bluuebunny/crossref_metadata_2025 huggingface dataset:
Resistance of human T cell leukemia virus type 1 to APOBEC3G restriction is mediated by elements in nucleocapsid
Authors: Derse David , Hill Shawn A. , Princler Gerald , Lloyd Patricia , Heidecker Gisela
Published: February 2007

Human T cell leukemia virus type 1 (HTLV-1) has evolved a remarkable strategy to thwart the antiviral effects of the cellular cytidine deaminase APOBEC3G (hA3G). HTLV-1 infects T lymphocytes
in vivo
, where, like HIV-1, it is likely to encounter hA3G. HIV-1 counteracts the innate antiviral activity of hA3G by producing an accessory protein, Vif, which hastens the degradation of hA3G. In contrast, HTLV-1 does not encode a Vif homologue; instead, HTLV-1 has evolved a cis-acting mechanism to prevent hA3G restriction. We demonstrate here that a peptide motif in the C terminus of the HTLV-1 nucleocapsid (NC) domain inhibits hA3G packaging into nascent virions. Mutation of amino acids within this region resulted in increased levels of hA3G incorporation into virions and increased susceptibility to hA3G restriction. Elements within the C-terminal extension of the NC domain are highly conserved among the primate T cell leukemia viruses, but this extension is absent in all other retroviral NC proteins.
Selective defect of
in vivo
glycolysis in early Huntington's disease striatum
Authors: Powers William J. , Videen Tom O. , Markham Joanne , McGee-Minnich Lori , Antenor-Dorsey JoAnn V. , Hershey Tamara , Perlmutter Joel S.
Published: February 2007

Activity of complexes II, III, and IV of the mitochondrial electron transport system (ETS) is reduced in postmortem Huntington's disease (HD) striatum, suggesting that reduced cerebral oxidative phosphorylation may be important in the pathogenesis of neuronal death. We investigated mitochondrial oxidative metabolism
in vivo
in the striatum of 20 participants with early, genetically proven HD and 15 age-matched normal controls by direct measurements of the molar ratio of cerebral oxygen metabolism to cerebral glucose metabolism (CMRO
2
/CMRglc) with positron emission tomography. There was a significant increase in striatal CMRO
2
/CMRglc in HD rather than the decrease characteristic of defects in mitochondrial oxidative metabolism (6.0 ± 1.6 vs. 5.1 ± 0.9,
P
= 0.04). CMRO
2
was not different from controls (126 ± 37 vs. 134 ± 31 μmol 100 g
−1
min
−1
,
P
= 0.49), whereas CMRglc was decreased (21.6 ± 6.1 vs. 26.4 ± 4.6 μmol 100 g
−1
min
−1
,
P
= 0.01). Striatal volume was decreased as well (13.9 ± 3.5 vs. 17.6 ± 2.0 ml,
P
= 0.001). Increased striatal CMRO
2
/CMRglc with unchanged CMRO
2
is inconsistent with a defect in mitochondrial oxidative phosphorylation due to reduced activity of the mitochondrial ETS. Because HD pathology was already manifest by striatal atrophy, deficient energy production due to a reduced activity of the mitochondrial ETS is not important in the mechanism of neuronal death in early HD. Because glycolytic metabolism is predominantly astrocytic, the selective reduction in striatal CMRglc raises the possibility that astrocyte dysfunction may be involved in the pathogenesis of HD.
Dual mode of paraxial mesoderm formation during chick gastrulation
Authors: Iimura Tadahiro , Yang Xuesong , Weijer Cornelis J. , Pourquié Olivier
Published: February 2007

The skeletal muscles and axial skeleton of vertebrates derive from the embryonic paraxial mesoderm. In amniotes, paraxial mesoderm is formed bilaterally to the nerve cord as a result of primitive streak and tail-bud regression during body axis formation. In chick and mouse embryos, paraxial mesoderm was proposed to derive from a population of resident cells located in the regressing primitive streak and tail bud. In contrast, in lower vertebrates, paraxial mesoderm is formed as a result of the continuation of ingression movements of gastrulation. Here, we reinvestigate paraxial mesoderm formation in the chicken embryo and demonstrate that these two modes are concomitantly at work to set up the paraxial mesoderm. Although the medial part of somites derives from stem cells resident in the primitive streak/tail bud, the lateral part derives from continuous ingression of epiblastic material. Our fate mapping further shows that the paraxial mesoderm territory in the epiblast is regionalized along the anteroposterior axis as in lower vertebrates. These observations suggest that the mechanisms responsible for paraxial mesoderm formation are largely conserved across vertebrates.
The
Saccharomyces cerevisiae
14-3-3 proteins Bmh1 and Bmh2 directly influence the DNA damage-dependent functions of Rad53
Authors: Usui Takehiko , Petrini John H. J.
Published: February 2007

In this study, we mutated autophosphorylation sites in Rad53 based on their conservation with previously identified autophosphorylation sites in the mammalian Rad53 ortholog, Chk2. As with wild-type Rad53, the autophosphorylation mutant, rad53-TA, undergoes Mec1/Tel1-dependent interactions with Rad9 and Dun1 in response to genotoxic stress. Whereas rad53-TA
in vitro
kinase activity is severely impaired, the
rad53-TA
strains are not completely deficient for cell-cycle checkpoint functions, indicating that the mutant kinase retains a basal level of function. We describe a genetic interaction among Rad53, Dun1, and the 14-3-3 proteins Bmh1 and Bmh2 and present evidence that 14-3-3 proteins directly facilitate Rad53 function
in vivo
. The data presented account for the previously observed checkpoint defects associated with 14-3-3 mutants in
Saccharomyces pombe
and
Saccharomyces cerevisiae
. The 14-3-3 functional interaction appears to modulate Rad53 activity, reminiscent of 14-3-3's effect on human Raf1 kinase and distinct from the indirect mode of regulation by 14-3-3 observed for Chk1 or Cdc25.
Accurate automated clustering of two-dimensional data for single-nucleotide polymorphism genotyping by a combination of clustering methods: evaluation by large-scale real data
Authors: Takitoh Shuichi , Fujii Shogo , Mase Yoichi , Takasaki Junichi , Yamazaki Toshimasa , Ohnishi Yozo , Yanagisawa Masao , Nakamura Yusuke , Kamatani Naoyuki
Published: February 2007

Motivation: The Invader assay is a fluorescence-based high-throughput genotyping technology. If the output data from the Invader assay were classified automatically, then genotypes for individuals would be determined efficiently. However, existing classification methods do not necessarily yield results with the same accuracy as can be achieved by technicians. Our clustering algorithm, Genocluster, is intended to increase the proportion of data points that need not be manually corrected by technicians.

Results: Genocluster worked well even when the number of clusters was unknown in advance and when there were only a few points in a cluster. The use of Genocluster enabled us to achieve an acceptance rate (proportion of assay results that did not need to be corrected by expert technicians) of 84.4% and a proportion of uncorrected points of 95.8%, as determined using the data from over 31 million points.

Availability: Information for obtaining the executable code, example data and example analysis are available at

Contact:  kamatani@ior.twmu.ac.jp
A new mouse model to explore the initiation, progression, and therapy of BRAFV600E-induced lung tumors
Authors: Dankort David , Filenova Elena , Collado Manuel , Serrano Manuel , Jones Kirk , McMahon Martin
Published: February 2007

Mutationally activated BRAFV600E (BRAFVE) is detected in ∼6% of human malignancies and promotes sustained MEK1/2–ERK1/2 pathway activation. We have designed BRafCA mice to express normal BRaf prior to Cre-mediated recombination after which BRafVE is expressed at physiological levels. BRafCA mice infected with an Adenovirus expressing Cre recombinase developed benign lung tumors that only rarely progressed to adenocarcinoma. Moreover, BRafVE-induced lung tumors were prevented by pharmacological inhibition of MEK1/2. BRafVE expression initially induced proliferation that was followed by growth arrest bearing certain hallmarks of senescence. Consistent with Ink4a/Arf and TP53 tumor suppressor function, BRafVE expression combined with mutation of either locus led to cancer progression.
First European record of Carassius langsdorfii from the Elbe basin
Authors: Kalous L. , ŠLechtová V. , Bohlen J. , Petrtýl M. , ŠVátora M.
Published: February 2007

Morphological, cytogenetic and molecular genetic identification of two specimens of Carassius langsdorfii from the upper Elbe basin is given. Probably, the species was introduced by accident with commercial fish imports. Potentially, this introduced species may be of harm to native fish species.
Recent introgressive hybridization revealed by exclusive mtDNA transfer from Oreochromis leucostictus (Trewavas, 1933) to Oreochromis niloticus (Linnaeus, 1758) in Lake Baringo, Kenya
Authors: Nyingi D. W. , Agnèse J.‐F.
Published: February 2007

Nuclear DNA and mtDNA polymorphisms were surveyed in various species of East African Oreochromis. In Lake Baringo, where only Oreochromis niloticus baringoensis is present, alien mtDNA haplotypes were observed, apparently the result of introgressive hybridization with Oreochromis leucostictus. This introgression is not accompanied by any substantial or recorded transfer of nuclear genes into O. n. baringoensis.
Mitochondrial DNA phylogeography ofGlyptothorax fokiensisandGlyptothorax hainanensisin Asia
Authors: Chen X.‐L. , Chiang T.‐Y. , Lin H.‐D. , Zheng H.‐S. , Shao K.‐T. , Zhang Q. , Hsu K.‐C.
Published: February 2007

Whole mitochondrial DNA cytochromebsequences in 62 fish from 13 locations in Southeast China identified two major clades corresponding to two allopatric taxa,Glyptothorax fokiensis fokiensisandGlyptothorax fokiensis hainanensis. Reciprocal monophyly and a molecular clock separation between these two taxa of 2·3 million years indicate these taxa should be elevated to species. Mismatch distributions and Fu’sFSstatistic suggest that bothG. fokiensisandG. hainanensishave experienced recent population expansions. Analysis of molecular variance indicates that most of the genetic variation resides among populations within both species, withΦST= 0·645 forG. fokiensisand 0·801 forG. hainanensis, suggesting restricted gene flow among populations. Significant correlations between the geographic and the genetic distances provide support for the importance of geographic isolations between populations. Nested clade analysis also confirms low levels of genetic exchanges between the two major groups and between populations within each group. The phylogeographical pattern among populations ofGlyptothoraxin East Asia can be attributed to historical fragmentations, demographic expansions and occasional long‐distance dispersals stimulated by tectonic activity and Ice Age climate changes.
Genetic variation among trout in the River Neretva basin, Bosnia and Herzegovina
Authors: Razpet A. , Sušnik S. , Jug T. , Snoj A.
Published: February 2007

Mitochondrial DNA haplotypes, characteristic of the Adriatic, Danubian and Atlantic lineages of brown trout Salmo trutta and of Salmo obtusirostris were found in trout inhabiting the River Neretva basin. With the exception of the one associated with softmouth trout, haplotypes were not correlated with operational taxonomic units based on phenotype. Nuclear DNA analysis identified four genetic assemblages corresponding to S. obtusirostris, different geographically confined autochthonous S. trutta populations, introduced S. trutta and a genetically heterogeneous group located between S. obtusirostris and S. trutta in the dendrogram of individuals, indicating the existence of hybrid swarms in the Neretva basin. Genetic assemblages corresponding to Salmo marmoratus and the recently proposed Salmo cf. montenigrinus were not detected. The presence of genetic intermediates indicates that the studied taxa are not completely reproductively isolated and that genetic stability has been either anthropogenically interrupted or not yet achieved among Neretva trout. This finding should be considered in management decisions since such an unstable community must be particularly susceptible to breakdown in genetic population structure as a result of hybridization between native and non‐native introduced trout stocks.
Parallel evolution? Microsatellite variation of recently isolated marine and freshwater three‐spined stickleback
Authors: ÓLafsdóttir G. Á. , Snorrason S. S. , Ritchie M. G.
Published: February 2007

Variation at nine microsatellite loci, four of which are linked to phenotypic traits (spine length and lateral plate morphology) in Canadian three‐spined sticklebackGasterosteus aculeatus, are used to test for selection on marine and freshwater three‐spined stickleback morphs in Iceland. There are indications of strong selection on loci linked to dorsal spine length, providing another potential example of parallel divergence at the genomic level in three‐spined stickleback.
Gender‐related differences in computer‐mediated communication and computer‐supported collaborative learning
Authors: Prinsen F.R. , Volman M.L.L. , Terwel J.
Published: February 2007

Abstract  A question associated with the introduction of computer‐supported collaborative learning (CSCL) is whether all participants profit equally from working in CSCL environments. This article reports on a review study into gender‐related differences in participation in CSCL. As many of the processes in CSCL are similar to those in computer‐mediated communication (CMC), studies into CMC are also included in the review. Male dominance is found to play a role in many CMC settings. A learning culture with an explicit focus on participation by all students seems to be related to a more gender‐balanced participation in CMC, however. A tendency for boys to be more active participants than girls is also present in CSCL environments, but it is less pronounced than in CMC. This may be explained by the fact that participation is explicitly promoted in most CSCL environments. Gender differences in the character of students' contributions are found in both CMC and CSCL. It is concluded that in order to avoid gender‐stereotyped participation and communication patterns, it is necessary to explicitly address inclusiveness as an aspect of a collaborative classroom culture. A plea is made for further research into differential participation by students in CSCL, and the effects thereof on cognitive and affective learning outcomes. Research should also focus on the question how classroom cultures can be promoted that support active participation of all students aimed at collaborative knowledge construction.
Effects of Adrenalectomy on the Excitability of Neurosecretory Parvocellular Neurones in the Hypothalamic Paraventricular Nucleus
Authors: Yang J. H. , Li L. H. , Lee S. , Jo I. H. , Lee S. Y. , Ryu P. D.
Published: February 2007

Glucocorticoids are well known to inhibit the release of hypophysiotrophic hormones from neurones originating in the paraventricular nucleus (PVN), but the cellular mechanisms of the inhibition are not well understood. Here, we examined the effects of adrenalectomy (ADX) on the spontaneous firing activity in the neurosecretory parvocellular PVN neurones of rat brain slices. The neurones were identified by injecting a retrograde dye into the pituitary stalk and classified according to their electrophysiological properties. The intranuclear distribution, electrophysiological properties, and hypophysiotrophic hormone phenotype of the labelled type II PVN neurones were similar to neurosecretory parvocellular PVN neurones. In the neurones of sham‐operated rats under the cell‐attached recording mode, we observed three spontaneous activity patterns: tonic regular (24%), tonic irregular (36%), and silent (40%). Noradrenaline (100 µM) induced an excitatory or an inhibitory effect on the spontaneous activity. Noradrenergic excitation was blocked by prazosin (2 µM, α1‐adrenoceptor antagonist), and mimicked by phenylephrine (100 µM, α1‐adrenoceptor agonist), whereas noradrenergic inhibition was blocked by yohimbine (2 µM, α2‐adrenoceptor antagonist) and mimicked by clonidine (50 µM, α2‐adrenoceptor agonist). In the neurones of ADX rats, we found burst firing in 35% of neurones tested and an increase in the frequency of spontaneous firing. The burst firing was not observed in the neurones of the sham‐operated rats. ADX caused a 1.7‐fold increase in the proportion of neurones showing the noradrenergic excitation. Supplementation of the ADX rats with corticosterone (10 mg pellet) reversed the ADX‐induced burst firing, and the potentiation of noradrenergic excitation. In summary, our results show that removal of corticosterone by ADX can elevate the neuronal excitability by increasing the spontaneous firing rate and by potentiating the α1‐adrenoceptor‐mediated noradrenergic excitation, and it can facilitate hormone release by inducing burst firing. Our results provide new insight to the cellular mechanisms of the feedback inhibition by glucocorticoids in the neurosecretory parvocellular neurones of the PVN.
Epidural ropivacaine – where are the benefits? A prospective, randomized, double‐blind trial in patients with retropubic prostatectomy
Authors: Heid F. , Schmidt‐Glintzer A. , Piepho T. , Jage J.
Published: February 2007

Background:  In comparison with bupivacaine, ropivacaine exhibits comparable anaesthetic effects but with less motor impairment and systemic toxicity. However, the analgesic potency may differ. For example, ropivacaine during obstetric epidural analgesia provides an approximately 40% lower analgesic potency than bupivacaine. Equal visual analogue pain scores require significantly higher dosages of ropivacaine, and general statements about a favourable benefit–risk profile relative to that of bupivacaine may therefore have limited clinical impact. We addressed this topic in a male pain model by evaluating the analgesic efficacy of epidural ropivacaine 0.2% vs. bupivacaine 0.125% after retropubic prostatectomy.

Methods:  Forty patients scheduled for retropubic prostatectomy were randomly assigned to two groups (20 patients per group). In a double‐blind prospective design, patient‐controlled lumbar epidural analgesia was provided by ropivacaine 0.2% in the ropivacaine group and by bupivacaine 0.125% in the bupivacaine group. The primary endpoint was the total amount of local anaesthetic consumption. The secondary endpoints were the numeric rating scale scores for rest and dynamic pain and the degree of motor impairment.

Results:  Ropivacaine consumption was 60% higher (mean ± standard deviation, 1372.5 ± 108.3 mg) than that of bupivacaine (852 ± 75.2 mg) (P < 0.001). There were no significant differences in the numeric rating scale scores and motor impairment.

Conclusions:  In male patients, lumbar epidural administration of ropivacaine 0.2% after retropubic prostatectomy does not appear to provide benefits over bupivacaine 0.125%. Moreover, in view of the significantly higher drug requirements, general statements focusing on the favourable therapeutic index of ropivacaine may require critical analysis, at least during epidural administration.
Prospective randomized controlled study of Hydrofiber® dressing containing ionic silver or calcium alginate dressings in non‐ischaemic diabetic foot ulcers
Authors: Jude E. B. , Apelqvist J. , Spraul M. , Martini J. ,   the Silver Dressing Study Group
Published: February 2007

Aims  Diabetic foot ulcers (DFUs) are at risk of infection and impaired healing, placing patients at risk of lower extremity amputation. DFU care requires debridement and dressings. A prospective, multicentre study compared clinical efficacy and safety of AQUACEL® Hydrofiber® dressings containing ionic silver (AQAg) with those of Algosteril® calcium alginate (CA) dressings in managing out‐patients with Type 1 or 2 diabetes mellitus and non‐ischaemic Wagner Grade 1 or 2 DFUs.

Methods  Patients stratified by antibiotic use on enrolment were randomly assigned to similar protocols including off‐loading, AQAg (n = 67) or CA (n = 67) primary dressings and secondary foam dressings for 8 weeks or until healing. Clinical efficacy measures were healing outcomes and primarily healing speed. Adverse events were recorded.

Results  AQAg and CA groups were comparable at baseline. All ulcer healing outcomes improved in both groups. The mean time to healing was 53 days for AQAg ulcers and 58 days for CA ulcers (P = 0.34). AQAg‐treated ulcers reduced in depth nearly twice as much as CA‐treated ulcers (0.25 cm vs. 0.13 cm; P = 0.04). There was more overall ulcer improvement and less deterioration in AQAg subjects (P = 0.058), particularly in the subset initially using antibiotics (P = 0.02). Safety profiles of both groups were similar.

Conclusion  When added to standard care with appropriate off‐loading, AQAg silver dressings were associated with favourable clinical outcomes compared with CA dressings, specifically in ulcer depth reduction and in infected ulcers requiring antibiotic treatment. This study reports the first significant clinical effects of a primary wound dressing containing silver on DFU healing.
The changing role of fairs in the long eighteenth century: evidence from the north midlands1
Authors: MITCHELL IAN
Published: February 2007

Despite the recent interest of historians in retailing and distribution, little attention has been paid to fairs. It has often been assumed that by 1800 they were mainly occasions for entertainment. Using a range of sources and focusing mainly on the north midlands, this article argues that many fairs remained significant during the eighteenth century for agricultural marketing, some business and financial transactions, and retailing. By the early nineteenth century, rapidly changing economic conditions, coupled with changed attitudes, threatened these traditional roles and fairs had to adapt or face inevitable decline.
Calculating credibility: print culture, trust and economic figures in early eighteenth‐century England1
Authors: GLAISYER NATASHA
Published: February 2007

Credit in early modern England has been studied by both social historians of the market and historians of the book. The intersection of these literatures is explored by asking the question: how did producers of books about interest (which was closely connected to credit) convince readers that their books could be trusted? One particular book is considered: a palm‐sized book of interest calculations by John Castaing. Most importantly, and unusually, many copies of this book contain his signature, which, it is argued, must be interpreted in the context of the particular role that signatures played in guaranteeing financial transactions.
NONPARAMETRIC BOOTSTRAP PROCEDURES FOR PREDICTIVE INFERENCE BASED ON RECURSIVE ESTIMATION SCHEMES*
Authors: Corradi Valentina , Swanson Norman R.
Published: February 2007

We introduce block bootstrap techniques that are (first order) valid in recursive estimation frameworks. Thereafter, we present two examples where predictive accuracy tests are made operational using our new bootstrap procedures. In one application, we outline a consistent test for out‐of‐sample nonlinear Granger causality, and in the other we outline a test for selecting among multiple alternative forecasting models, all of which are possibly misspecified. In a Monte Carlo investigation, we compare the finite sample properties of our block bootstrap procedures with the parametric bootstrap due to Kilian (Journal of Applied Econometrics 14 (1999), 491–510), within the context of encompassing and predictive accuracy tests. In the empirical illustration, it is found that unemployment has nonlinear marginal predictive content for inflation.
REASSESSING THE IMPACT OF BARRIERS TO CAPITAL ACCUMULATION ON INTERNATIONAL INCOME DIFFERENCES*
Authors: Landon‐Lane John S. , Robertson Peter E.
Published: February 2007

Can barriers to capital accumulation account for large differences in GDP per capita? We reconsider the claim that these barriers have an amplified effect on income levels in a model where both modern and traditional sector technologies are active. We show that this claim is not correct. We do find, however, that the removal of barriers to capital accumulation can cause large changes in the employment shares of labor. Thus the model can account for an important stylized fact of the development process, with labor moving from the traditional to the modern sector as income levels rise.
ECONOMIC INTEGRATION AND RULES OF ORIGIN UNDER INTERNATIONAL OLIGOPOLY*
Authors: Ishikawa Jota , Mukunoki Hiroshi , Mizoguchi Yoshihiro
Published: February 2007

Free trade agreements (FTAs) have rules of origin (ROOs) to prevent tariff circumvention by firms of nonmember countries. This article points out that in imperfectly competitive markets, ROOs have another role overlooked in the existing literature. Instead of focusing on the impacts of ROOs in the intermediate‐good markets, we draw our attention to the final‐good markets to examine the effects of ROOs. We find that under some conditions, ROOs benefit both firms at the expense of consumers. Under some other conditions, ROOs benefit the firm producing outside the FTA and hurt the firm producing inside the FTA.
THE BECKER PARADOX AND TYPE I VERSUS TYPE II ERRORS IN THE ECONOMICS OF CRIME*
Authors: Persson Mats , Siven Claes‐Henric
Published: February 2007

Two real‐world observations are not easily replicated in models of crime. First, although capital punishment is optimal in the standard Becker model, it is rarely observed in the real world. Second, criminal procedure and the evaluation of evidence vary across societies and historical periods, the standard of proof being sometimes very high and sometimes quite low. In this article, we develop a general equilibrium model of judicial procedure allowing for innocent persons being convicted. We show that the median voter theorem applies to this model, making judicial procedure endogenous. So formulated, the model can replicate both empirical observations.
PRACTICAL GUIDE TO REAL OPTIONS IN DISCRETE TIME*
Authors: Boyarchenko Svetlana , Levendorskiǐ Sergei
Published: February 2007

Continuous time models in the theory of real options give explicit formulas for optimal exercise strategies when options are simple and the price of an underlying asset follows a geometric Brownian motion. This article suggests a general, computationally simple approach to real options in discrete time. Explicit formulas are derived even for embedded options. Discrete time processes reflect the scarcity of observations in the data, and may account for fat tails and skewness of probability distributions of commodity prices. The method of this article is based on the use of the expected present value operators.
Is Headache Related to Asthma, Hay Fever, and Chronic Bronchitis? The Head‐HUNT Study
Authors: Aamodt Anne H. , Stovner Lars J. , Langhammer Arnulf , Hagen Knut , Zwart John‐Anker
Published: February 2007

Objectives.—To examine the relationship between migraine and nonmigrainous headache and asthma, hay fever, and chronic bronchitis in a large cross‐sectional population‐based study.

Background.—Associations between prevalence of migraine and asthma or allergy have been demonstrated in clinic‐based and epidemiologic studies whereas studies on chronic bronchitis are scarce.

Methods.—A total of 51,383 subjects completed a headache questionnaire and constituted the “Head‐HUNT” Study. Of these 50,401 (98.1%) answered the questions about asthma and chronic bronchitis, and 47,029 (91.5%) answered the question about hay fever. Associations were assessed in multivariate analyses, estimating prevalence odds ratios (ORs) with 95% confidence intervals (CI).

Results.—Both migraine and nonmigrainous headache were approximately 1.5 times more likely among those with current asthma, asthma related symptoms, hay fever, and chronic bronchitis than those without. The association increased with increasing headache frequency.

Conclusions.—This large questionnaire‐based study confirms that migraine and other headaches are associated with respiratory and allergic disorders. The magnitude of the association between headache and asthma, hay fever, and chronic bronchitis tended to be in the same order. Headache frequency seems to have a greater impact on the association with respiratory or allergic conditions than headache diagnoses. Whether it is a causal relationship is uncertain, but the results underline the importance of considering comorbid disorders among patients with frequent headache.
Early Intervention With Almotriptan: Results of the AEGIS Trial (AXERT® Early Migraine Intervention Study)
Authors: Mathew Ninan T. , Finlayson Gary , Smith Timothy R. , Cady Roger K. , Adelman James , Mao Lian , Wright Pamela , Greenberg Steven J. ,   on behalf of the AEGIS Investigator Study Group
Published: February 2007

Objective.—To evaluate prospectively the efficacy and safety of almotriptan 12.5 mg as compared to placebo when administered within 1 hour of headache pain onset for the acute treatment of 3 migraine headaches.

Background.—Although clinical trials have reported improved outcomes when triptans were used early or to treat mild pain, acceptance of this treatment strategy has been hampered by both efficacy and tolerability issues.

Methods.—In this multicenter, double‐blind, placebo‐controlled, parallel‐group trial, patients with IHS‐migraine were randomized in a 1:1 ratio to treat 3 consecutive migraine attacks with either almotriptan 12.5 mg or placebo. Patients were instructed to take their study medication at the first sign of headache pain of any intensity, within 1 hour of onset, and to record their symptoms at multiple time points during their headaches using a personal digital assistant. Clinical trial efficacy results for the first study headache and safety data for the entire study are presented.

Results.—A total of 378 patients were randomized, 189 to each group; 162 almotriptan‐treated patients, and 155 placebo‐treated patients were evaluable for efficacy. Almotriptan treatment, compared to placebo, resulted in a significantly greater proportion of patients achieving 2‐hour pain free (37.0% vs 23.9%, P= .010), 2‐hour pain relief (72.3% vs 48.4%, P < .001) and sustained pain free (24.7% vs 16.1%, P= .040). Significant differences in pain free (P= .026) and pain relief (P= .019) between almotriptan and placebo also were observed at 1 hour. At 2 to 4 hours and 4 to 24 hours after treatment, the mean intensity of phonophobia and photophobia were significantly lower in the patients treated with almotriptan compared to the placebo‐treated patients. A greater proportion of patients treating with almotriptan versus placebo reported normal functionality within 2 hours postdose (54.4% vs 38.1%, P= .007) and 4 hours postdose (74.5% vs 54.3%, P < .001). The percentage of patients experiencing 1 or more treatment‐emergent adverse events (AE) was 9.8% for almotriptan and 6.4% for placebo. The only treatment‐emergent AEs that occurred with a frequency of at least 1% (equivalent to 2 or more patients) in the almotriptan and placebo groups, respectively, were somnolence (1.1% and 2.3%), nausea (1.1% and 1.7%), vomiting (1.1% and 0.6%), and fatigue (1.1% and 0%).

Conclusion.—Treatment with almotriptan within 1 hour of migraine onset resulted in significantly better clinical outcomes than placebo and tolerability similar to placebo. Acute medications, such as almotriptan, that are both effective and well tolerated may encourage patients to access acute treatment earlier.
Atypical Spontaneous Intracranial Hypotension (SIH) With Nonorthostatic Headache
Authors: Kong Doo‐Sik , Park Kwan , Nam Do‐Hyun , Lee Jung‐Il , Kim Eun‐Sang , Kim Jong Soo , Hong Seung‐Chyul , Shin Hyung Jin , Eoh Whan , Kim Jong Hyun
Published: February 2007

Background.—Some patients with spontaneous intracranial hypotension (SIH) often do not demonstrate typical orthostatic headache, which is contrary to the typical SIH syndrome. They usually have an obscure and intermittent headache, regardless of their positional change.

Object.—The objective of this study is to investigate the clinical course of atypical SIH that manifests with diffuse pachymeningeal enhancement, but no orthostatic headaches.

Methods.—Between January 1997 and December 2005, we observed a total of 6 patients who revealed atypical presentations including nonpostural headaches and normal cerebrospinal fluid (CSF) pressure, despite the diffuse pachymeningeal enhancement seen on their MR images. For a comparison of the clinical features and the disease course, 13 other SIH patients with typical clinical manifestations were selected as a control group.

Results.—Cerebrospinal fluid leakage sites were confirmed in only one patient through a variety of diagnostic tools; in contrast, definite focal CSF leakage sites were found in 12 of 13 patients with typical SIH. The 6 atypical SIH patients were treated with conservative treatment, including strict bed rest and intravenous hydration for 2 to 3 weeks. After a mean follow‐up of 12 months, their headaches were gradually relieved after 2 to 3 weeks of conservative treatment only.

Conclusions.—All SIHs do not necessarily show the typical clinical manifestations. The atypical finding of SIH such as nonorthostatic headache or normal CSF pressure may be the result of a normal physiologic response to the typical SIH as a compensatory reaction. Therefore, when faced with patients showing findings compatible with SIH on the brain MR images, regardless of nonpostural headache, atypical SIH should be suspected.
Influence of MTHFR Genotype on Contingent Negative Variation And MRI Abnormalities in Migraine
Authors: De Tommaso Marina , Difruscolo Olimpia , Sardaro Michele , Losito Luciana , Serpino Claudia , Pietrapertosa Anna , Santeramo Maria Teresa , Dicuonzo Franca , Carella Aristide , Lamberti Paolo , Livrea Paolo
Published: February 2007

Background.—The MTHFR C677T genotype has been associated with increased risk of migraine, particularly of migraine with aura (MA) in selected clinical samples and with elevated homocysteine. The hyper‐homocysteinemia may favor the vascular and neuronal mechanism underlying migraine, and the risk of stroke.

Objective.—The first aim of the present study was to examine the Contingent Negative Variation (CNV) amplitude and habituation pattern in a migraine sample versus non‐migraine subjects, at the light of the MTHFR genotype, according to an unrelated and clinical based case‐control panel. The second aim was to compare the frequency of Magnetic Resonance Imaging (MRI) subclinical brain lesions across the different C677 genotypes in the same migraine sample, selected for the young age and the absence of any cardiovascular risk factor.

Methods.—One hundred and five 18‐45 year old out‐patients, 90 affected by migraine without aura (MO) and 15 by MA, and 97 non‐migraine healthy subjects, age and sex matched, were selected for the genetic analysis. All subjects had a common ethnic origin from Puglia. Sixty‐four migraine subjects and 33 control subjects were submitted to the recording of the CNV. All migraine subjects underwent the MRI evaluation.

Results.—The frequency of homozygosis was 14.33% in normal subjects, versus 25.7% in MA + MO group (χ2‐test: 10.80 P= .001). The frequency of homozygosis in MO patients, was 25.5% (MA versus N: χ2‐test: 9 P= .003), in MA group it was 26.6%.

Considering the MTHFR genotype in migraine patients and controls, the C677TT subjects exhibited a reduced habituation index of the early CNV (iCNV), in respect with both C677TC and C677CC; in the migraine group, there was a significant decrease of CNV habituation in patients with homozygosis and a positive correlation between the habituation index values and the homocysteine levels. Nineteen migraine patients exhibited subclinical brain lesions (18.05%): patients with C677T homozygosis did not exhibit a higher risk for MRI abnormalities.

Conclusions.—This unrelated and clinical based case‐control study showed that genetically induced hyper‐homocysteinemia may favor the neuronal factors predisposing to migraine, while it does not influence the presence of subclinical vascular brain lesions probably linked with increased risk of stroke.
The Serotonin Syndrome, Triptans, and the Potential for Drug–Drug Interactions
Authors: Shapiro Robert E. , Tepper Stewart J.
Published: February 2007

The serotonin syndrome is an acute adverse reaction to medications that enhance serotonergic activity. The severity of cases ranges from mild to fatal. Recently, the U.S. Food and Drug Administration issued an alert that the risk of developing serotonin syndrome may be increased by the concomitant administration of triptan medications with certain other medications. However, a review of published data does not allow an accurate assessment of such risks related to triptans. We conclude that it is currently unclear whether administration of triptans with other serotonergic medications increases the risk of serotonin syndrome.
Headaches Amongst Pool Players
Authors: Seet Raymond C.S. , Chan Yiong Huak , Lim Erle C.H.
Published: February 2007

Background.—Pool‐players' headache is a newly described entity. We studied the prevalence and risk factors for the development of headaches amongst pool players.

Methods.—We obtained demographic information, history of pre‐existing headaches, frequency and duration of pool‐playing, history of pre‐existing headaches and their subtypes, competitive pool‐playing and worsening or development of headaches amongst pool‐players at 2 pool centers. Univariate and multivariate analyses were performed and statistical significance was set at P < .05.

Results.—Two hundred and three players, of mean age 22.6 (SD 7.7 years), participated in this study. Of the 21 respondents who reported headaches when playing pool, 11 (52.4%) had pre‐existing headaches and 10 (47.6%) had no pre‐existing headaches. Age and history of pre‐existing headaches were significantly associated with worsening of headaches.

Conclusion.—Pool‐players are susceptible to the development of headaches. Avoidance and reduction in the frequency of pool‐playing may reduce the frequency of headaches amongst pool players.
Symptomatic Occipital Epilepsy Misdiagnosed as Migraine
Authors: Menon Bindu
Published: February 2007

Two young patients with symptomatic occipital lobe epilepsy due to discrete lesions of cysticercosis were misdiagnosed and treated for 2 years as migraine with visual aura. The patients suffered from frequent visual seizures often followed by migraine‐like headache. Seizures manifested with colored and mainly circular elementary visual hallucinations of up to 1 minute duration. Headache, often severe and of long duration, was frequently associated with nausea, photophobia, and phonophobia. Both patients became seizure‐free with appropriate treatment of the underlying disease and epileptic seizures.
In vitro osteogenesis on a microstructured titanium surface with additional submicron‐scale topography
Authors: Schwartz Fo Humberto Osvaldo , Novaes Arthur Belém , De Castro Larissa Moreira Spinola , Rosa Adalberto Luiz , De Oliveira Paulo Tambasco
Published: February 2007

Abstract: The present study aimed to evaluate key parameters of in vitro osteogenesis on (1) commercially pure titanium (cpTi) discs with 20–200‐μm‐scale microtopography patterned with additional micron‐ and submicron‐scale topography (0.5–20 μm; Plus surface, Dentsply Friadent), (2) control cpTi discs with 20–200‐μm‐scale microtopography (DPS, Deep Profile Surface, Dentsply Friadent), and (3) a machined surface. Using calvaria‐derived osteogenic cultures, the following parameters were assessed: cell adhesion and spreading, growth curve and cell viability, alkaline phosphatase (ALP) activity and total protein content, immunolocalization of fibronectin, bone sialoprotein (BSP) and osteopontin (OPN), and bone‐like tissue formation. The results showed no major differences between surfaces in terms of cell adhesion, growth curve, cell viability (days 4 and 11), ALP activity, or total protein content (days 11 and 17). At day 11, cultures grown on Plus exhibited small, well‐defined nodular areas of calcified matrix, which were only rarely observed on DPS and absent on the machined surface. Such areas were larger at day 17 and were not associated with the typical mineralized bone‐like nodules (with BSP‐ and OPN‐positive osteoblastic cells on top). At day 17, the total mineralized area was significantly larger on DPS than on a Plus or machined surface (DPS>Plus>machined; Kruskal–Wallis test, P<0.05). Direct fluorescence allowed the straightforward observation of higher amounts of apoptotic bodies associated with mineralized nodules for Plus. The results suggested the occurrence of an additional, early pattern of matrix mineralization mostly for the Plus microstructured surface, which did not necessarily translate into larger bone‐like tissue formation in vitro.
The anti‐angiogenic substance TNP‐470 impairs peri‐implant bone formation: a pilot study in the rabbit metaphysis model
Authors: Mair Birgit , Fuerst Gabor , Kubitzky Pawel , Tangl Stefan , Bergmeister Helga , Losert Udo , Watzek Georg , Gruber Reinhard
Published: February 2007

Objectives: To study the osseointegration of dental implants under the conditions of impaired blood vessel formation in a rabbit model.

Material and methods: Twenty‐four titanium implants were placed in the diaphyses of 12 rabbits, two in each tibia. After 2 days, six animals received TNP‐470, an anti‐angiogenic substance, 10 mg/kg body weight, three times a week, by subcutaneous injection. The remaining six animals served as controls. All animals were sacrificed 6 weeks post implantation.

Results: The amount of newly formed bone (NFB) within a peri‐implant distance of 0.2 mm and the percentage of bone‐to‐implant contacts (BIC) were determined in undecalcified ground sections. In both groups, appositional bone growth originating from the cortex was associated with a dense network of blood vessels. Within 1 mm apical from the implant shoulder, NFB was 29.3±6.7% in TNP‐470 treated animals vs. 44.2±13.1% in the controls (P=0.03). In the adjacent cortical area NFB was 46.1±10.0% in TNP‐470 treated animals and 58.4±3.0% in the control group (P=0.02). In the endosteal area, 3 mm from the implant shoulder NFB was 24.8±11.8% in TNP‐470‐treated animals and 27.0±9.6% in controls (P=0.73) and in the most apical peri‐implant area corresponding to the bone marrow cavity 4.3±3.2% in TNP‐470‐treated animals and 10.5±5.2% in the controls (P=0.03). No decrease in BIC in response to TNP‐470 was observed.

Conclusion: The data suggest that TNP‐470 decreases the formation of peri‐implant bone, whereas BIC overall are not affected by it. The rabbit model presented here supports the importance of angiogenesis in the process of peri‐implant bone formation.
Effects of a novel calcium titanate coating on the osseointegration of blasted endosseous implants in rabbit tibiae
Authors: Suh Jo‐Young , Jeung Oh‐Cheol , Choi Byung‐Ju , Park Jin‐Woo
Published: February 2007

Objective: The purpose of this study was to investigate the effects of a nanostructured calcium coating on the surfaces of blasted Ti implants on peri‐implant bone formation in the rabbit tibiae.

Material and methods: Threaded implants (3.75 mm in diameter, 6 mm in length) were roughened by hydroxyapatite (HA) blasting (control; blasted implants). The implants were then hydrothermally treated in a Ca‐containing solution for 24 h to prepare Ca‐incorporated Ti surfaces (experimental; blasted/Ca implants). Surface characterizations were performed by scanning electron microscopy and stylus profilometry before and after Ca coating. Forty‐two implants (21 control and 21 experimental) were placed in the proximal tibiae of seven New Zealand White rabbits. Each rabbit received six implants. To evaluate the effects of the nanostructured Ca coating on the peri‐implant bone‐healing response, removal torque tests and histomorphometric analyses were performed 6 weeks after surgery.

Results: The Ca coating did not significantly change the surface properties produced by blasting at the micron level. Histologically, active bone apposition was observed in the blasted/Ca implants in the marrow space. Compared with the blasted implants, the blasted/Ca implants showed significantly increased bone‐to‐implant contact over the total implant length (P<0.01) and greater mean removal torque values (P<0.05).

Discussion and conclusion: The nanostructured, Ca‐incorporated surface significantly enhanced the peri‐implant bone‐healing response of HA‐blasted Ti implants. It may be concluded that the use of nanostructured, Ca‐coated surfaces may have synergic effects in enhancing osseointegration of blasted Ti implants due to their micron‐scaled surface properties and biologically active surface chemistry.
Peri‐implant hard and soft tissue integration to dental implants made of titanium and gold
Authors: Abrahamsson Ingemar , Cardaropoli Giuseppe
Published: February 2007

Objectives: The aim of the study is to compare the peri‐implant hard and soft tissue integration around dental implants made of commercially pure (c.p.) titanium or a gold alloy but with the same shape and surface roughness.

Material and methods: In four beagle dogs, all mandibular premolars were extracted. Three months later, four experimental non‐submerged implants were placed in each edentulous premolar region. Each implant comprised three different zones: zone A (coronal), zone B (central) and zone C (apical). Each zone was made of either c.p. titanium or a gold alloy. Four different combinations of metal and zone were used. A plaque control program was initiated and 6 months later, the animals were sacrificed and biopsies were obtained. The biopsies including the implant and the surrounding tissues were processed for ground sectioning.

Results: The height of the peri‐implant mucosa and the length of the barrier epithelium were similar at the four experimental sites. The marginal bone level in the different metal combinations was located between 4.5 and 4.8 mm apical of the implant rim. The percent of mineralized bone that was in direct contact with the implant surface (BIC%) was consistently greater in the marginal than in the apical portion of the implants. The BIC% for the marginal and apical zone were consistently greater for implant portions made of titanium than for portions made of gold alloy (zone B: 42.7% vs. 36.5%, zone C: 33.2% vs. 19%).

Conclusions: Osseointegration was achieved to surfaces made of both c.p. titanium and a gold alloy. BIC% was higher at titanium than at gold surfaces. Moreover, the peri‐implant soft tissue dimensions were not influenced by the metal used in the ‘marginal’ zone of the implant.
Bone healing in critical‐size defects treated with bioactive glass/calcium sulfate: a histologic and histometric study in rat calvaria
Authors: Furlaneto Flávia A. C. , Nagata Maria J. H. , Fucini Stephen E. , Deliberador Tatiana M. , Okamoto Tetuo , Messora Michel R.
Published: February 2007

Objective: The purpose of this study was to analyze histologically the influence of bioactive glass (BG) with or without a calcium sulfate (CS) barrier on bone healing in surgically created critical‐size defects (CSD) in rat calvaria.

Material and methods: A CSD was made in each calvarium of 48 rats. They were divided into three groups: C (control): blood clot only; BG: defect filled with BG; and BG/CS: defect filled with BG covered by a CS barrier. Animals were euthanized at 4 or 12 weeks. Formation of new bone was evaluated histomorphometrically.

Results: No defect completely regenerated with bone. BG particles were observed in Groups BG and BG/CS at both periods of analysis. The thickness throughout the healing area in Groups BG and BG/CS was similar to the original calvarium, while Group C presented a thin connective tissue in the center of the defect in both periods of analysis. At 4 weeks, Groups C and BG/CS presented significantly more bone formation than Group BG. No significant differences were found between Groups C and BG/CS. At 12 weeks, no significant differences in the amount of bone formation were observed among the three groups. When comparing 4 and 12 weeks, there was a significant increase in new bone formation within groups BG and BG/CS, but not C.

Conclusion: BG particles, used with or without a CS barrier, maintained the volume and contour of the area grafted in CSD. However, they did not lead to a significant difference in bone formation when compared with control at 12 weeks post‐operative.