroconvulsive therapy in adolescents: a retrospective study from north India.

    PubMed

    Grover, Sandeep; Malhotra, Savita; Varma, Sannidhya; Chakrabarti, Subho; Avasthi, Ajit; Mattoo, Surendra K

    2013-06-01

    There are minimal data on the use of electroconvulsive therapy (ECT) in adolescents from India. The present study aimed to evaluate the clinical profile and effectiveness of ECT in adolescents (aged 13-18 years). A retrospective chart review was carried out to identify adolescents (aged 13-18 years) who had received ECT during the period 1999-2011. During the study period, 39 such patients received ECT; complete records of 25 patients were available. Details regarding their sociodemographic, clinical, and treatment data were extracted from these records for the present study. During the study period, 658 patients received ECT, of which 39 were aged 18 or younger (5.9%). Schizophrenia (n = 14; 56%) was the commonest diagnosis for which ECT was used in adolescents, followed by depression (n = 3; 12%). Catatonic symptoms (n = 17; 68%) were the most common symptoms among these subjects. Electroconvulsive therapy was considered as a treatment of choice taking the clinical picture account in about three fourths of the patients (n = 19; 76%). The mean (SD) numbers of ECTs administered per patient were 10.1 (4.87) (range, 2-21). The mean (SD) response rate to ECT was 76% (23.3%) (range, 31%-100%). Response rates according to diagnosis were the following: 76.3% for schizophrenia, 87.2% for depression, 81.8% for psychosis (not otherwise specified), and 77.7% for acute and transient psychosis. Response rate in patients with catatonia was 91.6%. Prolonged seizures, nausea and vomiting, and headache were reported in 2 cases each. Electroconvulsive therapy is used less frequently in children and adolescents compared to the older patients. This study shows that ECT is effective in the treatment of severe psychiatric disorders in adolescents and is associated with the same frequency of adverse effects as the adults.

  9. Relapse Following Successful Electroconvulsive Therapy for Major Depression: A Meta-Analysis

    PubMed Central

    Jelovac, Ana; Kolshus, Erik; McLoughlin, Declan M

    2013-01-01

    High rates of early relapse following electroconvulsive therapy (ECT) are typically reported in the literature. Current treatment guidelines offer little information to clinicians on the optimal nature of maintenance therapy following ECT. The aim of this study was to provide a systematic overview of the existing evidence regarding post-ECT relapse. A keyword search of electronic databases was performed for studies appearing in the peer-reviewed literature before January 2013 reporting on relapse rates in responders to an acute course of ECT administered for a major depressive episode. Meta-analyses were performed where appropriate. Thirty-two studies with up to 2 years' duration of follow-up were included. In modern era studies of continuation pharmacotherapy, 51.1% (95% CI=44.7–57.4%) of patients relapsed by 12 months following successful initial treatment with ECT, with the majority (37.7%, 95% CI=30.7–45.2%) relapsing within the first 6 months. The 6-month relapse rate was similar in patients treated with continuation ECT (37.2%, 95% CI=23.4–53.5%). In randomized controlled trials, antidepressant medication halved the risk of relapse compared with placebo in the first 6 months (risk ratio=0.49, 95% CI=0.39–0.62, p<0.0001, number needed to treat=3.3). Despite continuation therapy, the risk of relapse within the first year following ECT is substantial, with the period of greatest risk being the first 6 months. The largest evidence base for efficacy in post-ECT relapse prevention exists for tricyclic antidepressants. Published evidence is limited or non-existent for commonly used newer antidepressants or popular augmentation strategies. Maintenance of well-being following successful ECT needs to be improved. PMID:23774532

  10. Adverse Effects of Electroconvulsive Therapy.

    PubMed

    Andrade, Chittaranjan; Arumugham, Shyam Sundar; Thirthalli, Jagadisha

    2016-09-01

    Electroconvulsive therapy (ECT) is an effective treatment commonly used for depression and other major psychiatric disorders. We discuss potential adverse effects (AEs) associated with ECT and strategies for their prevention and management. Common acute AEs include headache, nausea, myalgia, and confusion; these are self-limiting and are managed symptomatically. Serious but uncommon AEs include cardiovascular, pulmonary, and cerebrovascular events; these may be minimized with screening for risk factors and by physiologic monitoring. Although most cognitive AEs of ECT are short-lasting, troublesome retrograde amnesia may rarely persist. Modifications of and improvements in treatment techniques minimize cognitive and other AEs. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Electroconvulsive therapy: administrative codes, legislation, and professional recommendations.

    PubMed

    Harris, Victoria

    2006-01-01

    Government regulatory involvement in electroconvulsive therapy (ECT) is due to several factors, including patient advocate groups, prior abuse by psychiatrists, and a general trend of state authority to move into areas traditionally governed by medical authorities. Regardless of the specific reasons, ECT is both highly effective in the treatment of many psychiatric disorders and heavily regulated by state administrative codes and legislation. The purpose of this article is to conduct a systematic review of the state administrative codes and legislation for the 50 states, the District of Columbia, and Puerto Rico and to compare the findings with professional recommendations for the administration of ECT.

  12. Knowledge of and attitudes toward electroconvulsive therapy among medical students, psychology students, and the general public.

    PubMed

    Aki, Ozlem Erden; Ak, Sertac; Sonmez, Yunus Emre; Demir, Basaran

    2013-03-01

    Electroconvulsive therapy (ECT) is safe and effective for the treatment of various psychiatric disorders. Despite being a well-known treatment method among health care professionals, lay people generally have a negative opinion of ECT. The present study aimed to examine knowledge of and attitudes toward ECT among medical students, psychology students, and the general public. Psychology students were included because they are among the important groups in mental health care in Turkey. A Likert-type questionnaire was administered to fifth-year medical students (n = 28), master of science and doctor of philosophy clinical psychology students (n = 35), and a sample of the general public (n = 26). The questionnaire included questions about the general principles of and indications for ECT, and sources of knowledge of and attitudes toward ECT. The medical students were the most knowledgeable about ECT, as expected. The medical students also had a more positive attitude toward ECT than the other 2 groups. More psychology students had negative attitudes on some aspects than general public sample, despite being more knowledgeable. Medical school theoretical and practical training in ECT played an important role in increasing the level of knowledge of and decreasing the prevalence of negative attitudes toward ECT among the medical students; similar training for psychology students is required to achieve similar results.

  13. Electroconvulsive treatment--more than electricity?: An Odyssey of facilities.

    PubMed

    Berg, John E

    2009-12-01

    To investigate whether the practice of electroconvulsive treatment (ECT) today is done in a comparable way in different hospitals on several continents. During visits to the ECT facilities of 14 hospitals on 3 continents, comparisons were made, and responsible health professionals were interviewed using a semistructured guide. It is emphasized that the present article is not the result of a well-structured research, but of reflections after observing a lack of homogeneity among facilities. A total of more than 18,000 modified ECT sessions were given per year in the 14 hospitals. The opinion of the public and regulatory bodies on ECT strongly influences the possibility of giving ECT to patients. Indications for ECT are wider than the cases of depression in most facilities visited. A psychiatrist gives ECT in all but 1 facility. Anesthesia is given by an anesthesiologist in all but 1 facility. A mouthpiece was not used in 2 (or 3) facilities, although the rationale was the same as in facilities using mouthpieces. No facility gave unmodified ECT. Holding on to the patient during seizures was judged unnecessary in 12 of 14 facilities. In severe mental illness, the practice of using ECT seems to have its merit also in cases with debilitating illnesses other than unipolar and bipolar depression. Giving ECT may be done by qualified or specially certified nurses, but the giving of anesthesia should be the realm of the anesthesiologist. Mouthpieces are judged by some facilities to be a superfluous device. The holding of patients during seizure can be omitted. Some of the facilities visited give ECT to a huge number of patients each year. They differ in the practice of ECT and could be the focus of comparative research. Despite the differences observed, and procedures that could be altered, giving ECT in a modified way effectively relieves suffering in the patients.

  14. Comparison of current distributions in electroconvulsive therapy and transcranial magnetic stimulation

    NASA Astrophysics Data System (ADS)

    Sekino, Masaki; Ueno, Shoogo

    2002-05-01

    We compared current density distributions in electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS) by numerical calculations. The model consisted of an air region and three types of tissues with different conductivities representing the brain, the skull, and the scalp. In the ECT model, electric currents were applied through electrodes with a voltage of 100 V. In the TMS model, a figure-eight coil (6 cm diameter per coil) was placed on the vertex of the head model. An alternating current with a peak intensity of 3.0 kA and a frequency of 4.2 kHz was applied to the coil. The maximum current densities inside the brain in ECT (bilateral electrode position) and TMS were 234 and 322 A/m2, respectively. The results indicate that magnetic stimulators can generate comparable current densities to ECT. While the skull significantly affected current distributions in ECT, TMS efficiently induced eddy currents in the brain. In addition, TMS is more beneficial than ECT because the localized current distribution reduces the risk of adverse side effects.

  15. Mental Health Service Career Ladder

    DTIC Science & Technology

    1994-01-01

    suicide risk patients 54 H315 Adjust or inspect refrigerators for proper temperatures 54 1372 Participate in rehashes of therapy sessions 53 H320...included biofeedback (paragraph 13c), electroconvulsive therapy (ECT) (paragraph 13h), and combat/disaster casualty management (paragraph 13m). Two other...focused on identifying marital and family counseling factors and determining the purpose and procedures for administering electroconvulsive therapy (ECT

  16. ARHGEF17 is an essential spindle assembly checkpoint factor that targets Mps1 to kinetochores

    PubMed Central

    Isokane, Mayumi; Walter, Thomas; Mahen, Robert; Nijmeijer, Bianca; Hériché, Jean-Karim; Miura, Kota; Maffini, Stefano; Ivanov, Miroslav Penchev; Kitajima, Tomoya S.; Peters, Jan-Michael

    2016-01-01

    To prevent genome instability, mitotic exit is delayed until all chromosomes are properly attached to the mitotic spindle by the spindle assembly checkpoint (SAC). In this study, we characterized the function of ARHGEF17, identified in a genome-wide RNA interference screen for human mitosis genes. Through a series of quantitative imaging, biochemical, and biophysical experiments, we showed that ARHGEF17 is essential for SAC activity, because it is the major targeting factor that controls localization of the checkpoint kinase Mps1 to the kinetochore. This mitotic function is mediated by direct interaction of the central domain of ARHGEF17 with Mps1, which is autoregulated by the activity of Mps1 kinase, for which ARHGEF17 is a substrate. This mitosis-specific role is independent of ARHGEF17’s RhoGEF activity in interphase. Our study thus assigns a new mitotic function to ARHGEF17 and reveals the molecular mechanism for a key step in SAC establishment. PMID:26953350

  17. ARHGEF17 is an essential spindle assembly checkpoint factor that targets Mps1 to kinetochores.

    PubMed

    Isokane, Mayumi; Walter, Thomas; Mahen, Robert; Nijmeijer, Bianca; Hériché, Jean-Karim; Miura, Kota; Maffini, Stefano; Ivanov, Miroslav Penchev; Kitajima, Tomoya S; Peters, Jan-Michael; Ellenberg, Jan

    2016-03-14

    To prevent genome instability, mitotic exit is delayed until all chromosomes are properly attached to the mitotic spindle by the spindle assembly checkpoint (SAC). In this study, we characterized the function of ARHGEF17, identified in a genome-wide RNA interference screen for human mitosis genes. Through a series of quantitative imaging, biochemical, and biophysical experiments, we showed that ARHGEF17 is essential for SAC activity, because it is the major targeting factor that controls localization of the checkpoint kinase Mps1 to the kinetochore. This mitotic function is mediated by direct interaction of the central domain of ARHGEF17 with Mps1, which is autoregulated by the activity of Mps1 kinase, for which ARHGEF17 is a substrate. This mitosis-specific role is independent of ARHGEF17's RhoGEF activity in interphase. Our study thus assigns a new mitotic function to ARHGEF17 and reveals the molecular mechanism for a key step in SAC establishment. © 2016 Isokane et al.

  18. Transient serotonin syndrome by concurrent use of electroconvulsive therapy and selective serotonin reuptake inhibitor: a case report and review of the literature.

    PubMed

    Okamoto, Nagahisa; Sakamoto, Kota; Yamada, Maki

    2012-01-01

    The serotonin syndrome, which is characterized by psychiatric, autonomic nervous and neurological symptoms, is considered to be caused by excessive stimulation of the 5-HT1A and 5-HT2 receptors in the gray matter and spinal cord of the central nervous system, after the start of dosing or increase of the dose of a serotoninergic drug. There have been hardly any reports of induction of serotonin syndrome by electroconvulsive therapy (ECT) in combination with antidepressant. We present the case of a female patient with major depressive disorder (MDD) who developed transient serotonin syndrome soon after the first session of ECT in combination with paroxetine. Paroxetine was discontinued, and her psychiatric, autonomic nervous and neurological symptoms were gradually relieved and disappeared within 2 days. We performed the second ECT session 5 days after the initial session and performed 12 sessions of ECT without any changes in the procedure of ECT and anesthesia, but no symptoms of SS were observed. Finally, her MDD remitted. ECT might cause transiently increased blood-brain barrier (BBB) permeability and enhance the transmissivity of the antidepressant in BBB. Therefore, it is necessary to pay attention to rare side effect of serotonin syndrome by ECT in combination with antidepressant.

  19. Electroconvulsive Therapy Hasn't Negative Effects on Short-Term Memory Function, as Assessed Using a Bedside Hand-Held Device.

    PubMed

    Müller, Helge H O; Reike, Mareen; Grosse-Holz, Simon; Röther, Mareike; Lücke, Caroline; Philipsen, Alexandra; Kornhuber, Johannes; Grömer, Teja W

    2017-03-22

    Electroconvulsive therapy (ECT) is effective in the treatment of treatment-resistant major depression. The fear of cognitive impairment after ECT often deters patients from choosing this treatment option. There is little reliable information regarding the effects of ECT on overall cognitive performance, while short-term memory deficits are well known but not easy to measure within clinical routines. In this pilot study, we examined ECT recipients' pre- and post-treatment performances on a digital ascending number tapping test. We found that cognitive performance measures exhibited good reproducibility in individual patients and that ECT did not significantly alter cognitive performance up to 2 hours after this therapy was applied. Our results can help patients and physicians make decisions regarding the administration of ECT. Digital measurements are recommended, especially when screening for the most common side effects on cognitive performance and short-term memory.

  20. Using the Cambridge Neuropsychological Test Automated Battery (CANTAB) to assess the cognitive impact of electroconvulsive therapy on visual and visuospatial memory.

    PubMed

    Falconer, D W; Cleland, J; Fielding, S; Reid, I C

    2010-06-01

    The cognitive impact of electroconvulsive therapy (ECT) is rarely measured systematically in everyday clinical practice even though patient and clinician acceptance is limited by its adverse affect on memory. If patients are tested it is often with simple paper and pencil tests of visual or verbal memory. There are no reported studies of computerized neuropsychological testing to assess the cognitive impact of ECT on visuospatial memory. Twenty-four patients with severe depression were treated with a course of bilateral ECT and assessed with a battery of visual memory tests within the Cambridge Neuropsychological Test Automated Battery (CANTAB). These included spatial and pattern recognition memory, pattern-location associative learning and a delayed matching to sample test. Testing was carried out before ECT, during ECT, within the week after ECT and 1 month after ECT. Patients showed significant impairments in visual and visuospatial memory both during and within the week after ECT. Most impairments resolved 1 month following ECT; however, significant impairment in spatial recognition memory remained. This is one of only a few studies that have detected anterograde memory deficits more than 2 weeks after treatment. Patients receiving ECT displayed a range of visual and visuospatial deficits over the course of their treatment. These deficits were most prominent for tasks dependent on the use of the right medial temporal lobe; frontal lobe function may also be implicated. The CANTAB appears to be a useful instrument for measuring the adverse cognitive effects of ECT on aspects of visual and visuospatial memory.