Primary CNS lymphoma with intravitreal metastasis : using vitreous cavity samples to monitor response to therapy

A fifty-eight year old male patient presented to the ophthalmic department with a 3 day history of reduced visual acuity, blurred vision and floaters, associated with recent lethargy, headaches and behavioural changes. Fundal examination revealed a bilateral vitritis. Steroid therapy was started. MRI of the brain revealed multiple hypodense and hyperdense lesions. Vitrectomy was performed in view of the poor response to steroids. A biopsy showed non-hodgkin B-Cell lymphoma. The patient was started on intravenous Methotrexate and Cytarabine. Repeat vitreous cavity biopsies were performed in order to assess response to therapy. All biopsies to date have revealed evidence of on-going lymphoma.peer-reviewe

25-Hydroxy vitamin-D, obesity, and associated variables as predictors of breast cancer risk and tamoxifen benefit in NSABP-P1.

Observational studies suggest that host factors are associated with breast cancer risk. The influence of obesity, vitamin-D status, insulin resistance, inflammation, and elevated adipocytokines in women at high risk of breast cancer is unknown. The NSABP-P1 trial population was used for a nested case-control study. Cases were drawn from those who developed invasive breast cancer and controls selected from unaffected participants (≤4 per case) matched for age, race, 5 year Gail score, and geographic location of clinical center as a surrogate for latitude. Fasting serum banked at trial enrolment was assayed for 25-hydroxy vitamin-D (25OHD), insulin, leptin (adipocytokine), and C-reactive protein (CRP, marker of inflammation). Logistic regression was used to test for associations between study variables and the risk of invasive breast cancer. Two hundred and thirty-one cases were matched with 856 controls. Mean age was 54, and 49% were premenopausal. There were negative correlations for 25OHD with body mass index (BMI), insulin, CRP, and leptin. BMI ≥ 25 kg/m(2) was associated with higher breast cancer risk (odds ratio [OR] 1.45, p = 0.02) and tamoxifen treatment was associated with lower risk (OR = 0.44, p < 0.001). Suboptimal 25OHD (<72 nmol/l) did not influence breast cancer risk (OR = 1.06, p = 0.76). When evaluated as continuous variables, 25OHD, insulin, CRP, and leptin levels were not associated with breast cancer risk (all p > 0.34). In this high risk population, higher BMI was associated with a greater breast cancer risk. Serum levels of 25OHD, insulin, CRP, and leptin were not independent predictors of either breast cancer risk or tamoxifen benefit

Dance movement therapy and falls prevention

Falls are a leading cause of morbidity, healthcare use and mortality. Dance is a popular form of physical activity among older people and previous research has suggested that it may improve various health outcomes in this population, including balance, gait and muscle performance. A systematic review of the potential benefits of dance on falls and fear of falling is lacking. Thus, we conducted a systematic review considering all randomized controls trials (RCTs) investigating if dance can reduce falls and improve fear of falling in older adults. Major databases were searched from inception until 1 March 2017 and a total of 10 RCTs were identified, which included a total of 680 people (n = 356 dance, n = 324 control). Overall, the mean age of the samples was 69.4 years, and 75.2% were female. Across four RCTs, dance therapy reduced falls versus usual care in only one study. Dance therapy improved fear of falling in two out of three included RCTs. There were no serious adverse events reported in the RCTs. In summary, we found a paucity of studies investigating the effect of dance on falls and fear of falling and the evidence base is preliminary and equivocal. Given the heterogeneity of the included samples and interventions, in addition to the short-term follow-up, no firm conclusions can be drawn. However, dance appears to be safe and, given its popularity and demonstrated benefits on other health/wellbeing outcomes in older adults, it is important that future research considers its potential benefits on falls/fear of falling in older age

A road map for designing and reporting clinical trials in paediatric dentistry

Background Unless clinical trials are well‐designed, there is a risk that they will not be usable to improve patient care. Aim This paper discusses some factors important in designing clinical trials in paediatric dentistry. It uses the prevention and management of dental caries in children as the lens through which to look at these. Findings Amongst the factors to consider are clear research questions and objectives; appropriate outcomes and outcome measures; sample size calculation and the level of randomisation; methods for random allocation; and operator/assessor training. Experts in trial design including statisticians and a trialist should be consulted early in the design process. The aspects of trial design unique to cariology trials such as ‘clustering’ of data items, mixed dentition issues and those related to trials involving children (communication, consent etc) should be considered. Comprehensive reporting of trial results is essential. Conclusion There are many readily available resources and tools to help the researcher design a trial of good quality that will yield results useful to the research community and beyond, to those who will implement the findings and ultimately those who will benefit from them

Protein complexes in neurodegenerative diseases

The 14-3-3 family of proteins are important signalling proteins involved in a number of cellular processes. These include cell cycle regulation, apoptosis, signal transduction and cell signalling. There is also considerable evidence in the literature that 14-3-3 proteins play a vital role in the pathology of neurodegenerative diseases, including Alzheimer’s, Parkinson’s, Huntington’s and Prion disease. The neurodegenerative disease of focus in this research is Spinocerebellar Ataxia Type 1 (SCA1). SCA1 is a polyglutamine-repeat disease and the interaction of the disease protein ataxin-1 with 14-3-3 proteins leads to the toxic accumulation and subsequent protein aggregation which is characteristic of this disease. This study focused on attempting to elucidate the structure of various domains of the disease protein and also in identifying potential inhibitors of this deleterious interaction. Unfortunately, structural studies were not successful due to a number of caveats encountered in the expression and purification of the ataxin-1 protein domains. By utilising computational methods and small molecule inhibitors, a number of potential lead compounds which possess the ability to at least partly disrupt the interaction of 14- 3-3ζ have been identified. As 14-3-3 proteins play roles in other neurodegenerative diseases, successful identification of potential drug lead treatments can have far reaching benefits in a number of neurodegenerative diseases including SCA1. Lipid rafts are also involved in neurodegenerative disease pathology. Lipid rafts are cholesterol and sphingolipid rich domains which organise the plasma membrane into discrete microdomains and act as signalling platforms and processing centres which attach specific proteins and lipids. A number of disease proteins are processed at these membrane regions, including those involved in Alzheimer’s, Parkinson’s and Prion disease. This processing is a step which is critical in the pathology of disease and abnormal processing leads to the formation of toxic protein aggregates. Previous research in the lab identified the association of low levels of the five main brain isoforms of 14-3-3 proteins with rafts. This study expanded on this to positively identify the presence of the two phospho-forms of 14-3-3, α and δ. The mechanism by which 14-3-3 proteins associate with rafts was also investigated, indicating that 14-3-3 associates with rafts via an unidentified raftbound protein(s). In addition, the phosphorylation status and quaternary structure of 14-3-3 in the presence of sphingolipids has been explored

Comunidades de pequenos mamíferos como indicadores de qualidade ambiental no planalto norte catarinense

A Floresta Ombrofila Densa (Floresta Atlantica) e a Floresta Ombrófila Mista (Floresta com Araucaria) sofreram nas ultimas décadas de um dos mais altos níveis de degradação de habitats e consequentemente perda da biodiversidade, em detrimento da especulação imobiliária e avanço das fronteiras agrícolas e pastoris. No entanto, atualmente tem-se destinado esforços em vários sentidos para minimizar estas acoes, buscando compreender o funcionamento destes sistemas com base no conhecimento dos elementos que o compõem. Para tanto, faz-se necessário o conhecimento dos processos ecologicos entre as comunidades vegetais e animais e e nesse sentido, que foram descritas e comparadas as comunidades de marsupiais e pequenos roedores em quatros diferentes ambientes no Planalto Norte Catarinense, alem de investigados alguns paramentos populacionais de Akodon gr. cursor. Neste estudo foram selecionados quatro sítios amostrais denominados de area ciliar com capoeirinha (A1), área ciliar dominada por regeneração de gramíneas (A2), plantio de pinus (A3) e remanescente de floresta nativa (A4). Em cada sitio de amostragem foi instalada uma grade de captura de 120x30m, com 105 armadilhas cada. Para cada individuo marcado foram anotados os seguintes dados: especie, ponto de captura, sexo, idade, condi coes reprodutivas e em seguida foram marcados com brincos, anilhas ou perfurações nas orelhas e em seguida liberados no mesmo ponto de captura. No periodo de novembro de 2005 a julho de 2007 foram registradas 13 especies, destas cinco eram marsupiais (Didelphis albiventris, Didelphis aurita, Gracilinanus microtarsus, Philander frenatus e Monodelphis sorex) e oito pequenos roedores (Akodon gr. cursor, Delomys dorsalis, Euryzygomatomys spinosus, Nectomys squamipe, Olygoryzomys nigripes, Oryzomys sp., Oxymycterus aff. judex e Thaptomys nigrita). O esforço de captura total foi de 7.875 armadilhas-noite ao todo, sendo 6.300 armadilhas-noite no chão e 1.575 armadilhas-noite no sub-bosque do fragmento de floresta e sucesso total de captura de 1,36% para marsupiais e 10,51% para pequenos roedores. Para os marsupiais o ambiente com maior sucesso de captura foi o remanescente de floresta nativa, enquanto que para os roedores foi a area ciliar dominada por regeneração de gramíneas. Para ambos os grupos, o ambiente com menor sucesso de captura foi o plantio de pinus. Dentre os marsupiais Monodelphis sorex foi a especie com maior abundancia relativa (42,06%) e para os pequenos roedores a maior abundancia relativa foi obtida para Akodon gr. cursor. Registrou-se a maior abundancia relativa em floresta secundaria (37,33%) para os marsupiais e em área ciliar dominada por regeneração de gramíneas (29,11%) para os pequenos roedores. Monodelphis sorex, dentre os marsupiais, foi a especie mais abundante, porem nenhum individuo foi registrado no remanescente de floresta nativa. A diversidade dada pelo índice de Shannon-Wiener foi de 1,32 ' H = para ambos os grupos estudados, sendo o remanescente de floresta nativa o ambiente com maior diversidade, tanto para marsupiais quanto, para pequenos roedores. Para os marsupiais, o índice de similaridade de Morisita indicou grande similaridade entre a área ciliar com capoeirinha e a área ciliar dominada por regeneração de gramíneas e, baixa similaridade entre a área ciliar com capoeirinha e o remanescente de floresta nativa. Para os pequenos roedores, foi observada uma alta similaridade entre todos os ambientes amostrados. Os parâmetros populacionais foram avaliados para Akodon gr. cursor, com razão sexual desviada para machos e tamanho populacional médio de 93,36 ind./ha. As taxas de sobrevivência e recrutamento foram de 0,559% e 1,558% respectivamente. Os resultados sugerem que a estrutura populacional de Akodon gr. cursor esteja intimamente relacionada com a disponibilidade de recursos alimentares, em especial aqueles ligados a floração da taquara, no período de estudo. A maior distancia media percorrida para os machos de Akodon gr. Cursor foi observada em A2 (225,22m) e para as fêmeas em A1 (101,23m), enquanto que a menor distancia media percorrida, para machos e fêmeas, foi registrada em A4 (122,06m e 28,28m respectivamente). Não foram observadas variações significativas para os deslocamentos de machos e fêmeas entre as áreas amostradas. Assim como não foram observadas diferenças expressivas das distâncias percorridas por Akodon gr. cursor entre os quatro ambientes analisados. Não foi registrada preferencia por armadilhas dispostas próximas ao curso d’água por Akodon gr. cursor. Os resultados sugerem que os marsupiais são mais sensíveis em relação a estrutura dos ambientes do que os pequenos roedores. Akodon gr. cursor apresentou-se como especie generalista em relação ao habitat, e sua elevada abundancia esteve relacionada ao fenômeno da “ratada”

Pathways linking car transport for young adults and the public health in Northern Ireland: a qualitative study to inform the evaluation of graduated driver licensing.

BACKGROUND: Novice drivers are at relatively high risk of road traffic injury. There is good evidence that Graduated Driving Licensing (GDL) schemes reduce collisions rates, by reducing exposure to risk and by extending learning periods. Legislation for a proposed scheme in Northern Ireland was passed in 2016, providing an opportunity for future evaluation of the full public health impacts of a scheme in a European context within a natural experiment. This qualitative study was designed to inform the logic model for such an evaluation, and provide baseline qualitative data on the role of private cars in health and wellbeing. METHODS: Nine group interviews with young people aged 16-23 (N = 43) and two group interviews with parents of young people (N = 8) were conducted in a range of settings in Northern Ireland in 2015. Data were analysed using thematic content analysis. RESULTS: Informal car-pooling within and beyond households led to routine expectations of lift provision and uptake. Experiences of risky driving situations were widespread. In rural areas, extensive use of farm vehicles for transport needs meant many learner drivers had both early driving experience and expectations that legislation may have to be locally adapted to meet social needs. Cars were used as a site for socialising, as well as essential means of transport. Alternative modes (public transport, walking and cycling) were held in low esteem, even where available. Recall of other transport-related public health messages and parents' existing use of GDL-type restrictions suggested GDL schemes were acceptable in principle. There was growing awareness and use of in-car technologies (telematics) used by insurance companies to reward good driving. CONCLUSIONS: Key issues to consider in evaluating the broader public health impact of GDL will include: changes in injury rates for licensed car occupants and other populations and modes; changes in exposure to risk in the licensed and general population; and impact on transport exclusion. We suggest an important pathway will be change in social norms around offering and accepting lifts and to risk-taking. The growing adoption of in-car telematics will have implications for future GDL programmes and for evaluation

Critical political economy in practice: the case of an advertising/editorial conflict at Brainstorm

Critical political economists argue that media in a democratic society are not inherently free, as they rely on advertisers for revenue, and their editorial content can be influenced by commercial considerations. However, liberal pluralist theorists argue that journalists’ and editors’ normative attachment to independence and professionalism provide a counterbalance to advertisers’ wants. In South Africa, where commercial pressures have been exacerbated in increased competition for adspend, local publications have sought to create alternative revenue streams, such as supplements specifically targeted at advertisers. This research report examines the issues raised by such products by examining a conflict at the ICT publication Brainstorm over one of its supplements. The study looks at an incident of an advertiser demanding changes to editorial content and reactions to the demands within the media organisation, considering individual journalists’ reactions and how the issue played out in several different departments in the publishing house. The research found that companies within the ICT sector, who are often also advertisers, routinely try to have editorial copy changed to their advantage, and that these companies do not have a clear understanding of the media industry and its processes. Journalists resist these changes, but the research found that supplements are not viewed as seriously by journalists as other types of editorial content, because the supplements are financed by advertisers. The research demonstrates that such supplements operate in a grey area because they blur the boundaries between advertising and editorial. As such, journalists and editors find it harder to defend their professional independence in producing the content. The fuzziness about whether the supplements are advertorial or editorial casts doubt on the credibility of such products