bluuebunny/crossref_metadata_2025 huggingface dataset:
Boosted protease inhibitors as a therapeutic option in the treatment of HIV‐infected children
Authors: Ramos JT
Published: July 2009

Objective

Paediatric HIV treatment must address various special considerations. Administration of pharmacokinetically enhanced protease inhibitors (PIs) can improve paediatric therapeutic outcomes. The objective of this study was to review the use of boosted PI regimens in children.

Methods

Systematic literature searches of published manuscripts and conference databases using generic drug names and specific keywords were performed to ensure thorough and balanced reporting of available data.

Results

Boosted PI regimens offer multiple options across a range of ages and are efficacious in naïve and experienced children; safety and tolerability are similar to those observed in adults. Novel boosted PI simplification approaches may foster adherence and diminish resistance.

Conclusions

Boosted PIs are key components of first‐ and second‐line treatments in children. Identifying factors associated with the response to highly active antiretroviral therapy in children may ultimately permit individualized therapies.
Active tuberculosis and Mycobacterium tuberculosis latent infection in patients with HIV/AIDS
Authors: Gutierrez EB , Gomes V , Picone CM , Suga H , Atomiya AN
Published: July 2009

Objectives

Tuberculosis (TB) remains an important disease associated with HIV infection and AIDS in Brazil, even in a setting of free access to antiretroviral therapy (ART) and TB treatment. In previous studies, isoniazid therapy (IT) for latent infection with Mycobacterium tuberculosis (LIMTb) was found to reduce the risk of TB by 62% in patients with a tuberculin test (TT)>5 mm. The objectives of this study were to investigate the occurrence of TB, the prevalence of LIMTb and the coverage of the TT and IT, and to estimate the number of missed opportunities to prevent TB in patients with HIV/AIDS.

Methods

A random sample of patients with HIV/AIDS was selected; data from the medical files were obtained, and a TT was performed in consenting subjects.

Results

In the 203 subjects included in the study, TB occurrence was 13.3%, LIMTb prevalence was 20% and the coverage of the TT and IT was 59.2 and 55%, respectively. Patients with TB had a lower nadir CD4 cell count, but their CD4 recovery was comparable to that of non‐TB patients. Patients with LIMTb always had a higher CD4 cell count.

Conclusions

By expanding the coverage of the TT and IT to nearly 100%, we could more than double the number of prevented cases of TB. TB prevention programmes must be reinforced to reduce the number of missed opportunities for diagnosis, and IT must be improved to reduce TB among patients with HIV/AIDS. Empowering patients with knowledge about TB, the preventive role of IT and the need for an annual TT may be the best way of lowing rates of TB in patients with HIV/AIDS.
Changes in biomarkers of cardiovascular risk after a switch to abacavir in HIV‐1‐infected individuals receiving combination antiretroviral therapy
Authors: Kristoffersen US , Kofoed K , Kronborg G , Benfield T , Kjaer A , Lebech A‐M
Published: July 2009

Objectives

To investigate, using a longitudinal design, whether biomarkers of cardiovascular risk change after a switch to an abacavir (ABC)‐containing regimen in HIV‐1‐infected individuals already receiving combination antiretroviral therapy (ART).

Methods

Thirty‐five HIV‐1‐infected individuals who switched ART to an ABC‐containing regimen were identified. Twenty‐two HIV‐1‐infected individuals who switched ART from and to a non‐ABC‐containing regimen served as controls. Plasma concentrations of soluble vascular cell adhesion molecule 1 (sVCAM‐1), soluble intercellular adhesion molecule 1 (sICAM‐1), matrix metallopeptidase 9 (MMP9), myeloperoxidase (MPO) and high sensitivity C‐reactive protein (hs‐CRP) were measured in blood samples before the switch in ART, and 3 months and 12 months afterwards. Log10‐transformed data were compared with paired t‐tests.

Results

Median MMP9 increased from 45.5 to 64.4 μg/mL after 3 months of ABC exposure (P=0.011) and remained increased after 12 months (64.2 μg/mL; P=0.013). MPO increased from median 8.8 to 10.4 μg/mL (P=0.036) after 3 months of ABC exposure but was not increased after 12 months of exposure (9.1 μg/mL). hs‐CRP increased from 3.3 to 4.2 μg/mL after 3 months (P=0.031) but was not increased after 12 months of exposure (2.8 μg/mL). Neither sVCAM‐1 nor sICAM‐1 changed after the initiation of ABC. No changes were observed in the control group.

Conclusions

MMP9, MPO and hs‐CRP all increased after a switch in ART to an ABC‐containing regimen. This indicates increased cardiovascular risk in viral load‐suppressed HIV‐1‐infected individuals switching to ABC and proposes a proinflammatory potential as the underlying pathogenetic mechanism.
A Retrograde Step: The Potential Impact of High Visibility Uniforms Within Youth Justice Reparation
Authors: PAMMENT NICHOLAS , ELLIS TOM
Published: July 2009

Abstract: The Labour government has recently introduced uniforms for adult offenders undertaking community service as part of their community orders. There have also been calls within the youth justice arena to introduce uniforms to young offenders undertaking reparation. Through observations, interviews and questionnaires with young offenders and their supervising staff, we argue that the introduction of uniforms will be counterproductive on a number of levels. In short, it would be a retrograde step. We conclude with a suggestion on how to increase the visibility of unpaid work by offenders within the community, without the negative impact of uniforms.
Perspectives on narrative methods in social work research
Authors: Larsson Sam , Sjöblom Yvonne
Published: July 2009

Larsson S, Sjöblom Y. Perspectives on narrative methods in social work research

Int J Soc Welfare 2010: 19: 272–280 © 2009 The Author, Journal compilation © 2009 Blackwell Publishing Ltd and the International Journal of Social Welfare.

The narrative turn has entered many different academic disciplines and is now also emerging in social work. This article focuses on a discussion of the possibilities and limitations of doing narrative research in social work, including a scrutiny of definitions and of a number of theoretical and methodological arguments often used by some of the leading narrative researchers.
Cartographies of Race and Class: Mapping the Class‐Monopoly Rents of American Subprime Mortgage Capital
Authors: WYLY ELVIN , MOOS MARKUS , HAMMEL DANIEL , KABAHIZI EMANUEL
Published: July 2009

The worst global financial crisis since the Great Depression has drawn worldwide attention to America's subprime mortgage sector and its linkages with predatory exploitation in working‐class and racially marginalized communities. During nearly two decades of expansion, agents of subprime capital fought regulation and reform by (1) using the doctrine of risk‐based pricing to equate financial innovation with democratized access to capital, (2) appealing to the cultural myths of the ‘American Dream’ of homeownership, and (3) dismissing well‐documented cases of racial discrimination and predatory abuse as anecdotal evidence of rare problems confined to a few lost‐cause places in what is otherwise a benevolent free‐market landscape. In this article, we challenge these three tactics. Properly adapted and updated,Harvey's (1974) theory of class‐monopoly rent allows us to map and interpret the localized, neighborhood exploitations of class and race in several hundred US metropolitan areas as they were woven through Wall Street securitization conduits into global networks of debt and investment. Understanding the structural inequalities of class‐monopoly rent is essential for analysis, organizing, and policy responses to the crisis.

La crise financière mondiale la plus grave depuis la Grande Dépression a attiré le regard de la planète sur le secteur américain des prêts hypothécaires à risque (subprime) et sur ses liens avec une exploitation abusive au sein des communautés ouvrières et raciales marginalisées. Durant près de vingt ans de prospérité, les établissements de crédit hypothécaire à risque ont combattu réglementations et réformes: ils ont appliqué une ‘tarification au risque’ pour rapprocher innovation financière et accès démocratisé au capital; ils ont tiré parti des mythes culturels liés au ‘Rêve américain’ de la propriété individuelle; ils ont écarté les cas vérifiés de discrimination raciale et de comportement abusif, sous prétexte d’anecdotes isolées circonscrites à de rares sites voués à l’échec dans ce qui est par ailleurs une sphère bienveillante du libéralisme de marché. L’article met en cause ces trois tactiques. Une fois adaptée et actualisée, la théorie de Harvey (1974) sur les rentes de monopole de classe permet de cartographier les exploitations localisées (quartiers) de classes et de races dans plusieurs centaines de zones métropolitaines américaines, et d’expliquer comment elles ont glissé, via les canaux de titrisation de Wall Street, jusqu’aux réseaux internationaux d’endettement et de placement. Il faut appréhender les inégalités structurelles des rentes de monopole de classe pour pouvoir analyser, organiser et répondre à la crise par des politiques publiques.
Creating Liquidity out of Spatial Fixity: The Secondary Circuit of Capital and the Subprime Mortgage Crisis
Authors: GOTHAM KEVIN FOX
Published: July 2009

Since the classic work of Henri Lefebvre and David Harvey, the ‘secondary circuit of capital’ has been a focal point for debate among critical urban scholars. Against the background of contemporary debates on financialization, this article investigates the institutional and political roots of the subprime mortgage crisis. Empirically, the article situates the current turmoil of the US mortgage sector with reference to a series of ad hoc legal and regulatory actions taken since the 1980s to promote the securitization of mortgages and expand the secondary mortgage market. Securitization is a process of converting illiquid assets into transparent securities and is a critical component of the financialization of real estate markets and investment. Specifically, I examine the crucial role played by the US Treasury Department's Office of the Comptroller of the Currency (OCC) and the Department of Housing and Urban Development (HUD) in creating the polices and legal‐regulatory conditions that have nurtured the growth of a market for securitizing subprime loans. Theoretically, the article examines the subprime mortgage crisis as an illustration of the contradictions of capital circulation as expressed in the tendency of capital to annihilate space through time.

Depuis les travaux de référence d’Henri Lefebvre et de David Harvey, le ‘circuit secondaire des capitaux’ a suscité de nombreuses discussions entre spécialistes critiques de la ville. Avec en toile de fond les débats contemporains sur la financiarisation, cet article étudie les racines institutionnelles et politiques de la crise des subprimes. Sur le plan empirique, il situe le bouleversement actuel du secteur américain des prêts hypothécaires par rapport à une série de mesures de Droit et de réglementations spécifiques adoptées depuis les années 1980 pour promouvoir la titrisation et le marché secondaire des crédits hypothécaires. La titrisation, qui permet de convertir des actifs peu liquides en valeurs mobilières transparentes, est une composante essentielle de la financiarisation de l’investissement et des marchés immobiliers. Une attention particulière est accordée au rôle crucial qu’ont joué, aux États‐Unis, l’autorité de surveillance des banques relevant du ministère des Finances (OCC), ainsi que le ministère du Logement et de l’Urbanisme (HUD), dans la création des cadres et des conditions juridico‐réglementaires qui ont nourri l’essor du marché de la titrisation des prêts hypothécaires à risque. Sur le plan théorique, l’article analyse la crise des subprimes comme une illustration des contractions de la circulation des capitaux, ces derniers tendant à anéantir l’espace par le temps.
Laying the Foundations for a Crisis: Mapping the Historico‐Geographical Construction of Residential Mortgage Backed Securitization in the UK
Authors: WAINWRIGHT THOMAS
Published: July 2009

This article will explore the geographical origins of Residential Mortgage Backed Securitization (RMBS) in the United States and map the subsequent migration of RMBS, as idea, technology and investment vehicle, to the United Kingdom and other nation‐states during the 1990s. It will illustrate how RMBS was used as a medium to circulate capital and construct urban space, and seek to interpret the development of RMBS and the contemporary credit crisis in the UK through a series of historical, political and sociological lenses. It argues that, despite travelling across the globe, this financial innovation has maintained a spatial sensitivity since the idea of securitization has been embodied and (re)interpreted in specific spaces to comply with local economic, political and social institutions. It also argues that this is an important primer to understanding the ‘credit crunch’ of 2007 and its repercussions. The article focuses particularly on how the current significance of securitization and RMBS can be traced back to the ‘Big Bang’ and the wider processes of the competitive re‐regulation of the City of London and the British financial system more generally during the mid‐1980s. It shows the differential evolution of securitization in the UK and US, and in so doing argues that such spatial variations have left different financial institutions in the two economies exposed to different forms of credit and market risk.

Cet article revient sur les origines géographiques de la titrisation adossée à des crédits hypothécaires au logement (RMBS) aux États‐Unis, puis cartographie la migration ultérieure de cette titrisation, en tant que concept, technologie et véhicule d’investissement, vers le Royaume‐Uni et d’autres États‐nations, au cours des années 1990. Après avoir montré comment les titres RMBS ont servi de support pour faire circuler les capitaux et construire l’espace urbain, il expliquera l’évolution des RMBS et de la crise du crédit contemporaine au Royaume‐Uni selon plusieurs angles (historique, politique et sociologique). Malgré sa migration planétaire, cette innovation financière a conservé une sensibilité spatiale, l’idée de titrisation ayant été concrétisée et (ré)interprétée dans des espaces particuliers en adéquation avec des institutions économiques, politiques et sociales locales. Ce point est important pour comprendre le ‘resserrement du crédit’ de 2007 et ses répercussions. Toutefois, on peut déterminer que l’importance actuelle de la titrisation et des RMBS est due au ‘Big Bang’ et aux vastes processus de rerégulation par la concurrence de la City de Londres et, de façon plus générale, du système financier britannique au milieu des années 1980. On constate des divergences d’évolution de la titrisation entre Royaume‐Uni et États‐Unis, ces variations exposant différentes institutions financières des deux économies à différentes formes de risques liés au crédit et au marché.
Anne Haila's ‘The Market as the New Emperor’
Authors: ZHU JIEMING
Published: July 2009

The ideal type of laissez‐faire markets only exists in textbooks. In reality, markets as coordination mechanisms are always relative. China's ‘emerging land markets’ should be understood in the context of economic reforms which phase in market elements gradually and incrementally, and phase out planning factors in the same manner. In academic debates, it is constructive criticism that promotes the progress of knowledge. It is the solid alternative that opens people's minds.

Le marché idéaltypique du laisser‐faire n'existe que dans les manuels. Dans la réalité, les marchés en tant que mécanismes de coordination sont toujours relatifs. En Chine, il faut appréhender les ‘marchés fonciers émergents’ dans le contexte de réformes économiques qui introduisent pas à pas des composantes de marché tout en éliminant, de la même manière, des facteurs de planification. Dans les débats universitaires, la critique se doit d'être constructive pour que les connaissances progressent car, sans proposition d'alternative solide, l'esprit s'ouvre difficilement au propos.
Property as Abstraction
Authors: BLOMLEY NICHOLAS , STURGEON JANET C.
Published: July 2009

Haila questions the dominant ‘story’ that ‘imperfections’ in Chinese urban land markets can only be resolved through state sanctioned private property rights. She interrogates the meaning of concepts such as ‘market’ or ‘property’, wary of the ‘ontological fallacy’ in which concepts are confused for real objects. Drawing from Mitchell (1991), we seek to take this farther, by tracing how a distinction between property as representation and as reality is produced, and seeking to evaluate the effects this divide has on social practice. Rather than treating property in the Chinese context as an abstraction, we urge scholars to be alive to its empirically and ethically diverse manifestations.

Haila conteste le ‘récit’ dominant selon lequel les ‘imperfections’ des marchés fonciers urbains chinois ne peuvent se résoudre que par des droits de propriété privée cautionnés par l'État. Elle interroge la signification de concepts tels que ‘le marché’ ou ‘la propriété’, se méfiant de ‘l'illusion ontologique’ où l'on confond concepts et objets réels. Partant des travaux de Mitchell (1991), nous prolongeons cette idée en décrivant la distinction qui s'établit entre la propriété comme représentation et la propriété comme réalité; sont aussi évalués les effets de cette différenciation sur la pratique sociale. Au lieu de traiter la propriété dans le cadre chinois comme une abstraction, nous invitons les chercheurs à prendre conscience de la diversité de ses manifestations tant sur le plan empirique que sur le plan éthique.
One Size Does Not Fit All: Land Markets and Property Rights for the Construction of the Just City
Authors: IRAZÁBAL CLARA
Published: July 2009

This essay reflects on alternative urban markets and property right systems in some Latin American countries. What becomes clear is that one size does not fit all: land markets and property rights are multifaceted and their conception and implementation should be context‐sensitive. In recent experiments and proposals in Brazil, El Salvador and Venezuela, among other countries, they are being used as instruments for the expansion of rights to the city and the construction of the just city.

Ce texte s'intéresse aux formes alternatives de marchés urbains et de systèmes de droits de propriété dans certains pays d'Amérique latine. Il devient évident qu'un même modèle ne convient pas à tous: marchés fonciers et droits de propriété comportent de nombreux aspects, et il vaut mieux adapter au contexte leur élaboration et mise en oeuvre. Dans de récentes expériences et propositions au Brésil, au Salvador et au Venezuela (pour ne citer que ces pays), ils servent d'instruments pour étendre les droits en faveur de la ville et pour construire une ville juste.
Combining Microarray‐based Genomic Selection (MGS) with the Illumina Genome Analyzer Platform to Sequence Diploid Target Regions
Authors: Okou David T. , Locke Adam E. , Steinberg Karyn M. , Hagen Katie , Athri Prashanth , Shetty Amol C. , Patel Viren , Zwick Michael E.
Published: July 2009

Novel methods of targeted sequencing of unique regions from complex eukaryotic genomes have generated a great deal of excitement, but critical demonstrations of these methods efficacy with respect to diploid genotype calling and experimental variation are lacking. To address this issue, we optimized microarray‐based genomic selection (MGS) for use with the Illumina Genome Analyzer (IGA). A set of 202 fragments (304 kb total) contained within a 1.7 Mb genomic region on human chromosome X were MGS/IGA sequenced in ten female HapMap samples generating a total of 2.4 GB of DNA sequence. At a minimum coverage threshold of 5X, 93.9% of all bases and 94.9% of segregating sites were called, while 57.7% of bases (57.4% of segregating sites) were called at a 50X threshold. Data accuracy at known segregating sites was 98.9% at 5X coverage, rising to 99.6% at 50X coverage. Accuracy at homozygous sites was 98.7% at 5X sequence coverage and 99.5% at 50X coverage. Although accuracy at heterozygous sites was modestly lower, it was still over 92% at 5X coverage and increased to nearly 97% at 50X coverage. These data provide the first demonstration that MGS/IGA sequencing can generate the very high quality sequence data necessary for human genetics research.

All sequences generated in this study have been deposited in NCBI Short Read Archive (http://www.ncbi.nlm.nih.gov/Traces/sra, Accession # SRA007913).
Association Study and Mutation Analysis of Adiponectin Shows Association of Variants in APM1 with Complex Obesity in Women
Authors: Beckers Sigri , Peeters Armand V. , De Freitas Fenna , Mertens Ilse L. , Verhulst Stijn L. , Haentjens Dominique , Desager Kristine N. , Van Gaal Luc F. , Van Hul Wim
Published: July 2009

We performed an association study and mutation analysis of the adiponectin (APM1) gene to study its involvement in the development of obesity. We also studied the interaction with peroxisome proliferator‐activated receptor γ (PPARγ). 223 obese women and 87 healthy female control subjects were used for association analysis. Mutation analysis was done on 95 morbidly obese adults and 123 overweight and obese children and adolescents. We selected 6 haplotype tagging SNPs in APM1 and the Pro12Ala variant (rs1805192) in PPARγ to study the interaction. The G allele of rs2241766 was more common in controls (cases 10.8% vs. controls 18.4%, nominal p = 0.011; OR = 0.57, nominal p = 0.018). The rs2241766/rs3774261 haplotype was also associated with obesity (nominal p = 0.004). Only the latter association remained significant after controlling for the False Discovery Rate. Resequencing of exon 2, exon 3 and intron 2 in 95 individuals did not reveal any SNPs in high linkage disequilibrium with rs2241766. No interaction with the Pro12Ala variant in PPARγ was detected. Mutation analysis of APM1 did not identify mutations. In conclusion, we found an association of an APM1 haplotype with obesity and found that APM1 mutations are not a common cause of monogenic obesity in our cohort.
Insulin receptor signaling regulates actin cytoskeletal organization in developing photoreceptors
Authors: Rajala Raju V. S. , Rajala Ammaji , Brush Richard S. , Rotstein Nora P. , Politi Luis E.
Published: July 2009

The insulin receptor (IR) and IR signaling proteins are widely distributed throughout the CNS. IR signaling provides a trophic signal for transformed retinal neurons in culture and we recently reported that deletion of IR in rod photoreceptors by Cre/lox system resulted in stress‐induced photoreceptor degeneration. These studies suggest a neuroprotective role of IR in rod photoreceptor cell function. However, there are no studies available on the role of insulin‐induced IR signaling in the development of normal photoreceptors. To examine the role of insulin‐induced IR signaling, we analyzed cultured neuronal cells isolated from newborn rodent retinas. In insulin‐lacking cultures, photoreceptors from wild‐type rat retinas exhibited an abnormal morphology with a wide axon cone and disorganization of the actin and tubulin cytoskeleton. Photoreceptors from IR knockout mouse retinas also exhibited a similar abnormal morphology. A novel finding in this study was that addition of docosahexaenoic acid, a photoreceptor trophic factor, restored normal axonal outgrowth in insulin‐lacking cultures. These data suggest that IR signaling pathways regulate actin and tubulin cytoskeletal organization in photoreceptors; they also imply that insulin and docosahexaenoic acid activate at least partially overlapping signaling pathways that are essential for the development of normal photoreceptors.
Interleukin‐10 provides direct trophic support to neurons
Authors: Zhou Zhigang , Peng Xiangmin , Insolera Ryan , Fink David J. , Mata Marina
Published: July 2009

Interleukin (IL)‐10, a prototypical anti‐inflammatory cytokine, has been shown to provide beneficial effects in neuronal injuryin vivobut the full range of actions has not been established. In order to understand the neuronal mechanisms underlying IL‐10‐mediated neuroprotection, we examined the effect of IL‐10 on primary neurons in culture. We found that IL‐10 exerted a direct trophic influence on spinal cord neurons, and that activation of the neuronal IL‐10 receptor provided trophic support and survival cues to overcome the neurotoxic effects of glutamatein vitro. IL‐10 treatment resulted in activation of janus‐associated kinases/signal transducers and transcription factors and phosphatidylinositol 3‐kinase‐AKT pathways in neurons to enhance expression of Bcl‐2 and Bcl‐xL; under stress conditions IL‐10 blocks cytochromecrelease and caspase cleavage. IL‐10 activation of the canonical nuclear factor κB pathway enhanced translocation of p50 and p65 and enhanced their binding to κB DNA sequences, with p50 playing a more prominent role in neuronal survival. These data indicate that in addition to known anti‐inflammatory effects through astroglia in other inflammatory cells, IL‐10 has direct neuronal effects with important implications for development and neuroprotection.
NgR RNA interference, combined with zymosan intravitreal injection, enhances optic nerve regeneration
Authors: Chen Chunlin , Chen Xiaofan , Yin Xiaolei , Yuan Rongdi , Wang Baichuan , Ye Jian
Published: July 2009

Mature retinal ganglion cells like other CNS neurons are unable to regenerate their axons after injury. Regenerative failure has been attributed, in part, to two factors: the existence of myelin‐derived inhibitors that bind to the Nogo receptor (NgR) and a deficiency of trophic support factors. We investigated the regrowth of injured axons both by inhibiting NgR by RNA interference and by recruiting exogenous trophic support by zymosan intravitreal injection. Our results showed that either approach can stimulate optic nerve axon regrowth but regenerated axons can grow longer and extend further when both methods are combined. We conclude that endogenous NgR inhibition and exogenous trophic support both play independent, important roles in enhancing optic nerve axon regrowth and that the regenerative effect can be augmented when the two are combined. This may provide a therapeutic strategy for promoting axon regeneration in the CNS as well.
Factors associated with treatment failure of patients with psychiatric diseases and injecting drug users in the treatment of genotype 2 or 3 hepatitis C chronic infection
Authors: Alvarez‐Uria Gerardo , Day Jeremy N. , Nasir Anisa J. , Russell Susan K. , Vilar Francisco Javier
Published: July 2009

Background: Genotype 2/3 hepatitis C virus (HCV) has a good response to treatment with peginterferon and ribavirin. Patients with psychiatric disorders and injecting drug users (IDUs) are considered ‘difficult to treat’ and are often excluded from treatment despite the lack of evidence supporting this decision.

Aims: To investigate the outcome and factors associated with treatment failure in these groups.

Methods: This is an observational study of a cohort of patients infected by genotype 2/3 HCV. IDUs and patients with psychiatric diseases were not excluded from treatment. We performed an intention‐to‐treat analysis to evaluate factors related to treatment failure.

Results: A sustained virological response (SVR) was achieved in 91 of the 125 patients treated (72.8%). Patients with chronic psychotic disorders or former IDUs had SVR rates similar to other groups. After multivariate analysis, independent factors associated with treatment failure were liver cirrhosis [odds ratio (OR) 3.4, 95% confidence interval (CI) 1.1–10.4], a history of depression and not being on antidepressants at the commencement of HCV treatment (OR 4.4, 95% CI 1.2–16) and active IDUs (OR 7.3, 95% CI 1.77–30.4).

Conclusions: Patients with a history of depression who were not receiving antidepressants and active IDUs are more likely to fail treatment for genotype 2/3 HCV and will need additional support.
The expression profile of glypican‐3 and its relation to macrophage population in human hepatocellular carcinoma
Authors: Takai Hirotake , Kato Atsuhiko , Kato Chie , Watanabe Takeshi , Matsubara Koichi , Suzuki Masami , Kataoka Hiroaki
Published: July 2009

Background:Glypican‐3 (GPC3) is frequently upregulated in hepatocellular carcinoma (HCC). Analysis of GPC3‐deficient mice implies GPC3 involvement in macrophage‐lineage cells.

Aim:In this study, we first assessed the association of GPC3 expression with the macrophage population in liver tissues from 30 HCC patients using immunohistochemistry.

Methods:The GPC3 expression was categorized into three patterns – one with GPC3‐negative staining and two with GPC3‐positive staining (one with unclear membrane staining and one with clear membrane staining, designated GPC3+/C). The number of macrophages that were stained with resident macrophage (rMϕ) or pan‐macrophage (pMϕ) markers was counted for each GPC3 expression pattern.

Results:GPC3 immunoreactivity was observed in 76.7% of the HCC specimens. No significant differences were observed in the number of rMϕ marker‐positive cells among the three expression patterns. In contrast, the GPC3+/C pattern showed a significantly higher number of pMϕ‐positive cells compared with the other two patterns, most of which tended to take on the morphology of migrating macrophages. A second experiment conducted to compare macrophage infiltration between the xenograft tissues of a GPC3‐transfected HCC cell line and its parent GPC3‐nonexpressing cell line revealed that the increase in macrophages was stimulated by membrane expression of GPC3.

Conclusion:The observations suggest that the increased macrophages in the GPC3+/C pattern are likely to be recruited macrophages, not resident macrophages, and that the expression of GPC3 in the membrane is involved in macrophage recruitment.
Active matrix metalloproteinase‐2 promotes apoptosis of hepatic stellate cells via the cleavage of cellular N‐cadherin
Authors: Hartland Stephen N. , Murphy Frank , Aucott Rebecca L. , Abergel Armand , Zhou Xiaoying , Waung Julian , Patel Nishit , Bradshaw Catherine , Collins Jane , Mann Derek , Benyon R. Christopher , Iredale John P.
Published: July 2009

Background and Aims: Hepatic stellate cells (HSC) are known to synthesise excess matrix that characterises liver fibrosis and cirrhosis. Activated HSC express the matrix‐degrading matrix metalloproteinase enzymes (MMPs) and their tissue inhibitors (TIMPs). During spontaneous recovery from experimental liver fibrosis, the expression of TIMP‐1 declines and hepatic collagenolytic activity increases. This is accompanied by HSC apoptosis. In this study, we examine a potential mechanism whereby MMP activity might induce HSC apoptosis by cleaving N‐cadherin at the cell surface.

Results: N‐cadherin expression was upregulated in human HSC during activation in culture. Addition of function‐blocking antibodies or a peptide targeting the extracellular domain of N‐cadherin, to cultured HSC, promoted apoptosis. During apoptosis, there was cleavage of N‐cadherin into 20–100 kDa fragments. MMP‐2 became activated early during HSC apoptosis and directly cleaved N‐cadherin in vitro. Addition of activated MMP‐2 to HSCs in culture resulted in enhanced apoptosis and loss of N‐cadherin.

Conclusions: Together, these studies identify a role for both N‐cadherin and MMP‐2 in mediating HSC apoptosis, where N‐cadherin works to provide a cell survival stimulus and MMP‐2 promotes HSC apoptosis concomitant with N‐cadherin degradation.
Landscape Structural Complexity of High‐Mountain Polylepis australis Forests: A New Aspect of Restoration Goals
Authors: Renison Daniel , Hensen Isabell , Suarez Ricardo
Published: July 2009

Forest restoration efforts should aim at creating landscapes with a balanced array of forest stands at varying successional stages, thus providing habitat for a wealth of species and multiple ecosystem services. In most high‐mountain ecosystems of South America, long‐term livestock rearing activities that include fires, browsing, and trampling have delayed or stopped forest succession resulting in simplified landscapes. To determine appropriate restoration goals for Polylepis australis mountain forests of Central Argentina, we established 146 plots of 900 m2 plots throughout five river basins with different historic livestock stocking rates. In each plot, we measured tree heights, canopy cover, estimated age of oldest tree, volume of standing and fallen dead wood, fern cover, and abundance of shade tolerant Maytenus boaria trees. K‐means cluster analysis using tree heights and canopy cover as classificatory variables yielded four biologically meaningful clusters. Clusters 1, 2, 3, and 4 comprising 68, 10, 13, and 9% of the plots, respectively, showed increasing amounts of standing and fallen dead wood, fern cover, and abundance of shade tolerant M. boaria trees. Plots in clusters 1 and 2 were proportionally more abundant in basins with high human impact and at the altitudinal extremes of P. australis distribution, whereas plots in clusters 3 and 4 were relatively more abundant in well‐preserved basins and at the optimum of their altitudinal distribution. We interpret clusters 1, 2, 3, and 4 as degraded, regenerating, young, and mature forests, respectively. Restoration goals should focus on attaining an even distribution of forest types similar to that found in our best‐preserved basins.
Natural Regeneration in Plantations of Native Trees in Lowland Brazilian Atlantic Forest: Community Structure, Diversity, and Dispersal Syndromes
Authors: Sansevero Jerônimo Boelsums Barreto , Prieto Pablo Viany , de Moraes Luiz Fernando Duarte , Rodrigues Pablo JoséFrancisco Pena
Published: July 2009

Plantations of native‐tree species are often recommended for ecological restoration, but the understanding of how these techniques catalyze natural ecological processes is limited. We investigated natural regeneration in five plantations of native trees in the Poço das Antas Biological Reserve (PABR) in the state of Rio de Janeiro, Brazil. The plantations were 9–11 years old, and contained 8–14 native‐tree species with different compositions and relative density of species. We analyzed floristic composition, structure (density and basal area) of overstory and understory strata, as well as other ecological attributes (dispersal syndromes, fruit or seed size, and the availability of fruit for frugivores). Zoochorous species comprised 77% of the community, with a prevalence of the two smallest size classes of propagules (< 0.6 and 0.6–1.6 cm) in natural regeneration. The density of zoochorous plants in the understory was positively correlated with their density in the overstory, indicating their influence on natural regeneration (r2 = 0.36; p < 0.0002). Fruit availability for frugivores (density and richness of plants fruiting during the year) was also positively correlated with the density of stems in the understory. Therefore, attributes such as dispersal syndrome and fruiting season should be considered in selecting species to be planted. The differences in natural regeneration observed in each of the native‐tree plantations indicated that the performance of plantations as a restoration strategy may differ, depending on initial species composition, planting density, and site conditions.
Assessment of a Multi‐Species Planting Approach for Restoring Thick‐Mat Floating Marsh, Louisiana, U.S.A.
Authors: Mayence C. Ellery , Hester Mark W.
Published: July 2009

Planting multiple species in wetland restoration sites could potentially accelerate ecological succession while enhancing ecological services. Our study of thick‐mat floating marsh demonstrated that two species performed better than monocultures for developing a more structurally sound root mat. AlthoughPanicum hemitomonis the typical dominant and focal species of all restoration efforts of this habitat type, we evaluated the effects of additional species, includingSagittaria lancifolia, a ubiquitous floating marsh constituent, and three laterally growing specialists (Alternanthera philoxeroides,Hydrocotyle ranunculoides, andLudwigia peploides). In a mesocosm experiment, we found greaterP. hemitomonbiomass in monocultures but greater vegetative cover and total mat biomass withP. hemitomonplusL. peploides, but not greater biomass in the most species‐rich treatment or treatment with the greatest initial planting density. We conclude thatL. peploidesaids restoration of thick‐mat floating marsh by increasing mat buoyancy, enhancing lateral growth, and providing greater root mat structural integrity. This type of laterally growing specialist should accelerate coalescence of neighboring constructed and naturally formed mats. Planting species that occupy complementary niches should also minimize competition for key resources.
Ring chromosome 20 syndrome: A link between epilepsy onset and neuropsychological impairment in three children
Authors: Vignoli Aglaia , Canevini Mario Paola , Darra Francesca , La Selva Lorita , Fiorini Elena , Piazzini Ada , Lazzarotto Francesca , Zucca Claudio , Dalla Bernardina Bernardo
Published: July 2009

Purpose: Ring chromosome 20 [r(20)] syndrome is a well‐defined chromosomal disorder characterized by epilepsy, mild‐to‐moderate mental retardation, and lack of recognizable dysmorphic features. Epilepsy is often the most important clinical manifestation of the syndrome, even if its appearance is not constantly precocious. Seizures are frequently drug resistant.

Methods: We describe three children with [r(20)] syndrome in whom the onset of epilepsy (age at onset range: 4 years and 6 months to 9 years and 4 months) determined a kind of epileptic status (age at onset range: 6 years and 10 months to 9 years and 8 months) with dramatic neuropsychological deterioration. This epileptic status lasted for several months because of refractoriness to most antiepileptic drugs (AEDs), but it was treated successfully with a combination of valproate and lamotrigine in two children.

Results: As soon as seizures stopped, the children showed prompt recovery with partial restoration of the neuropsychological impairment.

Conclusion: This clinical picture can be described as abrupt epileptic encephalopathy.
Doublecortin‐like (DCL) expression in focal cortical dysplasia and cortical tubers
Authors: Boer Karin , Lucassen Paul J. , Spliet Wim G. M. , Vreugdenhil Erno , Van Rijen Peter C. , Troost Dirk , Jansen Floor E. , Aronica Eleonora
Published: July 2009

Purpose: Focal cortical dysplasia type IIB (FCD IIB) and cortical tubers of patients with tuberous sclerosis complex (TSC) are malformations of cortical development that are frequently associated with intractable epilepsy. Their histopathologic and molecular features suggest developmental abnormalities during the early stages of cortical development, which may involve neural progenitor cells. The aim of our study was to define the expression and cell‐specific distribution of doublecortin‐like (DCL), a protein critically involved in neuronal division and radial migration during early corticogenesis, in both FCD and TSC.

Methods: DCL was studied in epilepsy surgery cases with FCD IIB (n = 8) and TSC (cortical tubers; n = 8) using immunocytochemistry, confocal analysis, and Western blotting.

Results: Autopsy and surgical control neocortical specimens were characterized by modest DCL immunoreactivity (IR) throughout all cortical layers, but DCL IR was not detectable in the white matter. Balloon cells (BCs) in FCD and giant cells (GCs) in TSC expressed strong DCL IR. Most of the large dysplastic neurons (DNs) were positive for DCL in both FCD and TSC. Coexpression of DCL with the neural progenitor or neuroblast markers nestin, GFAPδ, and doublecortin was observed in both FCD and TSC specimens. The increased DCL expression within the dysplastic cortex, compared to control cortex, was confirmed by Western blot analysis.

Discussion: The prominent postnatal expression of DCL by BCs/GCs and DNs in FCD and TSC supports an important role for this microtubule associated protein, also during early human cortical development, which could be relevant to the pathogenesis of these developmental glioneuronal malformations.
Assessing the Effect of a Polypharmacy Medication Adherence Simulation Project in a Geriatrics Course in a College of Pharmacy
Authors: Divine Holly S. , Cain Jeff
Published: July 2009

The Geriatric Pharmacy elective course at the University of Kentucky College of Pharmacy uses a simulated medication adherence project to increase awareness of adherence concerns facing older adults who take multiple medications. This study evaluated the effect of this project. Students enrolled in this 3–credit hour course in 2002 to 2007 participated in the 10‐day project followed by a live classroom discussion and a reflective assignment. Evaluations of the project were administered to the students on Blackboard. Two hundred thirty‐seven health professional students (99% pharmacy) participated in the course project. Open‐ended comments in the evaluations and reflective assignments were retrospectively analyzed using a qualitative research method known as thematic analysis. The majority (83%) of comments were positive. Students indicated the greatest learning experiences in the categories of empathy and adherence. This simulated medication adherence project is one tool that may be used to increase students' awareness of the difficulties with medication adherence that their patients may encounter.
Cardiac Effects of Seizures
Authors: Nei Maromi
Published: July 2009

Seizures frequently affect the heart rate and rhythm. In most cases, seizure-related cardiac changes are transient and do not appear to cause clinically significant abnormalities for the patient. Great interest in this area of research has been generated because of a possible connection with sudden unexpected death in epilepsy (SUDEP). While there are clear, but rare complications from seizure-related cardiac arrhythmias, such as ictal asystole that causes syncope, the overall risk of seizures on cardiac status and any potential connection between seizures and SUDEP still remain uncertain.
Seizures in Patients Undergoing Resection of Low-Grade Gliomas
Authors: Hirsch Lawrence J.
Published: July 2009

Seizure Characteristics and Control Following Resection in 332 Patients with Low-Grade Gliomas. Chang EF, Potts MB, Keles GE, Lamborn KR, Chang SM, Barbaro NM, Berger MS. J Neurosurg 2008;108(2):227–235. OBJECT: Seizures play an important role in the clinical presentation and postoperative quality of life of patients who undergo surgical resection of low-grade gliomas (LGGs). The aim of this study was to identify factors that influenced perioperative seizure characteristics and postoperative seizure control. METHODS: The authors performed a retrospective chart review of all cases involving adult patients who underwent initial surgery for LGGs at the University of California, San Francisco between 1997 and 2003. RESULTS: Three hundred and thirty-two cases were included for analysis; 269 (81%) of the 332 patients presented with ≥1 seizures (generalized alone, 33%; complex partial alone, 16%; simple partial alone, 22%; and combination, 29%). Cortical location and oligodendroglioma and oligoastrocytoma subtypes were significantly more likely to be associated with seizures compared with deeper midline locations and astrocytoma, respectively ( p = 0.017 and 0.001, respectively; multivariate analysis). Of the 269 patients with seizures, 132 (49%) had pharmacoresistant seizures before surgery. In these patients, seizures were more likely to be simple partial and to involve the temporal lobe, and the period from seizure onset to surgery was likely to have been longer ( p = 0.0005, 0.0089, and 0.006, respectively; multivariate analysis). For the cohort of patients that presented with seizures, 12-month outcome after surgery (Engel class) was as follows: seizure free (I), 67%; rare seizures (II), 17%; meaningful seizure improvement (III), 8%; and no improvement or worsening (IV), 9%. Poor seizure control was more common in patients with longer seizure history ( p < 0.001) and simple partial seizures ( p = 0.004). With respect to treatment-related variables, seizure control was far more likely to be achieved after gross-total resection than after subtotal resection/biopsy alone (odds ratio 16, 95% confidence interval 2.2–124, p = 0.0064). Seizure recurrence after initial postoperative seizure control was associated with tumor progression ( p = 0.001). CONCLUSIONS: The majority of patients with LGG present with seizures; in approximately half of these patients, the seizures are pharmacoresistant before surgery. Postoperatively, > 90% of these patients are seizure free or have meaningful improvement. A shorter history of seizures and gross-total resection appear to be associated with a favorable prognosis for seizure control.
Pharmacokinetics of Phenytoin: Reminders and Discoveries
Authors: Bergen Donna C.
Published: July 2009

Phenytoin Half-Life and Clearance during Maintenance Therapy in Adults and Elderly Patients with Epilepsy. Ahn JE, Cloyd JC, Brundage RC, Marino SE, Conway JM, Ramsay RE, White JR, Musib LC, Rarick JO, Birnbaum AK, Leppik IE. Neurology 2008;71(1):38–43. BACKGROUND: Phenytoin (PHT) is widely used to treat epilepsy in elderly patients, but information on its pharmacokinetics in this population is limited. OBJECTIVE: The purpose of this study was to investigate the effects of age and sex on PHT pharmacokinetics using stable-labeled (SL) isotopes of PHT or fosphenytoin (FOS) administered IV or IM while patients remained on their oral maintenance regimen. METHODS: Subjects were patients 18 years or older with epilepsy, but otherwise healthy, on a maintenance regimen of PHT who were not taking interacting medications. Subjects were given a single injection of a 100 mg dose of SL-PHT or SL-FOS followed by their usual morning PHT dose less 100 mg. Serial blood samples were collected up to 196 hours after the SL dose. Plasma PHT and SL-PHT concentrations were measured by a gas chromatographic-mass spectrometric assay. PHT pharmacokinetics were characterized using a population-based, nonlinear, mixed-effects model. RESULTS: Sixty-three subjects completed the study, 45 of whom were 65 years or older. There was no difference between adult and elderly or men and women in PHT clearance, distribution volume, and elimination half-life. The mean elimination half-life was 40 hours. CONCLUSIONS: Healthy elderly adults appear to have the same phenytoin (PHT) pharmacokinetics as younger adults. Reduced PHT dosage requirements may be due to age-related changes in patients’ sensitivity to the therapeutic and toxic effects of the drug. The prolonged elimination half-life suggests that most patients can take PHT once daily and the time to reach steady-state may extend to 2–3 weeks.