Measurement of Th1/Th2 serum cytokines by flow cytometry in classical Hodgkin lymphoma

O linfoma de Hodgkin clássico (LHC) é uma neoplasia com distúrbio na produção de citocinas. Estudos demonstram que o padrão anormal das citocinas no linfonodo acometido pela lesão contribui não somente com a proliferação das células malignas H-RS, como também com o característico infiltrado hiper-reativo que compõe o tecido no LHC. Esta disfunção pode ser observada tanto no quadro clínico dos pacientes, como nas características histopatológicas: sintomas B, deficiência na resposta imune celular, bandas de colágeno e eosinofilia. As concentrações séricas das citocinas Th1 (IL-2, TNF, INF-&#947;) e Th2 (IL-4, IL-5, IL-10) foram estudadas em 45 pacientes com LHC, ao diagnóstico, e em 34 doadores saudáveis, por citometria de fluxo (CBA - cytometric beads array). Houve aumento das concentrações das citocinas TNF (p<0,01), INF-&#947; (p<0,01), IL-4 (p=0,01), IL-5 (p<0,01) e IL-10 (p<0,01) dos pacientes quando comparados com o grupo controle. Não foi evidenciada diferença em relação a IL-2. Ao correlacionarmos as concentrações das citocinas Th1/Th2 com as variáveis clínico-laboratoriais dos pacientes, observou-se que níveis elevados da IL-10 (Th2) estão correlacionados com as variáveis que implicam em pior prognóstico: estádios III/IV (p=0,01), presença de sintomas B (p=0,04), hemoglobina < 10,5g/dL (p=0+,01), linfócitos <600 mm³ (p=0,01) e, de acordo com o IPI, os pacientes de alto risco (p=0,01). Por outro lado, níveis séricos elevados da IL-2 (Th1) foram encontrados em estádio I/II, quando comparados com III/IV (p=0,03), o que indica que a IL-2 diminui com a progressão da doença. Os resultados sugerem que a IL-10 possa estar regulando negativamente a resposta imune citotóxica (Th1) pela inibição da IL-2. Há uma possível associação entre progressão da doença e níveis elevados da IL-10. Esse estudo evidenciou que a utilização do CBA é factível na detecção das citocinas, e que as alterações encontradas podem estar envolvidas na biologia do LHC.Classical Hodgkin lymphoma (CHL) is a malignancy with an abnormal or unbalanced secretion/production of cytokines, which might support the growth of H-RS cells, their surrounding reactive bystander cells and may be responsible for the typical clinical and histopathologic features of CHL: systemic B symptoms, an apparent defect in cell-mediated immune response, tumor fibrosis and eosinophilic infiltrate. Serum concentrations of IL-2, IL-4, IL5, IL-10, TNF and IFN-&#947; (Th1/Th2) were measured in 45 patients at diagnosis of classical Hodgkin lymphoma and in 34 healthy controls by cytometric beads array (CBA). Levels of TNF (p<0.01), INF-&#947;(p<0.01), IL-4 (p=0.01), IL-5 (p<0.01) e IL-10 (p<0.01) were significantly higher in patients compared to the control group. No difference was observed for IL-2 between the two groups. On correlating Th1/Th2 cytokine concentrations with clinical risk factors, elevated IL-10 (Th2) levels are associated with variables that suggest worse prognoses including III/IV stage (p=0.01), B-symptoms (p=0.04), hemoglobin < 10.5g/dL (p=0.01), lymphocytes < 600/mm³ (p=0.01) and according to the seven-factored international prognostic score (IPI), a subset of patients with a particularly high risk of failure (p=0.01). Furthermore, the serum levels of IL-2 (Th1) were significantly higher in a group of I/II stage patients compared to III/IV patients (p=0.03) which implies that, the levels of IL-2 might decrease with disease progression. The elevated IL-10 levels in a subset of patients with poor clinical risk factors might down regulate a Th1 immune response by inhibiting IL-2 production causing survival disadvantage by suppression of the cytotoxic immune response against the tumor. This suggests an association between progression of CHL and higher levels of the IL-10 cytokine. This study showed that measurement of serum cytokines using the CBA methodology is highly reproducible, and that changes in concentrations seem to be involved in the biology of this diseas

Drilling for ‘New Oil’ in Care Integration – Co-Production of the Concept and Specification of an Integrated Data Centre for Policy Decision Making, Care Planning, and Research in Estonia

Introduction: Care integration needs to take place on different levels, including that of infrastructure and especially data infrastructure. Only integrated data allow for policy making, care planning, research, and evaluation that spans across different sectors of care and support. Methods: In the course of an EU-funded reform initiative on integrated care, the Estonian government and various agencies have developed a concept for an integrated data centre, bringing together information from social, medical, and vocational support services. The concept was developed in co-production with many stakeholders. A test data set from all covered sectors, including the pseudonymised data of 17,945 citizens of an Estonian municipality, was created and analysed as a proof-of-concept exercise. Results: The co-production approach resulted in a set of requirements and use cases as well as a specification of premises, processes, and data flows for the data centre. The analysis of the test dataset showed the principal feasibility of the dataset for the intended purposes. Conclusion: The concept development phase showed that an integrated data centre for Estonia is feasible per se and helped to specify concrete actions required for its realisation. Strategic and financial decisions from the Estonian Reform Steering Committee are now needed to create the data centre

A scientific transition to support the 21st century dietary transition

Background Eating habits must change substantially in order to address the urgent societal challenges of personal, public and planetary health. Research surrounding various facets of the dietary transition remains siloed, hindering breakthroughs. Scope and approach We argue the scientific case for transdisciplinary research centered around the transition to healthy, sustainable, and acceptable diets. This transition requires tackling the broad societal challenges of engaging consumers in the diet transition, improving nutritional health and achieving environmental sustainability of foods and food systems. Key findings The crucial synergies and trade-offs from addressing single challenges in isolation are discussed, as well as obstacles when considering the collaboration between the multiple scientific disciplines concerned with the dietary transition. Currently, interactions between these challenges remain understudied and/or ambiguous, in part due to a lack of interoperable data and standards. Intersectional research entry points acting at the intersection of the three challenges are explored: food taste and texture reformulation, food pricing strategies and food literacy. The implementation of such cross-cutting interventions urgently requires both the generation of new data and exploitation of the breadth of existing data. Researchers must therefore be facilitated to find, access and use interoperable data to model and measure food intake and all its determinants. Conclusions The dietary transition requires underpinning by a research infrastructure that supports access to transdisciplinary data, facilities and research tools, alongside training and capacity building. Filling these unmet data, tools and training needs is the first step towards delivering breakthrough innovations to foods and food environments, mobilizing consumers to engage in the dietary transition

Common Breast Cancer Susceptibility Alleles and the Risk of Breast Cancer for BRCA1 and BRCA2 Mutation Carriers: Implications for Risk Prediction

The known breast cancer (BC) susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1,LSP1 and 2q35 confer increased risks of BC for BRCA1 or BRCA2 mutation carriers. We evaluated the associations of three additional SNPs, rs4973768 in SLC4A7/NEK10, rs6504950 in STXBP4/COX11 and rs10941679 at 5p12 and reanalyzed the previous associations using additional carriers in a sample of 12,525 BRCA1 and 7,409 BRCA2 carriers. Additionally, we investigated potential interactions between SNPs and assessed the implications for risk prediction. The minor alleles of rs4973768 and rs10941679 were associated with increased BC risk for BRCA2 carriers (per-allele Hazard Ratio (HR)=1.10, 95%CI:1.03-1.18, p=0.006 and HR=1.09, 95%CI:1.01-1.19, p=0.03, respectively). Neither SNP was associated with BC risk for BRCA1 carriers and rs6504950 was not associated with BC for either BRCA1 or BRCA2 carriers. Of the nine polymorphisms investigated, seven were associated with BC for BRCA2 carriers (FGFR2, TOX3, MAP3K1, LSP1, 2q35, SLC4A7, 5p12, p-values:7×10−11-0.03), but only TOX3 and 2q35 were associated with the risk for BRCA1 carriers (p=0.0049, 0.03 respectively). All risk associated polymorphisms appear to interact multiplicatively on BC risk for mutation carriers. Based on the joint genotype distribution of the seven risk associated SNPs in BRCA2 mutation carriers, the 5% of BRCA2 carriers at highest risk (i.e. between 95th and 100th percentiles) were predicted to have a probability between 80% and 96% of developing BC by age 80, compared with 42-50% for the 5% of carriers at lowest risk. Our findings indicated that these risk differences may be sufficient to influence the clinical management of mutation carriers

Impact of the Healthcare System, Macro Indicator, General Mandatory Quarantine, and Mask Obligation on COVID-19 Cases and Death in Six Latin American Countries: An Interrupted Time Series Study

Background: Different coping strategies have been implemented by various governments worldwide to address the emerging health crisis of COVID-19. While most developed countries count on supporting healthcare and social systems, developing countries face additional challenges due to low macro indicators. The implementation of measurements such as quarantine are shown to be successful to flatten the curve of infection and death. In this context, it is important to test whether those measurements have an impact on the distribution of cases of COVID-19 in developing countries that face additional challenges such as lack of social security due to informal employment. A country comparison for Colombia, Costa Rica, Peru, Ecuador, Mexico, and Chile has therefore been conducted. Method: The healthcare systems and macro indicator as well as the distribution of death due to COVID-19 per thousand inhabitants are compared descriptively. Using Multiple Interrupted Time Series Analysis with synthetic control units the impact of the General Mandatory Quarantine in Colombia, Peru, and Ecuador as well as the impact of Mask Obligation in public in Colombia and Chile have been tested. Results: No clear impact of the poverty headcount ratio at the national poverty line and urban population on the percentage of death within the confirmed cases has been found. The out-of-pocked spending within health expenditure as a barrier in access to healthcare can be considered as a determinant of death within the confirmed cases of COVID-19. The implementation of a general mandatory quarantine did not show a curve-flattening effect in Ecuador and Peru but did so in Colombia. The implementation of Mask obligation in public spaced showed positive impact on the distribution of confirmed case in both countries tested. Conclusion: The implementation of a general mandatory quarantine does not guarantee the curve-flattening effect. Various macro indicators should therefore always be considered while analyzing the effect of policies

The effect of non-pharmaceutical policy interventions on COVID-19 transmission across three cities in Colombia

Governments across the globe have implemented different strategies to handle the COVID-19 pandemic. A national mandatory quarantine was the most applied policy tool. While there are studies that tested the effectiveness of a national mandatory quarantine, the question about the effectiveness of additional quarantine policies is not yet answered. In this study we focus on three large cities in Colombia (Bogota, Medellin and Cali) with similar socio-economic conditions but made use of different COVID-19 prevention measures. We examine whether different non-pharmaceutical policy interventions (NPIs) conducted in these three cities are effective against the spread of the COVID-19 pandemic. We inspect the effect of the quarantine policies restricting exit from home by sex, ID number, whereby only Bogota implemented the restriction to leave the home according to sex followed by a restriction according to ID number, and Medellin and Cali implemented a restriction by ID number only. Data for the analysis are obtained from the National Administrative Department of Statistics of Colombia [Departamento Administrativo Nacional de Estadística (DANE)]. The data on pandemic severity is measured by the number of confirmed COVID-19 cases per city. We conduct single-group interrupted time series analysis (ITSA) to examine differences in the extent of the pandemic severity in Bogota, Medellin and Cali. We found that NPIs in all three Colombian cities had a positive effect on slowing the spread of the pandemic.</p

A patient post hoc perspective on advantages and disadvantages of blended cognitive behaviour therapy for depression: A qualitative content analysis

Blended treatment seems to balance missing aspects of stand-alone internet-based and face-to-face treatment for depression. Patients suffering from major depression perceived the blended format as purposive and effective after 18 weeks. Patients with different levels of depression severity may perceive different advantages and disadvantages of blended treatment for depression

V olimpíada brasileira de astronomia

Neste trabalho, apresentamos os resultados da V Olimpíada Brasileira de Astronomia, que ocorreu em 11/05/2002 em todos os estabelecimentos de ensino fundamental e médio, previamente cadastrados. Participaram do evento 60.338 alunos, distribuídos por 1469 escolas pertencentes a todos os Estados brasileiros. Uma equipe de 5 alunos foi escolhida para representar o Brasil na VII Olimpíada Internacional de Astronomia, que ocorreu na Rússia, em 2002, e dois de nossos alunos ganharam a medalha de bronze.In this work we show the results of the V Brazilian Olympiad of Astronomy, which took place on 11/05/2002 in all primary or secondary schools that previously registered. 60338 students distributed over 1.469 schools from all Brazilian States took part in this event. A team of 5 students was selected to represent Brazil at the VII International Olympiad of Astronomy that occurred in Russia in 2002. Two of our students were awarded the bronze medal in that event