Graded Exercise Therapy Guided Self-Help Trial for Patients with Chronic Fatigue Syndrome (GETSET): Protocol for a Randomized Controlled Trial and Interview Study

Background: Chronic fatigue syndrome, also known as myalgic encephalomyelitis (CFS/ME), is characterized by chronic disabling fatigue and other symptoms, which are not explained by an alternative diagnosis. Previous trials have suggested that graded exercise therapy (GET) is an effective and safe treatment. GET itself is therapist-intensive with limited availability. Objective: While guided self-help based on cognitive behavior therapy appears helpful to patients, Guided graded Exercise Self-help (GES) is yet to be tested. Methods: This pragmatic randomized controlled trial is set within 2 specialist CFS/ME services in the South of England. Adults attending secondary care clinics with National Institute for Health and Clinical Excellence (NICE)-defined CFS/ME (N=218) will be randomly allocated to specialist medical care (SMC) or SMC plus GES while on a waiting list for therapist-delivered rehabilitation. GES will consist of a structured booklet describing a 6-step graded exercise program, supported by up to 4 face-to-face/telephone/Skype™ consultations with a GES-trained physiotherapist (no more than 90 minutes in total) over 8 weeks. The primary outcomes at 12-weeks after randomization will be physical function (SF-36 physical functioning subscale) and fatigue (Chalder Fatigue Questionnaire). Secondary outcomes will include healthcare costs, adverse outcomes, and self-rated global impression change scores. We will follow up all participants until 1 year after randomization. We will also undertake qualitative interviews of a sample of participants who received GES, looking at perceptions and experiences of those who improved and worsened. Results: The project was funded in 2011 and enrolment was completed in December 2014, with follow-up completed in March 2016. Data analysis is currently underway and the first results are expected to be submitted soon. Conclusions: This study will indicate whether adding GES to SMC will benefit patients who often spend many months waiting for rehabilitative therapy with little or no improvement being made during that time. The study will indicate whether this type of guided self-management is cost-effective and safe. If this trial shows GES to be acceptable, safe, and comparatively effective, the GES booklet could be made available on the Internet as a practitioner and therapist resource for clinics to recommend, with the caveat that patients also be supported with guidance from a trained physiotherapist. The pragmatic approach in this trial means that GES findings will be generalizable to usual National Health Service (NHS) practice.

Blurred Lines: Performance Enhancement, Common Mental Disorders and Referral in the U.K. Athletic Population

Through the awareness-raising efforts of several high-profile current and former athletes, the issue of common mental disorders (CMD) in this population is gaining increasing attention from researchers and practitioners alike. Yet the prevalence is unclear and most likely, under-reported. Whilst the characteristics of the sporting environment may generate CMD within the athletic population, it also may exacerbate pre-existing conditions, and hence it is not surprising that sport psychology and sport science practitioners are anecdotally reporting increased incidences of athletes seeking support for CMDs. In a population where there are many barriers to reporting and seeking help for CMD, due in part to the culture of the high performance sporting environment, anecdotal reports suggest that those athletes asking for help are approaching personnel who they are most comfortable talking to. In some cases, this may be a sport scientist, the sport psychologist or sport psychology consultant. Among personnel in the sporting domain, there is a perception that the sport psychologist or sport psychology consultant is best placed to assist athletes seeking assistance for CMD. However, sport psychology as a profession is split by two competing philosophical perspectives; one of which suggests that sport psychologists should work exclusively with athletes on performance enhancement, and the other views the athlete more holistically and accepts that their welfare may directly impact on their performance. To add further complication, the development of the profession of sport psychology varies widely between countries, meaning that practice in this field is not always clearly defined. This article examines case studies that illustrate the blurred lines in applied sport psychology practice, highlighting challenges with the process of referral in the U.K. athletic population. The article concludes with suggestions for ensuring the field of applied sport psychology is continually evolving and reconfiguring to ensure that it continues to meet the demands of its clients.

Reading Between the Lines of Teaching and Learning

Some students lack reading skills due to biological or environmental factors. Accordingly, in my role as an educator, I would like to know if Dialogic Reading Strategies can help Spanish speaking caregivers to facilitate an interactive reading routine at home with their child.

Impact of Glycosyltransferases on the Phenotype, Signaling and Transcriptome of Colorectal Cancer Cell Lines. Focus on the role of glycosyltransferases B4GALNT2 and FUT6 and their cognate Sda and sLex antigens

In colorectal cancer (CRC), two carbohydrate structures are modulated: the Sda antigen, synthesized by B4GALNT2, and sLex antigen, mainly synthesized by FUT6. sLex antigen is often overexpressed and associated with worse prognosis; B4GALNT2/Sda antigen are dramatically downregulated but their role in tumor progression and development is not fully clear. TCGA interrogation revealed a dramatic down-regulation of B4GALNT2 mRNA in CRC, compared with normal samples. Patients with higher B4GALNT2 mRNA in CRC samples displayed longer survival. Yet, methylation and miRNA expression play a relevant role in B4GALNT2 downregulation in CRC. To clarify the mechanisms linking the B4GALNT2/Sda expression level to CRC phenotype, three different CRC cell lines were modified to express B4GALNT2: LS174T cell line, in which the constitutively expressed sLex antigen was partially replaced by Sda; SW480/SW620 pair, both lacking Sda and sLex antigens. In LS174T cells, the expression of B4GALNT2 reduced the ability to grow in poor adherence conditions and the expression of ALDH, a stemness marker. In SW620 cells, B4GALNT2 expression impacted on the main aspects of malignancy. In SW480 cells the expression of B4GALNT2 left unchanged the proliferation rate and the wound healing ability. To clarify the impact of sLex on CRC phenotype, the SW480/SW620 pair were permanently transfected to express FUT6 cDNA. In both cell lines, overexpression of FUT6/sLex boosted the clonogenic ability in standard growth conditions. Conversely, the growth in soft agar and the capacity to close a wound were enhanced only in SW620 cells. Transcriptome analysis of CRC cell lines transfected either with B4GALNT2 or FUT6 showed a relevant impact of both enzymes on gene expression modulation. Overall, current data may help to personalize therapies for CRC patients according to the B4GALNT2 levels and support a causal effect of this glycosyltransferase on reducing malignancy independently of sLex inhibition.

Solid Lipid Nanoparticles For Hydrophilic Biotech Drugs: Optimization And Cell Viability Studies (caco-2 & Hepg-2 Cell Lines).

Insulin was used as model protein to developed innovative Solid Lipid Nanoparticles (SLNs) for the delivery of hydrophilic biotech drugs, with potential use in medicinal chemistry. SLNs were prepared by double emulsion with the purpose of promoting stability and enhancing the protein bioavailability. Softisan(®)100 was selected as solid lipid matrix. The surfactants (Tween(®)80, Span(®)80 and Lipoid(®)S75) and insulin were chosen applying a 2(2) factorial design with triplicate of central point, evaluating the influence of dependents variables as polydispersity index (PI), mean particle size (z-AVE), zeta potential (ZP) and encapsulation efficiency (EE) by factorial design using the ANOVA test. Therefore, thermodynamic stability, polymorphism and matrix crystallinity were checked by Differential Scanning Calorimetry (DSC) and Wide Angle X-ray Diffraction (WAXD), whereas the effect of toxicity of SLNs was check in HepG2 and Caco-2 cells. Results showed a mean particle size (z-AVE) width between 294.6 nm and 627.0 nm, a PI in the range of 0.425-0.750, ZP about -3 mV, and the EE between 38.39% and 81.20%. After tempering the bulk lipid (mimicking the end process of production), the lipid showed amorphous characteristics, with a melting point of ca. 30 °C. The toxicity of SLNs was evaluated in two distinct cell lines (HEPG-2 and Caco-2), showing to be dependent on the concentration of particles in HEPG-2 cells, while no toxicity in was reported in Caco-2 cells. SLNs were stable for 24 h in in vitro human serum albumin (HSA) solution. The resulting SLNs fabricated by double emulsion may provide a promising approach for administration of protein therapeutics and antigens.

Carbon Nanoparticles For Gene Transfection In Eukaryotic Cell Lines.

For the first time, oxygen terminated cellulose carbon nanoparticles (CCN) was synthesised and applied in gene transfection of pIRES plasmid. The CCN was prepared from catalytic of polyaniline by chemical vapour deposition techniques. This plasmid contains one gene that encodes the green fluorescent protein (GFP) in eukaryotic cells, making them fluorescent. This new nanomaterial and pIRES plasmid formed π-stacking when dispersed in water by magnetic stirring. The frequencies shift in zeta potential confirmed the plasmid strongly connects to the nanomaterial. In vitro tests found that this conjugation was phagocytised by NG97, NIH-3T3 and A549 cell lines making them fluorescent, which was visualised by fluorescent microscopy. Before the transfection test, we studied CCN in cell viability. Both MTT and Neutral Red uptake tests were carried out using NG97, NIH-3T3 and A549 cell lines. Further, we use metabolomics to verify if small amounts of nanomaterial would be enough to cause some cellular damage in NG97 cells. We showed two mechanisms of action by CCN-DNA complex, producing an exogenous protein by the transfected cell and metabolomic changes that contributed by better understanding of glioblastoma, being the major finding of this work. Our results suggested that this nanomaterial has great potential as a gene carrier agent in non-viral based therapy, with low cytotoxicity, good transfection efficiency, and low cell damage in small amounts of nanomaterials in metabolomic tests.

Going Beyond Seizure Control: Can Pharmacotherapy Help To Restore Cognitive Network Function?

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Função vísuo-espacial em paralisia cerebral e proposta de novo teste com a ajuda de computador

The first idea of this study is trat there may be a disturbance of the visuo-spatial function in cerebral palsy. This idea is based upon the theories of Luria and Piaget. The second idea of this study is that the computer can help the investigation of visuo-spatial function. With the intention of evaluating the spatial function in cerebral palsy, the literature related to these themes was revised. We justify the proposal of a new test to study visuo-spatial function. This test uses straight lines in four different orientations and the subject has to recognize and arrange them individually or sets of them. This was done through the use of pencil and papel, and computer. The results confirm that there is a spatial disturbance and that a better understanding of the subject's difficulties was made possible through the use of the computer and the Logo computer language.

Vimentin expression and the influence of Matrigel in cell lines of head and neck squamous cell carcinoma

Vimentin is a cytoeskeletal intermediate filament protein commonly observed in mesenchymal cells; however, it can also be found in malignant epithelial cells. It is demonstrated in several carcinomas, such as those of the cervix, breast and bladder, in which it is widely used as a marker of the epithelial to mesenchymal transition that takes place during embryogenesis and metastasis. Vimentin is associated with tumors that show a high degree of invasiveness, being detected in invasion front cells. Its expression seems to be influenced by the tumor microenvironment. The aim of this study was to evaluate vimentin expression in head and neck squamous cell carcinoma (HNSCC) cell lines, and to investigate the contribution of the microenvironment to its expression. HNSCC cell lines (HN6, HN30 and HN31) and an immortalized nontumorigenic cell line (HaCaT) were submitted to a three-dimensional assay with Matrigel. Cytoplasmatic staining of the HN6 cell line cultured without Matrigel and of the HN30 and HN31 cell lines cultured with Matrigel was demonstrated through immunohistochemistry. Western Blotting revealed a significant decrease in vimentin expression for the HN6 cell line and a significant increase for the HN30 and HN31 cell lines cultured with Matrigel. The results suggest that vimentin can be expressed in HNSCC cells and its presence is influenced by the microenvironment of a tumor.

Tori embedded in S³ with dense asymptotic lines

In this paper are given examples of tori T² embedded in S³ with all their asymptotic lines dense.

Inquérito de saúde no Município de Campinas, São Paulo, Brasil (ISACamp): comparação de estimativas segundo posse de linha telefônica residencial

O estudo avalia diferenças quanto às características sociodemográficas, de estilo de vida e de condições de saúde entre adultos com e sem linha telefônica residencial, valendo-se de dados de inquérito domiciliar de saúde realizado em Campinas, São Paulo, Brasil (2008/2009). Trata-se de estudo transversal de base populacional com 2.637 adultos (18 anos e mais). Análises descritivas, testes qui-quadrado, prevalências e respectivos intervalos de 95% de confiança foram calculados. Estimaram-se os vícios associados à não cobertura da população sem telefone antes e após o ajuste de pós-estratificação. O impacto do vício nos intervalos de confiança foi avaliado pela razão de vício. Cerca de 76% dos entrevistados possuíam linha telefônica residencial. Exceto para situação conjugal, foram observadas diferenças sociodemográficas segundo posse de telefone. Após o ajuste de pós-estratificação, houve redução do vício das estimativas para as variáveis associadas à posse de linha telefônica, no entanto, exceto para osteoporose, o ajuste de pós-estratificação foi insuficiente para corrigir o vício de não cobertura.

Gender and schooling inequalities in risk and protective factors for chronic diseases among Brazilian adults, through telephone survey

OBJECTIVES: To assess risk and protective factors for chronic noncommunicable diseases (CNCD) and to identify social inequalities in their distribution among Brazilian adults. METHODS: The data used were collected in 2007 through VIGITEL, an ongoing population-based telephone survey. This surveillance system was implemented in all of the Brazilian State capitals, over 54,000 interviews were analyzed. Age-adjusted prevalence ratios for trends at different schooling levels were calculated using Poisson regression with linear models. RESULTS: These analyses have shown differences in the prevalence of risk and protective factors for CNCD by gender and schooling. Among men, the prevalence ratios of overweight, consumption of meat with visible fat, and dyslipidemia were higher among men with more schooling, while tobacco use, sedentary lifestyle, and high-blood pressure were lower. Among women, tobacco use, overweight, obesity, high-blood pressure and diabetes were lower among men with more schooling, and consumption of meat with visible fat and sedentary lifestyles were higher. As for protective factors, fruit and vegetables intake and physical activity were higher in both men and women with more schooling. CONCLUSION: Gender and schooling influence on risk and protective factors for CNCD, being the values less favorable for men. vigitel is a useful tool for monitoring these factors amongst the Brazilian population.

Vigilância de Fatores de Risco para Doenças Crônicas por Inquérito Telefônico nas capitais dos 26 estados brasileiros e no Distrito Federal (2006)

OBJETIVO: Descrever métodos e resultados iniciais do Sistema de Vigilância de Fatores de Risco e Proteção para Doenças Crônicas não Transmissíveis por Inquérito Telefônico - VIGITEL implantado no Brasil em 2006. MÉTODOS: O VIGITEL estudou amostras probabilísticas da população com 18 ou mais anos de idade residente em domicílios conectados à rede de telefonia fixa de cada uma das capitais dos 26 Estados brasileiros e do Distrito Federal (54.369 indivíduos no total, sendo pelo menos 2.000 por cidade). A amostragem foi realizada a partir de cadastros eletrônicos completos das linhas residenciais fixas de cada cidade, envolvendo sorteio de linhas (domicílios) e sorteio de um morador por linha para ser entrevistado. O questionário aplicado investigou características demográficas e socioeconômicas, padrão de alimentação e de atividade física, consumo de cigarros e de bebidas alcoólicas, e peso e altura recordados, entre outros quesitos. Estimativas sobre a freqüência de fatores de risco selecionados, estratificadas por sexo e acompanhadas de Intervalo de Confiança de 95%, foram calculadas para a população adulta de cada cidade empregando-se fatores de ponderação que igualam a composição sociodemográfica da amostra em cada cidade àquela observada no Censo Demográfico de 2000. Estimativas para o conjunto das cidades empregam fator de ponderação adicional que leva em conta a população de adultos de cada cidade. RESULTADOS: Os cinco fatores de risco selecionados (tabagismo, consumo abusivo de bebidas alcoólicas, excesso de peso, consumo de carnes com excesso de gordura e sedentarismo) tenderam a ser mais freqüentes em homens do que em mulheres. Dentre os fatores de proteção, o consumo regular de frutas e hortaliças foi mais freqüente em mulheres do que em homens, observando-se situação inversa no caso da atividade física de lazer. Diferenças substanciais na freqüência dos fatores de risco e proteção foram observadas entre as cidades, com padrões de distribuição regional diferenciados por fator. DISCUSSÃO: O desempenho do sistema, avaliado a partir da qualidade dos cadastros telefônicos e de taxas de resposta e de recusas, mostrou-se adequado e, de modo geral, superior ao encontrado em sistemas equivalentes existentes em países desenvolvidos. O custo do sistema de R$ 31,15 por entrevista realizada, foi a metade do custo observado no sistema americano de vigilância de fatores de risco para doenças crônicas por inquérito telefônico e um quinto do custo estimado em inquérito domiciliar tradicional realizado recentemente no Brasil.

Prevalência de fatores de risco para doenças crônicas: inquérito populacional mediante entrevistas telefônicas em Botucatu, São Paulo, 2004

OBJETIVO: Descrever resultados da aplicação de um sistema de monitoramento de fatores de risco para doenças crônicas não transmissíveis (DCNT) por meio de entrevistas telefônicas (SIMTEL) no município de Botucatu/SP. MÉTODOS: Entrevistou-se amostra probabilística (n = 1.410) da população de indivíduos com 18 ou mais anos de idade residente em domicílios do município de Botucatu/SP, conectados à rede de telefonia fixa. A amostragem foi realizada em três etapas: sorteio de linhas do cadastro da companhia telefônica; seleção de linhas residenciais ativas; sorteio para entrevista de um morador com 18 ou mais anos de idade por linha elegível. A taxa de sucesso (entrevistas realizadas: linhas elegíveis sorteadas) foi de 86,9%, sendo de 5,8% a proporção de recusas. Foi aplicado um questionário com 74 questões sobre consumo alimentar, atividade física, tabagismo, consumo de bebidas alcoólicas, peso e estatura recordados e auto-referência a diagnósticos médicos de hipertensão arterial e diabetes. Apresentam-se estimativas brutas da prevalência de fatores de risco/proteção para DCNT e estimativas ajustadas que levam em conta a distribuição segundo idade, sexo e escolaridade da população adulta total do município no Censo Demográfico de 2000. RESULTADOS: Foram observadas altas prevalências de excesso de peso (46.7%) e sedentarismo (57.9%). Houve desvantagem para os homens quanto ao consumo excessivo de bebidas alcoólicas e vantagem no que se refere à prática de atividade física em 1 ou mais dias da semana. Nas mulheres, observou-se associação inversa entre escolaridade e os seguintes fatores de risco: obesidade, excesso de peso, sedentarismo, consumo de carnes com gordura e hábito de fumar. Resultado semelhante foi observado para homens, exceto com relação a obesidade e excesso de peso. CONCLUSÕES: A segunda experiência de aplicação do SIMTEL confirmou o desempenho satisfatório e a utilidade do sistema em nosso meio.

Vigilância de fatores de risco para doenças crônicas por inquérito telefônico nas capitais dos 26 estados brasileiros e no Distrito Federal (2006)

Objetivo: Descrever métodos e resultados iniciais do Sistema de Vigilância de Fatores de Risco e Proteção para Doenças Crônicas ão Transmissíveis por Inquérito Telefônico - VIGITEL implantado no Brasil em 2006. Métodos: O VIGITEL estudou amostras probabilísticas da população com 18 ou mais anos de idade residente em domicílios conectados à rede de telefonia fixa de cada uma das capitais dos 26 Estados brasileiros e do Distrito Federal (54.369 indivíduos no total, sendo pelo menos 2.000 por cidade). A amostragem foi realizada a partir de cadastros eletrônicos completos das linhas residenciais fixas de cada cidade, envolvendo sorteio de linhas (domicílios) e sorteio de um morador por linha para ser entrevistado. O questionário aplicado investigou características demográficas e socioeconômicas, padrão de alimentação e de atividade física, consumo de cigarros e de bebidas alcoólicas, e peso e altura recordados, entre outros quesitos. Estimativas sobre a freqüência de fatores de risco selecionados, estratificadas por sexo e acompanhadas de Intervalo de Confiança de 95%, foram calculadas para a população adulta de cada cidade empregando-se fatores de ponderação que igualam a composição sociodemográfica da amostra em cada cidade àquela observada no Censo Demográfico de 2000. Estimativas para o conjunto das cidades empregam fator de ponderação adicional que leva em conta a população de adultos de cada cidade. Resultados: Os cinco fatores de risco selecionados (tabagismo, consumo abusivo de bebidas alcoólicas, excesso de peso, consumo de carnes com excesso de gordura e sedentarismo) tenderam a ser mais freqüentes em homens do que em mulheres. Dentre os fatores de proteção, o consumo regular de frutas e hortaliças foi mais freqüente em mulheres do que em homens, observando-se situação inversa no caso da atividade física de lazer. ) Diferenças substanciais na freqüência dos fatores de risco e proteção foram observadas entre as cidades, com padrões de distribuição regional diferenciados por fator.Discussão: O desempenho do sistema, avaliado a partir da qualidade dos cadastros telefônicos e de taxas de resposta e de recusas, mostrou-se adequado e, de modo geral, superior ao encontrado em sistemas equivalentes existentes em países desenvolvidos. O custo do sistema de R$ 31,15 por entrevista realizada, foi a metade do custo observado no sistema americano de vigilância de fatores de risco para doenças crônicas por inquérito telefônico e um quinto do custo estimado em inquérito domiciliar tradicional realizado recentemente no Brasil