bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of inhibition in the motor control of finger function
Authors: Gerloff Christian , Hummel Friedhelm
Published: April 2012

Successful music performance requires adequate contextual control of behaviour, that is, the retrieval and non-retrieval, or inhibition, of learned actions. This chapter describes recent advances in the understanding of neural correlates of controlling motor behaviour, as identified with transcranial magnetic stimulation (TMS), electroencephalography (EEG), and functional magnetic resonance imaging (fMRI). It stresses two main points: first, neuroimaging studies on motor physiology in musicians need to take into account the essential role of inhibitory neuronal circuits; second, these studies may help further our understanding of neurological diseases frequently affecting professional musicians, such as focal dystonia.
The end of the song? Robert Schumann's focal dystonia
Authors: Altenmüller Eckart
Published: April 2012

This chapter focuses on Robert Schumann, one of the most prominent composers of the early romantic period. Early in his adolescence he displayed extraordinary skills in piano playing and attempted to become a concert pianist. After an initial success, however, he developed a focal, task-specific dystonia of the right hand, also referred to as pianist's cramp. This disorder is characterised by a painless loss of skilled motor control in a task-specific context. Risk factors for developing musician's dystonia are male gender, extensive cumulative practice time, extreme motor workload concerning the temporal and spatial quality of the affected movements and personality traits such as proneness to anxiety and perfectionism. All these factors can be demonstrated in Robert Schumann's early life.
Dualism and Archetype
Authors: Simmonds N.E.
Published: April 2012

It has often been argued that law is simply a morally neutral instrument that is equally serviceable for good purposes and for bad: on this view, law’s connection with moral value is purely contingent and not inherent in law’s nature. But while it is true that law can be employed as an instrument of evil, it does not follow from this that law is merely a morally neutral instrument. Law’s availability for evil purposes is fully compatible with law’s status as a moral ideal. The idea of law is best understood by reference to an archetype which corresponds to the idea of “the rule of law”. In common with many others, Raz takes the view that the idea of “law” is wholly distinct from the idea of “the rule of law”. He acknowledges that the rule of law embodies a moral virtue but he claims that this is only a “negative virtue” in that it only protects us from evils that only the law can cause. Raz’s views on these matters are shown to rest on some simple confusions.
Evil Regimes and the Rule of Law
Authors: Simmonds N.E.
Published: April 2012

Lon Fuller’s idea of the “inner morality of law” is examined, alongside two alternative readings of H.L.A. Hart’s response to Fuller. The ambiguities in Hart’s response mean that it is not impossible (although it is implausible) to interpret him as substantially agreeing with Fuller. For that reason, the focus of the chapter switches to Matthew Kramer’s criticisms of Fuller, and Kramer’s claim that “the rule of law” is not an intrinsically moral idea since even evil regimes would have good reasons for compliance with the rule law. Kramer’s argument is criticised, and it is suggested that the rule of law is the only way in which the value of “freedom as independence” may be protected.
Ideal and Experience
Authors: Simmonds N.E.
Published: April 2012

Moral judgement is often thought of as the application of a principle to a set of facts. On this approach, our principles are to be judged independently of particular circumstances to which they apply, while an understanding of the circumstances calls for descriptive accuracy rather than moral insight. This outlook makes it hard to see how the understanding of any existing social institution can be anything other than a descriptive or purely analytical enterprise. In fact, jurisprudence can be properly understood only in the light of the possibility that moral insight may be derived from reflection upon our institutions and practices: in particular, reflection upon those value-oriented practices in which we engage. We can learn more about the content of a value by reflection upon the experience of pursuing it. Legal thought is reflexive: it is guided in part by inquiry into its own nature. Understanding how and why this might be so enables us to understand how the knowledge of law’s content (expressed in doctrinal legal scholarship) is not reducible to knowledge of a finite body of rules.
Legality as a Value
Authors: Simmonds N.E.
Published: April 2012

Hart’s discussions of legality vacillate between a variety of different views. This manifests his discomfort with the general perspective of his own theory and his wavering endorsement of value pluralism. Justice and legality appear, on the face of things, to be very different values. But they stand to each other in an intimate relationship. This is difficult to understand so long as we are thinking of the philosophy of values in terms of a contrast between pluralism (which asserts the existence of diverse values which clash and compete) and monism (which asserts the mutual compatibility of values). Between the two possibilities of pluralism and monism lies a third approach. This depends upon the thought that values can be realised to varying degrees. When the realisation of justice and legality falls short, justice and legality can clash and compete. Nevertheless, justice and legality are intimately related in so far as each can be fully attained only in conjunction with the other: the rule of law is fully achievable only when the legal texts can be interpreted as embodying a coherent conception of justice; and justice can be achieved only when its general requirements are given determinacy by positive law. Since the judge’s duty is one of fidelity to the idea of law, that duty also encompasses a duty to construe the law as just, so far as possible
Attending to emerging representations: the importance of task context and time of response
Authors: Hunt Amelia R. , van Zoest Wieske , Kingstone Alan
Published: April 2012

This chapter examines human attention as indexed by the time-to-respond-to-stimulus events and evaluates the use of this behavioural metric. It discusses the limitations of using reaction time (RT) to make inferences about attention and explains the results of experiences that extend this approach by examining changes in responses over time and across different response systems. The findings reveal that multiple stages and aspects of task performance can contribute to RT and that it is not always clear how exactly attention interacts with these various processes to produce faster responses.
A stream of thought: temporal organization of mental operations
Authors: Sigman Mariano
Published: April 2012

This chapter reviews behavioural and psychological refractory period (PRP) experiments, which provide evidence for the dynamic organization of two qualitatively different operations involved in a task. These operations are the slow, large-scale systems related to attention, conscious processing, and effortful mental operations, and the dedicated circuits that can very rapidly and in parallel execute stereotyped programs typically related to encoding and memory retrieval. It discusses the temporal organization of mental operations that suggests that a decision involves systematic coactivation of parietal and premotor regions of the brain.
Prior entry: attention and temporal perception
Authors: Spence Charles
Published: April 2012

This chapter examines the prior entry hypothesis and provides a brief review of the empirical literature investigating the effects of attention on multisensory temporal perception in humans. The findings suggest that most research has found convincing empirical evidence in support of the existence of the prior entry effect. The results also reveal that attention does indeed speed the relative latency of perceptual processing no matter the dimension or channel along which attention is oriented and no matter whether attention is directed in an endogenous or exogenous manner.
Timing, resources, and interference: attentional modulation of time perception
Authors: Brown Scott W.
Published: April 2012

This chapter describes a research that investigated the attentional modulation of time perception. It explains that this research involved various techniques for modifying attention to time including manipulations of temporal awareness and variations in the nature of the distractor tasks. All of the different approaches produced a consistent set of findings which indicate that interval timing requires attentional resources and that time judgement performance is influenced strongly by the allocation of those resources.
Duration illusions and predictability
Authors: Eagleman David M.
Published: April 2012

This chapter proposes a hypothesis which holds that the subjective duration assigned to a stimulus reflects the magnitude of the neural response to the stimulus. It evaluates whether attention alone can modulate subjective duration or whether the process involves stimulus predictability and the concomitant amplitudes of neural responses. The findings indicate that the subjective duration assigned to a stimulus parallels the magnitude of the neural response to the stimulus and that the explanation for this lies with predictability, not with attention.
Temporal dilation: the chronostasis illusion and spatial attention
Authors: Yarrow Kielan
Published: April 2012

This chapter examines the relation between chronostasis illusion and spatial attention. It discusses saccadic chronostasis which describes the temporal overestimation of a stimulus seen immediately following a saccade. The findings indicate that prior entry and attention-based temporal dilation are not particularly convincing explanations for the chronostasis illusion. However, there is some controversy regarding the spatial extent of chronostasis and its relationship with the shift of attention that precedes a saccade.
Space-time in the brain
Authors: Morrone Concetta , Burr David
Published: April 2012

This chapter reviews recent studies concerning the perception of event duration and the relation between space and time in the brain. It explains evidence showing that the perception of event duration is strongly linked to our perception of space. The results of the studies reviewed collectively show that space and time are intrinsically interconnected and that adaptation to duration is spatially selective while the temporal distortions that occur during saccades are closely linked to contemporaneous spatial distortions.
Modulation of time perception by visual adaptation
Authors: Johnston Alan
Published: April 2012

This chapter examines the modulation of time perception by visual adaptation and identifies temporal representations in the visual domain. The evidence from functional imaging suggests that temporal judgements involve a network of sensory and motor areas. The findings also indicate that there may be no purely abstract temporal areas and all temporal processing are connected to the sensory-motor and cognitive systems.
Excitatory and inhibitory motor mechanisms of temporal preparation
Authors: Burle Boris , Tandonnet Christophe , Hasbroucq Thierry
Published: April 2012

This chapter examines the excitatory and inhibitory motor mechanisms involved in temporal preparation. It discusses between-block manipulations and proposes new perspectives for deciphering the neural mechanisms underlying within-block designs. It describes complementary neurophysiological approaches related to temporal preparation and suggests that temporal preparation does not only involve an increase in neural activity but also varies as a function of a subtle interplay between response activation and inhibition.
Foreperiod and sequential effects: theory and data
Authors: Los Sander A.
Published: April 2012

This chapter describes the sequential effect of foreperiod and explains how this may cast light on some fundamental properties of temporal attention. It discusses the results of studies concerning trace-conditioning and also talks about the dual-process views regarding the sequential effect of foreperiod. It suggests that the classical response time-foreperiod function conceals a highly robust source of variance embodied by the asymmetric sequential effect of foreperiod.
Attending to sound patterns and the role of entrainment
Authors: Jones Mari Riess
Published: April 2012

This chapter focuses on attention to sounds. It reviews tasks requiring judgements about time in the context of sound sequences and discusses evidence for listeners' sensitivities to temporal regularities in these events. It investigates issues about timing and attention in the context of entrainment and dynamic attending theory and evaluates the impact of implicit rhythmic timing on the ability to judge the pitch component of melodic sound sequences.
Temporal orienting in audition, touch, and across modalities
Authors: Lange Kathrin , Röder Brigitte
Published: April 2012

This chapter examines the possible role of temporal orienting of attention in modulating early perceptual processing. It discusses the results of four studies that provide evidence that explicit temporal orienting enhances early, perceptual stages of auditory processing. This chapter shows that early tactile processing stages are also enhanced by temporal attention and suggests that future related studies should focus on investigating the preconditions for enhancement of perceptual processing steps by temporal orienting.
Neurophysiology of temporal orienting in ventral visual stream
Authors: Anderson Britt , Sheinberg David L.
Published: April 2012

This chapter examines the neurophysiological aspects of temporal orienting in the ventral visual stream. It analyses cellular events which might underlie enhanced perceptual performance and discusses the neurophysiological correlates of spatial attention. The findings reveal that whether visual stimulus is cued spatially or temporally, there are changes in neuronal firing rates, increases in the gamma band visual stimulus which are cued spatially or temporally, and increases in the spectral power of the local field potential (LFP).
Boundless Competition: Subcontracting and the London Economy in the Late Nineteenth Century
Authors: Riello Giorgio
Published: April 2012

Why did subcontracting remain, well until the end of the nineteenth century, a viable way to organize metropolitan manufacturing? This article addresses historically and theoretically the reasons for the permanence of subcontracting as a viable alternative to centralized forms of production in London. It also questions the literature that equates the decline of subcontracting with the rise of sweating and argues for a reinterpretation of traditional explanations that saw the “sweater” as a central figure in the “degeneration” of the metropolitan productive system. The article concludes by proposing a reinterpretation of the “decline of subcontracting” and argues that the logic of flexibility of subcontracting was challenged by the increasing power of London wholesalers and retailers and the demands offin-de-sièclemass consumption.
Analysis of chlorophyll a concentration along the Galician coast: seasonal variability and trends
Authors: Alvarez I. , Lorenzo M. N. , deCastro M.
Published: April 2012

Alvarez, I., Lorenzo, M. N., and deCastro, M. 2012. Analysis of chlorophyll a concentration along the Galician coast: seasonal variability and trends. – ICES Journal of Marine Science, 69: 728–738. The spatial and temporal distribution of chlorophyll a (Chl a) concentration was analysed along the Galician coast from 1998 to 2007. Sea surface temperature and Ekman transport data were also used to investigate the relationship between the ocean–atmosphere conditions and Chl a formation and variability. The west coast showed the highest Chl a concentration, with three peaks of maximum values (February, April–May, and July–September). Along the central coast, the pattern was similar, with the highest concentrations measured during spring and summer, but with lower values. The north coast was the least productive, with much lower values. The high seasonal variability of Chl a was mainly related to upwelling events during spring and summer. During autumn and winter, Chl a variations depended on other factors such as the input of nutrients from land run-off. There was no clear seasonal trend in Chl a.
TT-301 Inhibits Microglial Activation and Improves Outcome after Central Nervous System Injury in Adult Mice
Authors: James Michael L. , Wang Haichen , Cantillana Viviana , Lei Beilei , Kernagis Dawn N. , Dawson Hana N. , Klaman Lori D. , Laskowitz Daniel T.
Published: April 2012

Background

Microglial inhibition may reduce secondary tissue injury and improve functional outcome following acute brain injury. Utilizing clinically relevant murine models of traumatic brain injury and intracerebral hemorrhage, neuroinflammatory responses and functional outcome were examined in the presence of a potential microglial inhibitor, TT-301.

Methods

TT-301 or saline was administered following traumatic brain injury or intracerebral hemorrhage, and then for four subsequent days. The effect of TT-301 on neuroinflammatory responses and neuronal viability was assessed, as well as short-term vestibulomotor deficit (Rotorod) and long-term neurocognitive impairment (Morris water maze). Finally differential gene expression profiles of mice treated with TT-301 were compared with those of vehicle.

Results

Reduction in F4/80+ staining was demonstrated at 1 and 10 days, but not 28 days, after injury in mice treated with TT-301 (n = 6). These histologic findings were associated with improved neurologic function as assessed by Rotorod, which improved by 52.7% in the treated group by day 7, and Morris water maze latencies, which improved by 232.5% as a function of treatment (n = 12; P < 0.05). Similar benefit was demonstrated following intracerebral hemorrhage, in which treatment with TT-301 was associated with functional neurologic improvement of 39.6% improvement in Rotorod and a reduction in cerebral edema that was independent of hematoma volume (n = 12; P < 0.05). Differential gene expression was evaluated following treatment with TT-301, and hierarchical cluster analysis implicated involvement of the Janus kinase-Signal Transducer and Activator of Transcription pathway after administration of TT-301 (n = 3/group).

Conclusions

Modulation of neuroinflammatory responses through TT-301 administration improved histologic and functional parameters in murine models of acute neurologic injury.
Awake Fiberoptic or Awake Video Laryngoscopic Tracheal Intubation in Patients with Anticipated Difficult Airway Management
Authors: Rosenstock Charlotte V. , Thøgersen Bente , Afshari Arash , Christensen Anne-Lise , Eriksen Claus , Gätke Mona R.
Published: April 2012

Background

Awake flexible fiberoptic intubation (FFI) is the gold standard for management of anticipated difficult tracheal intubation. The purpose of this study was to compare awake FFI to awake McGrath® video laryngoscope, (MVL), (Aircraft Medical, Edinburgh, Scotland, United Kingdom) intubation in patients with an anticipated difficult intubation. The authors examined the hypothesis that MVL intubation would be faster than FFI.

Methods

Ninety-three adult patients with anticipated difficult intubation were randomly allocated to awake FFI or awake MVL, patients were given glycopyrrolate, nasal oxygen, topical lidocaine orally, and a transtracheal injection of 100 mg lidocaine. Remifentanil infusion was administered intravenously to a Ramsay sedation score of 2-4. Time to tracheal intubation was recorded by independent assessors. The authors also recorded intubation success on the first attempt, investigators' evaluation of ease of the technique, and patients reported intubation-discomfort evaluated on a visual analog scale.

Results

Eighty-four patients were eligible for analysis. Time to tracheal intubation was median [interquartile range, IQR] 80 s [IQR 58-117] with FFI and 62 s [IQR 55-109] with MVL (P = 0.17). Intubation success on the first attempt was 79% versus 71% for FFI and MVL, respectively. The median visual analog scale score for ease of intubation was 2 (IQR 1-4) versus 1 (IQR 1-6) for FFI and MVL, respectively. The median visual analog scale score for patients' assessment of discomfort for both techniques was 2, FFI (IQR 0-3), MVL (IQR 0-4).

Conclusions

The authors found no difference in time to tracheal intubation between awake FFI and awake MVL intubation performed by experienced anesthesiologists in patients with anticipated difficult airway.
ATP-Binding Cassette B4, an Auxin-Efflux Transporter, Stably Associates with the Plasma Membrane and Shows Distinctive Intracellular Trafficking from That of PIN-FORMED Proteins
Authors: Cho Misuk , Lee Zee-Won , Cho Hyung-Taeg
Published: April 2012

Intracellular trafficking of auxin transporters has been implicated in diverse developmental processes in plants. Although the dynamic trafficking pathways of PIN-FORMED auxin efflux proteins have been studied intensively, the trafficking of ATP-binding cassette protein subfamily B proteins (ABCBs; another group of auxin efflux carriers) still remains largely uncharacterized. In this study, we address the intracellular trafficking of ABCB4 in Arabidopsis (Arabidopsis thaliana) root epidermal cells. Pharmacological analysis showed that ABCB4 barely recycled between the plasma membrane and endosomes, although it slowly endocytosed via the lytic vacuolar pathway. Fluorescence recovery after photobleaching analysis revealed that ABCB4 is strongly retained in the plasma membrane, further supporting ABCB4’s nonrecycling property. The endocytosis of ABCB4 was not dependent on the GNOM-LIKE1 function, and the sensitivity of ABCB4 to brefeldin A required guanine nucleotide exchange factors for adenosyl ribosylation factor other than GNOM. These characteristics of intracellular trafficking of ABCB4 are well contrasted with those of PIN-FORMED proteins, suggesting that ABCB4 may be a basic and constitutive auxin efflux transporter for cellular auxin homeostasis.
What predicts high risk acute graft‐versus‐host disease (GVHD) at onset?: identification of those at highest risk by a novel acuteGVHDrisk score
Authors: MacMillan Margaret L. , DeFor Todd E. , Weisdorf Daniel J.
Published: April 2012

To define high‐risk acute graft‐versus‐host disease (GVHD) at onset, we examined the initialGVHDstage and grade of 864 patients at theUniversity ofMinnesota who received uniform therapy with prednisone 60 mg/m2 per d. We compared the prognostic utility of theMinnesota (MN; modified fromConsensus)versusCenter forInternationalBlood andMarrowTransplantResearch (CIBMTR)GVHDorgan stage‐derived grading systems. As neitherGVHDgrading system optimally predicted outcomes, a novel acuteGVHDrisk score was devised by combining theMNandCIBMTRsystems. Using multiple regression analysis, we could dichotomize patients into high risk (HR,n = 86) acuteGVHDwith initial gradeIIIC,IIIDorIVDwho were less likely to respond to steroid therapy by day 28 [relative risk (RR), 0·3,P < 0·001] and had a higher risk for transplant‐related mortality (RR, 2·0,P < 0·001) than patients with standard risk (SR, initial gradeIA–IIIB,n = 778)GVHD. Using this novel acuteGVHDRisk Score,HR GVHDis either skin stage 4, lower gastrointestinal (GI) stage 3+, liver stage 3+, or skin stage 3 and lowerGIor liver stage 2+GVHD. Patients withHRacuteGVHDhave a poor prognosis, require alternative initial therapy and should be the focus of novel therapeutic trials.
Is there sufficient evidence to consider the use of 11β‐hydroxysteroid dehydrogenase type 1 inhibition in children?
Authors: Fürst‐Recktenwald Sabine , Dörr Helmuth G. , Quinkler Marcus , Dötsch Jörg , Stewart Paul M.
Published: April 2012

Manifestations of the metabolic syndrome [obesity, dyslipidaemia, hypertension, blood glucose derangements including prediabetes or type 2 diabetes mellitus (T2DM)] in juvenile populations are becoming increasingly prevalent throughout the world and are at the point of being a global public health concern. Derangements in cortisol regeneration seem to be involved in the pathophysiology. Treatment with selective 11β‐hydroxysteroid dehydrogenase 1 (11β‐HSD1) inhibitors could be a therapeutic strategy in paediatric patients with manifestations of the metabolic syndrome. Based on preclinical and clinical data regarding development of the 11β‐HSD1 enzyme, it appears that maturation occurs within the first year of life. Different changes in biomarkers for assessing the efficacy and safety of 11β‐HSD1 inhibitors are to be expected in paediatric patients compared to adults, reflecting differences in metabolism. The effect of 11β‐HSD1 treatment in children on bone differentiation and development as well as adrenocorticotropic hormone (ACTH), circulating and local cortisol tissue concentrations, androgens and respective stress response is not yet known. Based on current literature, the concept of inhibition of 11β‐HSD1 is considered a potentially effective mean to regulate local cortisol levels in the paediatric population, and 11β‐HSD1 inhibitors may provide a valuable target and treatment option for the metabolic syndrome in paediatric patients. However, the uncertainty over effects on the developing skeleton combined with mild increases in adrenal androgen levels raises potential concerns regarding growth as well as onset of puberty as to their future use in children. Future clinical studies are needed to thoroughly assess the risks and benefits of this new class of drugs in the paediatric population.
Wrong place, wrong time: climate change‐induced range shift across fragmented habitat causes maladaptation and declined population size in a modelled bird species
Authors: Cobben Marleen M. P. , Verboom Jana , Opdam Paul F. M. , Hoekstra Rolf F. , Jochem René , Smulders Marinus J. M.
Published: April 2012

Many species are locally adapted to decreased habitat quality at their range margins, and therefore show genetic differences throughout their ranges. Under contemporary climate change, range shifts may affect evolutionary processes at the expanding range margin due to founder events. In addition, populations that are affected by such founder events will, in the course of time, become located in the range centre. Recent studies investigated evolutionary changes at the expanding range margin, but have not assessed eventual effects across the species' range. We explored the possible influence of range shift on the level of adaptation throughout the species' total range. For this we used a spatially explicit, individual‐based simulation model of a woodland bird, parameterized after the middle spotted woodpecker (
Dendrocopos medius) in fragmented habitat. We simulated its range under climate change, and incorporated genetic differences at a single locus that determined the individual's degree of adaptation to optimal temperature conditions. Generalist individuals had a large thermal tolerance, but relatively low overall fitness, whereas climate specialists had high fitness combined with a small thermal tolerance. In equilibrium, the populations in the range centre were comprised of the specialists, whereas the generalists dominated the margins. In contrast, under temperature increase, the generalist numbers increased at the expanding margin and eventually also occupied the centre of the shifting range, whereas the specialists were located in the retracting margins. This was caused by founder events and led to overall maladaptation of the species, which resulted in a reduced metapopulation size and thus impeded the species' persistence. We therefore found no evidence for a complementary effect of local adaptation and range shifts on species' survival. Instead, we showed that founder events can cause local maladaptation which can amplify throughout the species' range, and, as such, hamper the species' persistence under climate change.
Significance of liver histology in HBsAg‐positive, IgM anti‐HBc‐negative acute hepatitis B virus‐related hepatitis
Authors: Delladetsima Ioanna , Papatheodoridis George V , Tiniakos Dina G , Hatzakis Angelos , Tassopoulos Nikolaos C
Published: April 2012

Delladetsima I, Papatheodoridis G V, Tiniakos D G, Hatzakis A & Tassopoulos N C  (2012) Histopathology 61, 881–888

Significance of liver histology in HBsAg‐positive, IgM anti‐HBc‐negative acute hepatitis B virus‐related hepatitis

Aims:  The natural course of HBsAg‐positive, IgM anti‐HBc‐negative acute hepatitis B virus (HBV)‐related hepatitis is unclear. The aim of this study was to evaluate the prognostic significance of histological features and hepatic expression of HBV antigens in such patients.

Methods and results:  Fifty patients with HBsAg‐positive, IgM anti‐HBc‐negative acute hepatitis B who underwent liver biopsy during the acute hepatitis episode were studied [HBeAg seroconversion (n = 16), persistently positive for HBeAg (n = 9), and persistently negative for HBeAg (n = 25)]. Twenty‐six cases had features of typical acute hepatitis only (group A), and 24 cases had changes suggesting pre‐existing chronic hepatitis (group B). HBcAg and/or HBsAg immunoreactivity was detected less frequently in group A than in group B (31% versus 79%, P = 0.01). HBsAg clearance was observed in 24% of patients, almost exclusively in cases with HBeAg seroconversion. HBsAg loss was significantly more frequent in group A than in group B (52% versus 0%, P < 0.001), and in cases without rather than with immunohistochemical expression of HBV antigens (55% versus 0%, P < 0.001). In group A, HBsAg clearance was observed in 80%, 54% and 0% of patients with mild, moderate or severe acute hepatitis, respectively (P = 0.034).

Conclusions:  Histological information is very important for the prognosis of HBsAg‐positive, IgM anti‐HBc‐negative acute hepatitis B. HBeAg seroconversion with underlying typical acute hepatitis changes of mild to moderate severity without hepatic expression of HBV antigens strongly predicts subsequent HBsAg loss.
CD36 modulates proinflammatory cytokine responses to Plasmodium falciparum glycosylphosphatidylinositols and merozoites by dendritic cells
Authors: KUMAR S. , GOWDA N. M. , WU X. , GOWDA R. N. , GOWDA D. C.
Published: April 2012

Studies have shown that glycosylphosphatidylinositols (GPIs) of Plasmodium falciparum activate macrophages mainly through Toll‐like receptor 2 (TLR2)‐mediated signalling and to certain extent through TLR4‐mediated signalling to induce proinflammatory cytokine production. However, the ability of parasite GPIs to activate dendritic cells (DCs) has not been reported. Here, we show that parasite GPIs efficiently activate DCs through TLR2‐mediated signalling mechanism and induce the production of TNF‐α and IL‐12. We also studied the role of scavenger receptor CD36 in P. falciparum GPI‐ and merozoite‐induced cytokine responses by DCs. The results indicate that CD36 modulates the cytokine‐inducing activity of the parasite GPIs by collaborating with TLR2 in DCs. Furthermore, our data reveal that CD36 modulates the activity of P. falciparum merozoites, likely by the contribution of phagocytosis‐coupled CD36‐mediated signalling to the signalling induced by merozoites. Altogether, these results contribute towards understanding of signalling mechanisms in malaria parasite‐induced activation of the innate immune system.
Intra‐ and inter‐observer reliability of the application of the cellulite severity scale to a Spanish female population
Authors: De La Casa Almeida M. , Suarez Serrano C. , Jiménez Rejano J.J. , Chillón Martínez R. , Medrano Sánchez E.M. , Rebollo Roldán J.
Published: April 2012

Background  ‘Hexsel, dal’Forno and Hexsel Cellulite Severity Scale’ (CSS) was developed to evaluate cellulite with an objective and easy to apply tool.

Objective  Study CSS intra‐ and inter‐observer reliability in a Spanish female population by evaluating patients’ cellulite through photographs of their overall gluteofemoral zone as opposed to its creators who distinguished between buttocks and thigh.

Methods  Cellulite Severity Scale was applied to 27 women, evaluating gluteofemoral cellulite, differentiating between left and right. Evaluations were made by three expert examiners each at three times with a 1‐week separation. Variables were the five CSS dimensions (number of evident depressions; depth of depressions; morphological appearance of skin surface alterations; grade of laxity, flaccidity, or sagging skin; and the Nürnberger and Müller classification scale), and the overall CSS score. Cronbach’s alpha, intra‐class correlation and item total correlation were analysed.

Results  Cronbach’s alpha values were 0.951 (right) and 0.944 (left). In the intra‐observer reliability analysis, intra‐class correlation coefficient ranged from 0.993 to 0.999 (P < 0.001) and in the inter‐observer analysis were 0.937 (right) and 0.947 (left) (P < 0.001). Item total correlation showed all dimensions to be needed except grade of laxity, flaccidity or sagging skin (0.959 right; 0.955 left).

Conclusion  Cellulite Severity Scale has excellent reliability and internal consistency when used to evaluate cellulite on the buttocks and back of the thighs considered together. Nevertheless, the dimension grade of laxity, flaccidity or sagging skin does not contribute positively to the final consistency of the scale. This dimension needs to be analysed in greater depth in future studies.
Phosphotyrosine enrichment identifies focal adhesion kinase and other tyrosine kinases for targeting in canine hemangiosarcoma
Authors: Marley K. , Maier C. S. , Helfand S. C.
Published: April 2012

Canine hemangiosarcoma (HSA) is an endothelial cell malignancy driven, in part, by activating mutations in receptor and non‐receptor tyrosine kinases. Proteomics, Western blots and a tyrosine kinase inhibitor were used to elucidate activating mechanisms in HSA cell lines. Phosphotyrosine peptides from focal adhesion kinase (FAK) STAT3, Lyn, Fyn and other signal transduction kinases were identified by mass spectrometry. FAK was constitutively activated at tyrosine 397, the autophosphorylation site, and this was reversible with high concentrations of a FAK inhibitor. FAK inhibitor‐14 suppressed migration and phosphorylation of FAK tyrosine 397 and tyrosines 576/577 and was cytotoxic to HSA cells suggesting FAK signalling may be an important contributor to canine HSA survival.
Acceptance of Naltrexone by Pregnant Women Enrolled in Comprehensive Drug Addiction Treatment: An Initial Survey
Authors: Jones Hendrée E.
Published: April 2012

This paper reports the results of an initial survey regarding the potential interest in naltrexone treatment by pregnant women enrolled in comprehensive treatment for substance use disorders. Pregnant women (N = 112) were asked about their interest in taking either an oral or long‐acting injectable medication that would stop heroin and/or alcohol use, leave them “clear‐headed,” and without neonatal withdrawal. Results indicate strong interest among pregnant women in antagonist treatment, in either form, with clear interest in learning more about naltrexone. Findings lend support for patient's acceptance of a clinical trial of antagonist treatment in this population. (Am J Addict 2012;21:199–201)
TGI Monday?: Drug‐Dependent Outpatients Report Lower Stress and More Happiness at Work than Elsewhere
Authors: Epstein David H. , Preston Kenzie L.
Published: April 2012

In the general population, experience‐sampling studies show that work is the aspect of daily life most associated with momentary unhappiness and a desire to be elsewhere. We assessed whether this holds true for urban outpatients in treatment for heroin and cocaine dependence. In a 25‐week natural‐history study, 79 employed methadone‐maintained misusers of heroin and cocaine carried electronic diaries on which mood and behavior were assessed up to five times per day. Being at work was associated with lower stress, greater happiness, and lower drug craving. Work accounted for 14% of the variance in stress, 30% of the variance in happiness, and 50% of the variance in cocaine craving. Participants with skilled jobs reported more positive and less negative mood states (and lower cocaine craving) at all times compared to participants with semi/unskilled jobs, although the latter reported greater mood improvement at work. In all participants, mood improvements occurred specifically in the presence of coworkers (not other companions). Our seemingly unusual findings might be specific to substance‐disorder patients (for whom work may be a respite from drug‐using companions), but might also hold for other urban dwellers of similar socioeconomic backgrounds (for whom work may be a respite from environmental stressors). (Am J Addict 2012;21:189–198)
Comparison of the Effect of the GABAB Receptor Agonist, Baclofen, and the Positive Allosteric Modulator of the GABAB Receptor, GS39783, on Alcohol Self‐Administration in 3 Different Lines of Alcohol‐Preferring Rats
Authors: Maccioni Paola , Zaru Alessandro , Loi Barbara , Lobina Carla , Carai Mauro A. M. , Gessa Gian Luigi , Capra Alessandro , Mugnaini Claudia , Pasquini Serena , Corelli Federico , Hyytiä Petri , Lumeng Lawrence , Colombo Giancarlo
Published: April 2012

Background

Administration of the GABAB receptor agonist, baclofen, and positive allosteric modulator, GS39783, has been repeatedly reported to suppress multiple alcohol‐related behaviors, including operant oral alcohol self‐administration, in rats. This study was designed to compare the effect of baclofen and GS39783 on alcohol self‐administration in 3 lines of selectively bred, alcohol‐preferring rats: Indiana alcohol‐preferring (P), Sardinian alcohol‐preferring (sP), and Alko Alcohol (AA).

Methods

Rats of each line were initially trained to respond on a lever, on a fixed ratio (FR) 4 (FR4) schedule of reinforcement, to orally self‐administer alcohol (15%, v/v) in daily 30‐minute sessions. Once responding reached stable levels, rats were exposed to a sequence of experiments testing baclofen (0, 1, 1.7, and 3 mg/kg; i.p.) and GS39783 (0, 25, 50, and 100 mg/kg; i.g.) on FR4 and progressive ratio (PR) schedules of reinforcement. Finally, to assess the specificity of baclofen and GS39783 action, rats were slightly food‐deprived and trained to lever‐respond for food pellets.

Results

The rank of order of the reinforcing and motivational properties of alcohol was P>sP>AA rats. Under both FR and PR schedules of reinforcement, the rank of order of potency and efficacy of baclofen and GS39783 in suppressing alcohol self‐administration was P>sP>AA rats. Only the highest dose of baclofen reduced lever‐responding for food pellets; this effect was common to all 3 rat lines. Conversely, no dose of GS39783 altered lever‐responding for food in any rat line.

Conclusions

These results suggest that: (i) the strength of the reinforcing and motivational properties of alcohol differ among P, sP, and AA rats; (ii) the reinforcing and motivational properties of alcohol in P, sP, and AA rats are differentially sensitive to treatment with baclofen and GS39783; (iii) the heterogeneity in sensitivity to baclofen and GS39783 of alcohol self‐administration in P, sP, and AA rats may resemble the differential effectiveness of pharmacotherapies among the different typologies of human alcoholics; and (iv) the GABAB receptor is part of the neural substrate mediating the reinforcing and motivational properties of alcohol.
Selenium or Selenium Plus Folic Acid–Supplemented Diets Ameliorate Renal Oxidation in Ethanol‐Exposed Pups
Authors: Ojeda Maria Luisa , Nogales Fatima , Murillo Maria Luisa , Carreras Olimpia
Published: April 2012

Background

Ethanol (EtOH) exposure during gestation and lactation induces an oxidative stress in offspring. In kidney, the oxidative damage is the primary pathway to alcohol‐induced injury. In this study, we have demonstrated that a diet supplemented with selenium (Se) (0.5 ppm) or with Se (0.5 ppm) + folic acid (8 ppm) administered to EtOH‐exposed (20% v/v) dams during gestation and lactation prevents the oxidative EtOH‐provoked effects in their offspring's kidneys.

Methods

All the studies were performed on 21‐day‐old pups. Serum, urine, and kidney Se levels were assessed by graphite‐furnace atomic absorption spectrometry. Se and creatinine clearance, antioxidant enzyme activities, and lipid and protein peroxidation were determined by a spectrophotometric method in kidney.

Results

Dietary supplementation treatments used could not improve the glomerular filtration function altered by EtOH exposure during gestation and lactation; however, they did improve renal Se deposits, renal development, and renal protein content while decreasing lipid and protein oxidation and modifying antioxidant enzymes' activity.

Conclusions

Se or Se + folic acid supplementations improve renal development and protein content and modify antioxidant enzymes' activity, decreasing lipid and protein oxidation after EtOH exposure. In this context, a double‐supplemented diet appears to reduce protein peroxidation more efficiently than the Se‐only‐supplemented one, probably via superoxide dismutase and catalase.
Pilot Study of iPS‐Derived Neural Cells to Examine Biologic Effects of Alcohol on Human Neurons In Vitro
Authors: Lieberman Richard , Levine Eric S. , Kranzler Henry R. , Abreu Christine , Covault Jonathan
Published: April 2012

Background

Studies of the effects of alcohol on N‐methyl‐d‐aspartate (NMDA) receptor function and gene expression have depended on rodent or postmortem human brain models. Ideally, the effects of alcohol might better be examined in living neural tissue derived from human subjects. In this study, we used new technologies to reprogram human subject‐specific tissue into pluripotent cell colonies and generate human neural cultures as a model system to examine the molecular actions of alcohol.

Methods

Induced pluripotent stem (iPS) cells were generated from skin biopsies taken from 7 individuals, 4 alcohol‐dependent subjects, and 3 social drinkers. We differentiated the iPS cells into neural cultures and characterized them by immunocytochemistry using antibodies for the neuronal marker beta‐III tubulin, glial marker s100β, and synaptic marker synpasin‐1. Electrophysiology was performed to characterize the iPS‐derived neurons and to measure the effects of acute alcohol exposure on the NMDA receptor response in chronically alcohol exposed and nonexposed neural cultures from 1 nonalcoholic. Finally, we examined changes in mRNA expression of the NMDA receptor subunit genes GRIN1, GRIN2A, GRIN2B, and GRIN2D after 7 days of alcohol exposure and after 24‐hour withdrawal from chronic alcohol exposure.

Results

Immunocytochemistry revealed positive staining for neuronal, glial, and synaptic markers. iPS‐derived neurons displayed spontaneous electrical properties and functional ionotropic receptors. Acute alcohol exposure significantly attenuated the NMDA response, an effect that was not observed after 7 days of chronic alcohol exposure. After 7 days of chronic alcohol exposure, there were significant increases in mRNA expression of GRIN1, GRIN2A, and GRIN2D in cultures derived from alcoholic subjects but not in cultures derived from nonalcoholics.

Conclusions

These findings support the potential utility of human iPS‐derived neural cultures as in vitro models to examine the molecular actions of alcohol on human neural cells.
STR Melting Curve Analysis as a Genetic Screening Tool for Crime Scene Samples*
Authors: Nguyen Quang , McKinney Jason , Johnson Donald J. , Roberts Katherine A. , Hardy Winters R.
Published: April 2012

Abstract: In this proof‐of‐concept study, high‐resolution melt curve (HRMC) analysis was investigated as a postquantification screening tool to discriminate human CSF1PO and THO1 genotypes amplified with mini‐STR primers in the presence of SYBR Green or LCGreen Plus dyes. A total of 12 CSF1PO and 11 HUMTHO1 genotypes were analyzed on the LightScanner HR96 and LS‐32 systems and were correctly differentiated based upon their respective melt profiles. Short STR amplicon melt curves were affected by repeat number, and single‐source and mixed DNA samples were additionally differentiated by the formation of heteroduplexes. Melting curves were shown to be unique and reproducible from DNA quantities ranging from 20 to 0.4 ng and distinguished identical from nonidentical genotypes from DNA derived from different biological fluids and compromised samples. Thus, a method is described which can assess both the quantity and the possible probative value of samples without full genotyping.
The Use of Vertebral Osteoarthritis and Osteophytosis in Age Estimation*
Authors: Listi Ginesse A. , Manhein Mary H.
Published: April 2012

Abstract:  Previous research on age and vertebral degenerative change has focused on osteophytosis. The present study expands this research by examining the association between osteoarthritis and osteophytosis and by assessing their relationship to age. Researchers scored the bodies and facets in 104 individuals. Statistical analyses assessed relationships between age and degenerative change for the bodies and facets, both separately and combined, for all vertebrae collectively, and for subcategories of vertebral types. Separate analyses were conducted which included only regions that experience heavier stress loads. Results indicate that osteophytosis and osteoarthritis are not associated with each other for all subcategories of vertebrae. Also, the inclusion of osteoarthritis does not enhance the relationship between age and degenerative change, nor does limiting analyses to areas of heaver stress. Finally, although both conditions are significantly correlated with age, the relationship is not strong enough to yield predictive power for establishing age beyond a general estimate.
Adiposity in 277 young adult male offspring of women with diabetes compared with controls: A Danish population‐based cohort study
Authors: NIELSEN GUNNAR LAUGE , DETHLEFSEN CLAUS , LUNDBYE‐CHRISTENSEN SØREN , PEDERSEN JAN FOG , MØLSTED‐PEDERSEN LARS , GILLMAN MATT W.
Published: April 2012

Objective. To examine the associations of maternal diabetes, overall and stratified according to treatment of diabetes, with weight‐related outcomes at the time of military conscription, at age 18–20 years. Design and setting. Cohort study of 277 Danish male offspring of mothers with recognized pre‐gestational or gestational diabetes. As population‐based controls we selected 870 men matched from the Civil Registration Office. Methods. Data on weight‐related outcomes were retrieved from the Danish military conscription registry. Main outcome measures. Military rejection due to adiposity and body mass index (BMI) at conscription. Results. Army rejection rate due to adiposity was 5.8% (n= 16) among 277 diabetes mellitus‐exposed men compared with 3.1% (n= 27) in 870 controls (risk difference 2.7 (95% confidence interval (CI) −0.3–5.7)) and mean BMI at conscription was 1.4 kg/m2 (95%CI 0.8–2.0) higher among those diabetes mellitus‐exposed men. In analyses adjusted for birthweight and gestational age, compared with controls, the BMI was 0.6 kg/m2 (95%CI −0.3–1.5) higher in sons of mothers with pre‐gestational and 2.7 kg/m2 (95% (CI): 0.9–4.5) higher with gestational diabetes. The greatest BMI difference was in offspring of mothers with gestational diabetes in whom insulin was initiated during pregnancy. We found no difference in conscript height. Conclusions. Compared with controls, male offspring of women with diabetes had a higher rejection rate due to adiposity and higher adult BMI. Subgroup analyses showed that the association was most pronounced in sons of mothers with gestational diabetes, whereas pre‐gestational diabetes was only weakly associated with higher offspring BMI.