bluuebunny/crossref_metadata_2025 huggingface dataset:
Priming third‐party ostracism increases affiliative imitation in children
Authors: Over Harriet , Carpenter Malinda
Published: January 2009

Human beings are intensely social creatures and, as such, devote significant time and energy to creating and maintaining affiliative bonds with group members. Nevertheless, social relations sometimes collapse and individuals experience exclusion from the group. Fortunately for adults, they are able to use behavioral strategies such as mimicry to reduce their social exclusion. Here we test whether children, too, increase their imitation following an experience of ostracism. Given humans’ profound need to belong, we predicted that the mere hint of social exclusion – even third‐party social exclusion – would be sufficient to increase affiliative imitation in 5‐year‐olds. As predicted, children primed with videos in which one shape was ostracized by a group of other shapes subsequently imitated the actions of a model more closely than children in a control condition. These findings highlight just how sensitive humans are to social exclusion and demonstrate that children, like adults, modify their social behavior in response to ostracism.
The Teach‐ins: Anti‐war protest in the Old Stoned Age
Authors: Sahlins Marshall
Published: January 2009

A largely personal as well as anthropological reflection on the 60s teach‐in movement, delivered in a 2008 AAA Session of the Association of Radical Anthropologists, with a view toward reminding us of the differences to the current ‘structure of the conjuncture’ with regard to the Iraq war.
Post‐communist ironies in an East German hotel
Authors: Rethmann Petra
Published: January 2009

On 1 May 2007, a new hotel opened in Berlin: Ostel. As its name implies, it is located in the former East of the city, now ‘Berlin Mitte’. The Ostel joined Berlin's burgeoning hotel scene at a time when Ostalgie ‐ the supposed longing East Germans feel for the past ‐ marked no longer a condition of mourning and loss but had become ‘hip’. In this article to carry the analysis of Ostalgie beyond the themes of trauma or resistance into the more playful dimensions of what Czech‐French writer Milan Kundera (1992) has called ‘the joke,’ that is, an ironic form of humor ubiquitous in former Soviet and East European contexts. I engage irony as a situated experience and practice chiefly through the ‘artful lens’ of material culture. In focusing on the Ostel's interior, I am especially interested in irony's ‘critical edge’. I argue that it is this edge that makes it possible to open up critical interpretations of German post‐unification history.
Assessing the Debate, Assessing the Damage: Transatlantic Relations after Bush
Authors: Dunn David Hastings
Published: January 2009

Transatlantic relations during the Bush administration sank to the lowest point in the post-war period following the invasion of Iraq in 2003. This article provides an analysis of both the current state of that relationship and the academic debate which accompanies it. Arguments over the impact of various factors are analysed to determine the extent of transatlantic divergence. Thus, demographic change in America and Europe, divergence of political values between Europe and America, power differences, post-war geopolitical realignments, European integration and American unilateralism and exceptionalism are all analysed and evaluated. While some of these arguments presented are challenged, the article argues that the process of constructing separate European and American identities from within the transatlantic community is the single most significant contemporary challenge to transatlantic relations.
Securing the Homelands: Transatlantic Co-Operation after Bush
Authors: Rees Wyn
Published: January 2009

Since 9/11, internal security co-operation has grown into a major feature of transatlantic relations. This article seeks to appraise both the achievements of the Bush administration in this field and the prospects for President Obama's period of office. Homeland security has been a new and difficult area of co-operation to foster, yet both sides of the Atlantic have come to recognise their shared interests in working together. The article cautions those European policy-makers who are hoping for a major change in homeland security co-operation under the new president. It is likely that the policies of the new administration will be characterised more by continuity than by change.
Post-Hegemonic Climate Politics?
Authors: Paterson Matthew
Published: January 2009

The article argues that the effects of a new US president on global climate politics will be rather less than might be expected. This is partly because the rhetorical differences between Bush, his predecessor Clinton and President Obama mask great continuities in US climate change politics since the early 1990s. It is also because, unlike in other issue areas, the EU has moved into a position of clear international leadership, which is likely to provoke diplomatic conflict, both for standard reasons of realpolitik but more precisely because of the different growth strategies pursued by each side and the different implications of those strategies for climate policy. Finally, the emergence of a dense pattern of transnational climate governance will increasingly constrain the options for either side in pursuing new climate change agreements after 2012.
The United States, Germany and France: Balancing Transatlantic Relations
Authors: Mahncke Dieter
Published: January 2009

Relations between the United States, France and Germany significantly determine the content and structure of the broader transatlantic relationship. Relations improved after the changes of government in Germany in 2005 and France in 2007, and they can be expected to improve further after the change of administration in the United States in 2009. Washington is likely to pay more attention to its European allies while these may become more involved in issues beyond Europe's borders. Sharing leadership will be the challenge for the United States, while bringing more intellectual and material input will be the challenge for the Europeans. At the same time, France and Germany will develop and maintain independent views. But if partnership is the aim on both sides of the Atlantic, a more promising relationship can be expected even where differences exist.
Natural Compatibilism versus Natural Incompatibilism: Back to the Drawing Board
Authors: FELTZ ADAM , COKELY EDWARD T. , NADELHOFFER THOMAS
Published: January 2009

Abstract:  In the free will literature, some compatibilists and some incompatibilists claim that their views best capture ordinary intuitions concerning free will and moral responsibility. One goal of researchers working in the field of experimental philosophy has been to probe ordinary intuitions in a controlled and systematic way to help resolve these kinds of intuitional stalemates. We contribute to this debate by presenting new data about folk intuitions concerning freedom and responsibility that correct for some of the shortcomings of previous studies. These studies also illustrate some problems that pertain to all of the studies that have been run thus far.
Illocutionary Forces and What Is Said
Authors: KISSINE M.
Published: January 2009

Abstract: A psychologically plausible analysis of the way we assign illocutionary forces to utterances is formulated using a ‘contextualist’ analysis of what is said. The account offered makes use of J. L. Austin’s distinction between phatic acts (sentence meaning), locutionary acts (contextually determined what is said), illocutionary acts, and perolocutionary acts. In order to avoid the conflation between illocutionary and perlocutionary levels, assertive, directive and commissive illocutionary forces are defined in terms of inferential potential with respect to the common ground. Illocutionary forces are conceived as automatic but optional components of the process of interpretation.
Turning on and tuning out: new technology, image, analysis
Authors: Hauke Christopher
Published: January 2009

Abstract:  There was a time when the answer‐phone was thought too alienating for patients; now there is the question of whether therapists feel OK being paid by electronic bank transfer. Since the start of modern psychotherapy, new communications technology—the telephone, radio, TV, and now electronic messaging—have become universally accessible. The question arises: do email, texts and the mobile (cell‐phone) enhance and enable communication or do they merely offer the fantasy of doing so? Equally, can computer simulations and software diagnostic and treatment programmes offer anything to mental health practice? Furthermore, since the mid‐nineteenth century, the technology of visual communication, in particular, paralleled the development of psychodynamic theory and practice. Nowadays, photographic images have become so prevalent and available that clients can bring pictures in many forms. They also bring movies, movie‐scenes and characters, either in description or to show, and these may constitute the images and material of analysis in some cases just as dreams always have done. How are we to respond to these unconventional communications of our clients' emotional lives? Are they legitimate expressions of their inner worlds? This paper discusses the influence of the new technologies of communication with a special focus on the place of film themes and images in psychotherapy and analytic sessions.
The session of the two dreams
Authors: Giannoni Massimo
Published: January 2009

Abstract:  Through the discussion of the clinical material the author tries to show how numerous aspects of traditional Jungian analysis are close to several theoretical and clinical developments of Relational Psychoanalysis. A short introduction about relational psychoanalysis is given. The relational aspects of Jungian theory and praxis are underlined. If we refer to these theoretical constructs, it becomes possible to work in an original way and think of the clinical setting as different from the classical Freudian one, without abandoning Jungian tradition.
Articular chondrocytes express connexin 43 hemichannels and P2 receptors – a putative mechanoreceptor complex involving the primary cilium?
Authors: Knight M. M. , McGlashan S. R. , Garcia M. , Jensen C. G. , Poole C. A.
Published: January 2009

Mechanical loading is essential for the health and homeostasis of articular cartilage, although the fundamental mechanotransduction pathways are unclear. Previous studies have demonstrated that cyclic compression up‐regulates proteoglycan synthesis via an intracellular Ca2+signalling pathway, mediated by the release of ATP. However, the mechanism(s) of ATP release has not been elucidated. The present study examines expression of the putative mechanosensitive ATP‐release channel, connexin 43 and whether it is expressed on the chondrocyte primary cilium, which acts as a mechanosensor in a variety of other cell types. In addition the study characterized the expression of a range of purine receptors through which ATP may activate downstream signalling events controlling cell function. Bovine articular chondrocytes were isolated by sequential enzyme digestion and seeded in agarose constructs. To verify the presence of functional hemichannels, Lucifer yellow (LY) uptake into viable cells was quantified following treatment with a hemichannel agonist (EGTA) and antagonist (flufenamic acid). LY uptake was observed in 45% of chondrocytes, increasing to 83% following EGTA treatment (P < 0.001). Treatment with the hemichannel blocker, flufenamic acid, significantly decreased LY uptake to less than 5% with and without EGTA. Immunofluorescence and confocal microscopy confirmed the presence of primary cilia and the expression of connexin 43. Approximately 50% of bovine chondrocyte primary cilia were decorated with connexin 43. Human chondrocytesin situwithin cartilage explants also expressed connexin 43 hemichannels. However, expression was confined to the upper 200 µm of the tissue closest to the articular surface. Immunofluorescence revealed the expression of a range of P2X and P2Y receptor subtypes within human articular cartilage. In conclusion, the expression of functional hemichannels by articular chondrocytes may represent the mechanism through which mechanical loading activates ATP release as part of a purinergic mechanotransduction pathway. Furthermore, the expression of connexin 43 on the chondrocyte primary cilium suggests the possible involvement of the cilium in this pathway.
Beta‐keratins of turtle shell are glycine‐proline‐tyrosine rich proteins similar to those of crocodilians and birds
Authors: Dalla Valle Luisa , Nardi Alessia , Toni Mattia , Emera Deena , Alibardi Lorenzo
Published: January 2009

This study presents, for the first time, sequences of five beta‐keratin cDNAs from turtle epidermis obtained by means of 5′‐ and 3′‐rapid amplification of cDNA ends (RACE) analyses. The deduced amino acid sequences correspond to distinct glycine‐proline‐serine‐tyrosine rich proteins containing 122–174 amino acids. In situ hybridization shows that beta‐keratin mRNAs are expressed in cells of the differentiating beta‐layers of the shell scutes. Southern blotting analysis reveals that turtle beta‐keratins belong to a well‐conserved multigene family. This result was confirmed by the amplification and sequencing of 13 genomic fragments corresponding to beta‐keratin genes. Like snake, crocodile and avian beta‐keratin genes, turtle beta‐keratins contain an intron that interrupts the 5′‐untranslated region. The length of the intron is variable, ranging from 0.35 to 1.00 kb. One of the sequences obtained from genomic amplifications corresponds to one of the five sequences obtained from cDNA cloning; thus, sequences of a total of 17 turtle beta‐keratins were determined in the present study. The predicted molecular weight of the 17 different deduced proteins range from 11.9 to 17.0 kDa with a predicted isoelectric point of 6.8–8.4; therefore, they are neutral to basic proteins. A central region rich in proline and with beta‐strand conformation shows high conservation with other reptilian and avian beta‐keratins, and it is likely involved in their polymerization. Glycine repeat regions, often containing tyrosine, are localized toward the C‐terminus. Phylogenetic analysis shows that turtle beta‐keratins are more similar to crocodilian and avian beta‐keratins than to those of lizards and snakes.
Energy expenditure during level locomotion in large desert ungulates: the one‐humped camel and the domestic donkey
Authors: Maloiy G. M. O. , Rugangazi B. M. , Rowe M. F.
Published: January 2009

This study sought to quantify the rate of energy expenditure (), the total cost of transport (COTtot) and the net cost of transport (COTnet) in camels Camelus dromedaries and donkeys Equus asinus during level locomotion. of camels and domestic donkeys were measured at exercise speeds between 0 and 4.17 m s−1. Resting for camels was significantly (P<0.05) lower than predicted, while donkeys exhibited resting values similar to mammals of the same body mass. In both camels and donkeys increased in a nearly linear fashion over the range of exercise speeds. The minimum COTtot of camels in the walking and pacing gaits were not significantly different (P=0.27). Similarly, donkeys exhibited no significant difference (P=0.09) in the minimum COTtot while walking and trotting. In both camels and donkeys, the minimum COTtot was significantly (P<0.05) lower than the predicted COTtot for mammals of the same body mass. The COTnet in both camels and donkeys was determined to be gait dependent and significantly (P<0.05) lower than the predicted minimum COTnet values for walking and running. The low COT seen in camels and donkeys results in energy and water savings.
Visual mismatch negativity: New evidence from the equiprobable paradigm
Authors: Kimura Motohiro , Katayama Jun'ichi , Ohira Hideki , Schröger Erich
Published: January 2009

In visual oddball studies, deviant compared to standard stimuli elicited a posterior negative ERP at around 100–250 ms. To determine the underlying processes of the negativity, we used the equiprobable sequence in which bar stimuli of five types of orientation were presented with equal probabilities (control 20% each) as well as the oddball sequence in which two stimuli with the closest orientation were presented with different probabilities (deviant 20% and standard 80%). Deviant compared to standard stimuli elicited two negativities at around 100–150 ms with no hemispheric dominance and 200–250 ms with right hemispheric dominance, while deviant compared to control stimuli elicited only a negativity at around 200–250 ms with right hemispheric dominance. These results suggest that the early negativity reflects refractory effect, while the late negativity reflects memory‐comparison‐based change detection effect (visual mismatch negativity).
Cardiovascular reactivity to psychological stress and carotid intima‐media thickness in children
Authors: Roemmich James. N. , Lobarinas Christina L. , Joseph Parveen N. , Lambiase Maya J. , Archer, III Fred D. , Dorn Joan
Published: January 2009

The relationship between cardiovascular stress reactivity and carotid artery intima‐media thickness (IMT) has been established in adults, but not yet studied in children. Cardiovascular reactivity to an ad lib speech was measured in 20 boys and 20 girls age 11.0 ± 1.4 years. Measures included heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressure reactivity, and mean common carotid artery IMT. Sequential regression analyses were used to establish the incremental increase in R2 for the prediction of IMT due to cardiovascular reactivity independent of age, socioeconomic status, race, percentage body fat, and baseline BP or HR. SBP reactivity (β=0.002, , p<.05), but not DBP reactivity (p=.12) or HR reactivity (p=.82), independently predicted carotid artery IMT. This study provides initial evidence that SBP reactivity is associated with IMT and perhaps the early pathogenesis of cardiovascular disease in childhood.
High maternal vitamin E intake by diet or supplements is associated with congenital heart defects in the offspring
Authors: Smedts HPM , de Vries JH , Rakhshandehroo M , Wildhagen MF , Verkleij‐Hagoort AC , Steegers EA , Steegers‐Theunissen RPM
Published: January 2009

Objective  To study associations between maternal dietary and supplement intake of antioxidants vitamin E, retinol and congenital heart defects (CHDs).

Design  Case–control study.

Setting  Erasmus MC, University Medical Center Rotterdam, the Netherlands.

Population  Participants were 276 case mothers of a child with CHD and 324 control mothers with their children.

Methods  Food frequency questionnaires covering the intake of the previous 4 weeks were filled out at 16 months after the index pregnancy. Data were compared between cases and controls using the Mann–Whitney U test. Risk estimates for the association between CHD and dietary intake of vitamin E and retinol were estimated in a multivariable logistic regression model.

Main outcome measures  Medians (5–95th percentile) and odds ratios with 95% CI.

Results  Dietary vitamin E intake was higher in case mothers than in controls, 13.3 (8.1–20.4) and 12.6 (8.5–19.8) mg/day (P= 0.05). CHD risk increased with rising dietary vitamin E intakes (P‐trend = 0.01). Periconception use of vitamin E supplements in addition to a high dietary vitamin E intake above 14.9 mg/day up to nine‐fold increased CHD risk. Retinol intakes were not significantly different between the groups and not associated with CHD risk.

Conclusions  High maternal vitamin E by diet and supplements is associated with an increased risk of CHD offspring.
Two mifepristone doses and two intervals of misoprostol administration for termination of early pregnancy: a randomised factorial controlled equivalence trial*
Authors: von Hertzen H , Piaggio G , Wojdyla D , Marions L , My Huong NT , Tang OS , Fang AH , Wu SC , Kalmar L , Mittal S , Erdenetungalag R , Horga M , Pretnar‐Darovec A , Kapamadzija A , Dickson K , Anh ND , Tai NV , Tuyet HTD , Peregoudov A ,   WHO Research Group on Post‐ovulatory Methods of Fertility Regulation
Published: January 2009

Objective  To compare the efficacy of 100 mg and 200 mg of mifepristone and 24‐ and 48‐hour intervals to administration of 800μg vaginal misoprostol for termination of early pregnancy.

Design  Placebo‐controlled, randomized, equivalence trial, stratified by centre.

Setting  13 departments of obstetrics and gynecology in nine countries.

Population  2181 women with 63 days or less gestation requesting medical abortion.

Methods  Two‐sided 95% CI for the risk differences of failure to complete abortion were calculated and compared with 5% equivalence margin between two doses of mifepristone and two intervals to misoprostol administration. Proportions of women with adverse effects were compared between the regimens using standard testes for proportions.

Outcome measures  Rates of complete abortion without surgical intervention and adverse effects associated with the regimens.

Results  Efficacy outcome was analysed for 2126 women (97.5%) excluding 55 lost to follow up. Both mifepristone doses were found to be similar in efficacy. The rate of complete abortion was 92.0% for women assigned 100 mg of mifepristone and 93.2% for women assigned 200 mg of mifepristone (difference 1.2%, 95% CI: –1.0 to 3.5). Equivalence was also evident for the two intervals of administration: the rate of complete abortion was 93.5% for 24‐hour interval and 91.7% for the 48‐hour interval (difference −1.8%, 95% CI: –4.0 to 0.5). Interaction between doses and interval to misoprostol administration was not significant (P = 0.92). Adverse effects related to treatments did not differ between the groups.

Conclusions  Both the 100 and 200 mg doses of mifepristone and the 24‐ and 48‐hour intervals have a similar efficacy to achieve complete abortion in early pregnancy when mifepristone is followed by 800 micrograms of vaginally administered misoprostol.
The effect of maternal alcohol consumption on fetal growth and preterm birth
Authors: O’Leary CM , Nassar N , Kurinczuk JJ , Bower C
Published: January 2009

Objective  To investigate the relationship between prenatal alcohol exposure and fetal growth and preterm birth and to estimate the effect of dose and timing of alcohol exposure in pregnancy.

Design  A population‐based cohort study linked to birth information on the Western Australian Midwives Notification System.

Setting  Western Australia.

Population  A 10% random sample of births restricted to nonindigenous women who had delivered a singleton infant (n= 4719) in 1995–1997.

Methods  The impact of alcohol consumption in pregnancy on fetal growth (small‐for‐gestational‐age [SGA] and large‐for‐gestational‐age infants [LGA]) and preterm birth (<37 weeks of gestation) was assessed using multivariate logistic regression analysis and adjusting for confounding factors.

Main outcome measures  Odds ratios and 95% CI, attributable risk, and population attributable risk were calculated.

Results  The percentage of SGA infants and preterm birth increased with higher levels of prenatal alcohol exposure; however, the association between alcohol intake and SGA infants was attenuated after adjustment for maternal smoking. Low levels of prenatal alcohol were not associated with preterm birth; however, binge drinking resulted in a nonsignificant increase in odds. Preterm birth was associated with moderate and higher levels of prenatal alcohol consumption for the group of women who ceased drinking before the second trimester. This group of women was significantly more likely to deliver a preterm infant than women who abstained from alcohol (adjusted OR 1.73 [95% CI 1.01–3.14]).

Conclusions  Alcohol intake at higher levels, particularly heavy and binge drinking patterns, is associated with increased risk of preterm birth even when drinking is ceased before the second trimester. This finding, however, is based on small numbers and needs further investigation. Dose and timing of prenatal alcohol exposure appears to affect preterm delivery and should be considered in future research and health education.
Use of povidone–iodine during the first trimester of pregnancy: a correct practice?
Authors: Velasco I , Naranjo S , López‐Pedrera C , Garriga MJ , García‐Fuentes E , Soriguer F
Published: January 2009

Povidone–iodine (PVP‐I) has been widely used as an antiseptic agent during invasive procedures for prenatal diagnosis. Women have been reported of thyroid dysfunction after simple exposure to PVP‐I. We studied the effect on thyroid function and urinary iodine excretion after a single topical application of PVP‐I in 31 women who had a miscarriage during the first trimester of pregnancy. PVP‐I is absorbed through the skin and the vaginal mucosa, resulting in a sudden increase in the urinary excretion of iodine and a short‐term variation in concentrations of thyroid hormones in maternal serum. This metabolic effect could have consequences for the embryo and the fetus during crucial stages of development.
Pain behaviour and pain intensity in older persons with severe dementia: reliability of the MOBID Pain Scale by video uptake
Authors: Husebo Bettina S. , Strand Liv I. , Moe‐Nilssen Rolf , Husebo Stein B. , Ljunggren Anne E.
Published: January 2009

Advancing age is associated with high prevalence of dementia, often combined with under‐diagnosed and under‐treated pain. A nurse‐administered assessment tool has been developed to unmask pain during standardised, guided movements, called Mobilisation–Observation–Behaviour–Intensity–Dementia (MOBID) Pain Scale. The aim was to examine intra‐ and inter‐rater reliability of pain behaviour indicators, inferred pain intensity, and the overall MOBID Pain Score. Twenty‐six nursing home patients with severe dementia and chronic pain, 11 primary caregivers and three external raters at the Red Cross Nursing Home, Bergen were included. During video uptake the patients were guided by their primary caregivers to standardised movements of different body parts. Pain behaviour indicators (pain noises, facial expression and defence) were registered for each movement with subsequent rating of pain intensity by external raters, who assessed and scored the videos concurrently and independently at day 1, 4 and 8. Facial expression was most commonly observed, followed by pain noises and defence. Repeated assessments increased the number of observed pain behaviours, but did not improve reliability. Inter‐rater reliability was highest for noises, followed by defence and facial expression (κ = 0.44–0.92, κ = 0.10–0.76 and κ = 0.05–0.76 respectively, at day 8). Mobilisation of arms and legs were rated most painful. Intra‐ and inter‐rater reliability of overall pain were very good [intraclass correlation coefficient (1,1) ranging 0.92–0.97 and 0.94–0.96 respectively, at day 8]. Reliability of pain intensity scores tended to increase by repeated assessment. Using video uptake, MOBID Pain Scale was shown to be sufficiently reliable to assess pain in older persons with severe dementia.
The lively process of interdisciplinarity
Authors: Buller Henry
Published: January 2009

Food chain research offers particular opportunities for the development of interdisciplinary problematics and approaches. For example, the issue of ‘quality’ cannot be interpreted solely from natural or from social science perspectives but rather requires a consilient and interdisciplinary vision. Suggesting a ‘ground upwards’ approach, building upon transitional objects and networks of practice and drawing upon a recently completed research project involving natural and social science research teams, this paper considers the practice and performance of interdisciplinarity as a lively process of knowledge creation that operates within what Luhmann calls ‘forums of articulation’ through which epistemologically mobile socio‐natural entities are defined and explored.
Potent anti‐inflammatory effects of two quinolinedione compounds, OQ1 and OQ21, mediated by dual inhibition of inducible NO synthase and cyclooxygenase‐2
Authors: Lim Kyung‐Min , Lee Joo‐Young , Lee Song‐Mi , Bae Ok‐Nam , Noh Ji‐Yoon , Kim Eun‐Jin , Chung Seung‐Min , Chung Jin‐Ho
Published: January 2009

Background and purpose:  Inducible nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX‐2) have been suggested as key components in various inflammatory diseases. Here we examined the effects of new quinolinedione derivatives, 6‐(4‐fluorophenyl)‐amino‐5,8‐quinolinedione (OQ1) and 6‐(2,3,4‐trifluorophenyl)‐amino‐5,8‐quinolinedione (OQ21) on activity and expression of iNOS and COX‐2 to explore their anti‐inflammatory properties.

Experimental approach:  The effects of OQ1 and OQ21 were assessed on lipopolysaccharide (LPS)‐induced iNOS and COX‐2 in murine macrophage cell line (RAW264.7), along with isolated enzyme assays to measure enzyme inhibition. Nuclear factor‐κB (NFκB) activation pathways were investigated to elucidate mechanisms underlying OQ‐mediated suppression of the expression of iNOS and COX‐2. In vivo anti‐inflammatory activities of OQ compounds were evaluated in mouse ear oedema, induced by topical 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA).

Key results:  LPS‐induced NO production in RAW264.7 cells was inhibited by OQ1 and OQ21 through the attenuation of iNOS expression as well as iNOS activity. Down‐regulation of iNOS followed blocking of NFκB activation, as assessed by inhibitory κB degradation and electrophoretic mobility shift assay for NFκB. Synthesis and accumulation of prostaglandin E2 were also suppressed by OQ1 and OQ21. LPS‐induced COX‐2 expression and cellular COX‐2 activities were attenuated by OQ1 and OQ21. Consistent with these results, OQ1 showed potent anti‐inflammatory effects in mouse ear oedema induced by TPA.

Conclusions and implications:  The novel quinolinedione derivatives, OQ1 and OQ21, showed potent anti‐inflammatory activity through dual inhibitory effects on iNOS and COX‐2, suggesting that OQ derivatives might provide a new therapeutic modality for chronic inflammatory diseases, refractory to conventional drug therapies.
How to use virological tools for optimal management of chronic hepatitis C
Authors: Chevaliez Stéphane , Pawlotsky Jean‐Michel
Published: January 2009

Chronic hepatitis C is a global health problem that may cause cirrhosis and progression to hepatocellular carcinoma. Currently available antiviral treatments are moderately effective. Several virological assays are available to help diagnose and manage patients infected with the hepatitis C virus (HCV). These include the anti‐HCV antibody assays, measurement of HCV RNA viral load and HCV genotyping. HCV RNA can be assayed by two types of molecular biology‐based techniques: target amplification as in polymerase chain reaction methods and signal amplification such as the branched DNA assay. Monitoring of viral kinetics during the early phases of antiviral treatment is crucial in making treatment decisions such as early stopping rules and also in optimizing the length of treatment. The HCV genotype can be determined by several methods. Whatever the method, pretreatment determination allows treatment length and ribavirin dose to be optimized and also offers prognostic information on treatment outcomes as certain genotypes respond more favourably to treatment. Thus, virological assays are indispensable in the diagnosis and management of individuals infected with the HCV.
Treatment of HBeAg‐positive patients with nucleos/tide analogues
Authors: Coffin Carla S. , Lee Samuel S.
Published: January 2009

The two main goals of hepatitis B therapy are durable viral suppression and avoidance of antiviral resistance. Recent treatment guidelines now recognize the importance of these treatment endpoints in the prevention of end‐stage liver disease and hepatocellular carcinoma rather then other surrogate markers such as HBeAg seroconversion and serum alanine aminotransferase normalization, especially in patients who acquired hepatitis B virus infection early in life. A variety of therapeutic options are now available for the treatment of chronic hepatitis B infection, including four nucleos/tide analogues (i.e lamivudine, adefovir, entecavir and telbivudine), along with standard and pegylated interferon. Newer oral nucleos/tide analogues that include tenofovir, emtricitabine and clevudine are soon likely to be approved worldwide. Given the wide array of choices and the complex nature of chronic hepatitis B infection, selection of the appropriate therapeutic agent can be challenging for clinicians. Effective treatment decisions require an understanding of the natural history of hepatitis B and knowledge of its life cycle and molecular biology. This review includes the range of treatment options and criteria for determining when and how to most effectively intervene with antiviral therapy for chronically infected patients positive for the HBeAg.
What future for ribavirin?
Authors: Shiffman Mitchell L.
Published: January 2009

The optimal therapy for patients with the chronic hepatitis C virus (HCV) is a combination of peginterferon and ribavirin. Treating HCV without ribavirin or prematurely discontinuing, frequently missing doses of ribavirin is associated with a significant decline in virological response, and an increase in both breakthrough viraemia and relapse. The major limitation of ribavirin is adverse events, the most common of which is haemolytic anaemia. Haemolysis is modest when ribavirin is utilized as monotherapy, but is significantly increased when combined with interferon or peginterferon. For these reasons, attempts to replace ribavirin with a less toxic alternative have been advanced. Unfortunately, even when ribavirin is replaced by a potent protease inhibitor, relapse is significantly increased and SVR is reduced. The future of HCV treatment is to combine peginterferon and ribavirin with several protease and/or polymerase inhibitors. Whether this strategy will allow ribavirin to be removed from the treatment paradigm remains to be proven. However, based on the results of clinical trials conducted to date, it is much more likely that peginterferon, not ribavirin, could be expendable.
Hepatitis D: the comeback?
Authors: Rizzetto Mario
Published: January 2009

Hepatitis D virus (HDV) infection has considerably diminished in Europe since the 1970–1980s. The prevalence rates of chronic hepatitis D in HBsAg carriers in Italy have declined from 25% at the beginning of the 1980s to 8% in the 1990s. Similar declines in prevalence have been reported in Spain, Taiwan and Turkey. Better public health standards, HBV vaccination and the effect of measures to control the spread of human immunodeficiency virus have brought about a decline in the numbers of HBsAg carriers and therefore a decline in the HBV‐dependent HDV. However, HDV has not declined further in Europe in the last decade, as the pool of fresh infections in migrants from HDV‐endemic areas is counterbalancing the shrinking cohort of long‐standing domestic infections acquired in the epidemic of the 1970–1980s. Hepatitis D remains an important health problem outside Europe, and new foci of infection continue to be identified in developing countries.
Screening and diagnosis of hepatocellular carcinoma
Authors: Colombo Massimo
Published: January 2009

Early diagnosis of hepatocellular carcinoma (HCC) is feasible because HCC develops in the background of well‐known, readily identifiable and potentially avoidable environmental risk factors. According to the American Association for the Study of the Liver Diseases and the European Association for the Study of the Liver, patients with cirrhosis and carriers of chronic viral hepatitis are the target of surveillance to be investigated with abdominal ultrasounds (US) every 6 or 12 months. The diagnostic confirmation of a ≥2 cm nodule in patients with cirrhosis detected during surveillance is possible with any imaging technique among second‐generation contrast US, contrast computed tomography and gadolinium‐contrast magnetic resonance imaging. HCC shows an early hyperenhanced arterial vascularization, followed by enhanced hypoattenuation (wash‐out) in the late phase of imaging. In patients with a ≤2 cm nodule, two imaging techniques are required for the final diagnosis, which, however, have a relatively low diagnostic sensitivity (33%). Nodules with negative imaging findings need to be investigated further with an echo‐guided liver biopsy or enhanced follow‐up with imaging (every 3 months) to reach a final diagnosis. The cost‐effectiveness ratio of surveillance depends on multiple factors, like HCC incidence, the cost and accuracy of diagnostic tests and the costs and outcome of the therapeutic interventions.
What are the comorbidities influencing the management of patients and the response to therapy in chronic hepatitis C?
Authors: Alberti Alfredo
Published: January 2009

The natural history of chronic hepatitis C has been defined in several retrospective and prospective studies conducted in the last 20 years. These studies have clearly demonstrated that the outcome of chronic hepatitis C virus infection is profoundly influenced by a variety of cofactors and comorbidities. Many of the cofactors that affect the course of liver disease in hepatitis C also have a significant influence on the result of antiviral therapy. Unfortunately, comorbidities that have been shown to negatively influence the course and outcome of liver disease often reduce the chance of achieving a sustained virological response with pegylated interferon (PEG‐IFN) and ribavirin treatment. The most important and frequent comorbidity influencing the course of chronic hepatitis C and the response to antiviral therapy is represented by the metabolic syndrome, and by the associated state of insulin resistance. Other comorbidities that have a negative influence on the progression of hepatitis C and on the response to antiviral therapy include excess alcohol intake, human immunodeficiency virus and hepatitis B virus co‐infection and a number of conditions that reduce the benefit of therapy by affecting negatively compliance and/or adherence to adequate PEG‐IFN or ribavirin doses.
Ten Years of Rizatriptan: From Development to Clinical Science and Future Directions
Authors: Hargreaves Richard J. , Lines Chris R. , Rapoport Alan M. , Ho Tony W. , Sheftell Fred D.
Published: January 2009

The year 2008 marked the 10th anniversary since rizatriptan was first launched for the acute treatment of migraine. In this article we discuss the concepts that motivated the preclinical and clinical development of rizatriptan, the clinical evidence that has driven its use over the past decade, rizatriptan's overall contribution to the field, and future directions for research.
Moving Forward – Essential Questions for the Next 10 Years
Authors: Lipton Richard B. , Sheftell Fred D.
Published: January 2009

The future is bright for migraine sufferers. For acute treatment, CGRP antagonists and combination products will provide more complete, longer lasting, and safer relief. “Designer drugs” for migraine prevention will be identified based on their ability to block cortical spreading depression and will improve migraine treatment. Genetic and environmental risk factors that promote migraine progression will be identified and preventing progression will become a standard goal in treatment. Some of the devices intended to treat migraine will be approved and will provide important options for sufferers seeking to avoid drugs. Clinical trials that evaluate behavioral and pharmacologic interventions and their impact on patient centered outcomes will emerge. The emergence of novel treatments, when coupled with strategies for individualizing and optimizing treatment while maximizing adherence, will result in ever improving patient outcomes.
Intrahippocampal infusion of botulinum neurotoxin E (BoNT/E) reduces spontaneous recurrent seizures in a mouse model of mesial temporal lobe epilepsy
Authors: Antonucci Flavia , Bozzi Yuri , Caleo Matteo
Published: January 2009

Mesial temporal lobe epilepsy (MTLE) is one of the most common forms of human epilepsy, and it is often resistant to conventional antiepileptic drug (AED) therapy. Here we tested whether a single intrahippocampal administration of the synaptic blocker botulinum neurotoxin E (BoNT/E) is effective in reducing spontaneous recurrent seizures (SRS) in a mouse model of MTLE. Unilateral intrahippocampal injection of kainic acid (KA) in mice was used as a model of MTLE. Electroencephalography (EEG) recordings of SRS were performed during the chronic phase of epilepsy, before and after administration of either BoNT/E or vehicle. Frequency of SRS was significantly decreased for at least 5 days following BoNT/E, but not vehicle, infusion. Our findings demonstrate that BoNT/E can effectively reduce seizure incidence in a mouse model of MTLE.
Blood–brain barrier damage and brain penetration of antiepileptic drugs: Role of serum proteins and brain edema
Authors: Marchi Nicola , Betto Giulia , Fazio Vincent , Fan Quinyuan , Ghosh Chaitali , Machado Andre , Janigro Damir
Published: January 2009

Purpose:  Increased blood–brain barrier (BBB) permeability is radiologically detectable in regions affected by drug‐resistant epileptogenic lesions. Brain penetration of antiepileptic drugs (AEDs) may be affected by BBB damage. We studied the effects of BBB damage on brain distribution of hydrophilic [deoxy‐glucose (DOG) and sucrose] and lipophilic (phenytoin and diazepam) molecules. We tested the hypothesis that lipophilic and hydrophilic drug distribution is differentially affected by BBB damage.

Methods:  In vivo BBB disruption (BBBD) was performed in rats by intracarotid injection of hyperosmotic mannitol. Drugs (H3‐sucrose, 3H‐deoxy‐glucose, 14C‐phenytoin, and C14‐diazepam) or unlabeled phenytoin was measured and correlated to brain water content and protein extravasation. In vitro hippocampal slices were exposed to different osmolarities; drug penetration and water content were assessed by analytic and densitometric methods, respectively.

Results:  BBBD resulted in extravasation of serum protein and radiolabeled drugs, but was associated with no significant change in brain water. Large shifts in water content in brain slices in vitro caused a small effect on drug penetration. In both cases, total drug permeability increase was greater for lipophilic than hydrophilic compounds. BBBD reduced the amount of free phenytoin in the brain.

Discussion:  After BBBD, drug binding to protein is the main controller of total brain drug accumulation. Osmotic BBBD increased serum protein extravasation and reduced free phenytoin brain levels. These results underlie the importance of brain environment and BBB integrity in determining drug distribution to the brain. If confirmed in drug‐resistant models, these mechanisms could contribute to drug brain distribution in refractory epilepsies.
Decreased cerebrospinal fluid hypocretin‐1 (orexin A) in patients after repetitive generalized tonic–clonic seizures
Authors: Rejdak Konrad , Papuć Ewa , Grieb Paweł , Stelmasiak Zbigniew
Published: January 2009

The effects of seizures on the hypocretin/orexin system have not yet been investigated in epileptic patients. The present study aimed to assay hypocretin‐1 in the cerebrospinal fluid (CSF) of patients after generalized tonic–clonic (GTC) seizures. Study groups consisted of 21 patients after GTC seizures and 19 controls. Diagnostic lumbar puncture was performed in control and epileptic patients within 48 h after the GTC seizures. Hypocretin‐1 levels were measured in unextracted CSF samples, using a standardized commercial radioimmunoassay. There was a significant overall difference in median CSF hypocretin‐1 concentrations between controls and patients with GTC patients (p < 0.001). The lowest concentrations were noted in a subgroup of patients with repetitive GTC seizures (RS) compared to those with a single GTC seizure (SS) (p > 0.05) or controls (p < 0.001). The current results suggest that the hypocretin‐1 system deficiency contributes to the complex pathophysiology of repetitive GTC seizures and status epilepticus (SE) and could be associated with typical somnolence after seizure attacks.
Duration of refractory status epilepticus and outcome: Loss of prognostic utility after several hours
Authors: Drislane Frank W. , Blum Andrew S. , Lopez Maria R. , Gautam Shiva , Schomer Donald L.
Published: January 2009

Purpose:  Outcome for patients with status epilepticus (SE) depends strongly on etiology. Duration of SE is also predictive, at least in the first 2 h, but beyond this it is unclear that duration of SE influences outcome significantly. We sought to determine the influence of duration of SE on outcome in patients with prolonged SE, and to compare this influence with that of other factors.

Methods:  We reviewed the clinical course and outcome of 119 patients with SE, diagnosed by both clinical manifestations and electroencephalography (EEG) evidence. Using univariate and multivariate analyses, we sought predictors of outcome (survival vs. death or vegetative state) among age, etiology (epilepsy, anoxia or severe hypoxia, or other), presence of earlier epilepsy, multiple medical problems, presentation in coma, and type of SE (focal or generalized).

Results:  Median duration of SE was 48 h. Survival was greater with a shorter duration, especially when <10 h (69% vs. 31% for longer duration; p < 0.05). Epilepsy as the etiology, and an earlier diagnosis of epilepsy offered a favorable prognosis (p < 0.01), but only the former on multivariate analysis. Coma and SE caused by anoxia/hypoxia were unfavorable factors. Once corrected for etiology, presentation in coma, and type of SE (focal or generalized), duration of SE did not have a significant effect on outcome. Overall mortality was high, 65%, but 10 patients survived SE lasting over 3.5 days.

Conclusions:  A duration of <10 h was associated with better outcome in SE, but this was not significant once etiology, presentation in coma, and type of SE were accounted for. Etiology of SE is still the primary determinant of outcome. Unless it follows anoxia, prolonged SE should not be considered a hopeless condition.
A Practice‐Based Intervention to Improve Primary Care for Falls, Urinary Incontinence, and Dementia
Authors: Wenger Neil S. , Roth Carol P. , Shekelle Paul G. , Young Roy T. , Solomon David H. , Kamberg Caren J. , Chang John T. , Louie Rachel , Higashi Takahiro , MacLean Catherine H. , Adams John , Min Lillian C. , Ransohoff Kurt , Hoffing Marc , Reuben David B.
Published: January 2009

OBJECTIVES: To determine whether a practice‐based intervention can improve care for falls, urinary incontinence, and cognitive impairment.

DESIGN: Controlled trial.

SETTING: Two community medical groups.

PARTICIPANTS: Community‐dwelling patients (357 at intervention sites and 287 at control sites) aged 75 and older identified as having difficulty with falls, incontinence, or cognitive impairment.

INTERVENTION: Intervention and control practices received condition case‐finding, but only intervention practices received a multicomponent practice‐change intervention.

MEASUREMENTS: Percentage of quality indicators satisfied measured using a 13‐month medical record abstraction.

RESULTS: Before the intervention, the quality of care was the same in intervention and control groups. Screening tripled the number of patients identified as needing care for falls, incontinence, or cognitive impairment. During the intervention, overall care for the three conditions was better in the intervention than the control group (41%, 95% confidence interval (CI)=35–46% vs 25%, 95% CI=20–30%, P<.001). Intervention group patients received better care for falls (44% vs 23%, P<.001) and incontinence (37% vs 22%, P<.001) but not for cognitive impairment (44% vs 41%, P=.67) than control group patients. The intervention was more effective for conditions identified by screening than for conditions identified through usual care.

CONCLUSION: A practice‐based intervention integrated into usual clinical care can improve primary care for falls and urinary incontinence, although even with the intervention, less than half of the recommended care for these conditions was provided. More‐intensive interventions, such as embedding intervention components into an electronic medical record, will be needed to adequately improve care for falls and incontinence.