bluuebunny/crossref_metadata_2025 huggingface dataset:
Mutually exclusive interactions drive handover of mRNA from export adaptors to TAP
Authors: Hautbergue Guillaume M. , Hung Ming-Lung , Golovanov Alexander P. , Lian Lu-Yun , Wilson Stuart A.
Published: March 2008

Adaptor proteins stimulate the nuclear export of mRNA, but their mechanism of action remains unclear. Here, we show that REF/ALY binds mRNA; but upon formation of a ternary complex with TAP the RNA is transferred from REF to TAP, and overexpression of TAP displaces REF from mRNA
in vivo
. RNA is also handed over from two other adaptors, 9G8 and SRp20 to TAP upon formation of a ternary complex. Interestingly, the RNA-binding affinity of TAP is enhanced 4-fold
in vitro
once it is complexed with REF. 9G8 and SRp20 also enhance the TAP RNA-binding activity
in vitro
. Consistent with a model in which TAP directly binds mRNA handed over from adaptors during export, we show that TAP binds mRNA
in vivo
by an arginine-rich motif in its N-terminal domain. The importance of direct TAP–mRNA interactions is confirmed by the observation that a mutant form of TAP that fails to bind mRNA but retains the ability to bind REF does not function in mRNA export.
The vitamin D receptor is required for iNKT cell development
Authors: Yu Sanhong , Cantorna Margherita T.
Published: March 2008

CD1d-reactive natural killer T (NKT) cells with an invariant T cell receptor Vα14 rearrangement are a unique subset of lymphocytes, which play important roles in immune regulation, tumor surveillance, and host defense against pathogens. Vitamin D is a nutrient/hormone that has been shown to regulate conventional T cell responses but not T cell development. The data show that expression of the vitamin D receptor (VDR) is required for normal development and function of iNKT cells. The iNKT cells from VDR KO mice are intrinsically defective and lack T-bet expression. VDR KO iNKT cells fail to express NK1.1, although they express normal levels of CD122. Extrinsic factors that impact iNKT cell development and function in VDR KO mice include a failure of the liver to support homeostatic proliferation and reduced thymic expression of CD1d and other factors important for optimal antigen presentation in the thymus. In addition, VDR KO iNKT cells were intrinsically defective even when WT antigen-presenting cells were used to stimulate them.
Circumstances of first crystal methamphetamine use and initiation of injection drug use among high‐risk youth
Authors: WOOD EVAN , STOLTZ JO‐ANNE , ZHANG RUTH , STRATHDEE STEFFANIE A. , MONTANER JULIO S. G. , KERR THOMAS
Published: March 2008

Background. Despite the widely noted increase in crystal methamphetamine (CM) use, there are few studies on circumstances of first CM use or correlates of use among high‐risk populations (e.g. street‐involved youth). Methods. Street‐involved youth in Vancouver, Canada, were enrolled in the At‐Risk Youth Study (ARYS) prospective cohort. Extensive outreach produced a representative sample of Vancouver street youth who use illicit drugs. We examined circumstances of first CM use and factors associated with CM use among the cohort. Results. Among 478 participants, 339 (70.9%) had used CM previously. Despite intensive covariate adjustment, a history of CM use was associated independently with having initiated injection drug use [OR = 3.15 (95% CI: 1.89–5.2); p < 0.001]. Among those who had used CM, route of first administration included: 11 (3.2%) oral ingestion; 25 (7.4%) injected; 105 (31.0%) snorted; 231 (68.1%) smoked. The proportion of respondents reporting current CM injection was significantly greater than the proportion reporting injection as the route for first CM use (18.3% vs. 7.4%; McNemar's test p < 0.001). Ability to obtain CM the first time was reported as ‘very easy’ or ‘easy’ by 93.5% and 5.3% of participants, respectively. Conclusions. Crystal methamphetamine use was independently associated with injection drug use, and significant increases in injecting as the primary mode of administration were observed when patterns of use were considered longitudinally. The easy accessibility of CM and its common use during transition into injection drug use demonstrate the need for innovative drug policy to address this growing concern.
Major physical and psychological harms of methamphetamine use
Authors: DARKE SHANE , KAYE SHARLENE , McKETIN REBECCA , DUFLOU JOHAN
Published: March 2008

Issues. The major physical and psychological health effects of methamphetamine use, and the factors associated with such harms. Approach. Comprehensive review. Key Findings. Physical harms reviewed included toxicity and mortality, cardiovascular/cerebrovascular pathology, dependence and blood‐borne virus transmission. Psychological harms include methamphetamine psychosis, depression, suicide, anxiety and violent behaviours. Implications. While high‐profile health consequences, such as psychosis, are given prominence in the public debate, the negative sequelae extend far beyond this. This is a drug class that causes serious heart disease, has serious dependence liability and high rates of suicidal behaviours. Conclusion. The current public image of methamphetamine does not portray adequately the extensive, and in many cases insidious, harms caused.
A placebo‐controlled trial of mirtazapine for the management of methamphetamine withdrawal
Authors: CRUICKSHANK CHRISTOPHER C. , MONTEBELLO MARK E. , DYER KYLE R. , QUIGLEY ALLAN , BLASZCZYK JOZEF , TOMKINS SALLY , SHAND DIANA
Published: March 2008

Introduction and Aims. As an antidepressant with sedative and anxiolytic properties, mirtazapine may be an appropriate pharmacotherapy for methamphetamine withdrawal. This study sought to examine whether mirtazapine improves retention and alleviates methamphetamine withdrawal symptoms in an out‐patient setting. Design and Methods. An out‐patient double‐blind, randomised placebo‐controlled trial of mirtazapine for the treatment of methamphetamine withdrawal was conducted (15 mg nocte for 2 days, 30 mg nocte for 12 days). Both groups were offered narrative therapy counselling. Measures recorded on days 0, 3, 7, 14 and 35 included: treatment retention, Amphetamine Cessation Symptoms Assessment, the Athens Insomnia Scale, the Brief Symptom Inventory, the Depression–Anxiety–Stress Scale (DASS), Severity of Dependence scale and the Opiate Treatment Index Drug Use subscale. Results. Thirty‐one participants were recruited (18 placebo, 13 mirtazapine) and 52% completed the 2‐week medication phase. No significant differences between the mirtazapine and placebo groups in retention, or any symptom measure were observed, except greater DASS–anxiety and longer sleep duration were measured at baseline among the mirtazapine group. Discussion and Conclusions. Results suggest that mirtazapine does not facilitate retention or recruitment in out‐patient methamphetamine withdrawal treatment, although recruitment may have been insufficient to identify a significant treatment effect. The potential role of narrative therapy for methamphetamine dependent patients deserves further exploration.
Deliquescence and Efflorescence Processes of Aerosol Particles Studied byin situFTIR and Raman Spectroscopy
Authors: Zhao Li-jun , Wang Feng , Zhang Kun , Zeng Qing-xuan , Zhang Yun-hong
Published: March 2008

Deliquescence and efflorescence are the two most important physicochemical processes of aerosol particles. In deliquescence and efflorescence cycles of aerosol particles, many fundamental problems need to be investigated in detail on the molecular level, including ion and molecule interactions in supersaturated aerosols, metastable solid phases that may be formed, and microscopic structures and deliquescence mechanisms of aerosol particles. This paper presents a summary of the progress made in recent investigations of deliquescence and efflorescence processes of aerosol particles by four common spectral techniques, which are known as Raman/electrodynamic balance, Fourier transform infrared/aerosol flow tube, Fourier transform infrared/attenuated total reflection, and confocal Raman on a quartz substrate.
Photodissociation Exploration for Near-Visible UV Absorption of Molecular Bromine
Authors: Zhang Dong-fang , Zhang Bing
Published: March 2008

The photodissociation of Br2 was investigated within the near-visible UV absorption band. Based on the potential curves for the ground and low-lying excited states, the optical cross-sections for the discrete transitions of C1u, B3+0u, A31uX1+g and their total energy absorption spectrum are derived, and the quantum yield of (Br + Br*) channel are determined correspondingly. The one-dimensional LandauZener model is used to evaluate the behavior of curve crossing during photodissociation. The results indicate that the influence of nonadiabatic mechanism, which may be caused by the electronic-vibrational interplay between the B and C states, is negligibly small for the (Br + Br*), channel. From the LandauZener modeling of the observed product recoil parameter (Br+Br), the best-fit value of the coupling matrix element or coupling strength between the diabatic B and C state potentials is obtained.
Enhancement in Magnetorheological Effect of Magnetorheological Elastomers by Surface Modification of Iron Particles
Authors: Jiang Wan-quan , Yao Jing-jing , Gong Xing-long , Chen Lin
Published: March 2008

In order to obtain magnetorheological (MR) elastomers with high magnetorheological effect, a family of anisotropic rubber-based MR elastomers was developed using a new form of chemical modification. Three different kinds of surfactants, i.e. anionic, nonionic and compound surfactants, were employed separately to modify iron particles. The MR effect was evaluated by measuring the dynamic shear modulus of MR elastomer with a magneto-combined dynamic mechanical analyzer. Results show that the relative MR effect can be up to 188% when the iron particles are modified with 15% Span 80. Besides the surface activity of Span 80, however, such high modifying effect is partly due to the plasticizing effect of Span 80. Compared with the single surfactant, the superior surface activity of compound surfactant makes the relative MR effect reach 77% at a low content of 0.4%. Scanning electron microscope observation shows that the modification of compound surfactant results in perfect compatibility between particles and rubber matrix and special self-assembled structure of particles. Such special structure has been proved beneficial to the improvement of the relative MR effect.
Bayesian inference of the sites of perturbations in metabolic pathways via Markov chain Monte Carlo
Authors: Jayawardhana Bayu , Kell Douglas B. , Rattray Magnus
Published: March 2008

Motivation: Genetic modifications or pharmaceutical interventions can influence multiple sites in metabolic pathways, and often these are ‘distant’ from the primary effect. In this regard, the ability to identify target and off-target effects of a specific compound or gene therapy is both a major challenge and critical in drug discovery.

Results: We applied Markov Chain Monte Carlo (MCMC) for parameter estimation and perturbation identification in the kinetic modeling of metabolic pathways. Variability in the steady-state measurements in cells taken from a population can be caused by differences in initial conditions within the population, by variation of parameters among individuals and by possible measurement noise. MCMC-based parameter estimation is proposed as a method to help in inferring parameter distributions, taking into account uncertainties in the initial conditions and in the measurement data. The inferred parameter distributions are then used to predict changes in the network via a simple classification method. The proposed technique is applied to analyze changes in the pathways of pyruvate metabolism of mutants of Lactococcus lactis, based on previously published experimental data.

Availability: MATLAB code used in the simulations is available from ftp://anonymous@dbkweb.mib.man.ac.uk/pub/Bioinformatics_BJ.zip

Contact:  bayujw@ieee.org

Supplementary information: Supplementary data are available at Bioinformatics online.
Deformation and rupture of lipid vesicles in the strong shear flow generated by ultrasound-driven microbubbles
Authors: Marmottant Philippe , Biben Thierry , Hilgenfeldt Sascha
Published: March 2008

Considering the elastic response of the membrane of a lipid vesicle (artificial cell) in an arbitrary three-dimensional shear flow, we derive analytical predictions of vesicle shape and membrane tension for vesicles close to a spherical shape. Large amplitude deviations from sphericity are described using boundary integral numerical simulations. Two possible modes of vesicle rupture are found and compared favourably with experiments: (i) for large enough shear rates the tension locally exceeds a rupture threshold and a pore opens at the waist of the vesicle and (ii) for large elongations the local tension becomes negative, leading to buckling and tip formation near a pole of the vesicle. We experimentally check these predictions in the case of strong acoustic streaming flow generated near ultrasound-driven microbubbles, such as those used in medical applications.
Earthworms counterbalance the negative effect of microorganisms on plant diversity and enhance the tolerance of grasses to nematodes
Authors: Wurst Susanne , Allema Bas , Duyts Henk , Van Der Putten Wim H.
Published: March 2008

Plant community composition is affected by a wide array of soil organisms with diverse feeding modes and functions. Former studies dealt with the high diversity and complexity of soil communities by focusing on particular functional groups in isolation, by grouping soil organisms into body size classes or by using whole communities from different origins. Our approach was to investigate both the individual and the interaction effects of highly abundant soil organisms (microorganisms, nematodes and earthworms) to evaluate their impacts on grassland plant communities. Earthworms increased total plant community biomass by stimulating root growth. Nematodes reduced the biomass of grasses, but this effect was alleviated by the presence of earthworms. Non‐leguminous forb biomass increased in the presence of nematodes, probably due to an alleviation of the competitive strength of grasses by nematodes. Microorganisms reduced the diversity and evenness of the plant community, but only in the absence of earthworms. Legume biomass was not affected by soil organisms, butLotus corniculatusflowered earlier in the presence of microorganisms and the number of flowers decreased in the presence of nematodes. The results indicate that earthworms have a profound impact on the structure of grassland plant communities by counterbalancing the negative effects of plant‐feeding nematodes on grasses and by conserving the evenness of the plant community. We propose that interacting effects of functionally dissimilar soil organisms on plant community performance have to be taken into account in future studies, since individual effects of soil organism groups may cancel out each other in functionally diverse soil communities.
Taurodontism: a review of the condition and endodontic treatment challenges
Authors: Jafarzadeh H. , Azarpazhooh A. , Mayhall J. T.
Published: March 2008

Taurodontism can be defined as a change in tooth shape caused by the failure of Hertwig’s epithelial sheath diaphragm to invaginate at the proper horizontal level. An enlarged pulp chamber, apical displacement of the pulpal floor, and no constriction at the level of the cementoenamel junction are the characteristic features. Although permanent molar teeth are most commonly affected, this change can also be seen in both the permanent and deciduous dentition, unilaterally or bilaterally, and in any combination of teeth or quadrants. Whilst it appears most frequently as an isolated anomaly, its association with several syndromes and abnormalities has also been reported. The literature on taurodontism in the context of endodontics up to March 2007 was reviewed using PubMed, MEDLINE and Cumulative Index to Nursing & Allied Health Literature. Despite the clinical challenges in endodontic therapy, taurodontism has received little attention from clinicians. In performing root canal treatment on such teeth, one should appreciate the complexity of the root canal system, canal obliteration and configuration, and the potential for additional root canal systems. Careful exploration of the grooves between all orifices particularly with magnification, use of ultrasonic irrigation; and a modified filling technique are of particular use.
Multigene analysis suggests ecological speciation in the fungal pathogen Claviceps purpurea
Authors: DOUHAN G. W. , SMITH M. E. , HUYRN K. L. , WESTBROOK A. , BEERLI P. , FISHER A. J.
Published: March 2008

Claviceps purpurea is an important pathogen of grasses and source of novel chemical compounds. Three groups within this species (G1, G2 and G3) have been recognized based on habitat association, sclerotia and conidia morphology, as well as alkaloid production. These groups have further been supported by Random Amplification of Polymorphic DNA (RAPD) and amplified fragment length polymorphism (AFLP) markers, suggesting this species may be more accurately described as a species complex. However, all divergent ecotypes can coexist in sympatric populations with no obvious physical barriers to prevent gene flow. In this study, we used both phylogenetic and population genetic analyses to test for speciation within C. purpurea using DNA sequences from ITS, a RAS‐like locus, and a portion of beta‐tubulin. The G1 types are significantly divergent from the G2/G3 types based on each of the three loci and the combined dataset, whereas the G2/G3 types are more integrated with one another. Although the G2 and G3 lineages have not diverged as much as the G1 lineage based on DNA sequence data, the use of three DNA loci does reliably separate the G2 and G3 lineages. However, the population genetic analyses strongly suggest little to no gene flow occurring between the different ecotypes, and we argue that this process is driven by adaptations to ecological habitats; G1 isolates are associated with terrestrial grasses, G2 isolates are found in wet and shady environments, and G3 isolates are found in salt marsh habitats.
Mating type distribution and genetic structure are consistent with sexual recombination in the Swedish population of Phaeosphaeria nodorum
Authors: Blixt E. , Olson Å. , Högberg N. , Djurle A. , Yuen J.
Published: March 2008

Mating type ratios and SSR marker analysis were used to study the genetic structure of Phaeosphaeria nodorum, the causal agent of glume blotch in wheat. The study was based on leaf collections in five fields located in different regions in Sweden. In total 302 isolates of P. nodorum were obtained from 203 sampling sites (including eight ascospore isolates). Three strong indications of sexual recombination were found: (i) the two mating types were present at a 1:1 ratio; (ii) the genetic structure was diverse, with many unique genotypes, and 69 of the 93 genotypes were only found once; and (iii) random association of alleles indicated that genetic recombination was frequent. However, asexual reproduction could not be excluded since identical genotypes were found within the fields. The fungal population had experienced a demographic bottleneck, as indicated by a low ratio of number of alleles to microsatellite size range (M‐value) of 0·5.
Unauthorised development and seismic hazard vulnerability: a study of squatters and engineers in Istanbul, Turkey
Authors: Green Rebekah A.
Published: March 2008

Many cities in developing nations have experienced an influx of poor migrants in search of work. This population influx has often been accommodated through land squatting, irregular construction and unauthorised housing. For the urban poor, this has resulted in immediate affordable housing; however, this housing frequently has long‐term vulnerability to natural hazards. This article examines the ways in which squatters in Istanbul, Turkey, understand the seismic vulnerability of their unauthorised housing. Distrust of professional engineers and contractors has led Istanbul squatters to believe that self‐built housing will not only be less costly but also safer than commercially built housing. The impact of residents' risk perceptions on their vulnerability to natural hazards is examined through a comparison of social attitudes regarding safe housing and the quality of unauthorised construction. This comparison highlights how squatters' risk perceptions necessitate innovative means of reducing vulnerability in unauthorised neighbourhoods of developing cities.
The underutilization of street markets as a source of food security indicators in Famine Early Warning Systems: a case study of Ethiopia
Authors: Companion Michèle
Published: March 2008

Famine Early Warning Systems (EWS) are reliant on data aggregated from multiple sources. Consequently, they are often insensitive to localized changes in food security status, leading to delayed response or interventions. While price and infrastructural data are often gathered, this case study suggests that local street markets and vendor knowledge are underutilized. Few efforts have been made to monitor systematically the street markets as an indicator of local stressors. Findings from Ethiopia show that knowledge generated by expanding food security indicators in this sector can be used in combination with EWS to facilitate earlier intervention in, or to monitor more effectively, on‐going humanitarian crises. Indicators developed from this study are accurate, cost effective, and sensitive to local climatic and food stressors.
Attitudes related to child sexual abuse: Scale construction and explorative study among psychologists
Authors: FINNILÄ‐TUOHIMAA KATARINA , SANTTILA PEKKA , BJÖRNBERG LINDA , HAKALA NIINA , NIEMI PEKKA , SANDNABBA KENNETH
Published: March 2008

A Child Sexual Abuse Attitude and Belief Scale was constructed and then answered by 242 child psychologists. Four CSA related attitude and belief subscales were identified through confirmatory factor analysis: (1) The Disclosure subscale reflecting favouring a disclosure at any cost; (2) The Pro‐Child subscale reflecting unconditional belief in children's reports; (3) The Intuition subscale reflecting favouring an intuitive approach to CSA investigations; and (4) The Anti Criminal Justice System subscale reflecting negative attitudes towards the legal system. Beliefs that were erroneous according to empirical research were analyzed separately. The results suggest that some psychologists hold extreme attitudes and many erroneous beliefs related to CSA. Some misconceptions are common. Female participants tended to have stronger attitudes than male participants. The more training in interviewing children the participants had had, the more erroneous beliefs and stronger attitudes they had. Experience did not affect attitudes and beliefs.
Rural Intelligentsia and Path Dependency in Post‐socialist Civic Organising: The Case of Lithuania
Authors: Juska Arunas , Poviliunas Arunas , Ziliukaite Ruta , Geguziene Vilma
Published: March 2008

Since the late 1990s the number of rural community development groups in Lithuania has grown exponentially. The article presents the results of one of the first representative surveys of rural NGOs (N = 326) in Lithuania designed to evaluate their structure and resources. Unlike civic organising during the perestroika period, which was characterised by charismatic personalities and organisational innovations, the most recent surge in rural activism follows a path‐dependent trajectory. The movement is lead by representatives of former collective farms, or kolkhoz intelligentsia (white‐collar professionals who served in collective farm social infrastructure during Soviet times) engaged in reconstituting volunteer groups based on a modified Soviet institution of the rural ‘culture house’ or Soviet civic centre (SCC). The prevalence of the SCC‐based rural organising model provided opportunities as well as imposed limitations on post‐socialist civic activism. Community development groups were relatively successful in the types of activities in which SCCs were effective as well (such as culture, leisure and sports), while their capacity to deliver social services were marginal. Although this survey reported relatively high levels of engagement by the community groups with local and county governments, their influence remains constrained by the paternalistic, client–patron type of power relationships that prevail in rural areas.
Atypical presentation of Old‐World cutaneous leishmaniasis, diagnosis and species identification by PCR
Authors: Karamian M , Motazedian MH , Fakhar M , Pakshir K , Jowkar F , Rezanezhad H
Published: March 2008

Background  The diagnosis of cutaneous leishmaniasis (CL) is traditionally based on microscopic demonstration of amastigote forms in tissue biopsies or smears. However, this method usually presents low sensitivity, and in atypical forms, CL may be overlooked because of similarity to other dermal diseases. Thus, it is necessary to apply specific diagnostic methods as polymerase chain reaction (PCR).

Objective  To evaluate the possible advantage of PCR in the diagnosis and species identification of CL in patients with atypical clinical presentation.

Methods  Fifty‐one patients clinically suspected of CL with positive and negative controls were tested. After microscopic examination, extraction of DNA was performed on their smears and analysed by two specific PCR assays for diagnosis and species identification. For these methods, conserved and variable regions of kinetoplastic DNA (KDNA) of Leishmania species have been amplified, respectively. Atypical forms of CL were evaluated among PCR‐positive patients.

Results  PCR results were positive in 37 out of 51 cases (72.5%), among whom microscopic examination revealed Leishmania amastigotes in only 3 (5.9%). Among these patients, 10 (27%) had atypical presentation of CL; using species‐specific primers, 6 patients had Leishmania major, 3 had Leishmania tropica and 1 patient had no species diagnosis. None of the samples of other dermal diseases revealed positive results (specificity, 100%). All patients were successfully treated by CL‐specific drug regimens.

Discussion  The results showed that KDNA PCR methods have a higher sensitivity compared with microscopic method. Moreover, PCR could identify the parasite species for specific therapy. Microscopic method had low sensitivity and less value in chronic and atypical CL cases.
Increased seed dispersal potential towards geographic range limits in a Pacific coast dune plant
Authors: Darling Emily , Samis Karen E. , Eckert Christopher G.
Published: March 2008

DOI:10.1111/j.1469-8137.2008.02414.x
The Persistence and Pricing of the Cash Component of Earnings
Authors: DECHOW PATRICIA M. , RICHARDSON SCOTT A. , SLOAN RICHARD G.
Published: March 2008

Prior research shows that the cash component of earnings is more persistent than the accrual component. We decompose the cash component into: (1) the change in the cash balance, (2) issuances/distributions to debt, and (3) issuances/distributions to equity. We find that the higher persistence of the cash component is entirely due to the subcomponent related to equity. The other subcomponents have persistence levels almost identical to accruals. We investigate whether investors understand the implications of the differential persistence of the three subcomponents. Our results suggest that investors correctly price debt and equity issuances/distributions but misprice the change in the cash balance in a similar manner to accruals. Our tests enable us to empirically distinguish the “accrual” and “external financing” anomalies with results implying that the accrual anomaly subsumes the external financing anomaly. Our results also suggest that naive fixation on earnings is unlikely to be a complete explanation for the accrual anomaly. Our findings are more consistent with investors misunderstanding diminishing returns to new investments.
Giambologna's Salviati reliefs of St Antoninus of Florence: saintly images and political manipulation
Authors: Debby Nirit Ben‐Aryeh
Published: March 2008

This paper focuses on the figure of St Antoninus and his representation in visual imagery. At its centre are Giambologna's bronze reliefs in the Salviati Chapel in Florence's church of San Marco, dating from 1581 to 1587, illustrating the life of Archbishop Antoninus (Antonino Pierozzi), who was active in Florence in the mid‐fifteenth century. Giambologna was also responsible for the design of the chapel itself. By and large, these reliefs have attracted little attention on the part of art historians and sermons specialists – perhaps because at the height at which they are set into the walls, they are largely inaccessible. Although executed a century after the demise of St Antoninus, these reliefs provide us with a valuable impression of the activities of the archbishop and their impact on Florence. Moreover, they shed important light on the cult of St Antoninus and its connection with the politics of Medicean Florence.
Clinical and psychopathological definition of the interictal dysphoric disorder of epilepsy
Authors: Mula Marco , Jauch Regina , Cavanna Andrea , Collimedaglia Laura , Barbagli Davide , Gaus Verena , Kretz Rebekka , Viana Michele , Tota Grazia , Israel Heike , Reuter Uwe , Martus Peter , Cantello Roberto , Monaco Francesco , Schmitz Bettina
Published: March 2008

Summary

Purpose: Different authors suggested the occurrence of a pleomorphic affective syndrome in patients with epilepsy named interictal dysphoric disorder (IDD). We sought to investigate whether IDD occurs only in patients with epilepsy and to validate IDD features against DSM‐IV criteria.

Methods: Consecutive patients with a diagnosis of epilepsy (E) or migraine (M) have been assessed using the BDI, MDQ, and the Interictal Dysphoric Disorder Inventory (IDDI), a questionnaire specifically created to evaluate IDD symptoms. Diagnosis of current and lifetime DSM‐IV Axis I disorders was established using the MINI Plus version 5.0.0.

Results: A total of 229 patients (E = 117; M = 112) were evaluated. Females were significantly more represented in the migraine group (E = 46.5% vs. M = 73.3% p = 0.009), but there was no difference in age, duration of the disease, or education level. Patients with epilepsy were more likely to screen positively at MDQ (E = 17% vs. M = 5.3% p = 0.006) and to have a diagnosis of bipolar disorder (E = 14.5% vs. M = 4.5% p = 0.013) as compared to migraine patients. There was no between‐groups difference in IDD prevalence (E = 17%; M = 18.7%) and IDDI total scores (E = 4.1 ± 2.0 vs. M = 3.8 ± 2.0). Validation of IDD against DSM‐IV categories showed current major depression being the foremost diagnostic category correlated with IDD in both epilepsy (OR = 0.32–0.12–0.88, p = 0.028) and migraine (OR = 0.10, 95% CI = 0.02–0.49, p = 0.004) samples. Current anxiety disorder correlated with IDD only in migraine patients (OR = 0.19, 95% CI = 0.05–0.77, p = 0.02).

Conclusion: IDD represents a homogenous construct that can be diagnosed in a relevant proportion of patients but it is not typical only of epilepsy, occurring in other central nervous system disorders such as migraine.
A Screening test for the prediction of Dravet syndrome before one year of age
Authors: Hattori Junri , Ouchida Mamoru , Ono Junko , Miyake Susumu , Maniwa Satoshi , Mimaki Nobuyoshi , Ohtsuka Yoko , Ohmori Iori
Published: March 2008

Summary

Purpose: Our aim was to develop a screening test to predict Dravet syndrome before the first birthday based on the clinical characteristics of infants and the SCN1A mutation analysis.

Methods: Ninety‐six patients who experienced febrile seizures before the age of one were enrolled. The patients were divided into two groups—the Dravet syndrome group (n = 46) and the non‐Dravet syndrome group (n = 50). We compared the clinical characteristics before one year of age of the two groups. We analyzed all coding exons of the SCN1A gene by the direct sequencing method. Scores from 0 to 3 were assigned to each risk factor based on the odds ratio and p‐value.

Results: An age of onset of febrile seizure ≤ 7 months, a total number of seizures ≥ 5, and prolonged seizures lasting more than 10 min. were regarded as significant risk factors for Dravet syndrome. Other factors highly predictive of this syndrome were hemiconvulsions, partial seizures, myoclonic seizures, and hot water–induced seizures. A total clinical score of six or above was the cutoff value indicating a high risk of Dravet syndrome. SCN1A missense and truncated mutations were detected significantly more often in the Dravet syndrome group than in the non‐Dravet syndrome group.

Discussion: This simple screening test was designed to be used by general pediatricians. It could help to predict Dravet syndrome before one year of age. If the sum of the clinical risk score is ≥ 6, then the performance of an SCN1A mutation analysis is recommended.
Primary Prevention with Defibrillator Therapy in Women: Results from the Sudden Cardiac Death in Heart Failure Trial
Authors: RUSSO ANDREA M. , POOLE JEANNE E. , MARK DANIEL B. , ANDERSON JILL , HELLKAMP ANNE S. , LEE KERRY L. , JOHNSON GEORGE W. , DOMANSKI MICHAEL , BARDY GUST H.
Published: March 2008

Introduction: The Sudden Cardiac Death in Heart Failure Trial (SCD‐HeFT) demonstrated that implantable cardioverter defibrillator (ICD) therapy reduced overall mortality in patients with class II or III heart failure and left ventricular ejection fraction (LVEF) ≤ 35%, while amiodarone had no effect on survival. There are limited data regarding the influence of gender on outcome of patients receiving ICDs for primary prevention.

Methods: We examined gender differences in response to treatment and outcome in this cohort.

Results: Women comprised 23% of the SCD‐HeFT cohort, with similar percentages in the amiodarone, ICD, and placebo groups. Compared with men, women were more likely to be non‐Caucasian, to have class III heart failure, and nonischemic heart disease. After adjustment for baseline differences, overall mortality risk was lower in women than in men. The gender difference in overall mortality was seen in the placebo group, while no gender difference in overall mortality was seen in the ICD group. There was a significantly lower absolute risk of death in the placebo arm women, compared with the placebo arm men (annual mortality rate approximately 4% vs. 6%).

Conclusions: The impact of ICD therapy appears to differ between men and women in this trial, with a smaller ICD benefit among women. However, the test for an interaction between gender and therapy was not significant. The lower overall mortality risk in women in the placebo group and the smaller number of women enrolled may help to explain why treatment differences in women were much smaller and difficult to detect.
Esophageal Luminal Temperature Measurement Underestimates Esophageal Tissue Temperature During Radiofrequency Ablation Within the Canine Left Atrium: Comparison Between 8 mm Tip and Open Irrigation Catheters
Authors: CUMMINGS JENNIFER E. , BARRETT CONOR D. , LITWAK KENNETH N. , DI BIASE LUIGI , CHOWDHURY PUNAM , OH SEIL , CHING CHI KEONG , SALIBA WALID I. , SCHWEIKERT ROBERT A. , BURKHARDT J. DAVID , DE MARCO SHARI , ARMAGANIJAN LUCIANA , NATALE ANDREA
Published: March 2008

Introduction: Evaluation of luminal temperature during left atrial ablation is used clinically; however, luminal temperature does not necessarily reflect temperature within the esophageal wall and poses a risk of atrioesophageal fistula. This animal study evaluates luminal esophageal temperature and its relation to the temperature of the external esophageal tissue during left atrial lesions using the 8 mm solid tip and the open irrigated tip catheters (OIC).

Methods and Results: A thermocouple was secured to the external surface of the esophagus at the level of the left atrium of the dogs. Luminal esophageal temperature was measured using a standard temperature probe. In four randomized dogs, lesions were placed using an 8 mm solid tip ablation catheter. In six randomized dogs, lesions were placed using the 3.5 mm OIC. The average peak esophageal tissue temperature when using the OIC was significantly higher than that of the 8 mm tip catheter (88.6°C ± 15.0°C vs. 62.3°C ± 12.5°C, P < 0.05). Both OIC and 8 mm tip catheter had significantly higher peak tissue temperatures than luminal temperatures (OIC: 88.6°C ± 15.0°C vs 39.7°C ± 0.82°C, P < 0.05) (8 mm: 62.3°C ± 12.5°C vs 39.0 ± 0.5°C, P < 0.05). Both catheters achieved peak temperatures faster in the tissue as compared to the lumen of the esophagus, although the tissue temperature peaked significantly faster for the OIC (OIC: 25 seconds vs 90 seconds, P < 0.05) (8 mm: 63 seconds vs 105 seconds, P < 0.05).

Conclusion: Despite the significant difference in actual tissue temperatures, no significant difference was observed in luminal temperatures between the OIC and 8 mm tip catheter.
Maintenance of Atrial Fibrillation by Pulmonary Vein Tachycardia with Ostial Conduction Block: Evidence of an Interpulmonary Vein Electrical Connection
Authors: MATSUO SEIICHIRO , JAÏS PIERRE , WRIGHT MATTHEW , LIM KANG‐TENG , KNECHT SÉBASTIEN , HAÏSSAGUERRE MICHEL
Published: March 2008

We report a case of a 56‐year‐old man with paroxysmal atrial fibrillation who underwent segmental, ostial pulmonary vein (PV) isolation while in arrhythmia. During isolation of the left superior PV (LSPV), organized electrical activity was seen within the vein, suggestive of a PV tachycardia with a cycle length of 90 ms. Simultaneously, organized electrical activity with a cycle length of 180 ms was seen in the left inferior PV (LIPV), suggestive of 2:1 conduction between the LSPV and the LIPV. Isolation of the LIPV resulted in conversion to sinus rhythm, while confirming isolation of the LSPV by the presence of ongoing PV tachycardia in this vein. This case demonstrates a direct electrical connection between the ipsilateral left PVs, leading to maintenance of atrial fibrillation.
CaMKIIT287 and T305 regulate history‐dependent increases in α agonist–induced vascular tone
Authors: Munevar S. , Gangopadhyay S.S. , Gallant C. , Colombo B. , Sellke F.W. , Morgan K.G.
Published: March 2008

CaMKII is a calcium and calmodulin‐activated kinase that has been shown to regulate learning and memory in the brain, and contractility in blood vessels. Following Ca activation, CaMKII autophosphorylates, gaining a calcium‐independent autonomous activity that reflects a molecular memory of having previously come into contact with calcium. The present study addresses whether the molecular memory properties of CaMKII are involved in the modulation of sustained vascular tone. We demonstrate a history‐dependence of α agonist‐induced vascular tone and show that CaMKII activation in vascular cells is also history dependent. Autophosphorylation of Thr287, which is classically associated with autonomous activity, does not persist during tone maintenance after transient increases in intracellular calcium levels. However, we have found that another site, Thr305, known from in vitro studies to be inhibitory, is regulated by α agonists in that the inhibitory action is removed, thus leading to a delayed reactivation of CaMKII as measured by Thr287 phosphorylation. By the use of a small molecule CaMKII inhibitor (KN93) as well as a decoy peptide (autoinhibitory peptide; AIP) we show a cause and effect relationship between CaMKII reactivation and sustained vascular tone maintenance. Thus, it appears that a complex interplay between the regulation of Thr305 and Thr287 provides a novel mechanism by which a history‐dependence is developed and contributes to a new facet of molecular memory for CaMKII of relevance to vascular tone maintenance.
Uncommon Endocytic and Trafficking Pathway of the Natural Killer Cell CD94/NKG2A Inhibitory Receptor
Authors: Masilamani Madhan , Narayanan Sriram , Prieto Martha , Borrego Francisco , Coligan John E.
Published: March 2008

The CD94/NKG2A inhibitory receptor, expressed by natural killer and T cells, is constantly exposed to its HLA‐E ligand expressed by surrounding cells. Ligand exposure often induces receptor downregulation. For CD94/NKG2A, this could potentiate activation receptor(s) induced responses to normal bystander cells. We investigated CD94/NKG2A endocytosis and found that it occurs by an amiloride‐sensitive, Rac1‐dependent macropinocytic‐like process; however, it does not require clathrin, dynamin, ADP ribosylation factor‐6, phosphoinositide‐3 kinase or the actin cytoskeleton. Once endocytosed, CD94/NKG2A traffics to early endosomal antigen 1+, Rab5+ early endosomes. It does appear in Rab4+ early/sorting endosome, but, in the time period examined, fails to reach Rab11+ recycling or Rab7+ late endosomes or lysosome‐associated membrane protein‐1+ lysosomes. These results indicate that CD94/NKG2A utilizes a previously undescribed endocytic mechanism coupled with an abbreviated trafficking pattern, perhaps to insure surface expression.
Cavernosometry: Is It a Dinosaur?
Authors: Vardi Yoram , Glina Sidney , Mulhall John P. , Menchini Fillipo , Munarriz Ricardo
Published: March 2008

Introduction

Is cavernosometry a useful tool in treating men with erectile dysfunction?

Methods

Five people with expertise and/or interest in the area of cavernosometry were asked to contribute their opinions.

Main Outcome Measure

To provide food for thought, discussion, and possible further research in a poorly discussed area of sexual medicine.

Results

While one urologist feels dynamic infusion cavernosography and cavernosometry seem to have found their place in history, another believes it is time to separate these tests and look at cavernosometry alone and its relevance to the use of duplex Doppler ultrasound, both useful tools in assessing surgical candidates. Three clinicians agree that cavernosography and cavernosometry have a role in specific cases, particularly before revascularization surgery.

Conclusion

Cavernosometry may not be a useful tool for the average clinician treating erectile dysfunction, but serves a purpose for the specialist.
Vardenafil in Men with Stable Statin Therapy and Dyslipidemia
Authors: Miner Martin , Gilderman Larry , Bailen James , Cook David , Dawson Katie , Stanislaus Marisha , Beresford Eric , Barnes Allison
Published: March 2008

Introduction

Phosphodiesterase type-5 (PDE-5) inhibitors have previously been evaluated for their efficacy and safety in various clinical trials in men with erectile dysfunction (ED) with or without associated comorbidities.

Aim

This is the first prospective, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of a PDE-5 inhibitor (i.e., vardenafil) in an exclusive population of men with ED and dyslipidemia.

Main Outcome Measures

Three coprimary efficacy measurements (Sexual Encounter Performance [SEP]2, SEP3, International Index of Erectile Function-Erectile Function [IIEF-EF] domain scores) were used to assess the differential effect of vardenafil vs. placebo in this patient population. Adverse events (AEs) safety data were obtained to compare safety outcomes.

Methods

This 12-week of randomized, double-blind, placebo-controlled study was conducted in 59 U.S. centers. Patients received either on-demand, flexible-dose vardenafil 10 mg (titrated to 5 mg or 20 mg based upon efficacy and safety) or placebo.

Results

Of the 712 patients screened and entered into the study, 395 were randomized. Baseline demographics for the intent-to-treat population included: mean age, 54.4 years (±7.5 standard deviation [SD]); 76% Caucasian; mean body mass index (BMI), 31.7 kg/m2 (±12.7 SD); 47% past/present smoker; and 42% severe ED. Aside from dyslipidemia, other comorbidities included hypertension, 61%; obesity (i.e., BMI ≥ 30), 51%; and type 1 or 2 diabetes, 40%. During the 12-week treatment period, the least squares (LS) adjusted mean success rates in patients on vardenafil vs. placebo were: SEP2, 79.09% vs. 51.92%; and SEP3, 66.69% vs. 33.83% (P <0.001). The LS adjusted mean IIEF-EF domain score for week 12 using LOCF was 21.99 in patients on vardenafil therapy vs. 14.83 in those on placebo (P <0.001). The most commonly encountered AEs were headache and nasal congestion.

Conclusions

Vardenafil was demonstrated to be safe and effective for managing ED in men with ED and associated dyslipidemia. The results of this study support the role of expanded research on outcomes related to effective ED treatment and aggressive lipid control.
Consolidation and Expansion of Agricultural Policy and Rural Development Policy is our Common Task La consolidation et l’expansion de la politique agricole et de la politique de développement rural est de notre responsabilité commune Die Konsolidierung und Ausdehnung der Agrarpolitik und der Politik zur Entwicklung des ländlichen Raums ist unsere gemeinsame Aufgabe
Authors: Jarc Iztok
Published: March 2008

Consolidation and Expansion of Agricultural Policy and Rural Development Policy is our Common Task

Discussions about adjustments to agricultural and rural development policy in the EU must not be burdened by historical restraints and taboos. The outcome should ensure a political and economic environment for the agricultural sector and rural areas that will enable far reaching and sustainable development. Policy and measures, therefore, should be targeted to achieve what the breadth of European society expects. The incorporation of the CAP was one of the hardest issues in the accession negotiations and the process of integration. We had to take on the CAP as an entity, with all its positive and negative elements. The CAP, however, in a rather limited time has actually contributed to the development of numerous agricultural holdings and added a new perspective to many areas and individuals in new Member States. The future CAP can only be based on a clear linkage between agricultural production and change in rural areas, which can together contribute to sustainable development. This means that agriculture and rural areas have an economic function as well as important social and environmental roles. The goal of the CAP must be to ensure the provision of ‘public goods’, however these public goods have to be clearly defined and evaluated and the debate should also consider the interests of our descendants.
Toward a US Shift from Agricultural to Rural Development Policy: Forces of Challenge and Change Auf einen Wechsel von der US‐Agrarpolitik zu einer Politik des ländlichen Raums hinarbeiten: Die Triebkräfte der Herausforderung und des Wandels Vers une transition des politiques agricoles vers des politiques de développement rural aux États‐Unis: Les forces du défi et du changement
Authors: Fluharty Charles W.
Published: March 2008

Toward a US Shift from Agricultural to Rural Development Policy: Forces of Challenge and Change

On the 5th of November 2007, Iowa Senator Tom Harkin, Chairman of the US Senate Committee on Agriculture, Forestry and Nutrition, in opening the floor debate on the 2007 Farm Bill, urged a new US commitment to rural policy, keeping in mind that nearly 85 per cent of total farm household income is now generated off‐farm. Recent institutional developments, moreover, evidence the success of a decade‐long effort to increase focus on the rural development Title of the Farm Bill. One result was the formation of the Alliance for Sensible Agriculture Policies (ASAP), a loose federation of over 30 national organizations, representing the entire political spectrum. It remains highly active in support of Farm Bill reform. Currently, the Senate Bill contains a US$ 400 million increase in mandatory rural development funding. As we move toward an end‐game, however, members of both the Senate and the House of Representatives will face the unbridled power of commodity organizations. It is likely that this will again overwhelm public sentiment and wise public choice. Despite overwhelming odds, a new commitment to a more innovative rural policy framework is emerging in the United States. I believe that this Farm Bill will ultimately be viewed as the beginning of a landscape‐changing legislative framework for rural people and places in America.