bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the ultrasound influence in the cutaneous penetration of d‐panthenol: test in vitro
Authors: Zague V , Polacow M L O , Pires‐de‐Campos M S M , Leonardi G R
Published: September 2009

Background  d‐panthenol is a popular additive in cosmetic and pharmaceutical preparations. However, in order for this vitamin to provide skin benefits, it must penetrate the stratum corneum.

Objective  To verify the penetrability of d‐panthenol in the skin and evaluate the effect of ultrasound on the cutaneous penetration of this vitamin.

Methods  The diffusion cell technique with pig skin as the membrane, distilled water as the receptor solution, and a hydrophilic d‐panthenol gel were used for the research. The experimental groups were gel + d‐panthenol (10%) and gel + d‐panthenol (10%) + ultrasound. The receptor solution was collected at predetermined times and the amount of d‐panthenol was determined by using a spectrophotometer at 406 nm.

Results  Ultrasound resulted in a statistically significant increase (P < 0.05) in the penetration of d‐panthenol at 2, 60, and 240 min.

Conclusion  d‐panthenol penetration through the pig's skin is enhanced through the use of ultrasound.
Corruption in Africa – Part 2
Authors: Mbaku John Mukum
Published: September 2009

In order to succeed in minimizing corruption in the African countries, one must start by examining the nature of institutional arrangements in each country with a review to modifying them. This calls for the reconstruction and reconstitution of the post‐colonial state through democratic constitution making to provide a new set of laws and institutions that reflects the values of each country’s relevant stakeholders. Most of today’s African countries have incentive structures, which actually encourage and enhance corruption. Increasing government intervention in the market‐place is not likely to reduce corruption as the evidence from more than 50 years of government attempts to control venality in Africa’s public sectors shows. The most effective way to deal with corruption in Africa is to engage the people in comprehensive institutional reforms that modify existing incentives and produce new ones, which are capable of successfully inducing participants in both political and economic markets to undertake only activities that produce the outcomes desired by society. Thus, to cleanup corruption from the African economies, improve both productive and allocative efficiency, and generally enhance development, national leaders must engage their people in democratic institutional reforms to provide society with transparent, accountable, and participatory governance structures.
Bartolomé de las Casas and the African Slave Trade
Authors: Clayton Lawrence
Published: September 2009

A revisionist view of Bartolomé de las Casas as the ‘author’ of the introduction of African slaves to the Indies/Americas in the early 16th century. The article details Las Casas’ thinking and actions and concludes that while Las Casas did—among other contemporaries—suggest the importation of African slaves to lift the burden of oppression off the Amerindians, his perspective and view was altered radically in the last third of his life. The article explores the meaning of African slavery in the context of the place and time where Las Casas grew up—Andalucia in southern Spain—where slavery was quite different from the way it developed on the plantations of the Americas. And the article relates how Las Casas’ theoretical and practical defense of Amerindians eventually was extended by Las Casas’ into a defense of liberty for all men, including African slaves.
Z and Mmalton‐1‐antitrypsin deficiency‐associated hepatocellular carcinoma: a genetic study
Authors: Francalanci Paola , Santorelli Filippo M. , Saccani Simona , Bonetti Maria F. , Medicina Daniela , Coni Pierpaolo , Faa Gavino , Callea Francesco
Published: September 2009

Background: The histological hallmark of α‐1‐antitrypsin deficiency (AATD) is the presence of periodic acid‐Schiff diastase (PASD)‐resistant positive globules in hepatocytes, with a heterogeneous distribution. It is noteworthy that hepatocellular carcinoma (HCC) arises specifically from the AAT‐negative areas but the reason for this remains unclear.

Aim: To determine whether the different distribution of AAT globules within neoplastic and non‐neoplastic hepatocytes is the result of a self‐induced correction of the genetic defect.

Patients and Methods: Two HCV‐positive patients with AATD‐associated HCC were studied. One patient harboured a compound heterozygous PiSZ genotype whereas the other showed the rarer PiMMmalton in heterozygosity. In both cases, neoplastic hepatocytes appeared globule devoid, while non‐neoplastic hepatocytes showed intracytoplasmic accumulation of PASD‐positive globules. Laser‐assisted microdissection was used to assess a genotype/phenotype correlation in single liver cells from HCC and from non‐neoplastic hepatocytes.

Results: Direct sequencing of DNA purified from globule‐devoid and globule‐filled hepatocytes demonstrated that all liver cells carried the same mutant genetic background.

Conclusion: Our findings indicate that (i) both variants of HCC arising in AAT deficiency (Z and Mmalton) do not accumulate the mutant protein and (ii) the different phenotypic appearance of hepatocytes is not the result of a retromutation during neoplastic transformation, but other mechanisms should be investigated.
Tectonic setting and sedimentology of Ganga River sediments, India
Authors: SINGH ADAL , BHARDWAJ BISHESHWAR D. , AHMAD ABUL H. M.
Published: September 2009

The Ganga basin provides a present‐day example of a peripheral foreland basin. The course of the river is controlled by Himalayan tectonics. Three main types of architectural elements, such as channels (CH), sandy bedforms (SB) and overbank fines (OF) have been developed in Ganga River sediments. The channels (CH) include gravelly (Gs) and sandy channel (Ss) lithofacies. The sandy bedforms (SB) include trough cross‐stratified (St), planar cross‐stratified (Sp), horizontal stratified (Sh), sandy massive (Sm) and climbing ripple cross‐laminated (Sr) lithofacies, all of which are active channel deposits. The overbank fines (OF) include massive silt and clay (Fm), parallel laminated silt and clay (FI) and climbing ripple cross‐laminated (Sr) lithofacies. Mega units have been developed in the lower part of the active channel deposits, while small units have been developed in the upper part of active channel deposits, in inactive channel deposits and overbank fines. This study illustrates the seasonal and tectonic control on sedimentation. Petrofacies studies of the sediments indicate a recycled orogen provenance. The sediments are derived from rapidly uplifted fault blocks comprising granite, gneiss and basic and ultrabasic rocks. Lack of textural and compositional maturity suggests a local source of derivation. The principal control on sand composition is source lithology. The hot and humid climate may slightly increase the content of quartz in sand derived from reworked foreland basin sediments. but the effect is neither sufficient to shift the sand compositions out of the recycled orogen field nor does it obscure composition mixing patterns.
Guideline concordant venous ulcer care predicts healing in a tertiary care Veterans Affairs Medical Center
Authors: Olson Jonathan M. , Raugi Gregory J. , Nguyen Viet Q. , Yu Onchee , Reiber Gayle E.
Published: September 2009

This study describes the impact of 80% adherence to guideline concordant care for compression therapy, moist wound‐healing environment, and debridement on venous ulcer outcomes. The retrospective cohort design included patients from a tertiary care Veterans Affairs Medical Center from October 2003 to September 2007. During this 5‐year interval, 155 patients with 400 venous ulcers met study inclusion. A majority of ulcers (n=362) healed, with an average time to healing of 18.1 weeks (range 2–209 weeks, median 10.4 weeks). From the multivariate Poisson regression, the likelihood of ulcer healing increased when compression therapy was provided during at least 80% of visits (relative risk [RR], 1.93; 95% confidence interval [CI], 1.27–2.92) or when a moist wound‐healing environment was provided during at least 80% of visits (RR, 1.63; 95% CI, 1.09–2.42). Debridement alone was not significantly associated with ulcer healing (RR, 1.0; 95% CI, 0.61–1.64). Patients who received all three treatments during at least 80% of their visits were more likely to heal than those who received < 80% treatment (RR, 2.52; 95% CI, 1.53–4.16). Guideline concordant venous ulcer care was significantly associated with venous ulcer healing, when provided at 80% or more of patient visits.
A multicenter clinical trial of recombinant human GM‐CSF hydrogel for the treatment of deep second‐degree burns
Authors: Zhang Liping , Chen Jiong , Han Chunmao
Published: September 2009

Wound healing is a complex and dynamic biological process. The efficacy and safety of a recombinant human granulocyte‐macrophage colony‐stimulating factor (rhGM‐CSF) hydrogel to promote deep‐second‐degree burn wound healing is evaluated in this study. In this multicenter, randomized, double‐blind, and placebo‐controlled clinical trial, 90 patients with deep second‐degree burns were randomly assigned into two groups. Complete healing time and percentage of wound healing at different time points were observed and side effects were recorded. A statistically significant difference was noted at each time point (p<0.01). No side effects were observed. These results suggest that rhGM‐CSF hydrogel can significantly accelerate deep second‐degree burn wound healing and is considered to be safe.
Homeostasis of the epidermal barrier layer: A theory of how occlusion reduces hypertrophic scarring
Authors: O'Shaughnessy Kristina D. , De La Garza Mauricio , Roy Nakshatra K. , Mustoe Thomas A.
Published: September 2009

The mechanism of hypertrophic scar reduction using silicone gel sheeting remains elusive. We hypothesize that the decrease in scar formation is due to occlusion and homeostasis of the barrier layer. Using an established model of hypertrophic scarring, rabbits were divided into four groups and scars were tape‐stripped or occluded with Kelocote, Cavilon, or Indermil, with each rabbit serving as its own internal control. All wounds were harvested on day 28 and examined histologically to measure the scar elevation index (SEI), epithelial thickness, and cellularity. Immunohistochemistry fluorescence was used to quantify inflammation in the dermis. Transepidermal water loss (TEWL) was measured for each occlusive agent and tape stripping. Ultrastructural analysis was performed by electron microscopy. Kelocote, Cavilon, and Indermil all significantly decreased SEI when compared with controls. Each of the occlusive treatments was shown to decrease TEWL while tape stripping increased TEWL. Tape stripping significantly increased the SEI, epithelial thickness, and cellularity. Immunostaining for macrophages showed increased density of inflammatory cells in the tape‐stripped scars. Under electron microscopy, the tape‐stripped wounds displayed extensive inflammation and keratinocyte damage. Both unwounded skin and occlusion‐treated scars did not display these characteristics. In conclusion, hypertrophic scarring was reduced regardless of occlusive method used. Furthermore, repeated disruption of the permeability barrier by tape stripping led to an increase in scarring. Ultrastructural analysis suggests that occluded wounds may be in an advanced state of wound repair. Occlusion may mediate its effects through establishing homeostasis of the epidermal barrier layer.
Accelerated closure of skin wounds in mice deficient in the homeobox gene Msx2
Authors: Yeh Jennifer , Green Lydia M. , Jiang Ting‐Xin , Plikus Maksim , Huang Eunice , Chang Richard N. , Hughes Michael W. , Chuong Cheng‐Ming , Tuan Tai‐Lan
Published: September 2009

Differences in cellular competence offer an explanation for the differences in the healing capacity of tissues of various ages and conditions. The homeobox family of genes plays key roles in governing cellular competence. Of these, we hypothesize that Msx2 is a strong candidate regulator of competence in skin wound healing because it is expressed in the skin during fetal development in the stage of scarless healing, affects postnatal digit regeneration, and is reexpressed transiently during postnatal skin wound repair. To address whether Msx2 affects cellular competence in injury repair, 3 mm full‐thickness excisional wounds were created on the back of C.Cg‐Msx2tm1Rilm/Mmcd (Msx2 null) mice and the healing pattern was compared with that of the wild type mice. The results show that Msx2 null mice exhibited faster wound closure with accelerated reepithelialization plus earlier appearance of keratin markers for differentiation and an increased level of smooth muscle actin and tenascin in the granulation tissue. In vitro, keratinocytes of Msx2 null mice exhibit increased cell migration and the fibroblasts show stronger collagen gel contraction. Thus, our results suggest that Msx2 regulates the cellular competence of keratinocytes and fibroblasts in skin injury repair.
HaCaT keratinocytes in co‐culture with Staphylococcus aureus can be protected from bacterial damage by polihexanide
Authors: Wiegand Cornelia , Abel Martin , Ruth Peter , Hipler Uta‐Christina
Published: September 2009

Wound healing is compromised by critical colonization and infection with bacteria. Hence, antimicrobial agents are used clinically to decrease the bacterial load and promote wound healing. Polihexanide (PHMB) has been found to be effective against a broad spectrum of micro‐organisms and is increasingly utilized in rinsing solutions or in combination with wound dressings because of its good biocompatibility. In the present study, a co‐culture of human keratinocytes and Staphylococcus aureus was established to serve as an in vitro model for infected wounds. Incubation of keratinocytes with increasing concentrations of S. aureus led to a dose‐dependent decline of cell viability and proliferation. Lactate dehydrogenase release and interleukin‐8 liberation were found to be elevated under these conditions. Polihexanide dose‐dependently was able to protect keratinocytes from bacterial damage and re‐establish normal human cell proliferation in vitro. Furthermore, a dressing consisting of biocellulose derived from Acetobacter xylinum with the addition of polihexanide was adept to safeguard keratinocytes against S. aureus. In conclusion, the co‐culture system presented embodies a valuable tool as a model system for infected cells in a non‐healing wound. Furthermore, the results obtained support the favorable function of polihexanide in the treatment of infected chronic wounds.
Heterochronic shift between early organogenesis and migration of cephalic neural crest cells in two divergent evolutionary phenotypes of archosaurs: crocodile and ostrich
Authors: Kundrát Martin
Published: September 2009

SUMMARY
Living archosaurs (crocodiles and birds) represent an intriguing evo‐devo model system. Although close in phylogenetic relationship, the two lineages show considerable divergence in trends of phenotypic evolution. The head anatomy of recent crocodilians has changed little in comparison with that of their crocodylomorph ancestors. The head phenotype of the avians (birds), as well as some non‐avian theropods, shows numerous evolutionary innovations that differ considerably from the crocodylomorph pattern. Most of the novel head structures, such as features of the craniofacial skeleton, cranial nerves, head muscles, and integument are derived from the same cellular source common to all archosaurs, the cephalic neural crest (CNC). Therefore, other factors must be involved in the developmental disparity of homologous structures in the aforementioned lineages. The present study analyzes the earliest developmental events that are associated with the appearance of the neural crest cells in the two archosaur models: Crocodylus niloticus and Struthio camelus. I found that both models share unique developmental features, the presence of an unpaired, rostrally migrating population of CNC cells, showing that the two are closely related to each other. On the other hand, the crocodile and the ostrich differ substantially in (1) timing, (2) duration, and (3) expression patterns of the CNC. Compared with the crocodile, the CNC cells in the ostrich (1) migrate much later into the embryonic head, (2) but relocate to their terminal positions faster, and (3) take specifically directed migratory routes in the mandibular/oral region and head/trunk‐interface regions. I suggest that accelerated relocation of CNC cells combined with delayed head organogenesis may represent important innovative conditions in the developmental evolution of a new archosaur head phenotype.
Shared and divergent expression domains on mimeticHeliconiuswings
Authors: Ferguson Laura C. , Jiggins Chris D.
Published: September 2009

SUMMARYHeliconiusbutterfly wing patterns show repeated convergence between species and have adaptive value in mimicry and mate choice, offering an opportunity to connect adaptive changes in phenotype with their underlying genotypes. Here we study forewing ommochrome pigmentation inHeliconius melpomene. We clone two new ommochrome pathway genes for the Lepidoptera,karmoisinandkynurenine formamidase(kf ), and analyze the expression patterns of all known ommochrome genes across pupal wing development. In combination with published work, this generates the first comparative gene expression data for the co‐mimicsHeliconius eratoandH. melpomene. In both speciescinnabarexpression correlates with the forewing band, but the expression pattern ofvermilliondiffers significantly between the mimics. This demonstrates that both shared and divergent expression patterns are associated with mimetic phenotypes betweenHeliconiusspecies. Two genes not studied inH. erato, scarletand possiblykf, also show enhanced expression in the forewing band ofH. melpomene, implying co‐ordinated upregulation of several members of this biosynthetic pathway during pattern formation.
Orthologs of key vertebrate neural genes are expressed during neurogenesis in the annelid Platynereis dumerilii
Authors: Kerner Pierre , Simionato Elena , Le Gouar Martine , Vervoort Michel
Published: September 2009

SUMMARY
The molecular mechanisms underlying the formation and patterning of the nervous system are relatively poorly understood for lophotrochozoans (like annelids) as compared with ecdysozoans (especially Drosophila) and deuterostomes (especially vertebrates). Therefore, we have undertaken a candidate gene approach to study aspects of neurogenesis in a polychaete annelid Platynereis dumerilii. We determined the spatiotemporal expression for Platynereis orthologs of four genes (SoxB, Churchill, prospero/Prox, and SoxC) known to play key roles in vertebrate neurogenesis. During Platynereis development, SoxB is expressed in the neuroectoderm and its expression switches off when committed neural precursors are formed. Subsequently, Prox is expressed in all differentiating neural precursors in the central and peripheral nervous systems. Finally, SoxC and Churchill are transcribed in patterns consistent with their involvement in neural differentiation. The expression patterns of Platynereis SoxB and Prox closely resemble those in Drosophila and vertebrates—this suggests that orthologs of these genes play similar neurogenic roles in all bilaterians. Whereas Platynereis SoxC, like its vertebrate orthologs, plays a role in neural cell differentiation, related genes in Drosophila do not appear to be involved in neurogenesis. Finally, conversely to Churchill in Platynereis, vertebrate orthologs of this gene are expressed during neuroectoderm formation, but not later during nerve cell differentiation; in the insect lineage, homologs of these genes have been secondarily lost. In spite of such instances of functional divergence or loss, the present study shows conspicuous similarities in the genetic control of neurogenesis among bilaterians. These commonalities suggest that key features of the genetic program for neurogenesis are ancestral to bilaterians.
An evolutionary transition of vasa regulation in echinoderms
Authors: Juliano Celina E. , Wessel Gary M.
Published: September 2009

SUMMARY
Vasa, a DEAD box helicase, is a germline marker that may also function in multipotent cells. In the embryo of the sea urchin Strongylocentrotus purpuratus, Vasa protein is posttranscriptionally enriched in the small micromere lineage, which results from two asymmetric cleavage divisions early in development. The cells of this lineage are subsequently set aside during embryogenesis for use in constructing the adult rudiment. Although this mode of indirect development is prevalent among echinoderms, early asymmetric cleavage divisions are a derived feature in this phylum. The goal of this study is to explore how vasa is regulated in key members of the phylum with respect to the evolution of the micromere and small micromere lineages. We find that although striking similarities exist between the vasa mRNA expression patterns of several sea urchins and sea stars, the time frame of enriched protein expression differs significantly. These results suggest that a conserved mechanism of vasa regulation was shifted earlier in sea urchin embryogenesis with the derivation of micromeres. These data also shed light on the phenotype of a sea urchin embryo upon removal of the Vasa‐positive micromeres, which appears to revert to a basal mechanism used by extant sea stars and pencil urchins to regulate Vasa protein accumulation. Furthermore, in all echinoderms tested here, Vasa protein and/or message is enriched in the larval coelomic pouches, the site of adult rudiment formation, thus suggesting a conserved role for vasa in undifferentiated multipotent cells set aside during embryogenesis for use in juvenile development.
Molecular markers comparing the extremely simple body plan of dicyemids to that of lophotrochozoans: insight from the expression patterns of Hox, Otx, and brachyury
Authors: Kobayashi Mari , Furuya Hidetaka , Wada Hiroshi
Published: September 2009

SUMMARY
Because of their extremely simple body plan, dicyemids have long been the subject of phylogenetic controversy, regarding whether their body plan reflects their primitiveness or a degeneration from complex metazoans. Several studies have argued that the simple body plan of dicyemids are likely secondarily derived from higher lophotrochozoan animals, as a result of their endoparasitic, or endosymbiotic, lifestyle in the cephalopod kidney. To clarify the evolution of their simple body plan, we investigated the developmental expression patterns of three important regulatory genes, the central type Hox gene (DoxC), otx, and brachyury homologs in the dicyemid mesozoa, Dicyema orientale. DoxC was expressed in the trunk and tail of the asexually developing vermiform embryo, with clear anterior boundaries. Do‐otx was expressed in the vegetal pole cells of the developing infusoriform embryos, suggesting that the invagination in infusoriform embryo is homologous to the gastrulation of other metazoans. Do‐bra is expressed in the presumptive ventral cells, which are ventral to the opening of the urn cavity. The expression of Do‐bra suggests that the urn cavity opening of the infusoriform embryo is comparable to the stomodium of trochophore larvae. These gene expression patterns provide molecular clues to trace the evolutionary history of degeneration in the dicyemid embryogenesis and life cycle from those of ancestral lophotrochozoan animals.
Nonconvulsive status epilepticus and coma
Authors: Bauer Gerhard , Trinka Eugen
Published: September 2009

Nonconvulsive status epilepticus (NCSE) in a comatose patient cannot be diagnosed without electroencephalography (EEG). In many advanced coma stages, the EEG exhibits continuous or periodic EEG abnormalities, but their causal role in coma remains unclear in many cases. To date there is no consensus on whether to treat NCSE in a comatose patient in order to improve the outcome or to retract from treatment, as these EEG patterns might reflect the end stages of a dying brain. On the basis of EEG, NCSE in comatose patients may be classified as generalized or lateralized. This review aims to summarize the ongoing debate of NCSE and coma and to critically reassess the available literature on coma with epileptiform EEG pattern and its prognostic and therapeutic implications. The authors suggest distinguishing NCSE proper and comatose NCSE, which includes coma with continuous lateralized discharges or generalized epileptiform discharges (coma‐LED, coma‐GED). Although NCSE proper is accompanied by clinical symptoms suggestive of status epilepticus and mild impairment of consciousness, such as in absence status or complex focal status epilepticus, coma‐LED and coma‐GED represent deep coma of various etiology without any clinical motor signs of status epilepticus but with characteristic epileptiform EEG pattern. Hence coma‐LED and coma‐GED can be diagnosed with EEG only. Subtle or stuporous status epilepticus and epilepsia partialis continua–like symptoms in severe acute central nervous system (CNS) disorders represent the borderland in this biologic continuum between NCSE proper and comatose NCSE (coma‐LED/GED). This pragmatic differentiation could act as a starting point to solve terminologic and factual confusion.
Placebo‐corrected efficacy of modern antiepileptic drugs for refractory epilepsy: Systematic review and meta‐analysis
Authors: Beyenburg Stefan , Stavem Knut , Schmidt Dieter
Published: September 2009

Although adjunctive treatment with modern antiepileptic drugs (AEDs) is standard care in refractory epilepsy, it is unclear how much of the effect can be attributed directly to the AEDs and how much to the beneficial changes seen with placebo. Therefore, we performed a systematic review and meta‐analysis of the evidence to determine the placebo‐corrected net efficacy of adjunctive treatment with modern AEDs on the market for refractory epilepsy. Of 317 potentially eligible articles reviewed in full text, 124 (39%) fulfilled eligibility criteria. After excluding 69 publications, 55 publications of 54 studies in 11,106 adults and children with refractory epilepsy form the basis of evidence. The overall weighted pooled‐risk difference in favor of AEDs over placebo for seizure‐freedom in the total sample of adults and children was 6% [95% confidence interval (CI) 4–8, z = 6.47, p < 0.001] and 21% (95% CI 19–24, z = 17.13, p < 0.001) for 50% seizure reduction. Although the presence of moderate heterogeneity may reduce the validity of the results and limit generalizations from the findings, we conclude that the placebo‐corrected efficacy of adjunctive treatment with modern AEDs is disappointingly small and suggest that better strategies of finding drugs are needed for refractory epilepsy, which is a major public health problem.
Extent of initial injury determines language lateralization in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE‐HS)
Authors: Rathore Chaturbhuj , George Annamma , Kesavadas Chandrasekharan , Sankara Sarma P. , Radhakrishnan Kurupath
Published: September 2009

Purpose:  To assess the prevalence and attributes of atypical language lateralization (ALL) in patients with left mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE‐HS).

Methods:  We recruited consecutive patients with left MTLE‐HS, who had undergone resective surgery and had pathologically proven HS. Based on the Wada test, language lateralization was classified into typical (left hemispheric) or atypical (right hemispheric or codominant). We assessed the attributes of patients with ALL using univariate and multivariate analyses.

Results:  Of 124 patients with left MTLE‐HS, 23 (18.5%) had ALL. ALL occurred more frequently in patients with severe initial precipitating injury (IPI), early onset of epilepsy, and a short latent period between IPI and onset of habitual seizures. ALL was more common in patients with bitemporal and extratemporal interictal epileptiform discharges (IEDs) on electroencephalogram (EEG) and extratemporal changes on magnetic resonance imaging (MRI). On multivariate analyses, the age at onset of habitual seizures <6 years, atypical IPI, nonunilateral temporal IEDs, and extratemporal MRI abnormalities independently predicted ALL. The likelihood of ALL was very low (∼1%) when all of these four risk factors were absent, whereas it was very high (>95%), if any three or all four of them were present.

Conclusions:  ALL occurs in one‐fifth of patients with left MTLE‐HS. ALL is more frequent in those with structural or functional extrahippocampal involvement and early onset of epilepsy interrupting the development of normal language networks. Because ALL is uncommon in those with damage/dysfunction restricted to the hippocampus, the hippocampus itself may have only a limited role in determining language lateralization.
Topiramate concentrations in neonates treated with prolonged whole body hypothermia for hypoxic ischemic encephalopathy
Authors: Filippi Luca , La Marca Giancarlo , Fiorini Patrizio , Poggi Chiara , Cavallaro Giacomo , Malvagia Sabrina , Pellegrini‐Giampietro Domenico E. , Guerrini Renzo
Published: September 2009

Purpose:  Therapeutic hypothermia reduces mortality and neurologic impairment in neonates with hypoxic–ischemic encephalopathy. Topiramate exerts a neuroprotective effect in asphyxiated neonatal animal models. However, no studies have investigated the association of hypothermia and topiramate, because topiramate pharmacokinetics during hypothermia and the optimal administration schedule are unknown. The influence of hypothermia on topiramate pharmacokinetics was evaluated in asphyxiated neonates treated with prolonged whole‐body hypothermia and topiramate.

Methods:  Thirteen term newborns were treated with mild or deep whole body hypothermia for 72 h; all received oral topiramate, 5 mg/kg once a day for the first 3 days of life, and seven had concomitant phenobarbital treatment. Topiramate concentrations were measured on serial dried blood spots.

Results:  Topiramate concentrations were within the reference range in 11 of 13 newborns, whereas concentrations exceeded the upper limit in 2 of 13, both newborns on deep hypothermia. Topiramate concentrations reached a virtual steady state in nine newborns, for whom pharmacokinetic parameters were calculated. Values of topiramate maximal and minimal concentration, half‐life, average concentration, and area under the time—concentration curve resulted in considerably higher values than those reported in normothermic infants. With respect to normothermic infants, time of maximal concentration was mildly delayed and apparent total body clearance was lower, suggesting slower absorption and elimination. Pharmacokinetic parameters did not differ significantly between infants on deep versus mild hypothermia and in those on topiramate monotherapy versus add‐on phenobarbital.

Conclusion:  Most neonates on prolonged hypothermia treated with topiramate 5 mg/kg once a day exhibited drug concentrations within the reference range for the entire treatment duration.
PHYLOGENY OF FOUR DINOPHYSIACEAN GENERA (DINOPHYCEAE, DINOPHYSIALES) BASED ON rDNA SEQUENCES FROM SINGLE CELLS AND ENVIRONMENTAL SAMPLES1
Authors: Handy Sara M. , Bachvaroff Tsvetan R. , Timme Ruth E. , Wayne Coats D. , Kim Sunju , Delwiche Charles F.
Published: September 2009

Dinoflagellates are a highly diverse and environmentally important group of protists with relatively poor resolution of phylogenetic relationships, particularly among heterotrophic species. We examined the phylogeny of several dinophysiacean dinoflagellates using samples collected from four Atlantic sites. As a rule, 3.5 kb of sequence including the nuclear ribosomal genes SSU, 5.8S, LSU, plus their internal transcribed spacer (ITS) 1 and 2 regions were determined for 26 individuals, including representatives of two genera for which molecular data were previously unavailable, Ornithocercus F. Stein and Histioneis F. Stein. In addition, a clone library targeting the dinophysiacean ITS2 and LSU sequences was constructed from bulk environmental DNA from three sites. Three phylogenetic trees were inferred from the data, one using data from this study for cells identified to genus or species (3.5 kb, 28 taxa); another containing dinoflagellate SSU submissions from GenBank and the 12 new dinophysiacean sequences (1.9 kb, 56 taxa) from this study; and the third tree combing data from identified taxa, dinophysiacean GenBank submissions, and the clone libraries from this study (2.1 kb, 136 taxa). All trees were congruent and indicated a distinct division between the genera Phalacroma F. Stein and Dinophysis Ehrenb. The cyanobionts containing genera Histioneis and Ornithocercus were also monophyletic. This was the largest molecular phylogeny of dinophysoid taxa performed to date and was consistent with the view that the genus Phalacroma may not be synonymous with Dinophysis.
CELL CYCLE AND CELL MORTALITY OF ALEXANDRIUM MINUTUM (DINOPHYCEAE) UNDER SMALL‐SCALE TURBULENCE CONDITIONS1
Authors: Llaveria Gisela , Figueroa Rosa Isabel , Garcés Esther , Berdalet Elisa
Published: September 2009

Decreased net population growth rates and cellular abundances have been observed in dinoflagellate species exposed to small‐scale turbulence. Here, we investigated whether these effects were caused by alterations in the cell cycle and/or by cell mortality and, in turn, whether these two mechanisms depended on the duration of exposure to turbulence. The study was conducted on the toxic dinoflagellate Alexandrium minutum Halim, with the same experimental design and setup used in previous studies to allow direct comparison among results. A combination of microscopy and Coulter Counter measurements allowed us to detect cell mortality, based on the biovolume of broken cells and thecae. The turbulence applied during the exponential growth phase caused an immediate transitory arrest in the G2/M phase, but significant mortality did not occur. This finding suggests that high intensities of small‐scale turbulence can alter the cell division, likely affecting the correct chromosome segregation during the dinomitosis. When shaking persisted for >4 d, mortality signals and presence of anomalously swollen cells appeared, hinting at the activation of mechanisms that induce programmed cell death. Our study suggests that the sensitivity of dinoflagellates to turbulence may drive these organisms to find the most favorable (calm) conditions to complete their division cycle.
Different Mechanisms Underlying Consecutive, Postoperative Atrial TachyArrhythmias in a Fontan Patient
Authors: DE GROOT NATASJA M.S. , BLOM NICO , VD WALL ERNST E. , SCHALIJ MARTIN J.
Published: September 2009

Introduction:

Atrial tachyarrhythmias (AT) frequently develop later after a Fontan operation and can be successfully treated by ablative therapy. However, new arrhythmias often develop.

Methods and Results:

Consecutive AT emerging in a Fontan patient were ablated using three‐dimensional electro‐anatomical mapping. During a 6‐year period, nine different AT were ablated, including intraatrial reentrant AT (N = 5), focal AT (N = 3), and focal atrial fibrillation (N = 1) originating from distinct right atrial sites.

Conclusion:

In a Fontan patient, successive AT can be caused by different mechanisms. These AT are most likely the result of progressive atrial cardiomyopathy and can be treated by catheter ablation.
Two Ventricular Tachycardias with Cycle Length and QRS Alternans: Insights into the Mechanism from Mapping and Ablation of the Tachycardias
Authors: KALBFLEISCH STEVEN , HART DAVID , WEISS RAUL
Published: September 2009

This case describes a patient with two separate foci of idiopathic ventricular tachycardia in the right ventricle. Both of the tachycardias manifested cycle length and QRS alternans. Both were successfully ablated and information from the electrophysiologic study and ablation procedure indicated that both tachycardias were focal, secondary to triggered activity, and that the best model to explain the cycle length and QRS alternans during tachycardia was that of “self‐entraining modulated parasystole.”
Ventricular Tachycardia in a Patient with Inclusion‐Body Myositis
Authors: PRUTKIN JORDAN M. , PATTON KRISTEN K.
Published: September 2009

We report a patient with a clinical history of inclusion‐body myositis presenting with monomorphic ventricular tachycardia. Comprehensive evaluation demonstrated no evidence of coronary artery disease or cardiomyopathy. Programmed electrical stimulation induced the patient's clinical tachycardia as well as a second monomorphic ventricular tachycardia of a different morphology. At the time of implantable cardioverter‐defibrillator implant, biopsy of the pectoralis major muscle was performed, which confirmed the diagnosis of inclusion‐body myositis. Ventricular tachycardia has not previously been reported in a patient with inclusion‐body myositis.
Acute Perforation in Spite of Implantation with an “Antiperforation” Defibrillator Lead
Authors: CHIEN WALTER W. , CHIN JOHN
Published: September 2009

A 74‐year‐old male underwent implantation of implantable cardioverter defibrillator per multicenter automatic defibrillator trial two criteria. The new St. Jude Medical Riata STS Durata defibrillator lead (St. Jude Medical, Sylmar, CA, USA) was used. This lead has a slight curve at the right ventricle shock coil and a silicone tip designed to decrease tip pressure at the endocardium interface. We presented a case of acute perforation during implantation of this lead. The patient was treated with pericardiocentesis and recovered.
Arrhythmogenic Right Ventricular Cardiomyopathy in an Octogenarian Presenting with Ventricular Tachycardia
Authors: KOULOURIS SPYRIDON , PASTROMAS SOCRATES , SAKELLARIOU DIMITRIS , KRATIMENOS THEODOROS , MANOLIS ANTONIS S.
Published: September 2009

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is one of the major causes of sudden death. Myocardial atrophy with subsequent fibro‐fatty replacement predominantly affects right ventricular myocardium and results in global and regional dysfunction as well as areas of slow conduction and dispersion of refractoriness, which are prerequisites for reentrant ventricular tachyarrhythmias. ARVC is commonly presented in patients <65 years old. However, few cases of elderly people suffering from this cardiomyopathy have been reported in the literature. We present a case of an 82‐year‐old woman with sustained ventricular tachycardia due to first diagnosed ARVC.
Predicting mechanisms across scales: amplified effects of abiotic constraints on the recruitment of yewTaxus baccata
Authors: Sanz Rubén , Pulido Fernando , Nogués‐Bravo David
Published: September 2009

Efforts to disentangle the mechanisms underlying large‐scale spatial patterns need to rely on multi‐scale approaches. We illustrate this key issue by analyzing the spatial consistency across scales of the effects of abiotic constraints on the regeneration of English yewTaxus baccatain Europe. We hypothesized that the recruitment rates in a given population would be strongly affected by water availability, which should result in a predictable pattern of regeneration success at regional and continental scales. Accordingly, we predicted: 1) at the regional scale water availability should be higher in sites occupied by yew populations than in random locations; 2) at the regional scale regeneration success should decrease when water availability is lower; and 3) at the continental scale, regeneration success should also decrease where water availability is lower, resulting in decreasing regeneration southwards. To test these predictions we first monitored seedling emergence and survival in two central Spanish populations over two years, and confirmed that yew recruitment is limited by water availability. Additionally, our analysis supported predictions 1 and 2: water availability strongly affected yew presence and regeneration success. At the continental scale (prediction 3), our results confirmed lower regeneration in southern European populations. Assessing the effect of climatic constraints across scales in key population parameters can help to improve large‐scale assessments of impacts of climate change on biodiversity.
Assessing ecosystem threats from global and regional change: hierarchical modeling of risk to sagebrush ecosystems from climate change, land use and invasive species in Nevada, USA
Authors: Bradley Bethany A.
Published: September 2009

Global change poses significant challenges for ecosystem conservation. At regional scales, climate change may lead to extensive shifts in species distributions and widespread extirpations or extinctions. At landscape scales, land use and invasive species disrupt ecosystem function and reduce species richness. However, a lack of spatially explicit models of risk to ecosystems makes it difficult for science to inform conservation planning and land management. Here, I model risk to sagebrush (Artemisia spp.) ecosystems in the state of Nevada, USA from climate change, land use/land cover change, and species invasion. Risk from climate change is based on an ensemble of 10 atmosphere‐ocean general circulation model (AOGCM) projections applied to two bioclimatic envelope models (Mahalanobis distance and Maxent). Risk from land use is based on the distribution of roads, agriculture, and powerlines, and on the spatial relationships between land use and probability of cheatgrass Bromus tectorum invasion in Nevada. Risk from land cover change is based on probability and extent of pinyon‐juniper (Pinus monophylla; Juniperus spp.) woodland expansion. Climate change is most likely to negatively impact sagebrush ecosystems at the edges of its current range, particularly in southern Nevada, southern Utah, and eastern Washington. Risk from land use and woodland expansion is pervasive throughout Nevada, while cheatgrass invasion is most problematic in the northern part of the state. Cumulatively, these changes pose major challenges for conservation of sagebrush and sagebrush obligate species. This type of comprehensive assessment of ecosystem risk provides managers with spatially explicit tools important for conservation planning.
The role of microRNAs in normal and malignant hematopoiesis
Authors: Vasilatou Diamantina , Papageorgiou Sotirios , Pappa Vassiliki , Papageorgiou Efstathios , Dervenoulas John
Published: September 2009

MicroRNAs are small non‐coding RNAs that act at the post‐transcriptional level, regulating protein expression by repressing translation or destabilizing mRNA target. Because of their discovery, microRNAs have been associated with almost every normal cell function, including proliferation, differentiation and apoptosis. Several lines of evidence suggest that they have an important role in normal hematopoiesis as exemplified by the role of mir‐155 and mir‐150 in the differentiation of B and T lymphocytes, the suppressive role of mir‐221 and mir‐222 in erythroid differentiation, the inhibitory effect of mir‐181 on hematopoietic differentiation and the induction of myeloid differentiation by mir‐223. Moreover, they play a role both as oncogenes, probably by a variety of mechanisms, namely through elimination of tumor suppressor proteins, or as tumor suppressor genes by targeting oncogenic mRNAs. Their aberrant expression has been associated with solid tumors and hematopoietic malignancies as suggested by the frequent deletion of mir‐15a and mir‐16‐1 in chronic lymphocytic leukemia, the increased levels of mir‐155 in diffuse large B‐cell lymphomas and the increased levels of mir‐181 in acute myeloid leukemia M1 and M2. The purpose of this review is to summarize current knowledge on the role of microRNAs in normal hematopoiesis and hematopoietic malignancies and, moreover, to highlight their role as potential therapeutic tools.
Elevated serum parathormone levels are associated with myocardial iron overload in patients with β‐thalassaemia major
Authors: Dimitriadou Meropi , Christoforidis Athanasios , Economou Marina , Tsatra Ioanna , Vlachaki Efthimia , Fidani Liana , Katzos George , Athanassiou‐Metaxa Miranda
Published: September 2009

Objectives:  Despite advances in conventional treatment, iron‐induced cardiomyopathy is still the most frequent cause of death among patients with β‐thalassaemia major. Recent studies have correlated increased myocardial iron content to decreased levels of vitamin D in thalassaemic patients. The aim of this study was to measure parathormone (PTH) and metabolites of vitamin D and consequently to investigate whether these parameters predispose to myocardial iron overload in patients with β‐thalassaemia major.

Methods:  In 62 patients (29 M and 33 F, mean age: 22.79 ± 6.18 yr) with β‐thalassaemia major levels of intact parathormone (iPTH) and vitamin D metabolites [25(ΟH)D3 and 1,25(ΟH)2D3] were measured in serum. Additionally, estimation of myocardial iron content was performed by magnetic resonance imaging, whereas mean serum ferritin concentrations were calculated for 1 yr prior to the study.

Results:  Results showed markedly decreased levels of serum 25(OH)D3 in 37 patients (60%), whereas 7 patients (11%) had borderline 25(OH)D3 levels (between 50 and 75 nmol/L). Serum iPTH levels were significantly higher in patients having increased myocardial iron compared to those having normal myocardial iron (44.04 ± 22.09 pg/mL vs. 31.39 ± 14.30 pg/mL, P = 0.017). Multivariant regression analysis identified PTH levels as the major predictor of increased myocardial iron.
Dendritic cell altered states: what role for calcium?
Authors: Salter Russell D. , Watkins Simon C.
Published: September 2009

Summary:  Ca2+‐driven responses in dendritic cells (DCs) are less well characterized than in lymphocytes. When DCs undergo a sequence of activation/maturation events, typically beginning with exposure to pathogens in the periphery, Ca2+ entry into the cytosol from stores in the endoplasmic reticulum or from outside the cell can occur at various steps and participate in intracellular signaling. However, not all cellular processes identified in these cells are Ca2+ dependent. While immigration of precursor DCs into the peripheral tissues as well as emigration to secondary lymphoid sites following microbial challenge depend on processes that involve Ca2+, other processes such as DC maturation in response to Toll‐like receptor agonist stimulation appear not to. Certain microbial stimuli and host‐derived chemokines induce Ca2+ entry that is important for the induced responses. In this article, we review the current state of our understanding of the role of Ca2+ in DC biology and argue that homeostatic control of Ca2+ levels in these cells is critical for maintaining their proper function. We also consider evidence for intercellular transmission of Ca2+ signals between DCs that are physically linked by thin membranous extensions termed tunneling nanotubules.