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During the COVID-19 pandemic, the Oswaldo Cruz Foundation (Fiocruz), a Brazilian federal research institution supported by the Brazilian Health Ministry, established a biobank. This biobank began by preserving the SARS-CoV-2 virus and human biological material related to COVID-19. This innovative initiative combined human and biodiversity materials within a single infrastructure. Designed for supporting research, development, and innovation in healthcare and preparedness and response to emerging and re-emerging infectious diseases, the biobank’s focus has since expanded to include various biological materials, leading to its renaming as the Biodiversity and Health Biobank - Fiocruz-BBS (Portuguese: Biobanco da Biodiversidade e Saúde da Fiocruz – BBS-Fiocruz). This paper outlines the challenges of creating and maintaining an adequate infrastructure in a developing country for promoting and supporting scientific research and biotechnological innovation activities in health through processes of depositing, characterizing, preserving, and supplying human and biodiversity biological materials, alongside associated data, while complying with prevailing legal and ethical rules. These processes adhere to stringent quality, biosafety, and biosecurity standards set forth in ISO 20387:2018. Additionally, the challenges of ensuring the Biobank’s long-term sustainability is discussed. This involves a) establishing benchmarks and best practices, b) developing a comprehensive business plan, c) forging partnerships, d) diversifying funding sources, e) ensuring ethical and legal compliance, f) implementing rigorous quality control procedures, and g) investing in human resources and infrastructure. The insights shared in this paper will benefit other biobanks engaged in services related to tropical infectious diseases.

On 14 February 2021, Lebanon implemented nationwide vaccination, offering the Pfizer-BioNTech (BNT162b2) vaccine to adults over 50 years of age. We estimated the effectiveness of the Pfizer-BioNTech vaccine in preventing symptomatic laboratory-confirmed COVID-19. We conducted a test-negative case–control (TND) study among symptomatic adults aged 50 years and older who presented with influenza-like illness (ILI) or COVID-19-like illness (CLI) in surveillance sentinel sites between 1 July and 31 December 2021. Unvaccinated participants did not receive any vaccine dose before symptom onset. Vaccinated participants received at least one dose within 14 days before onset of symptoms. We estimated vaccine effectiveness against symptomatic laboratory-confirmed COVID-19, adjusted for demographic and behavioral factors, using multivariable logistic regression. Out of 457 participants with symptoms, 150 (33%) were positive and 307 (67%) were negative for SARS-CoV-2. Adjusted vaccine effectiveness was 22% (95% CI: −70–65%) for those partially vaccinated and 44% (95% CI: 6–67%) for those fully vaccinated. Vaccination with two doses of the Pfizer-BioNTech vaccine was effective in preventing COVID-19 symptomatic illness in the older population. Vaccine effectiveness was lower for those partially vaccinated. We recommend enhancing vaccine uptake with at least one dose among risk groups for COVID-19 and keeping general recommendations on contact and droplet precautions in the general population.

El objetivo del presente trabajo consiste en la generación de un modelo conceptual para el análisis y evaluación del proceso de adopción de TIC en el ámbito de las pymes argentinas considerando cuatro entornos y factores asociados a los mismos. Este modelo conceptual será aplicado a un futuro trabajo de campo, para la realización de un proceso de calibración y propuesta de una nueva versión del modelo presentado. La mayor diferencia de los modelos previos tiene que ver con una visión actualizada de los modelos de negocios y mercados, producto fundamentalmente de la evolución de la conectividad.

Non-Hodgkin's Lymphoma (NHL) is a malignancy of the lymphoid lineage of the hematopoietic system has worldwide, especially in developed countries. Better diagnostic and recording techniques, longer life expectancy, and greater exposure to risk factors are hypotheses for this growing incidence curve. Occupational exposures to chemical, biological, and physical agents have also been associated with NHL development, but the results are still controversial. We have investigated the occupational and lifestyle case-control study design with 214 adult patients and 452 population controls. Socio-demographic, clinical, and occupational exposure data were obtained through individual interviews with a standardized questionnaire. Clinical, laboratory, and histopathological data were obtained through medical records. Risk of NHL (any subtype), B-cell lymphoma, DLBCL, Follicular lymphoma and T-cell lymphoma was elevated among the those who had ever been exposed to any solvents, hydrocarbon solvents, pesticides, meat and meat products, and sunlight and tended to increase by years of exposure. A significant upward trend with years of exposure was detected for any solvents and hydrocarbon solvents (NHL (any subtype) p-value for trend

Between September and October 2019, the Norwegian Institute for Public Health (NIPH) surveyed women born between 1991 and 1996 who were offered catch-up vaccination for human papilloma virus (HPV). The aim was to identify determinants of vaccine schedule adherence. A random sample of 10,000 women who were offered catch-up vaccination were invited to participate in the survey. We defined adherence as receiving all three doses. Determinants of HPV vaccination adherence were investigated using descriptive, univariable and multivariable logistic regression analyses providing adjusted odds ratios (aOR). Data from 3,762 respondents who received at least one dose were included. Overall, 92.1% (95% CI = 89.3–91.9) of those initiating vaccination adhered to the complete schedule. The following factors were significantly associated with HPV vaccination adherence compared to non-adherence: country of origin (aOR = 0.43; 95% CI = 0.47–0.97), having children (aOR = 0.51; 95% CI = 0.35–0.73), ease of finding out where to get vaccinated (aOR = 1.94; 95% CI = 1.69–2.23), preference for receiving information from health authorities (aOR = 1.37; 95% CI = 1.04–1.81) and vaccination being readily available (aOR = 2.28; 95% CI = 1.50–3.37). Information from NIPH via SMS and social media were negatively associated for Norwegians (aOR = 0.68, 95% CI = 0.46–1.01) and positively associated for those whose country of origin was not Norway (aOR = 1.48, 95% CI = 0.69–3.14; not significant). Those who did not adhere to the full vaccination schedule reported that they had forgotten (40.4%; 95% CI = 33.5–47.8) or had no time (32.9%; 95% CI = 26.2–40.4). Despite NIPH’s targeted communication campaign, the main barriers for HPV vaccination adherence were difficulty to find out where to get the vaccine, forgetting to take the vaccine or not having time to complete the schedule.

Between 2016 and 2019, a catch-up human papillomavirus (HPV) vaccination took place in Norway for women born between 1991 and 1996. The aim of this study was to identify sociodemographic determinants of complete vaccination (3 doses) and partial vaccination (1–2 doses). A random sample of 10,000 women who were offered catch-up HPV vaccination were invited. We assessed the association between sociodemographic characteristics and vaccination completion using univariable and multivariable multinomial logistic regression. Of 4,967 respondents, 3,464 (63%) received complete vaccination and 298 (7%) received partial vaccination. 30% did not receive any vaccination and functioned as reference group. Compared with having Norwegian caregivers, having a caregiver from non-western countries decreased the odds of partial and complete vaccination (aOR = 0.57; 95%CI = 0.35–0.95 and aOR = 0.57; 95%CI = 0.44–0.74). Having a caregiver from other western countries decreased the odds of complete vaccination (aOR = 0.72; 95%CI = 0.52–0.98). Residing in Norway for 10 years or longer significantly increased the odds of complete vaccination (aOR = 2.65; 95%CI = 1.58–4.43). Being in a relationship significantly increased the odds of partial vaccination compared with being single (aOR = 1.50; 95%CI = 1.02–2.21). Being married (aOR = 0.66; 95%CI = 0.50–0.86) and having children (aOR = 0.53; 95%CI = 0.42–0.68) decreased the odds of complete vaccination. Having university education increased the odds of both partial and complete vaccination (aOR = 2.19; 95%CI = 1.47–3.25 and aOR = 4.11; 95%CI = 3.33–5.06). Having a caregiver born outside of Norway, having children and being married decreased the odds of receiving complete HPV vaccination. This highlights the need to target communication around HPV vaccination toward different ethnic communities and include more specific messaging that having children and being married does not necessarily prevent HPV infections.

Global environmental change has influenced lake surface temperatures, a key driver of ecosystem structure and function. Recent studies have suggested significant warming of water temperatures in individual lakes across many different regions around the world. However, the spatial and temporal coherence associated with the magnitude of these trends remains unclear. Thus, a global data set of water temperature is required to understand and synthesize global, long-term trends in surface water temperatures of inland bodies of water. We assembled a database of summer lake surface temperatures for 291 lakes collected in situ and/or by satellites for the period 1985-2009. In addition, corresponding climatic drivers (air temperatures, solar radiation, and cloud cover) and geomorphometric characteristics (latitude, longitude, elevation, lake surface area, maximum depth, mean depth, and volume) that influence lake surface temperatures were compiled for each lake. This unique dataset offers an invaluable baseline perspective on global-scale lake thermal conditions as environmental change continues.

Background: The evaluation of the chemical impact on human health is usually constrained to the analysis of the health effects of exposure to a single chemical or a group of similar chemicals at one time. The effects of chemical mixtures are seldom analyzed. In this study, we applied three statistical models to assess the association between the exposure to a mixture of seven xenobiotics (three phthalate metabolites, two phenols, and two pesticides) and obesity. Methods: Urinary levels of environmental phenols, pesticides, and phthalate metabolites were measured in adults who participated in the U.S.-based National Health and Nutrition Examination Survey (NHANES) from 2013 to 2014. Body examination was conducted to determine obesity. We fitted multivariable models, using generalized linear (here both logistic and linear) regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models to estimate the association between chemical exposures and obesity. Results: Of 1269 individuals included in our final analysis, 38.5% had general obesity and 58.0% had abdominal obesity. In the logistic regression model established for each single chemical, bisphenol S (BPS), mono (carboxyoctyl) phthalate (MCOP), and mono (2-ethyl-5-carboxypentyl) phthalate (MECPP) were associated with both general and abdominal obesity (fourth vs. first quartile). In linear regression, MCOP was associated with BMI and waist circumference. In WQS regression analysis, the WQS index was significantly associated with both general obesity (OR = 1.63, 95% CI: 1.21–2.20) and abdominal obesity (OR = 1.66, 95% CI: 1.18–2.34). MCOP, bisphenol A (BPA), bisphenol S (BPS), and mono ethyl phthalate (MEP) were the most heavily weighing chemicals. In BKMR analysis, the overall effect of mixture was significantly associated with general obesity when all the chemicals were at their 60th percentile or above it, compared to all of them at their 50th percentile. MCOP, BPA, and BPS showed positive trends. By contrast, MECPP showed a flat and modest inverse trend. Conclusion: When comparing results from these three models, MCOP, BPA, and BPS were identified as the most important factors associated with obesity. We recommend estimating the joint effects of chemical mixtures by applying diverse statistical methods and interpreting their results together, considering their advantages and disadvantages. Keywords: Chemical mixture, Weighted quantile sum (WQS) regression, Bayesian kernel machine regression (BKMR), Obesity, Obesogen

(1) Background: This study aims to analyse the attitudinal components influencing paediatricians’ self-vaccination. (2) Methods: The national-cross survey was conducted among paediatricians involved in childhood vaccination within the immunisation program. (3) Results: A hypothetical model indicating the influence of cognitive and behavioural factors on influenza vaccination among paediatricians was verified based on a survey of Polish paediatricians. A simple mediation model, based on Triandis’ Theory of Interpersonal Behaviour, reflects a relationship in which knowledge and beliefs about outcomes contribute to whether paediatricians vaccinate against influenza. (4) Conclusions: The presented research shows that the pro-vaccination behaviours of paediatricians are not only influenced by cognitive factors but also the behavioural components of attitudes, which are equally important. The conclusions point to the pivotal role of shaping both knowledge and understanding of the effectiveness of immunisation programmes in building the pro-vaccination attitudes of paediatricians. (5) Practical Implications: This is the first representative study of Polish paediatricians to demonstrate how their attitudes and behaviour are related to self-vaccination. Its conclusions allow policymakers to develop programmes to support effective measures against the spread of infectious diseases through the self-vaccination of medical professionals.

Nos últimos anos, a pesquisa translacional tornou-se objeto de grandes debates na área biomédica e na política, gerando expectativas, promessas e preocupações e sendo referência constante em programas de pesquisa, artigos acadêmicos e periódicos, relatórios de políticas e programas educacionais em todo o mundo. Contudo, várias barreiras que atrasam esse processo precisam ser superadas para tornar a pesquisa translacional em câncer mais do que um conceito interessante. Para que a pesquisa translacional opere de maneira mais eficaz, devem existir interações funcionais entre a academia, o governo, a comunidade, agências de fomento, indústrias (farmacêutica, biotecnologia), entre outras.

In Poland, primary care physicians are the most used and most trusted source of information on immunisation. We aimed to explore factors influencing support for vaccinations among physicians employed in the childhood immunisation programme, in order to inform education of healthcare workers and programme organization. In June-July 2017, we carried out a national cross-sectional survey of physicians working in randomly selected primary healthcare practices, and interviewed them by telephone. We assessed support for vaccinations using an ordinal scale (0-6) comprised of three equally weighted questions on the respondent support of the programme and vaccination of self and family. We also created a scale (0-3) based on correct answers to vaccination myths. We used ordered logistic regression to investigate factors independently influencing support for vaccinations, reporting the proportional odds ratios and 95% confidence intervals for one unit increase in the support score. Of 2,609 respondents contacted, we interviewed 500 (19%). The median vaccination support score (0-6) was 5 (IQR 2). After adjusting for other variables, we did not find significant effects of sex, medical specialty, adhering to recommendations, attending a conference in previous year, using non-scientific sources of information and self-assessed knowledge on vaccination support score. Age over 60 years, correctly addressing vaccination myths and use of one or more than one scientific sources of knowledge, significantly improved support for vaccinations (aOR = 1.97, 1.57, 3.09 and 2.68, respectively). We recommend to increase the amount, quality and accessibility of evidence-based educational materials for primary care physicians working with childhood immunisations.

Abstract Background The approach to surveillance of Lyme borreliosis varies between countries, depending on the purpose of the surveillance system and the notification criteria used, which prevents direct comparison of national data. In Norway, Lyme borreliosis is notifiable to the Surveillance System for Communicable Diseases (MSIS). The current notification criteria include a combination of clinical and laboratory results for borrelia infection (excluding Erythema migrans) but there are indications that these criteria are not followed consistently by clinicians and by laboratories. Therefore, an evaluation of Lyme borreliosis surveillance in Norway was conducted to describe the purpose of the system and to assess the suitability of the current notification criteria in order to identify areas for improvement. Methods The CDC Guidelines for Evaluation of Surveillance Systems were used to develop the assessment of the data quality, representativeness and acceptability of MSIS for surveillance of Lyme borreliosis. Data quality was assessed through a review of data from 1996 to 2013 in MSIS and a linkage of MSIS data from 2008 to 2012 with data from the Norwegian Patient Registry (NPR). Representativeness and acceptability were assessed through a survey sent to 23 diagnostic laboratories. Results Completeness of key variables for cases reported to MSIS was high, except for geographical location of exposureThe NPR-MSIS linkage identified 1047 cases in both registries, while 363 were only reported to MSIS and 3914 were only recorded in NPR. A higher proportion of cases found in both registries were recorded as neuroborreliosis in MSIS (84.4 %) than those cases found only in MSIS (20.1 %). The trend (average yearly increase or decrease in reported cases) of neuroborreliosis in MSIS was not significantly different from the trend for all other clinical manifestations recorded in MSIS in negative binomial regression (p = 0.3). The 16 surveyed laboratories (response proportion 70 %) indicated differences in testing practices and low acceptability of the notification criteria. Conclusions Given the challenges associated with diagnosing Lyme borreliosis, the selected notification criteria should be closely linked with the purpose of the surveillance system. Restricting reportable Lyme borreliosis to neuroborreliosis may increase validity, while a more sensitive case definition (potentially including erythema migrans) may better reflect the true burden of disease. We recommend revising the current notification criteria in Norway to ensure that they are unambiguous for clinicians and laboratories.

Interleukin-10 (IL10) is an immune regulatory cytokine. Single nucleotide polymorphisms (SNPs) in IL10 promoter have been associated with prognosis in adult classical Hodgkin lymphoma (cHL). We analyzed IL10 SNPs −1082 and −592 in respect of therapy response, gene expression and tumor microenvironment (TME) composition in 98 pediatric patients with cHL. As confirmatory results, we found that −1082AA/AG; −592CC genotypes and ATA haplotype were associated with unfavourable prognosis: Progression-free survival (PFS) was shorter in −1082AA+AG (72.2%) than in GG patients (100%) (P = 0.024), and in −592AA (50%) and AC (74.2%) vs. CC patients (87.0%) (P = 0.009). In multivariate analysis, the −592CC genotype and the ATA haplotype retained prognostic impact (HR: 0.41, 95% CI 0.2–0.86; P = 0.018, and HR: 3.06 95% CI 1.03–9.12; P = 0.044, respectively). Our analysis further led to some new observations, namely: (1) Low IL10 mRNA expression was associated with −1082GG genotype (P = 0.014); (2) IL10 promoter polymorphisms influence TME composition;−1082GG/−592CC carriers showed low numbers of infiltrating cells expressing MAF transcription factor (20 vs. 78 and 49 vs. 108 cells/mm2, respectively; P< 0.05); while ATA haplotype (high expression) associated with high numbers of MAF+ cells (P = 0.005). Specifically, −1082GG patients exhibited low percentages of CD68+MAF+ (M2-like) intratumoral macrophages (15.04% vs. 47.26%, P = 0.017). Considering ours as an independent validation cohort, our results give support to the clinical importance of IL10 polymorphisms in the full spectrum of cHL, and advance the concept of genetic control of microenvironment composition as a basis for susceptibility and therapeutic response.

Background. Limited help-seeking behaviours, among adolescents with mental health concerns and many barriers to accessing mental health services, make innovative approaches to administering mental health therapies crucial. Therefore, this study evaluated the efficacy of e-CBT given via PowerPoint slides to treat adolescents with anxiety and/or depression. Method. 15 adolescents referred to an outpatient adolescent psychiatry clinic to treat a primary DSM-IV diagnosis of anxiety and/or depression chose between 8 weeks of e-CBT (n=7) or 7 weeks of live CBT (n=8). The e-CBT modules were presented using PowerPoint delivered weekly through email by either a senior psychiatry resident or an attending physician. Within each session, participants in both groups had personalized feedback on their mandatory weekly homework assignment from the previous week’s module. BYIs were completed before treatment and and after final treatment within both groups to assess changes in depression, anxiety, anger, disruption, and self-concept. Findings. Before treatment, BYI scores did not sig. differ between groups. After treatment, e-CBT participants reported sig. improved depression, anger, anxiety, and self-concept BYI scores while live CBT participants did not report any sig. changes. Only the Beck Anxiety Inventory sig. differed between groups after CBT. Conclusion. Despite the low sample size within this study, using email to deliver e-CBT PowerPoint slides and individualized homework feedback shows promise as an alternate method of CBT delivery that reduces barriers to receiving mental health treatment that occur internationally.

The association of lymphoma with necrotic granuloma can pose diagnostic challenges and delay treatment, especially in settings with a high burden of infection. In these settings, the timely use of cytogenetic and molecular methods is most relevant. Here, we report a case of B-cell lymphoma with t (8;14) in a 5-year-old male child. The lymphoma was associated with necrotic granuloma and was initially misdiagnosed as tuberculosis. Polymerase chain reaction was used to detect clonal lymphoproliferation and to rule out Mycobacterium tuberculosis infection. Tumor cells harbored Epstein-Barr virus and expressed CD20, CD10, BCL6, and Ki67 (30%), leading to the diagnosis of B-cell lymphoma with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma.

Chronic lymphocytic leukaemia (CLL) is a haematological malignancy for which reliable prognostic markers are needed in view of its clinical heterogeneity. In approximately 50% of CLL patients, immunoglobulin (Ig) rearrangements are modified by somatic hypermutation (SHM), a process that represents a reliable prognostic indicator of favourable progression. In this study, we investigated SHM in 37 Brazilian CLL patients and identified the preferential involvement of specific immunoglobulin gene families and segments through PCR-amplified fragments or subcloned fragments. Forty-one rearrangements were observed and 37 of them were functional. A 98% homology cut-off with germinal sequences showed 18 patients (48.7%) with SHM. Unmutated cases showed a poorer clinical outcome. V H3 was the most frequent V H family, followed by V H4. The V H4-39 segment was the most frequently used, mainly in unmutated cases, while the V H3 family was predominant in mutated cases. The D3 and J H4/J H6 families were the most frequently observed.

BackgroundTick-borne encephalitis (TBE) is endemic to Europe and medically highly significant. This study, focused on Poland, investigated individual risk factors for TBE symptomatic infection.Methods and findingsIn a nation-wide population-based case-control study, of the 351 TBE cases reported to local health departments in Poland in 2009, 178 were included in the analysis. For controls, of 2704 subjects (matched to cases by age, sex, district of residence) selected at random from the national population register, two were interviewed for each case and a total of 327 were suitable for the analysis. Questionnaires yielded information on potential exposure to ticks during the six weeks (maximum incubation period) preceding disease onset in each case. Independent associations between disease and socio-economic factors and occupational or recreational exposure were assessed by conditional logistic regression, stratified according to residence in known endemic and non-endemic areas. Adjusted population attributable fractions (PAF) were computed for significant variables. In endemic areas, highest TBE risk was associated with spending ≥10 hours/week in mixed forests and harvesting forest foods (adjusted odds ratio 19.19 [95% CI: 1.72-214.32]; PAF 0.127 [0.064-0.193]), being unemployed (11.51 [2.84-46.59]; 0.109 [0.046-0.174]), or employed as a forester (8.96 [1.58-50.77]; 0.053 [0.011-0.100]) or non-specialized worker (5.39 [2.21-13.16]; 0.202 [0.090-0.282]). Other activities (swimming, camping and travel to non-endemic regions) reduced risk. Outside TBE endemic areas, risk was greater for those who spent ≥10 hours/week on recreation in mixed forests (7.18 [1.90-27.08]; 0.191 [0.065-0.304]) and visited known TBE endemic areas (4.65 [0.59-36.50]; 0.058 [-0.007-0.144]), while travel to other non-endemic areas reduced risk.ConclusionsThese socio-economic factors and associated human activities identified as risk factors for symptomatic TBE in Poland are consistent with results from previous correlational studies across eastern Europe, and allow public health interventions to be targeted at particularly vulnerable sections of the population.

BackgroundIn the third season of I-MOVE (Influenza Monitoring Vaccine Effectiveness in Europe), we undertook a multicentre case-control study based on sentinel practitioner surveillance networks in eight European Union (EU) member states to estimate 2010/11 influenza vaccine effectiveness (VE) against medically-attended influenza-like illness (ILI) laboratory-confirmed as influenza.MethodsUsing systematic sampling, practitioners swabbed ILI/ARI patients within seven days of symptom onset. We compared influenza-positive to influenza laboratory-negative patients among those meeting the EU ILI case definition. A valid vaccination corresponded to > 14 days between receiving a dose of vaccine and symptom onset. We used multiple imputation with chained equations to estimate missing values. Using logistic regression with study as fixed effect we calculated influenza VE adjusting for potential confounders. We estimated influenza VE overall, by influenza type, age group and among the target group for vaccination.ResultsWe included 2019 cases and 2391 controls in the analysis. Adjusted VE was 52% (95% CI 30-67) overall (N = 4410), 55% (95% CI 29-72) against A(H1N1) and 50% (95% CI 14-71) against influenza B. Adjusted VE against all influenza subtypes was 66% (95% CI 15-86), 41% (95% CI -3-66) and 60% (95% CI 17-81) among those aged 0-14, 15-59 and ≥60 respectively. Among target groups for vaccination (N = 1004), VE was 56% (95% CI 34-71) overall, 59% (95% CI 32-75) against A(H1N1) and 63% (95% CI 31-81) against influenza B.ConclusionsResults suggest moderate protection from 2010-11 trivalent influenza vaccines against medically-attended ILI laboratory-confirmed as influenza across Europe. Adjusted and stratified influenza VE estimates are possible with the large sample size of this multi-centre case-control. I-MOVE shows how a network can provide precise summary VE measures across Europe.

We studied a group of 54 children with Burkitt’s lymphoma from Southeastern Brazil, where epidemiological status of Burkitt’s lymphoma is poorly understood. Epstein-Barr virus association showed an intermediate frequency (~60%) between endemic and sporadic subtypes. Median age was five years. Epstein-Barr virus infection was significantly associated to low age (Epstein-Barr virus+ four years vs. Epstein-Barr virus− eight years). Sex ratio (M:F) was 2:1, with a significantly higher number of males in old age classes. Young age at diagnosis and excess of males at older ages, as well as a causal relationship between low age, epstein-barr virus and Burkitt’s lymphoma risk, may characterize Burkitt’s lymphoma in Brazil.

Abstract Background Epstein-Barr virus (EBV) is associated to the etio-pathogenesis of an increasing number of tumors. Detection of EBV in pathology samples is relevant since its high prevalence in some cancers makes the virus a promising target of specific therapies. RNA in situ hybridization (RISH) is the standard diagnostic procedure, while polymerase chain reaction (PCR)-based methods are used for strain (EBV type-1 or 2) distinction. We performed a systematic comparison between RISH and PCR for EBV detection, in a group of childhood B-cell Non-Hodgkin lymphomas (NHL), aiming to validate PCR as a first, rapid method for the diagnosis of EBV-associated B-cell NHL. Methods EBV infection was investigated in formalin fixed paraffin-embedded tumor samples of 41 children with B-cell NHL, including 35 Burkitt's lymphoma (BL), from Rio de Janeiro, Brazil, by in situ hybridization of EBV-encoded small RNA (EBER-RISH) and PCR assays based on EBNA2 amplification. Results EBV genomes were detected in 68% of all NHL. Type 1 and 2 accounted for 80% and 20% of EBV infection, respectively. PCR and RISH were highly concordant (95%), as well as single- and nested-PCR results, allowing the use of a single PCR round for diagnostic purposes. PCR assays showed a sensitivity and specificity of 96% and 100%, respectively, with a detection level of 1 EBV genome in 5,000–10,000 EBV-negative cells, excluding the possibility of detecting low-number EBV-bearing memory cells. Conclusion We describe adequate PCR conditions with similar sensitivity and reliability to RISH, to be used for EBV diagnostic screening in high grade B-NHL, in "at risk" geographic regions.

Resumo O uso de placebo em pesquisa clínica tem sido motivo de debate nos últimos anos, sobretudo após a Associação Médica Mundial publicar, em 2002, nota de esclarecimento do parágrafo 29 da Declaração de Helsinki. O Brasil tem se destacado por sua posição firme e contrária ao uso flexível de placebo. Tanto o Conselho Federal de Medicina quanto o Conselho Nacional de Saúde editaram resoluções que normatizam seu uso no Brasil, de forma a não admiti-lo em caso da existência de um método terapêutico melhor. O presente artigo reforça essa posição e tem por objetivo descrever as diversas aplicações de placebo em pesquisa clínica, bem como trazer à luz a complexa decisão sobre a eticidade de seu uso. Além disso, os autores propõem uma reflexão acerca da utilização de placebo no âmbito da pesquisa, por meio de algoritmos decisórios baseados nas normativas éticas brasileiras.