bluuebunny/crossref_metadata_2025 huggingface dataset:
Model Calcium Sensors for Network Homeostasis: Sensor and Readout Parameter Analysis from a Database of Model Neuronal Networks
Authors: Günay Cengiz , Prinz Astrid A.
Published: February 2010

In activity-dependent homeostatic regulation (ADHR) of neuronal and network properties, the intracellular Ca2+concentration is a good candidate for sensing activity levels because it is correlated with the electrical activity of the cell. Previous ADHR models, developed with abstract activity sensors for model pyloric neurons and networks of the crustacean stomatogastric ganglion, showed that functional activity can be maintained by a regulation mechanism that senses activity levels solely from Ca2+. At the same time, several intracellular pathways have been discovered for Ca2+-dependent regulation of ion channels. To generate testable predictions for dynamics of these signaling pathways, we undertook a parameter study of model Ca2+sensors across thousands of model pyloric networks. We found that an optimal regulation signal can be generated for 86% of model networks with a sensing mechanism that activates with a time constant of 1 ms and that inactivates within 1 s. The sensor performed robustly around this optimal point and did not need to be specific to the role of the cell. When multiple sensors with different time constants were used, coverage extended to 88% of the networks. Without changing the sensors, it extended to 95% of the networks by letting the sensors affect the readout nonlinearly. Specific to this pyloric network model, the sensor of the follower pyloric constrictor cell was more informative than the pacemaker anterior burster cell for producing a regulatory signal. Conversely, a global signal indicating network activity that was generated by summing the sensors in individual cells was less informative for regulation.
Synergistic Effects of Transplanted Adult Neural Stem/Progenitor Cells, Chondroitinase, and Growth Factors Promote Functional Repair and Plasticity of the Chronically Injured Spinal Cord
Authors: Karimi-Abdolrezaee Soheila , Eftekharpour Eftekhar , Wang Jian , Schut Desiree , Fehlings Michael G.
Published: February 2010

The transplantation of neural stem/progenitor cells (NPCs) is a promising therapeutic strategy for spinal cord injury (SCI). However, to date NPC transplantation has exhibited only limited success in the treatment of chronic SCI. Here, we show that chondroitin sulfate proteoglycans (CSPGs) in the glial scar around the site of chronic SCI negatively influence the long-term survival and integration of transplanted NPCs and their therapeutic potential for promoting functional repair and plasticity. We targeted CSPGs in the chronically injured spinal cord by sustained infusion of chondroitinase ABC (ChABC). One week later, the same rats were treated with transplants of NPCs and transient infusion of growth factors, EGF, bFGF, and PDGF-AA. We demonstrate that perturbing CSPGs dramatically optimizes NPC transplantation in chronic SCI. Engrafted NPCs successfully integrate and extensively migrate within the host spinal cord and principally differentiate into oligodendrocytes. Furthermore, this combined strategy promoted the axonal integrity and plasticity of the corticospinal tract and enhanced the plasticity of descending serotonergic pathways. These neuroanatomical changes were also associated with significantly improved neurobehavioral recovery after chronic SCI. Importantly, this strategy did not enhance the aberrant synaptic connectivity of pain afferents, nor did it exacerbate posttraumatic neuropathic pain. For the first time, we demonstrate key biological and functional benefits for the combined use of ChABC, growth factors, and NPCs to repair the chronically injured spinal cord. These findings could potentially bring us closer to the application of NPCs for patients suffering from chronic SCI or other conditions characterized by the formation of a glial scar.
The Effect of Spatially Inhomogeneous Extracellular Electric Fields on Neurons
Authors: Anastassiou Costas A. , Montgomery Sean M. , Barahona Mauricio , Buzsáki György , Koch Christof
Published: February 2010

The cooperative action of neurons and glia generates electrical fields, but their effect on individual neurons via ephaptic interactions is mostly unknown. Here, we analyze the impact of spatially inhomogeneous electric fields on the membrane potential, the induced membrane field, and the induced current source density of one-dimensional cables as well as morphologically realistic neurons and discuss how the features of the extracellular field affect these quantities. We show through simulations that endogenous fields, associated with hippocampal theta and sharp waves, can greatly affect spike timing. These findings imply that local electric fields, generated by the cooperative action of brain cells, can influence the timing of neural activity.
γ-Secretase Composed of PS1/Pen2/Aph1a Can Cleave Notch and Amyloid Precursor Protein in the Absence of Nicastrin
Authors: Zhao Guojun , Liu Zhenyi , Ilagan Ma. Xenia G. , Kopan Raphael
Published: February 2010

γ-Secretase is a multiprotein, intramembrane-cleaving protease with a growing list of protein substrates, including the Notch receptors and the amyloid precursor protein. The four components of γ-secretase complex—presenilin (PS), nicastrin (NCT), Pen2, and Aph1—are all thought to be essential for activity. The catalytic domain resides within PS proteins, NCT has been suggested to be critical for substrate recognition, and the contributions of Pen2 and Aph1 remain unclear. The role of NCT has been challenged recently by the observation that a critical residue (E332) in NCT, which had been thought to be essential for γ-secretase activity, is instead involved in complex maturation. Here, we report that NCT is dispensable for γ-secretase activity. NCT-independent γ-secretase activity can be detected in two independent NCT-deficient mouse embryonic fibroblast lines and blocked by the γ-secretase inhibitorsN-[N-(3,5-difluorophenacetyl-l-alanyl)]-S-phenylglycinet-butyl ester and L-685,458. This catalytic activity requires prior ectodomain shedding of the substrate and can cleave ligand-activated endogenous Notch receptors, indicating presence of this activity at the plasma membrane. Small interfering RNA knockdown experiments demonstrated that NCT-independent γ-secretase activity requires the presence of PS1, Pen2, and Aph1a but can tolerate knockdown of PS2 or Aph1b. We conclude that a PS1/Pen2/Aph1a trimeric complex is an active enzyme, displaying biochemical properties similar to those of γ-secretase and roughly 50% of its activity when normalized to PS1 N-terminal fragment levels. This PS1/Pen2/Aph1a complex, however, is highly unstable. Thus, NCT acts to stabilize γ-secretase but is not required for substrate recognition.
The “Cutaneous Rabbit” Hopping out of the Body
Authors: Miyazaki Makoto , Hirashima Masaya , Nozaki Daichi
Published: February 2010

Rapid sequential taps delivered first to one location and then to another on the skin create the somatosensory illusion that the tapping is occurring at intermediate locations between the actual stimulus sites, as if a small rabbit were hopping along the skin from the first site to the second (called the “cutaneous rabbit”). Previous behavioral studies have attributed this illusion to the early unimodal somatosensory body map. A functional magnetic resonance imaging study recently confirmed the association of the illusion with somatotopic activity in the primary somatosensory cortex. Thus, the cutaneous rabbit illusion has been confined to one's own body. In the present paper, however, we show that the cutaneous rabbit can “hop out of the body” onto an external object held by the subject. We delivered rapid sequential taps to the left and right index fingers. When the subjects held a stick such that it was laid across the tips of their index fingers and received the taps via the stick, they reported sensing the illusory taps in the space between the actual stimulus locations (i.e., along the stick). This suggests that the cutaneous rabbit effect involves not only the intrinsic somatotopic representation but also the representation of the extended body schema that results from body–object interactions.
Neural Time Course of Echo Suppression in Humans
Authors: Backer Kristina C. , Hill Kevin T. , Shahin Antoine J. , Miller Lee M.
Published: February 2010

In reverberant environments, the brain can suppress echoes so that auditory perception is dominated by the primary or leading sounds. Echo suppression comprises at least two distinct phenomena whose neural bases are unknown: spatial translocation of an echo toward the primary sound, and object capture to combine echo and primary sounds into a single event. In an electroencephalography study, we presented subjects with primary-echo (leading–lagging) click pairs in virtual acoustic space, with interclick delay at the individual's 50% suppression threshold. On each trial, subjects reported both click location (one or both hemifields) and the number of clicks they heard (one or two). Thus, the threshold stimulus led to two common percepts:SuppressedandNot Suppressed. On some trials, a subset of subjects reported an intermediate percept, in which two clicks were perceived in the same hemifield as the leading click, providing a dissociation between spatial translocation and object capture. We conducted time–frequency and event-related potential analyses to examine the time course of the neural mechanisms mediating echo suppression. Enhanced gamma band phase synchronization (peaking at ∼40 Hz) specific to successful echo suppression was evident from 20 to 60 ms after stimulus onset. N1 latency provided a categorical neural marker of spatial translocation, whereas N1 amplitude still reflected the physical presence of a second (lagging) click. These results provide evidence that (1) echo suppression begins early, at the latest when the acoustic signal first reaches cortex, and (2) the brain spatially translocates a perceived echo before the primary sound captures it.
ERK1/2 Mitogen-Activated Protein Kinase Phosphorylates Sodium Channel Nav1.7 and Alters Its Gating Properties
Authors: Stamboulian Severine , Choi Jin-Sung , Ahn Hye-Sook , Chang Yu-Wen , Tyrrell Lynda , Black Joel A. , Waxman Stephen G. , Dib-Hajj Sulayman D.
Published: February 2010

Nav1.7 sodium channels can amplify weak stimuli in neurons and act as threshold channels for firing action potentials. Neurotrophic factors and pro-nociceptive cytokines that are released during development and under pathological conditions activate mitogen-activated protein kinases (MAPKs). Previous studies have shown that MAPKs can transduce developmental or pathological signals by regulating transcription factors that initiate a gene expression response, a long-term effect, and directly modulate neuronal ion channels including sodium channels, thus acutely regulating dorsal root ganglion (DRG) neuron excitability. For example, neurotrophic growth factor activates (phosphorylates) ERK1/2 MAPK (pERK1/2) in DRG neurons, an effect that has been implicated in injury-induced hyperalgesia. However, the acute effects of pERK1/2 on sodium channels are not known. We have shown previously that activated p38 MAPK (pp38) directly phosphorylates Nav1.6 and Nav1.8 sodium channels and regulates their current densities without altering their gating properties. We now report that acute inhibition of pERK1/2 regulates resting membrane potential and firing properties of DRG neurons. We also show that pERK1 phosphorylates specific residues within L1 of Nav1.7, inhibition of pERK1/2 causes a depolarizing shift of activation and fast inactivation of Nav1.7 without altering current density, and mutation of these L1 phosphoacceptor sites abrogates the effect of pERK1/2 on this channel. Together, these data are consistent with direct phosphorylation and modulation of Nav1.7 by pERK1/2, which unlike the modulation of Nav1.6 and Nav1.8 by pp38, regulates gating properties of this channel but not its current density and contributes to the effects of MAPKs on DRG neuron excitability.
TheN-Glycanasepng-1Acts to Limit Axon Branching during Organ Formation in Caenorhabditis elegans
Authors: Habibi-Babadi Nasrin , Su Anna , de Carvalho Carlos E. , Colavita Antonio
Published: February 2010

Peptide:N-glycanases (PNGases) are cytoplasmic de-N-glycosylation enzymes that have been shown in cultured cells to facilitate the degradation of misfolded glycoproteins during endoplasmic reticulum-associated degradation and in the processing of major histocompatibility complex class I antigens for proper cell-surface presentation. The gene encoding PNGase activity was initially described in budding yeast (Png1p) and shown to be highly conserved from yeast to humans, but physiological roles in higher organisms have not been elucidated. Here we describe peripheral nervous system defects associated with the first loss-of-function mutations in an animal PNGase. Mutations inpng-1, theCaenorhabditis elegansPNGase ortholog, result in an increase in axon branching during morphogenesis of the vulval egg-laying organ and egg-laying behavior changes. Neuronal defects include an increase in the branched morphology of the VC4 and VC5 egg-laying neurons as well as inappropriate branches from axons that run adjacent to the vulva but would normally remain unbranched. We show thatpng-1is widely expressed and can act from both neurons and epithelial cells to restrict axon branching. A deletion allele of the DNA repair generad-23, orthologs of which are known to physically interact with PNGases in yeast and mammals, displays similar axon branching defects and genetic interactions withpng-1. In summary, our analysis reveals a novel developmental role for a PNGase and Rad-23 in the regulation of neuronal branching during organ innervation.
A Role for the Ubiquitin–Proteasome System in Activity-Dependent Presynaptic Silencing
Authors: Jiang Xiaoping , Litkowski Patricia E. , Taylor Amanda A. , Lin Ying , Snider B. Joy , Moulder Krista L.
Published: February 2010

Chronic changes in electrical excitability profoundly affect synaptic transmission throughout the lifetime of a neuron. We have previously explored persistent presynaptic silencing, a form of synaptic depression at glutamate synapses produced by ongoing neuronal activity and by strong depolarization. Here we investigate the involvement of the ubiquitin–proteasome system (UPS) in the modulation of presynaptic function. We found that proteasome inhibition prevented the induction of persistent presynaptic silencing. Specifically, application of the proteasome inhibitor MG-132 (carbobenzoxy-l-leucyl-l-leucyl-l-leucinal) prevented decreases in the size of the readily releasable pool of vesicles and in the percentage of active synapses. Presynaptic silencing was accompanied by decreases in levels of the priming proteins Munc13-1 and Rim1. Importantly, overexpression of Rim1α prevented the induction of persistent presynaptic silencing. Furthermore, strong depolarization itself increased proteasome enzymatic activity measured in cell lysates. These results suggest that modulation of the UPS by electrical activity contributes to persistent presynaptic silencing by promoting the degradation of key presynaptic proteins.
Global Deprivation of Brain-Derived Neurotrophic Factor in the CNS Reveals an Area-Specific Requirement for Dendritic Growth
Authors: Rauskolb Stefanie , Zagrebelsky Marta , Dreznjak Anita , Deogracias Rubén , Matsumoto Tomoya , Wiese Stefan , Erne Beat , Sendtner Michael , Schaeren-Wiemers Nicole , Korte Martin , Barde Yves-Alain
Published: February 2010

Although brain-derived neurotrophic factor (BDNF) is linked with an increasing number of conditions causing brain dysfunction, its role in the postnatal CNS has remained difficult to assess. This is because thebdnf-null mutation causes the death of the animals before BDNF levels have reached adult levels. In addition, the anterograde axonal transport of BDNF complicates the interpretation of area-specific gene deletion. The present study describes the generation of a new conditional mouse mutant essentially lacking BDNF throughout the CNS. It shows that BDNF is not essential for prolonged postnatal survival, but that the behavior of such mutant animals is markedly altered. It also reveals that BDNF is not a major survival factor for most CNS neurons and for myelination of their axons. However, it is required for the postnatal growth of the striatum, and single-cell analyses revealed a marked decreased in dendritic complexity and spine density. In contrast, BDNF is dispensable for the growth of the hippocampus and only minimal changes were observed in the dendrites of CA1 pyramidal neurons in mutant animals. Spine density remained unchanged, whereas the proportion of the mushroom-type spine was moderately decreased. In line with thesein vivoobservations, we found that BDNF markedly promotes the growth of cultured striatal neurons and of their dendrites, but not of those of hippocampal neurons, suggesting that the differential responsiveness to BDNF is part of a neuron-intrinsic program.
Cognitive Loss in Zinc Transporter-3 Knock-Out Mice: A Phenocopy for the Synaptic and Memory Deficits of Alzheimer's Disease?
Authors: Adlard Paul A. , Parncutt Jacqui M. , Finkelstein David I. , Bush Ashley I.
Published: February 2010

Zinc transporter-3 (ZnT3) protein controls synaptic vesicular Zn2+levels, which is predicted to regulate normal cognitive function. Surprisingly, previous studies found that 6- to 10-week-old ZnT3 knock-out (KO) mice did not show impairment in the Morris water maze. We hypothesized that older ZnT3 KO animals would display a cognitive phenotype. Here, we report that ZnT3 KO mice exhibit age-dependent deficits in learning and memory that are manifest at 6 months but not at 3 months of age. These deficits are associated with significant alterations in key hippocampal proteins involved in learning and memory, as assessed by Western blot. These include decreased levels of the presynaptic protein SNAP25 (−46%;p< 0.01); the postsynaptic protein PSD95 (−37%;p< 0.01); the glutamate receptors AMPAR (−34%;p< 0.01), NMDAR2a (−64%;p< 0.001), and NMDAR2b (−49%;p< 0.05); the surrogate marker of neurogenesis doublecortin (−31%;p< 0.001); and elements of the BDNF pathway, pro-BDNF (−30%;p< 0.05) and TrkB (−22%;p< 0.01). In addition, there is a concomitant decrease in neuronal spine density (−6%;p< 0.05). We also found that cortical ZnT3 levels fall with age in wild-type mice (−50%;p< 0.01) in healthy older humans (ages, 48–91 years;r2= 0.47;p= 0.00019) and particularly in Alzheimer's disease (AD) (−36%;p< 0.0001). Thus, age-dependent loss of transsynaptic Zn2+movement leads to cognitive loss, and since extracellular β-amyloid is aggregated by and traps this pool of Zn2+, the genetic ablation of ZnT3 may represent a phenocopy for the synaptic and memory deficits of AD.
Entwurf sättigender Regler für polynomiale Systeme mit StellgrößenbeschränkungDesign of Saturating Controllers for Polynomial Systems with Input Constraints
Authors: Gußner Thomas , Lens Hendrik , Adamy Jürgen
Published: February 2010

In diesem Artikel wird eine Reglerentwurfsmethode für polynomiale Systeme mit Stellgrößenbeschränkungen vorgestellt, die auf der Sum-of-squares-Zerlegung von Polynomen basiert. Die betrachteten Regelgesetze bestehen aus einer Komposition der Sättigungsfunktion und einer polynomialen bzw. gebrochen rationalen Funktion. Neben dem Regelgesetz errechnet die Methode eine Abschätzung des Einzugsgebiets. Es werden zwei mögliche Entwurfsziele betrachtet: Die Konvergenzrate und die Größe des Einzugsgebiets. Das dem Entwurf zu Grunde liegende Optimierungsproblem ist multilinear in den Parametern und daher nicht konvex. Deshalb wird ein Algorithmus zur lokalen Optimierung solcher nichtkonvexen Probleme vorgeschlagen, der zur Lösung des zuvor aufgestellten Entwurfsproblems verwendet wird. Anhand eines Beispielsystems werden die Ergebnisse illustriert.
Process Zirconia Oxygen Analyzer — State of ArtZirkondioxid-Sauerstoffsensoren — Stand der Technik
Authors: Shuk Pavel
Published: February 2010

Different aspects of industrial zirconia oxygen sensor probes, i. e., design and application limits are discussed in details. Special consideration is given to the practical aspects of the oxygen sensor design.
Ein präziser Impedanzanalysator für resonante SensorenA Precise Impedance Analyser for Resonating Sensors
Authors: Niedermayer Alexander O. , Reichel Erwin K. , Jakoby Bernhard
Published: February 2010

Präzise Impedanzanalysatoren werden in jüngerer Vergangenheit vermehrt zur Auswertung resonanter Sensoren eingesetzt. In diesem Beitrag wird dazu ein Schaltungskonzept vorgestellt und der geplante Einsatz, ein Viskositätssensor basierend auf einem Quarz-Schwinger zur Überwachung eines Zeolith-Kristallisationsexperimentes auf der Internationalen Raumstation (ISS), präsentiert.
Massendurchflusssensor für pneumatisch geförderte, pulverisierte Feststoffe in Förderleitungen, basierend auf linkshändigen LeitungsstrukturenLeft-handed Transmission Line Mass Flow Meter for Particulate Solids in Pipelines
Authors: Penirschke Andreas , Puentes Margarita , Schüßler Martin , Jakoby Rolf
Published: February 2010

Ein Massendurchflusssensor zur Bestimmung von geförderten Stäuben mit Hilfe von resonanten “Composite Right-/Lefthanded”-Leitungsstrukturen (CRLH) wurde entwickelt. Das vorgestellte Sensorprinzip bietet die Möglichkeit, kostengünstige Massendurchflusssensoren für pneumatisch geförderte Feststoffe mit hoher Messgüte zu realisieren. Die Nutzung der Raumfiltermethode zur Geschwindigkeitsmessung eröffnet zudem die Möglichkeit, mit dem CRLH-Sensor die Materialkonzentration und -geschwindigkeit des Fördergutes mit einer einzigen Messung zu bestimmen. Mögliche Anwendungsgebiete dieser Art von Sensoren ist die Bestimmung des Massendurchflusses von Luft/Feststoff-, Luft/Flüssigkeit- und Flüssigkeit/Feststoff-Mischungen in der Prozessüberwachung.
The impact of the CAG repeat polymorphism of the androgen receptor gene on muscle and adipose tissues in 20–29-year-old Danish men: Odense Androgen Study
Authors: Nielsen Torben Leo , Hagen Claus , Wraae Kristian , Bathum Lise , Larsen Rasmus , Brixen Kim , Andersen Marianne
Published: February 2010

Background

The number of CAG repeats (CAGn) within the CAG repeat polymorphism of the androgen receptor gene correlates inversely with the transactivation of the receptor.

Objective

To examine the impact of CAGnon muscle, fat distribution, and circulating androgen levels.

Design, settings and participants

Population-based, cross-sectional study of 783 Danish men aged 20–29 years.

Methods

Genotyping was performed in 767 men. Areas of thigh and lower trunk muscle (musclethighand musclelower trunk), subcutaneous adipose tissues (SATthighand SATlower trunk), and deep adipose tissues (i.m. and visceral) were measured in 393 men by magnetic resonance imaging (MRI). Lean body mass (LBM) and fat mass (FM) were measured in all men by whole body dual-energy X-ray absorptiometry (DEXA). The absolute areas acquired by MRI were the main outcomes. The absolute DEXA measurements and relative assessments of both modalities were considered as the secondary outcomes.

Results

CAGn(range: 10–32) correlated inversely with absolute musclethigh(r=−0.108), absolute musclelower trunk(r=−0.132), relative musclethigh(r=−0.128), relative musclelower trunk(r=−0.126), relative LBMlower extremity(r=−0.108), and relative LBMtotal(r=−0.082), and positively with relative SATthigh(r=0.137), relative SATlower trunk(r=0.188), relative FMlower extremity(r=0.107), and relative FMtotal(r=0.082). These relationships remained significant, controlling for physical activity, smoking, chronic disease, and age. CAGndid not correlate with any circulating androgen.

Conclusions

The CAG repeat polymorphism affects body composition in young men: absolute musclethighand absolute musclelower trunkincrease as CAGndecreases. Expressed relatively, muscle areas and LBM increase, while SAT and FM decrease as CAGndecreases. The polymorphism does not affect deep adipose tissues or circulating androgen levels in young men.
Fabry disease diagnostic guideline
Authors: Constantin Tamás , Rákóczi Éva , Ponyi Andrea , Ambrus Csaba , Kádár Krisztina , Vastagh Ildikó , Dajnoki Angéla , Tóth Beáta , Bokrétás Gergely , Müller Veronika , Katona Mária , Csikós Márta , Fiedler Orsolya , Széchey Rita , Varga Edit , Rudas Gábor , Kertész Attila , Molnár Sándor , Kárpáti Sarolta , Nagy Viktor , Magyar Pál , Mahdi Mohamed , Németh Krisztina , Bereczki Dániel , Garami Miklós , Erdős Melinda , Maródi László , Fekete György
Published: February 2010

A Fabry-kór a lizoszomális tárolási betegségek csoportjába tartozó, X-kromoszómához kötötten, recesszív módon öröklődő betegség, amely a globotriaosylceramid felhalmozódásához vezet a szervezet legkülönbözőbb szöveteiben. A betegség első tünetei többnyire gyermekkorban jelentkeznek, a progresszió során a betegek súlyos szervi károsodásokkal és korai halálozással számolhatnak. Elsősorban fiúk és férfiak érintettek, azonban a betegség tüneteit heterozigóta nők esetében is megfigyelhetjük, de náluk a kórkép súlyossága változó, általában enyhébb lefolyású. Az enzimpótló kezelések megjelenése szükségessé tette, hogy részletes diagnosztikus és terápiás protokollt dolgozzunk ki. A jelen dolgozatban megjelenő ajánlásokat egy, a magyarországi Fabry-betegek kezelésében aktívan részt vevő orvosokból, a diagnosztika területén dolgozó biológosukból és egyéb szakemberekből álló multidiszciplináris munkacsoport foglalta össze. A munkacsoport áttekintette a korábbi klinikai tanulmányokat, a publikált vizsgálatokat és a közelmúltban megjelent nemzetközi és nemzeti útmutatókat.
Treatment adherence and use of complementary and alternative medicine in patients with inflammatory bowel disease
Authors: Lakatos László , Czeglédi Zsófia , Dávid Gyula , Kispál Zsófi , Kiss Lajos S. , Palatka Károly , Kristóf Tünde , Molnár Tamás , Salamon Ágnes , Demeter Pál , Miheller Pál , Szamosi Tamás , Banai János , Papp Mária , Bene László , Kovács Ágota , Rácz István , Lakatos Péter László
Published: February 2010

Az utóbbi évek tanulmányai a komplementer és alternatív gyógymódok (CAM) egyre gyakoribb alkalmazásáról tudósítanak gyulladásos bélbetegségben (IBD). Ugyanakkor az is egyre nyilvánvalóbb, hogy a betegek jelentős hányada nem tartja be az orvos előírásait. A tanulmány célja a terápiás nonadherencia és a CAM-alkalmazás gyakoriságának felmérése volt hazai IBD-betegekben.Módszer:multicentrikus vizsgálatban 655 IBD-beteg [Crohn-beteg (CD): 344, átlagos életkor: 38,2 (SD 12,9) év; colitis ulcerosa (UC): 311, átlagos életkor: 44,9 (SD 15,3) év] töltött ki a szokásos szakorvosi vizit során a demográfiai adatokra, gyógyszer-adherenciára és CAM-ra vonatkozó kérdőívet. A klinikai adatokat a kezelőorvos egészítette ki a betegdokumentáció alapján. Amennyiben a beteg az előírt gyógyszerek több mint 80%-át bevette, adherensnek tekintettük.Eredmények:a betegek által önként jelzett nonadherencia (CD: 20,9%, UC: 20,6%) és CAM (CD: 31,7%, UC: 30,9%) használata CD-ben és UC-ben nem tért el. A nonadherencia leggyakoribb okai: feledékenység (47,8%), túl sok/feleslegesnek gondolt gyógyszer (39,7%), mellékhatásoktól való félelem (27,9%), túl gyakori adagolás. A CAM leggyakoribb formája a gyógytea (47,3%), a homeopátia (14,6%), a speciális diéta (12,2%) és az akupunktúra (5,8%) volt. CD-ben a betegségtartam, az utolsó vizittől eltelt idő, az alacsonyabb iskolázottsági szint és a megelőző műtétek voltak a nonadherenciára hajlamosító tényezők. Az alternatív módszerek használata fiatalabb életkorban, magasabb iskolázottsági szint és immunszuppresszív szer szedése esetén volt jellemző. UC-ben ezenfelül a CAM igénybevétele gyakoribb volt nők és pszichiátriai/pszichológiai kezelés alatt állók körében.Következtetés:a nonadherencia és az alternatív gyógymódok igénybevétele gyakori IBD-ben. Az ellenőrző vizitek során különös figyelmet kell fordítani a hajlamosító tényezők feltárására, a betegek együttműködésének és az orvos–beteg kapcsolatnak a javítására.
Polyphony in Appraisal
Authors: Bednarek Monika
Published: February 2010

This paper examines the concept of polyphony in Appraisal (evaluation) - the combining (e.g. fusing or blending) of different kinds of Appraisal systems or sub-systems.It identifies and describes four different types of polyphonic phenomena: 1) Fused Appraisals 2) Invoked Apraisals 3) Border phenomena 4) Appraisal blends In so doing, this paper provides a preliminary systematisation of such phenomena, in some cases offering an alternative description to those currently available. It also discusses the adequacy of typology and topology in classifying Appraisal and provides a theoretical background to the multiple coding practices in the analysis of Appraisal.
An application of multiple coding for the analysis of ATTITUDE in an academic argument
Authors: Lee Sook Hee
Published: February 2010

The intention of this paper is to contribute to refining Appraisal theory, which has recently emerged from research within Systemic Functional Linguistics (SFL). Appraisal is basically concerned with a writer’s use of evaluative language. The specific aspect under investigation is the delineation of multiple coding in analysing one of the appraisal systems referred to as ATTITUDE. This paper proposes the concept of multiple coding consisting of multi-layering and double coding for the analysis of ATTITUDE. Analyses of argumentative essays written by undergraduate university students revealed that multiple coding is useful in identifying the differences between high-graded essays (HGEs) and low-graded essays (LGEs). Multi-layering and double coding of ATTITUDE occurred much more frequently in the analyses of the HGEs than LGEs.
Negotiating narrative
Authors: Martin J. R. , Zappavigna M. , Dwyer P.
Published: February 2010

Youth justice conferencing is one of a number of programs which have been introduced into western legal systems in recent years, typically under the banner of a ‘restorative justice’ reform movement. These conferences bring young people (who have admitted their guilt), victims and other parties into a face-to-face meeting in which the impact of the offence and possible reparative actions are discussed at length. In this paper, based on field observations and transcripts, we report on our preliminary efforts to analyse the generic structure of conferencing, focusing in particular on the accounts given by young people of their offending behaviour. The flat ideational focus of these accounts and the absence of an ongoing prosody of evaluation make them quite unlike the personal recounts typically produced by young people and, while seemingly appropriate to the context of a youth justice conference, also create a genre identity for the young person which may be at odds with the expectations of other conference participants (and indeed theorists of restorative justice) who are looking for signs of sincerity and remorse from the young person.
Role of bone morphogenetic proteins in adrenal physiology and disease
Authors: Johnsen Inga K , Beuschlein Felix
Published: February 2010

Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-β superfamily of ligands that impact on a multitude of biological processes including cell type specification, differentiation and organogenesis. Furthermore, a large body of evidence points towards important BMP-dependent mechanisms in tumorigenesis. In accordance with their diverse actions, BMPs have been demonstrated to serve as auto-, para- and endocrine modulators also in a number of hormonal systems. In this review, we highlight novel aspects of BMP-dependent regulatory networks that pertain to adrenal physiology and disease, which have been uncovered during recent years. These aspects include the role of BMP-dependent mechanism during adrenal development, modulating effects on catecholamine synthesis and steroidogenesis and dysregulation of BMP signalling in adrenal tumorigenesis. Furthermore, we summarize potential therapeutic approaches that are based on reconstitution of BMP signalling in adrenocortical tumour cells.
Management of Type 2 Diabetes and Pregnancy
Authors: Casson Ian F
Published: February 2010

Pregnancy complicated by diabetes presents risks for the mother and her baby and a challenge to those responsible for their care. Type 2 diabetes now represents a significant and rapidly increasing proportion of pregestational diabetes. Outcomes of pregnancies complicated by Type 2 diabetes are certainly no better and sometimes worse than for Type 1 diabetes. Perinatal mortality, stillbirths and congenital anomalies are increased between two- and fourfold. Women with Type 2 diabetes and who are of child-bearing age merit special attention for contraception and prepregnancy care. This review considers the implications for women with Type 2 diabetes before, during and after pregnancy.
Allergic Rhinitis in Women
Authors: Passalacqua Giovanni
Published: February 2010

Allergic rhinitis is a high-prevalence disease that significantly impairs the quality of life. Its pathogenesis is quite well understood, and involves numerous cells, cytokines and mediators, which result in an inflammatory process. The triggering IgE-mediated reaction does not differ between men and women, but in females some aspects, related mainly to the hormonal frame, must be taken into account. In fact, cyclic hormonal changes can affect the severity of rhinitis, as can pregnancy, which may result in a particular form of ‘pregnancy rhinitis’. The most important and challenging aspect is the management of allergic rhinitis in pregnancy, which require a careful evaluation of the risk:benefit ratio. This review will examine the aforementioned aspects, with particular regard to the pharmacotherapy of rhinitis in pregnancy.
Future of Endometriosis Research
Authors: Simsa Peter , Mihalyi Attila , Kyama Cleophas M , Mwenda Jason M , Fülöp Vilmos , D'Hooghe Thomas M
Published: February 2010

In women of reproductive age, health economic costs are estimated to be considerably higher for endometriosis than for conditions such as Crohn's disease, migraine and hypertension, and similar to the cost of diabetes. However, more awareness of endometriosis among patients and politicians is needed to create a better climate for research funding in the area of endometriosis in particular, and women's health in general. Recent collaboration between patients, physicians and politicians in the EU has shown that such efforts can be successful. Many arguments exist to organize the clinical care for women with advanced endometriosis in centers of excellence, but continuing education of primary-care physicians also remains a priority. New molecular techniques are resulting in new hormonal and nonhormonal targets for the noninvasive diagnosis and treatment of endometriosis. A future diagnostic serum assay might contain various elements from inflammatory serum markers to genetic/microarray/proteomics markers, owing to the multifactorial features of endometriosis.
Anticoagulation in Women with Nonvalvular Atrial Fibrillation: Insights from Clinical Trials
Authors: Reynolds Deborah A , Halperin Jonathan L
Published: February 2010

There is emerging evidence that women with atrial fibrillation, particularly those aged over 75 years, are more prone to strokes than men. It is also generally believed that older women are more vulnerable than men to warfarin-associated hemorrhage, leading to reluctance among physicians to anticoagulate women with atrial fibrillation. In the SPORTIF trials, the largest randomized cohort of women with atrial fibrillation on anticoagulation, including those aged over 75 years, women developed stroke (either ischemic or hemorrhagic) and systemic embolic events more often than men. In population-based studies such as the ATRIA study, female gender increased the relative risk of stroke significantly (incremental relative risk: 20–90%). Both types of studies demonstrated that maintaining the international normalized ratio within the therapeutic range of 2.0–3.0 was associated with similar rates of major bleeding in older women, younger women and men. Better validated predictors of bleeding than gender should be considered when selecting antithrombotic therapy. New oral anticoagulants are under development to reduce the burden and risk of warfarin-associated anticoagulation.
Preventive Oncology in the Postmenopausal Woman
Authors: Huber Johannes C , Ott Johannes , Tempfer Clemens B
Published: February 2010

Breast cancer and endometrial cancer are the most common gynecologic malignancies of the postmenopausal period. As preventive medicine becomes the focus of interest, preventive oncology with special regard to these diseases will undoubtedly become a substantial part of the practicing oncologist's field of duties. The aim of this review is to summarize recommendations dealing with the risk assessment and prevention of breast and endometrial cancer. Obesity, the level of exercise and dietary factors are associated with breast cancer. The selective estrogen receptor modulators tamoxifen and raloxifen have both been shown to decrease the risk to the same extent. Patients at particularly high risk are being detected through the use of the Gail model, a well-known statistical model of risk. Other factors, such as breast density, the serum level of endogenous estrogen and the presence of single nucleotide polymorphisms, have to be taken into consideration.
Paget's Disease of the Nipple
Authors: Seetharam Seema , Fentiman Ian S
Published: February 2010

Paget's disease of the nipple is an unusual epidermal presentation of underlying breast cancer. It presents as eczematous change or erythematous ulceration, but may also be an incidental histological finding in a mastectomy specimen. Approximately half of the underlying cancers are invasive, the remainder being ductal carcinoma in situ, and only rarely is there no associated malignancy. Routine clinical and mammographic assessment may significantly underestimate the extent of disease, but MRI may increase the sensitivity in detecting occult malignancy. Mastectomy maximizes local control; however, selected cases can be treated by nipple conisation with radiotherapy. Sentinel node biopsy is the standard of care for axillary staging in the clinically and ultrasonically node-negative case. Almost all invasive cases overexpress human EGF receptor-2 and, therefore, are likely to benefit from adjuvant chemotherapy and herceptin.
Screening for the Early Detection of Ovarian Cancer
Authors: Robertson David M
Published: February 2010

Evaluation of: Menon U, Gentry-Maharaj A, Hallett R et al.: Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Lancet Oncol. 10, 327–340 (2009). A randomized, controlled trial was undertaken to assess the use of serum CA125 and ovarian ultrasound as diagnostic markers in the early detection of ovarian cancer. The trial consisted of 202,638 postmenopausal women who were assessed annually between 2001 and 2005. A nonscreen group and two screening groups were investigated. The screening groups included serum CA125, which was based on a rate-of-change algorithm, plus transvaginal ultrasound (in at-risk women); and an ovarian ultrasound group only, prior to clinical review and surgery. The sensitivity, specificity and positive predictive values for all primary ovarian and tubal cancers for the combined test group was 89.4, 99.8 and 43.3%, respectively, and for the ultrasound group 84.9, 98.2 and 5.3%, respectively, with a significant difference in specificity between groups. The combined test provides the requisite specificity for a screening test for ovarian cancer in postmenopausal women.
Current Perspectives in Vulvodynia
Authors: Damsted-Petersen Christina , Boyer Stéphanie C , Pukall Caroline F
Published: February 2010

Vulvodynia, or chronic vulvar pain, is a common but poorly understood condition. Although its etiology is not well understood, it appears to be multifactorial. As such, treatment options are targeted to reduce singular symptoms in a piecemeal fashion. A number of randomized, controlled trials have been conducted and at least one paper on combination therapy has been published; however, further systematic research is needed in order to more fully inform clinical practice.
Polycystic Ovary Syndrome, Obesity and Reproductive Implications
Authors: Hirschberg Angelica Lindén
Published: February 2010

Polycystic ovary syndrome (PCOS) is one of the most common causes of female infertility, affecting 5–10% of women of reproductive age. The syndrome is characterized by anovulation, hyperandrogenism and polycystic ovaries. Furthermore, PCOS is associated with insulin resistance and obesity, which is present in approximately 50% of women with PCOS. Reproductive function in women with PCOS is strongly dependent on bodyweight and metabolic status. Obesity is associated with an increased risk of infertility and may also have a negative influence on pregnancy outcome. Considering the worldwide epidemic of obesity, clinical problems relating to PCOS may worsen and increase in frequency. Lifestyle interventions resulting in weight loss comprise the most successful strategy to improve symptoms of PCOS. However, many patients fail to lose weight or may quickly regain weight. It is an important challenge to develop effective lifestyle programs and adjuvant pharmacologic treatments in order to improve reproductive and metabolic health among women with PCOS.
Effect of Bilateral Oophorectomy on Women's Long-Term Health
Authors: Parker William H , Jacoby Vanessa , Shoupe Donna , Rocca Walter
Published: February 2010

Bilateral oophorectomy at the time of hysterectomy for benign disease is commonly practiced in order to prevent the subsequent development of ovarian cancer or other ovarian pathology that might require additional surgery. At present, bilateral oophorectomy is performed in 78% of women aged between 45 and 64 years having a hysterectomy, and a total of approximately 300,000 prophylactic oophorectomies are performed in the USA every year. Estrogen deficiency resulting from pre- and post-menopausal oophorectomies has been associated with higher risks of coronary heart disease, stroke, hip fracture, Parkinsonism, dementia, cognitive impairment, depression and anxiety in many studies. While ovarian cancer accounts for 14,800 deaths per year in the USA, coronary heart disease accounts for 350,000 deaths per year. In addition, 100,000 cases of dementia may be attributable annually to prior bilateral oophorectomy. At present, observational studies suggest that bilateral oophorectomy may do more harm than good. In women who are not at high risk of developing ovarian or breast cancer, removing the ovaries at the time of hysterectomy should be approached with caution.
Lapatinib in Metastatic Breast Cancer
Authors: Frenel J-S , Bourbouloux E , Berton-Rigaud D , Sadot-Lebouvier S , Zanetti A , Campone M
Published: February 2010

Lapatinib is an oral, small-molecule, dual kinase inhibitor that targets both HER2 and the EGF receptor. Lapatinib was approved in June 2008 in Europe for the treatment of advanced HER2-positive breast cancer. Promising results in trastuzumab-refractory metastatic breast cancer were obtained from Phase I, II and III studies in combination with chemotherapy. Diarrhea and rash are the most common side-effects and are mostly moderate and treatable. Cardiac toxicity occurs rarely and mostly as an asymptomatic and reversible decrease of left ventricular ejection fraction. Unlike trastuzumab, some data show that lapatinib could cross the blood–brain barrier, with some evidence of activity in treating or preventing brain metastases. Its evaluation is actively ongoing, in combination with trastuzumab and in the adjuvant setting.
Bevacizumab for Advanced Breast Cancer
Authors: Goldfarb Shari B , Traina Tiffany A , Dickler Maura N
Published: February 2010

Tumor angiogenesis is an important step in breast cancer development, progression, invasion and metastasis. Proangiogenic factors such as VEGF regulate angiogenesis and are targets for drug development. Bevacizumab, an anti-VEGF antibody, has demonstrated significant clinical benefit in several solid tumors, including breast cancer. Its use in combination with either paclitaxel or docetaxel has prolonged progression-free survival and increased response rates in the first-line treatment of patients with metastatic breast cancer. This review article discusses the clinical trials establishing the use of bevacizumab for the treatment of advanced breast cancer.
Educating today's democratic citizen
Authors: Bernstein Jeffrey L.
Published: February 2010

What are we in higher education to make of the recent calls for citizenship education to play a larger role in the academy? As Matt Hartley’s paper in this issue of Learning and Teaching suggests, colleges and universities in the United States have been paying increased attention to educating for citizenship in recent decades; Bob Simpson’s concluding commentary makes similar arguments about increased expectations for

citizenship education in Europe. As our institutions of higher learning confront economic pressures, increased competition (including from for-profit entities) and calls for accountability through meaningful assessments of student learning, they will also face increased pressure to graduate not just educated individuals, but also individuals who are connected, as citizens, to the local, national and transnational world in which they live.
Reclaiming the democratic purposes of American higher education: Tracing the trajectory of the civic engagement movement
Authors: Hartley Matthew
Published: February 2010

American colleges and universities have historically sought to promote an enlightened citizenry. In the early 1980s many felt that this civic purpose was in danger of being lost. What unfolded was a widespread educational reform movement aimed at reasserting the public and democratic purpose of American higher education. This article traces the trajectory of this movement and notes a significant emergent tension among movement members - the question of whether to seek broad-based legitimacy within the academy by aligning the efforts with disciplinary norms or to challenge the status quo and attempt to transform higher education and align its efforts with the pressing needs of America's democracy.
Learning for citizenship online: How can students develop intercultural awareness and construct knowledge together?
Authors: Starkey Hugh , Savvides Nicola
Published: February 2010

This article evaluates ways in which students on an online Master's programme are learning about citizenship and developing intercultural awareness in spite of the lack of face-to-face interaction. There is still debate about the effectiveness of online courses and whether they provide an adequate substitute for, or even an improvement on, classroom-based learning. We employ qualitative research methods and deploy instruments for analysing constructivist learning to evaluate the extent to which students are constructing knowledge through online discussions as well as learning from research-led teaching materials. We also analyse online discussions for evidence of social presence, including the interventions of the course tutor. We conclude that students do feel themselves to be members of an international learning community and that their interactions can promote higher-order learning. We draw attention to some advantages of online courses such as the possibility of crafting a contribution and the availability of discussions as a resource.