bluuebunny/crossref_metadata_2025 huggingface dataset:
Lazer, educação e políticas públicas em países emergentes: reflexões sobre o caso brasileiro
Authors: Moreno José Carlos de Almeida , Silva Luciene Ferreira da
Published: July 2013

A problemática abordada neste artigo, diz respeito à não eficácia de políticas setoriais atuantes na Educação de crianças, adolescentes e jovens brasileiros, sobretudo os de classe mais desfavorecida. Sustenta-se a tese de que políticas setoriais de lazer e Educação podem instaurar um movimento educacional crítico e emancipatório, quando focam o indivíduo, a sua essência humana e a vida enquanto instância superior e primeira, ultrapassando elementos como a mercantilização e chegando ao "imercantilizável". O objetivo foi refletir, analisando as possibilidades de proposição de saltos qualitativos na Educação, através da ampliação das políticas setoriais, abordando a de lazer, como de suma importância para o processo de desenvolvimento humano. Partiu-se do pressuposto que as camadas mais favorecidas economicamente possuam, por conta do seu lócus social, mais oportunidades de formação com o lazer, mas nem estas, estão salvaguardadas, se socialmente não lhes forem garantidas legislativamente, o tempo para serem crianças, adolescentes, jovens e adultos. E nem, de usufruírem o lazer no tempo-livre, se o trabalho for o único objetivo a ser alçado ou ainda, se o lazer proporcionado for do tipo "mercadoria". O artigo resgata a necessidade de Educação para formação da pessoa, para a liberdade, fazendo escolhas por caminhos "vistos". Buscou superar a visão clássica de desenvolvimento educacional via modelos "intra muros" das escolas brasileiras, e que não se resolvem sem que haja alteração do panorama político e econômico. Alerta para a necessidade de adaptações do sistema socioeconômico para a vida do homem e não de adaptação do homem a este, o que tem gerado desequilíbrio entre as nações e na homeostase, via políticas públicas setoriais, gestadas a partir de um "todo" bem estruturado. Conclui-se que estudos sociológicos, educacionais e culturais sobre o lazer, a Educação e as políticas públicas são significativos quando abordados conjuntamente.
Desafios a melhores resultados em alfabetização
Authors: Scliar-Cabral Leonor
Published: July 2013

Neste artigo, temos algumas estatísticas de países desenvolvidos, como os EUA e o Reino Unido, bem como o Brasil, com altas taxas de analfabetismo funcional, que são apresentadas. O programa de Iniciativa de Intervenção Precoce inspira outros países a aplicarem medidas similares tais como reformulação dos currículos, das práticas escolares, do material pedagógico; avaliação periódica e recuperação dos alunos que apresentam dificuldades de aprendizagem da leitura e escrita. Será dada ênfase à realidade psicológica da invariância dos traços que diferenciam as letras demonstrada por vários experimentos rodados pela neurociência
Desempenho de escolares de ensino público com e sem dificuldade de aprendizagem em habilidade fonológica, nomeação rápida, leitura e escrita
Authors: Capellini Simone Aparecida , Lanza Simone Cristina
Published: July 2013

Este estudo¹ teve por objetivos caracterizar e comparar o desempenho de escolares do ensino público com e sem dificuldades de aprendizagem em habilidades fonológicas, nomeação rápida, leitura e escrita. Participaram desse estudo 60 escolares de 2ª a 4ª séries de escola de ensino particular, distribuídos em seis grupos, sendo cada grupo composto por 10 escolares, sendo três grupos de escolares sem dificuldades de aprendizagem e três grupos de escolares com dificuldades de aprendizagem. Como procedimentos, foram realizadas a prova de nomeação automática rápida, a de consciência fonológica e a prova de leitura oral e escrita sob ditado. Os resultados deste estudo evidenciaram desempenho superior dos escolares sem dificuldades de aprendizagem em relação àqueles com dificuldades. Os escolares com dificuldades de aprendizagem apresentaram maior relação velocidade/tempo em tarefas de nomeação e, consequentemente, desempenho inferior em tarefas de consciência fonológica, leitura e escrita de palavras isoladas quando comparados aos sem dificuldades de aprendizagem. Os escolares com dificuldades de aprendizagem apresentaram comprometimento na relação entre as capacidades de nomeação e automatização dos estímulos apresentados com a capacidade de acesso lexical, discriminação visual, frequência de uso dos estímulos e competição para a apresentação do menor tempo possível na nomeação dos códigos necessários para o estabelecimento do mecanismo de conversão fonema-grafema, exigido para a realização da leitura e escrita em um sistema alfabético como o português
O uso social da leitura por meio de textos informativos
Authors: Vasconcelos Maria do Socorro
Published: July 2013

"Que sentido os textos informativos têm para os neoleitores egressos do AlfaSol?" é um projeto de pesquisa-ação que tem por objetivo exercitar a leitura dos adultos recém-alfabetizados em situações concretas da vida cotidiana. O projeto se apóia em consultas bibliográficas e realização de oficinas de leitura na Comunidade do Dendê, utilizando material informativo sobre integração social, exercício da cidadania, cuidados com a saúde, conservação do meio ambiente e melhoria da qualidade de vida das pessoas. Atende a necessidades específicas da população, segundo a Lei de Responsabilidade Social que levou as empresas privadas a atuarem em parceria com o Estado. Foram realizadas visitas à Comunidade do Dendê e feitos contatos com os líderes locais. Essas visitas tinham por objetivo apresentar e discutir com os líderes a viabilidade do projeto e selecionar o local mais adequado para funcionamento das oficinas de leitura. As pessoas da Comunidade do Dendê vêm recebendo uma grande contribuição no sentido de aperfeiçoar as técnicas de leitura, interpretar textos com informações úteis, criar o hábito de ler entre os adultos egressos dos programas de alfabetização, ler conjuntamente com os familiares, amigos e vizinhos, exercitando-se todos para uma convivência harmônica e solidária, em busca de soluções aos problemas atuais que afetam toda a coletividade
Visar ao sucesso dos alunos: a ortopedagogia e a alfabetização
Authors: Cote Stéphanie
Published: July 2013

Este depoimento fala da minha experiência profissional no campo da Ortopedagogia. A parceria entre ortopedagogos, alfabetizadores, demais profissionais da escola e da família é fundamental para o sucesso escolar dos alunos.
Prefácios de livros didáticos e o imaginário da leitura: do dado marginal à legitimação de um lugar da escrita
Authors: Pereira Anderson de Carvalho
Published: July 2013

Este artigo investiga o mecanismo discursivo que sustenta o valor de verdade agregado às definições e às proposições de uso da escrita, tal como aparecem em prefácios de livros didáticos de português brasileiro utilizados na alfabetização. Foram analisadas sequências discursivas que sinalizam mecanismos ideológicos de sustentação do sentido de natureza, transparência e instrumentalização da língua, que reforçam o sujeito cognitivo e apagam possibilidades de marcação de posições de intérprete por parte do sujeito do discurso.
uso e potencialidades na formação de leitores
Authors: Pimentel Susana Couto
Published: July 2013

Este trabalho é resultado de investigação realizada por docente e estudantes de Pedagogia no "projeto Prodocência: implantação de laboratórios para o ensino de licenciatura e formação de professores em pedagogia, matemática e física" desenvolvido no Centro de Formação de Professores da Universidade Federal do Recôncavo da Bahia com apoio e financiamento do Ministério da Educação (MEC). Através da metodologia pesquisa-ação foram realizadas atividades em uma turma de terceira série do Ensino Fundamental, de uma escola municipal de Amargosa-BA, caracterizada como tendo dificuldades no processo de compreensão leitora. Diante da turma investigada, a equipe de pesquisadores optou pela utilização de histórias em quadrinhos para o desenvolvimento do trabalho. Essa investigação teve duração de um semestre letivo distribuído em doze sessões, sendo na primeira aplicado um pré-teste e na última um pós-teste. Durante as dez sessões de efetiva intervenção foram propostas à classe atividades envolvendo: exploração de revistas em quadrinhos para conhecimento de personagens, aspectos textuais e gráficos; leitura de histórias e respostas a perguntas com diferentes níveis de complexidade; leitura de histórias para elaboração de questões; ordenação dos quadrinhos de uma história; construção de uma história com base nas imagens dos quadrinhos; explicação das atitudes dos personagens com base na compreensão de suas características; empréstimo de revistas para leitura. Essas atividades buscaram contribuir para a redução das dificuldades no desenvolvimento da compreensão leitora, entendendo que esta não se reduz a mera decodificação do texto, mas a compreensão e reflexão sobre o mesmo, compreendendo o que não está explícito. Ao final do trabalho de intervenção os indicadores utilizados para aferir o progresso da turma com relação a leitura demonstraram o desenvolvimento da compreensão leitora de 75% dos estudantes. Isso demonstra que as histórias em quadrinhos podem ser eficazmente utilizadas como recurso de mediação pedagógicapara contribuir na formação de leitores
Adaptação do método freireano para a alfabetização infantil
Authors: Rocha Eliane de Paula , Bulhões Ignácio César de
Published: July 2013

O presente artigo propõe-se a explicar como o método utilizado por Paulo Freire na alfabetização de adultos pode ser adaptado de maneira eficaz no processo de alfabetização infantil. A concretização do projeto "Minha escola... Minha vida..." permitiu constatar o quanto essa aplicação é válida, uma vez que contribuiu para expandir a ludicidade e possibilitou uma aprendizagem realmente significativa já nos primeiros anos da vida escolar da criança.
PROALFA (MG): Avaliação da alfabetização, em larga escala, no Brasil
Authors: Filgueiras Karina Fideles
Published: July 2013

O presente artigo pretende contextualizar o Programa de Avaliação da Alfabetização do Estado de Minas Gerais – PROALFA (MG), no cenário internacional, nacional e estadual. No Brasil, várias são as avaliações em larga escala realizadas, em diferentes instâncias, que se apresentam em todos os segmentos de ensino. Porém, estas avaliações sobre a alfabetização nos estados do Espírito Santo, Ceará e Minas Gerais, diferenciam-se por ultrapassar a visão do instrumento de avaliação. Além dos instrumentos avaliativos, também são aplicados questionários contextuais para gestores, professores e alunos, na tentativa de se estabelecer o cruzamento de dados quantitativos com dados qualitativos, buscando, assim, captar as especificidades regionais e por escolas, considerando-se os seus contextos de produção do ensino-aprendizagem. O objetivo final desses tipos de avaliação em larga escala, que também podem ter caráter longitudinal, é de prevenção dos resultados poucos satisfatórios, dos alunos brasileiros, nos segmentos de ensino avaliados por programas internacionais, tais como o PISA. Há que se considerar as diferenças na produção dos indicadores, na frequência da medição, no tipo de avaliação em larga escala, censitária ou amostral, e nos princípios sobre os quais se constroem os instrumentos avaliativos. A opção de analisar os resultados do PROALFA (MG), na rede estadual de ensino de Belo Horizonte foi motivada tanto pela veiculação de dados na mídia – em que é destacado o desempenho dos alunos mineiros – quanto pelos dados obtidos na Secretaria Estadual de Educação de Minas Gerais.
Controlled Reperfusion Versus Conventional Treatment of the Acutely Ischemic Limb
Authors: Heilmann Claudia , Schmoor Claudia , Siepe Matthias , Schlensak Christian , Hoh Andreas , Fraedrich Gustav , Beyersdorf Friedhelm
Published: July 2013

Background—

Amputation rates and mortality in patients with severe acute limb ischemia remain high. The protective effect of controlled reperfusion (CR) on tissue damage because of local and systemic reperfusion injury is unclear.

Methods and Results—

A total of 174 patients from 14 centers were randomized between conventional treatment (CT) by thrombembolectomy and normal blood reperfusion and thrombembolectomy followed by CR. The primary end point was amputation-free survival (AFS) after 4 weeks (CT, 82.4%; CR, 82.6%). Secondary end points were AFS (CT, 62.4%; CR, 63.1%) and overall survival (CT, 71.6%; CR, 76.3%) after 1 year. Analysis of the prognostic effects of preoperative factors revealed a strong adverse effect of bilateral involvement on AFS. In the subgroup with unilateral ischemia (n=160), age >80 years and central localization of the occlusion had independent negative prognostic effects on AFS. In the per-protocol population of 104 patients with unilateral ischemia, treatment per protocol, and successful revascularization, amputation or death within 4 weeks occurred in only 8% as compared with 33% in patients not fulfilling these criteria. No differences between treatment groups CT and CR were found, neither overall nor in the per-protocol population nor in patient subgroups defined by other pre- and intraoperative factors.

Conclusions—

Similar AFS in patients with CT or with CR was observed in this large randomized multicenter trial.

Clinical Trial Registration—

URL:
http://www.drks.de
. Unique identifier: DRKS00000579.
Smoking, Heart Rate, and Ischemic Stroke
Authors: Xu Tian , Bu Xiaoqing , Li Hongmei , Zhang Mingzhi , Wang Aili , Tong Weijun , Xu Tan , Sun Yingxian , Zhang Yonghong
Published: July 2013

Background and Purpose—

Smoking is a major public health challenge and an important risk factor for cardiovascular diseases. No previous studies have evaluated the association among smoking, heart rate, and ischemic stroke in an Inner Mongolian population. We aim to evaluate the cumulative effect of smoking and heart rate on ischemic stroke incidence in this population.

Methods—

A prospective cohort study from June 2003 through July 2012 was conducted among 2530 people ≥20 years of age from Inner Mongolia, China. We categorized the participants into 4 subgroups according to smoking status and heart rate. Cox proportional hazards models and receiver operating characteristic curves were used to evaluate the association among smoking, heart rate, and ischemic stroke.

Results—

The multivariate-adjusted hazard ratios (95% confidence intervals) of ischemic stroke incidence for nonsmokers with heart rate ≥80 bpm, smokers with heart rate <80 bpm, and smokers with heart rate ≥80 bpm were 1.42 (0.62–3.28), 2.11 (1.06–4.23), and 2.86 (1.33–6.14), respectively, compared with nonsmokers with heart rate <80 bpm. The area under receiver operating characteristic curve (area under the curve) for a model containing smoking status and heart rate, along with conventional factors (area under the curve=0.755), was significantly (
P
=0.018) larger than the one containing only conventional factors (area under the curve=0.739).

Conclusions—

Our study indicated that smoking was an independent risk factor of ischemic stroke, and smokers with faster heart rate had the highest risk of ischemic stroke among Inner Mongolians. These findings suggest that smoking status and heart rate may be valuable in predicting ischemic stroke incidence.
Use of Total Cerebral Blood Flow as an Imaging Biomarker of Known Cardiovascular Risks
Authors: Jennings J. Richard , Heim Alicia F. , Kuan Dora Chieh-Hsin , Gianaros Peter J. , Muldoon Matthew F. , Manuck Stephen B.
Published: July 2013

Background and Purpose—

This study examined whether overall cerebral blood flow was associated with known vascular risk factors, including cardiometabolic risk factors that comprise the metabolic syndrome, carotid artery intima-media thickness, and the Framingham risk score.

Methods—

Three separate samples were available for analysis. Two comparable samples were combined to form a primary sample of middle-aged participants (n=576; 30–55 years of age) that completed both a risk factor assessment and a resting brain scan. Samples were recruited via mailings and advertisements within an urban area. Quantitative measures of cerebral blood flow were derived from arterial spin–labeled MRI in this sample and in a validation/generalization sample (n=76; 30–55 years).

Results—

Cerebral blood flow was inversely associated with cardiometabolic risk indices, that is, associated with lower waist circumference, systolic blood pressure, glucose, and triglyceride and high-density lipoprotein. Moreover, cerebral blood flow was also related to Framingham risk and carotid intima-media thickness. In the validation sample, which used a slightly different brain imaging technique, significant relationships were replicated for cardiometabolic risk, but not for Framingham risk.

Conclusions—

Reduced cerebral blood flow seems to be a correlate of vascular disease risk factors associated with cardiometabolic dysregulation. Cerebral blood flow may provide a valid imaging biomarker for cardiovascular risk.
Are Emirate Rulers Immune from Civil Suits in English Courts?
Authors: Bastin Lucas
Published: July 2013

Abstract

This article considers whether the rulers of the seven United Arab Emirates are immune from civil suits before English courts. It commences by summarising the constitutional structure of the UAE and political roles which the Emirate rulers play within its federal government, before setting out the relevant English and international law of State and head of State immunity. Having explained this background, this article assesses the position of each ruler and concludes that the rulers of Abu Dhabi and Dubai are immune from civil suits before English courts but that the rulers of Sharjah, Ra’s al-Khaimah, Fujairah, Umm al-Qaiwain and Ajman are less likely to attract immunity.
Observed Impact of Atmospheric Aerosols on the Surface Energy Budget
Authors: Steiner Allison L. , Mermelstein Dori , Cheng Susan J. , Twine Tracy E. , Oliphant Andrew
Published: July 2013

Atmospheric aerosols scatter and potentially absorb incoming solar radiation, thereby reducing the total amount of radiation reaching the surface and increasing the fraction that is diffuse. The partitioning of incoming energy at the surface into sensible heat flux and latent heat flux is postulated to change with increasing aerosol concentrations, as an increase in diffuse light can reach greater portions of vegetated canopies. This can increase photosynthesis and transpiration rates in the lower canopy and potentially decrease the ratio of sensible to latent heat for the entire canopy. Here, half-hourly and hourly surface fluxes from six Flux Network (FLUXNET) sites in the coterminous United States are evaluated over the past decade (2000–08) in conjunction with satellite-derived aerosol optical depth (AOD) to determine if atmospheric aerosols systematically influence sensible and latent heat fluxes. Satellite-derived AOD is used to classify days as high or low AOD and establish the relationship between aerosol concentrations and the surface energy fluxes. High AOD reduces midday net radiation by 6%–65% coupled with a 9%–30% decrease in sensible and latent heat fluxes, although not all sites exhibit statistically significant changes. The partitioning between sensible and latent heat varies between ecosystems, with two sites showing a greater decrease in latent heat than sensible heat (Duke Forest and Walker Branch), two sites showing equivalent reductions (Harvard Forest and Bondville), and one site showing a greater decrease in sensible heat than latent heat (Morgan–Monroe). These results suggest that aerosols trigger an ecosystem-dependent response to surface flux partitioning, yet the environmental drivers for this response require further exploration.
Perceptions of Employees on Information Checks by Employers using Social Networking Sites in IT Sector
Authors: Tripathy Manas Ranjan , Kaur Tavleen
Published: July 2013

Social networking sites (SNSs) are used to interact with friends and stay connected. The SNSs are increasingly being used by employers as a source of background checks on employees, including the prospective candidates for employment. Employers are making decisions on the basis of information posted on SNSs. The decisions regarding selection, retention or exit are in part influenced by information posted on such sites. The present study examines the perceptions of current employees on the information checks done by employers using networking sites like Facebook. The current study also provides insights that can be followed by both the employees and employers related to usages of SNSs.
Human Resources
Authors: Pandey N.N.
Published: July 2013

The purpose of this paper is to examine the extent of human resources (HR) valuation and disclosure practices adopted in some of the leading Indian companies, thereby making an humble contribution to the existing body of knowledge in the field of HR reporting practices in India. Three years of annual reports of NIFTY-based fifty companies listed on the NSE, have been studied to achieve the purpose using the technique of content analysis. The findings reveal that out of fifty leading companies of India, only one company (ONGC) follows the HRA practices. Also, the extent of HR disclosure practices is far from satisfactory. Since the analysis of the Annual reports is based on only fifty NIFTY-based companies, findings cannot be generalized for all Indian companies.
On the Harary index of graph operations
Authors: Das Kinkar C , Xu Kexiang , Cangul Ismail Naci , Cevik Ahmet Sinan , Graovac Ante
Published: July 2013

The Harary index is defined as the sum of reciprocals of distances between all pairs of vertices of a connected graph. In this paper, expressions for the Harary indices of the join, corona product, Cartesian product, composition and disjunction of graphs are derived and the indices for some well-known graphs are evaluated. In derivations some terms appear which are similar to the Harary index and we name them the second and third Harary index.

MSC:05C05, 05C07, 05C90.
Construction of gene clusters resembling genetic causal mechanisms for common complex disease with an application to young-onset hypertension
Authors: Lynn Ke-Shiuan , Lu Chen-Hua , Yang Han-Ying , Hsu Wen-Lian , Pan Wen-Harn
Published: July 2013

Background

Lack of power and reproducibility are caveats of genetic association studies of common complex diseases. Indeed, the heterogeneity of disease etiology demands that causal models consider the simultaneous involvement of multiple genes. Rothman’s sufficient-cause model, which is well known in epidemiology, provides a framework for such a concept. In the present work, we developed a three-stage algorithm to construct gene clusters resembling Rothman’s causal model for a complex disease, starting from finding influential gene pairs followed by grouping homogeneous pairs.

Results

The algorithm was trained and tested on 2,772 hypertensives and 6,515 normotensives extracted from four large Caucasian and Taiwanese databases. The constructed clusters, each featured by a major gene interacting with many other genes and identified a distinct group of patients, reproduced in both ethnic populations and across three genotyping platforms. We present the 14 largest gene clusters which were capable of identifying 19.3% of hypertensives in all the datasets and 41.8% if one dataset was excluded for lack of phenotype information. Although a few normotensives were also identified by the gene clusters, they usually carried less risky combinatory genotypes (insufficient causes) than the hypertensive counterparts. After establishing a cut-off percentage for risky combinatory genotypes in each gene cluster, the 14 gene clusters achieved a classification accuracy of 82.8% for all datasets and 98.9% if the information-short dataset was excluded. Furthermore, not only 10 of the 14 major genes but also many other contributing genes in the clusters are associated with either hypertension or hypertension-related diseases or functions.

Conclusions

We have shown with the constructed gene clusters that a multi-causal pie-multi-component approach can indeed improve the reproducibility of genetic markers for complex disease. In addition, our novel findings including a major gene in each cluster and sufficient risky genotypes in a cluster for disease onset (which coincides with Rothman’s sufficient cause theory) may not only provide a new research direction for complex diseases but also help to reveal the disease etiology.
Characterization of the PAS domain in the sensor-kinase BvgS: mechanical role in signal transmission
Authors: Dupré Elian , Wohlkonig Alexandre , Herrou Julien , Locht Camille , Jacob-Dubuisson Françoise , Antoine Rudy
Published: July 2013

Background

In bacteria, signal-transduction two-component systems are major players for adaptation to environmental stimuli. The perception of a chemical or physical signal by a sensor-kinase triggers its autophosphorylation. The phosphoryl group is then transferred to the cognate response regulator, which mediates the appropriate adaptive response. Virulence of the whooping cough agent Bordetella pertussis is controlled by the two-component system BvgAS. Atypically, the sensor-kinase BvgS is active without specific stimuli at 37°C in laboratory conditions and is inactivated by the addition of negative chemical modulators. The structure of BvgS is complex, with two tandem periplasmic Venus flytrap domains and a cytoplasmic PAS domain that precedes the kinase domain, which is followed by additional phosphotransfer domains. PAS domains are small, ubiquitous sensing or regulatory domains. The function of the PAS domain in BvgS remains unknown.

Results

We showed that recombinant BvgS PAS proteins form dimers that are stabilized by α helical regions flanking the PAS core. A structural model of the PAS domain dimer was built and probed by site-directed mutagenesis and by biochemical and functional analyses. Although we found no ligands for the PAS domain cavity, its integrity is required for signaling. We also showed that the structural stability of the PAS core and its proper coupling to its flanking N- and C-terminal α helices are crucial for BvgS activity.

Conclusions

We propose that a major function of the BvgS PAS domain is to maintain conformational signals arising from mechanical strain generated by the periplasmic domain. The tight structure of the PAS core and its connections with the upstream and downstream helices ensure signaling to the kinase domain, which determines BvgS activity. Many mild substitutions that map to the PAS domain keep BvgS active but make it unresponsive to negative modulators, supporting that modulation increases conformational strain in the protein.
Primary Epstein-Barr virus infection with polyradiculitis: a case report
Authors: Hottenrott Tilmann , Rauer Sebastian , Bäuerle Jochen
Published: July 2013

Background

Nervous system complications of primary Epstein-Barr virus (EBV) infection in adults are rare, but may occur with encephalitis, meningitis, myelitis, cranial and peripheral neuropathies, or radiculitis.

Case presentation

We describe an immune competent adult with a primary EBV infection complicated by lumbosacral polyradiculitis with pure radicular pain. Prior to the onset of radicular pain the 35-year-old woman had been suffering from infectious mononucleosis misdiagnosed for streptococcal tonsillitis. The diagnosis of primary EBV infection associated polyradiculitis was proven by serology and PCR in serum and CSF. Under initially started empiric therapy with intravenous acyclovir and analgesics the patient completely recovered within a few days.

Conclusion

This case report highlights that EBV should be taken into consideration in the diagnostic work up of radicular pain syndromes, even in immune competent adults. There is no approved causal therapy for EBV infections. In accordance with our case, observations based on a few patients with EBV and nervous system involvement suggest, that acyclovir treatment might be associated a with better course. However, prospective randomized controlled trials addressing the question of the effectiveness of acyclovir in patients with primary EBV infection and neurological complications are lacking.
Gastro oesophageal reflux disease (GORD)-related symptoms and its association with mood and anxiety disorders and psychological symptomology: a population-based study in women
Authors: Sanna Livia , Stuart Amanda L , Berk Michael , Pasco Julie A , Girardi Paolo , Williams Lana J
Published: July 2013

Background

Psychopathology seems to play a role in reflux pathogenesis and vice versa, yet few population-based studies have systematically investigated the association between gastro-oesophageal reflux disease (GORD) and psychopathology. We thus aimed to investigate the relationship between GORD-related symptoms and psychological symptomatology, as well as clinically diagnosed mood and anxiety disorders in a randomly selected, population-based sample of adult women.

Methods

This study examined data collected from 1084 women aged 20-93 yr participating in the Geelong Osteoporosis Study. Mood and anxiety disorders were identified using the Structured Clinical Interview for DSM-IV-TR Research Version, Non-patient edition (SCID-I/NP), and psychological symptomatology was assessed using the General Health Questionnaire (GHQ-12). GORD-related symptoms were self-reported and confirmed by medication use where possible and lifestyle factors were documented.

Results

Current psychological symptomatology and mood disorder were associated with increased odds of concurrent GORD-related symptoms (adjusted OR 2.1, 95% CI 1.3-3.5, and OR 3.0, 95% CI 1.7-5.6, respectively). Current anxiety disorder also tended to be associated with increased odds of current GORD-related symptoms (p = 0.1). Lifetime mood disorder was associated with a 1.6-fold increased odds of lifetime GORD-related symptoms (adjusted OR 1.6, 95% CI 1.1-2.4) and lifetime anxiety disorder was associated with a 4-fold increased odds of lifetime GORD-related symptoms in obese but not non-obese participants (obese, age-adjusted OR 4.0, 95% CI 1.8-9.0).

Conclusions

These results indicate that psychological symptomatology, mood and anxiety disorders are positively associated with GORD-related symptoms. Acknowledging this common comorbidity may facilitate recognition and treatment, and opens new questions as to the pathways and mechanisms of the association.
Decreased APOE-containing HDL subfractions and cholesterol efflux capacity of serum in mice lacking Pcsk9
Authors: Choi Seungbum , Aljakna Aleksandra , Srivastava Ujala , Peterson Blake R , Deng Bin , Prat Annik , Korstanje Ron
Published: July 2013

Background

Studies in animals showed that PCSK9 is involved in HDL metabolism. We investigated the molecular mechanism by which PCSK9 regulates HDL cholesterol concentration and also whether Pcsk9 inactivation might affect cholesterol efflux capacity of serum and atherosclerotic fatty streak volume.

Methods

Mass spectrometry and western blot were used to analyze the level of apolipoprotein E (APOE) and A1 (APOA1). A mouse model overexpressing human LDLR was used to test the effect of high levels of liver LDLR on the concentration of HDL cholesterol and APOE-containing HDL subfractions. Pcsk9 knockout males lacking LDLR and APOE were used to test whether LDLR and APOE are necessary for PCSK9-mediated HDL cholesterol regulation. We also investigated the effects of Pcsk9 inactivation on cholesterol efflux capacity of serum using THP-1 and J774.A1 macrophage foam cells and atherosclerotic fatty streak volume in the aortic sinus of Pcsk9 knockout males fed an atherogenic diet.

Results

APOE and APOA1 were reduced in the same HDL subfractions of Pcsk9 knockout and human LDLR transgenic male mice. In Pcsk9/Ldlr double-knockout mice, HDL cholesterol concentration was lower than in Ldlr knockout mice and higher than in wild-type controls. In Pcsk9/Apoe double-knockout mice, HDL cholesterol concentration was similar to that of Apoe knockout males. In Pcsk9 knockout males, THP-1 macrophage cholesterol efflux capacity of serum was reduced and the fatty streak lesion volume was similar to wild-type controls.

Conclusions

In mice, LDLR and APOE are important factors for PCSK9-mediated HDL regulation. Our data suggest that, although LDLR plays a major role in PCSK9-mediated regulation of HDL cholesterol concentration, it is not the only mechanism and that, regardless of mechanism, APOE is essential. Pcsk9 inactivation decreases the HDL cholesterol concentration and cholesterol efflux capacity in serum, but does not increase atherosclerotic fatty streak volume.
Existence of periodic solutions of a p-Laplacian-Neumann problem
Authors: Hameed Raad Awad , Sun Jiebao , Wu Boying
Published: July 2013

In this paper, we study a periodic p-Laplacian equation with nonlocal terms and Neumann boundary conditions. We establish the existence of time periodic solutions of the p-Laplacian-Neumann problem by the theory of Leray-Schauder degree.
Identification of the feline foamy virus Bet domain essential for APOBEC3 counteraction
Authors: Lukic Dragana Slavkovic , Hotz-Wagenblatt Agnes , Lei Janet , Räthe Ann-Mareen , Mühle Michael , Denner Joachim , Münk Carsten , Löchelt Martin
Published: July 2013

Background

APOBEC3 (A3) proteins restrict viral replication by cytidine deamination of viral DNA genomes and impairing reverse transcription and integration. To escape this restriction, lentiviruses have evolved the viral infectivity factor (Vif), which binds A3 proteins and targets them for proteolytic degradation. In contrast, foamy viruses (FVs) encode Bet proteins that allow replication in the presence of A3, apparently by A3 binding and/or sequestration, thus preventing A3 packaging into virions and subsequent restriction. Due to a long-lasting FV-host coevolution, Bet proteins mainly counteract restriction by A3s from their cognate or highly related host species.

Results

Through bioinformatics, we identified conserved motifs in Bet, all localized in the bel2 exon. In line with the localization of these conserved motifs within bel2, this part of feline FV (FFV) Bet has been shown to be essential for feline A3 (feA3) inactivation and feA3 protein binding. To study the function of the Bet motifs in detail, we analyzed the ability of targeted deletion, substitution, and chimeric FFV-PFV (prototype FV) Bet mutants to physically bind and/or inactivate feA3. Binding of Bet to feA3Z2b is sensitive to mutations in the first three conserved motifs and N- and C-terminal deletions and substitutions across almost the complete bel2 coding sequence. In contrast, the Bel1 (also designated Tas) domain of Bet is dispensable for basal feA3Z2b inactivation and binding but mainly increases the steady state level of Bet. Studies with PFV Bel1 and full-length FFV Bel2 chimeras confirmed the importance of Bel2 for A3 inactivation indicating that Bel1 is dispensable for basal feA3Z2b inactivation and binding but increases Bet stability. Moreover, the bel1/tas exon may be required for expression of a fully functional Bet protein from a spliced transcript.

Conclusions

We show that the Bel2 domain of FV Bet is essential for the inactivation of APOBEC3 cytidine deaminase restriction factors. The Bel1/Tas domain increases protein stability and can be exchanged by related sequence. Since feA3 binding and inactivation by Bet are highly correlated, the data support the view that FV Bet prevents A3-mediated restriction of viral replication by creating strong complexes with these proteins.
Neural stem cell sparing by linac based intensity modulated stereotactic radiotherapy in intracranial tumors
Authors: Oehler Julia , Brachwitz Tim , Wendt Thomas G , Banz Nico , Walther Mario , Wiezorek Tilo
Published: July 2013

Background

Neurocognitive decline observed after radiotherapy (RT) for brain tumors in long time survivors is attributed to radiation exposure of the hippocampus and the subventricular zone (SVZ). The potential of sparing capabilities for both structures by optimized intensity modulated stereotactic radiotherapy (IMSRT) is investigated.

Methods

Brain tumors were irradiated by stereotactic 3D conformal RT or IMSRT using m3 collimator optimized for PTV and for sparing of the conventional OARs (lens, retina, optic nerve, chiasm, cochlea, brain stem and the medulla oblongata). Retrospectively both hippocampi and SVZ were added to the list of OAR and their dose volume histograms were compared to those from two newly generated IMSRT plans using 7 or 14 beamlets (IMSRT-7, IMSRT-14) dedicated for optimized additional sparing of these structures. Conventional OAR constraints were kept constant. Impact of plan complexity and planning target volume (PTV) topography on sparing of both hippocampi and SVZ, conformity index (CI), the homogeneity index (HI) and quality of coverage (QoC) were analyzed. Limits of agreement were used to compare sparing of stem cell niches with either IMSRT-7 or IMSRT-14. The influence of treatment technique related to the topography ratio between PTV and OARs, realized in group A-D, was assessed by a mixed model.

Results

In 47 patients CI (p ≤ 0.003) and HI (p < 0.001) improved by IMSRT-7, IMSRT-14, QoC remained stable (p ≥ 0.50) indicating no compromise in radiotherapy. 90% of normal brain was exposed to a significantly higher dose using IMSRT. IMSRT-7 plans resulted in significantly lower biologically effective doses at all four neural stem cell structures, while contralateral neural stem cells are better spared compared to ipsilateral. A further increase of the number of beamlets (IMSRT-14) did not improve sparing significantly, so IMSRT-7 and IMSRT-14 can be used interchangeable. Patients with tumors contacting neither the subventricular zone nor the cortex benefit most from IMSRT (p < 0.001).

Conclusion

The feasibility of neural stem cell niches sparing with sophisticated linac based inverse IMSRT with 7 beamlets in an unselected cohort of intracranial tumors in relation to topographic situation has been demonstrated. Clinical relevance testing neurotoxicity remains to be demonstrated.
Biogas production from wheat straw: community structure of cellulose-degrading bacteria
Authors: Sun Li , Müller Bettina , Schnürer Anna
Published: July 2013

Background

Wheat straw is one of the most abundant crop residues produced in the world, making it highly interesting as a substrate for biogas production. However, due to the complex structure, its degradability and gas yield are low. The degradability can be improved by pre-treatment, making the material more accessible to microbial degradation.

Methods

To investigate the microbial response to straw as a feed stock for biogas production, this study examined the community structure of cellulose-degrading bacteria in lab-scale biogas digesters operating with manure, alone or in co-digestion with straw, with and without pre-treatment (steam-explosion) at different temperatures. The community was studied by targeting the functional gene encoding glycoside hydrolases of families 5 and 48 using T-RFLP, clone libraries and qPCR.

Results

In general, bacteria belonging to the phyla Firmicutes and Bacteroidetes dominated the cellulose-degrading bacteria community in all digesters. The degree of similarity to the characterised bacteria was often low, and some clones were more closely related to the uncultured bacteria. The addition of straw, pre-treatment of straw and increasing operating temperature all affected the cellulose-degrading community structure, with differing responses in the cel48 and cel5 communities. Both communities changed in response to temperature, while only the cel5 community was affected by the addition of straw and cel48 community by straw pre-treatment.

Conclusions

The addition of straw, pre-treatment of straw and operating temperature all affected the cellulose-degrading community in biogas digesters, but there were no major differences in the digester performance and gas yield.
Natriuretic peptide receptors regulate cytoprotective effects in a human ex vivo 3D/bioreactor model
Authors: Peake Nicholas , Su Nyan , Ramachandran Manoj , Achan Pramod , Salter Donald M , Bader Dan L , Moyes Amie J , Hobbs Adrian J , Chowdhury Tina T
Published: July 2013

Introduction

The present study examined the effect of C-type natriuretic peptide (CNP) and biomechanical signals on anabolic and catabolic activities in chondrocyte/agarose constructs.

Methods

Natriuretic peptide (Npr) 2 and 3 expression were compared in non-diseased (grade 0/1) and diseased (grade IV) human cartilage by immunofluoresence microscopy and western blotting. In separate experiments, constructs were cultured under free-swelling conditions or subjected to dynamic compression with CNP, interleukin-1β (IL-1β), the Npr2 antagonist P19 or the Npr3 agonist cANF4-23. Nitric oxide (NO) production, prostaglandin E2 (PGE2) release, glycosaminoglycan (GAG) synthesis and CNP concentration were quantified using biochemical assays. Gene expression of Npr2, Npr3, CNP, aggrecan and collagen type II were assessed by real-time qPCR. Two-way ANOVA and a post hoc Bonferroni-corrected t-test were used to analyse the data.

Results

The present study demonstrates increased expression of natriuretic peptide receptors in diseased or older cartilage (age 70) when compared to non-diseased tissue (age 60) which showed minimal expression. There was strong parallelism in the actions of CNP on cGMP induction resulting in enhanced GAG synthesis and reduction of NO and PGE2 release induced by IL-1β. Inhibition of Npr2 with P19 maintained catabolic activities whilst specific agonism of Npr3 with cANF4-23 had the opposite effect and reduced NO and PGE2 release. Co-stimulation with CNP and dynamic compression enhanced anabolic activities and inhibited catabolic effects induced by IL-1β. The presence of CNP and the Npr2 antagonist abolished the anabolic response to mechanical loading and prevented loading-induced inhibition of NO and PGE2 release. In contrast, the presence of the Npr3 agonist had the opposite effect and increased GAG synthesis and cGMP levels in response to mechanical loading and reduced NO and PGE2 release comparable to control samples. In addition, CNP concentration and natriuretic peptide receptor expression were increased with dynamic compression.

Conclusions

Mechanical loading mediates endogenous CNP release leading to increased natriuretic peptide signalling. The loading-induced CNP/Npr2/cGMP signalling route mediates anabolic events and prevents catabolic activities induced by IL-1β. The CNP pathway therefore represents a potentially chondroprotective intervention for patients with OA, particularly when combined with physiotherapeutic approaches to stimulate biomechanical signals.
Obesity enhances nongenomic estrogen receptor crosstalk with the PI3K/Akt and MAPK pathways to promote in vitro measures of breast cancer progression
Authors: Bowers Laura W , Cavazos David A , Maximo Ilane XF , Brenner Andrew J , Hursting Stephen D , deGraffenried Linda A
Published: July 2013

Introduction

Epidemiological and clinical studies indicate that obesity is associated with a worse postmenopausal breast cancer prognosis and an increased risk of endocrine therapy resistance. However, the mechanisms mediating these effects remain poorly understood. Here we investigate the molecular pathways by which obesity-associated circulating factors in the blood enhance estrogen receptor alpha (ERα) positive breast cancer cell viability and growth.

Methods

Blood serum was collected from postmenopausal breast cancer patients and pooled by body mass index (BMI) category (Control: 18.5 to 24.9 kg/m2; Obese: ≥30.0 kg/m2). The effects of patient sera on MCF-7 and T47D breast cancer cell viability and growth were examined by MTT and colony formation assays, respectively. Insulin-like growth factor receptor 1(IGF-1R), Akt, and ERK1/2 activation and genomic ERα activity were assessed to determine their possible contribution to obese patient sera-induced cell viability and growth. To further define the relative contribution of these signaling pathways, cells grown in patient sera were treated with various combinations of ERα, PI3K/Akt and MAPK targeted therapies. Comparisons between cells exposed to different experimental conditions were made using one-way analysis of variance (ANOVA) and Student's t test.

Results

Cells grown in media supplemented with obese patient sera displayed greater cell viability and growth as well as IGF-1R, Akt and ERK1/2 activation relative to control sera. Despite the lack of a significant difference in genomic ERα activity following growth in obese versus control patient sera, we observed a dramatic reduction in cell viability and growth after concurrent inhibition of the ERα and PI3K/Akt signaling pathways. Further, we demonstrated that ERα inhibition was sufficient to attenuate obese serum-induced Akt and ERK1/2 activation. Together, these data suggest that obesity promotes greater ERα positive breast cancer cell viability and growth through enhanced crosstalk between nongenomic ERα signaling and the PI3K/Akt and MAPK pathways.

Conclusions

Circulating factors in the serum of obese postmenopausal women stimulate ERα positive breast cancer cell viability and growth by facilitating non-genomic ERα crosstalk with the PI3K/Akt and MAPK signaling pathways. These findings provide valuable insight into one mechanism by which obesity may promote ERα positive postmenopausal breast cancer progression and endocrine therapy resistance.
Cardiac index and oxygen delivery during low and high tidal volume ventilation strategies in patients with acute respiratory distress syndrome: a crossover randomized clinical trial
Authors: Natalini Giuseppe , Minelli Cosetta , Rosano Antonio , Ferretti Pierluigi , Militano Carmine R , De Feo Carlo , Bernardini Achille
Published: July 2013

Introduction

The beneficial effect of low tidal volume (TV) ventilation strategy on mortality in patients with acute respiratory distress syndrome (ARDS) has been attributed to the protective effect on ventilator-induced lung injury, and yet its effect on cardiovascular function might also play an important role. The aim of this study was to assess whether low TV ventilation improves cardiac output and oxygen delivery compared with high TV ventilation strategy in patients with ARDS.

Methods

In this crossover randomized clinical trial 16 ARDS patients were recruited in an intensive care unit at a university-affiliated hospital. Each patient was ventilated for 30 min with low (6 mL/kg) and 30 min with high (12 mL/kg) TV. The two experimental periods, applied in random order and with allocation concealment, were separated by 30 min of basal ventilation. Minute ventilation was constantly maintained by appropriate respiratory rate changes.

Results

Compared with high TV ventilation, low TV ventilation showed decreased pH (7.37 vs. 7.41, P = 0.001) and increased PaCO2 (49 vs. 43 mmHg; P = 0.002). Cardiac index and oxygen delivery index were increased with low compared with high TV ventilation (3.9 vs. 3.5 L.min-1.m-2, P = 0.012, and 521 vs. 463 mL.min-1.m-2, P = 0.002, respectively), while oxygen extraction ratio decreased (0.36 vs. 0.44, P = 0.027). In four patients oxygen extraction ratio was >0.5 during high TV but not during low TV strategy. The magnitude of the change in cardiac index was positively associated with PaCO2 variation (P = 0.004), while it was unrelated to the magnitude of changes in TV and airway pressure. The decrease of cardiac index was predicted by PaCO2 reduction, with and area under ROC curve of 0.72.

Conclusions

Our findings suggest that a low TV ventilation strategy increases cardiac index and oxygen delivery, thus supporting the hypothesis that the beneficial effect of low TV ventilation in patients with ARDS could be partially explained by hemodynamic improvement. In other words, low tidal volume ventilation could be protective also for the cardiovascular system and not only for the lung. The slight increase of PaCO2 during low TV ventilation seems to predict the increase of cardiac index.

Trial registration

ClinicalTrials.gov: NCT00713713