Caracterização do papel dos genes TYMS e MTR no desenvolvimento de Cancro Colo-Rectal

RESUMO: O cancro colo-rectal (CCR) é um dos cancros que possui maior taxa de mortalidade a nível mundial. Em Portugal esta patologia é responsável pela morte de cerca de 3700 pessoas por ano, sendo que estes números aumentam de ano para ano. Ao longo das últimas décadas o papel das alterações genéticas na etiologia das patologias oncológicas tem vindo a ter cada vez mais um maior destaque. O número de estudos que avaliam a importância de polimorfismos, mutações, alterações na regulação génica e interacções entre genes no desenvolvimento destas patologias tem aumentado exponencialmente. Com o aumento do conhecimento da forma como estas alterações influenciam o desenvolvimento do cancro surgiram os primeiros meios de diagnóstico genético, levando assim a uma alteração da forma como são encarados o diagnóstico e a prevenção destas doenças. No CCR as formas hereditárias com alterações genéticas inequivocamente identificadas representam apenas 5% dos casos. Existem cerca de 25% que representam formas hereditárias para as quais ainda não foram estabelecidos os padrões de alterações genéticas subjacentes. Desta forma, estudos que venham contribuir para um maior conhecimento dos mecanismos moleculares responsáveis pelo aumento da susceptibilidade dos indivíduos para o desenvolvimento de CCR são extremamente importantes. O CCR é uma patologia multifactorial, onde factores genéticos interagem com factores ambientais no surgimento e desenvolvimento da doença. Assim, torna-se essencial integrar o estudo das alterações genéticas no contexto ambiental onde os indivíduos em estudo se encontram. No caso desta patologia um dos principais factores ambientais estudado é a nutrição. Vários estudos têm sido realizados ao longo dos últimos anos de forma a compreender como pode a ingestão dos nutrientes influenciar o desenvolvimento de CCR e de que forma interage com as alterações genéticas individuais. O ciclo do folato é um dos processos metabólicos onde o papel da nutrição em interacção com alterações genéticas mais tem sido estudado nos últimos anos. Deste cruzamento entre o estudo das alterações genéticas e ambientais surge a Nutrigenética. O conjunto de estudos da presente tese tem como objectivo aumentar o conhecimento do papel das alterações em genes do ciclo do folato, em interacção com factores nutricionais e de estilo de vida, não só no desenvolvimento de CCR, mas também de outra patologia do tracto gastrointestinal, a Doença de Crohn (DC), uma doença inflamatória muitas vezes associada como factor de risco para o desenvolvimento de CCR. Este estudo debruçou-se essencialmente no estudo dos genes timidilato sintetase (TYMS) e metionina sintetase (MTR) em populações com CCR e DC, bem como no padrão nutricional destas populações com particular incidência nos nutrientes envolvidos no ciclo do folato (folato, metionina, vitamina B6, vitamina B12). Analisando o conjunto de resultados obtidos para os estudos do CCR podemos concluir que quer a TYMS quer a MTR possuem um papel relevante na susceptibilidade para desenvolver esta patologia, assim como têm destaque no funcionamento do ciclo celular durante o processo oncogénico. Os resultados demonstram que os factores que levam a uma menor disponibilidade de grupos metil no ciclo de folato (baixos níveis de folato, alteração da actividade de MTR, elevada expressão de TYMS) constituem factores de risco, muito provavelmente por contribuírem para uma desregulação dos níveis de metionina disponível para a metilação do DNA da célula. Demonstram ainda que em células tumorais ocorrem alterações na regulação do ciclo do folato de forma a favorecer a síntese de DNA em detrimento da metilação do mesmo, alterando para isso a expressão dos genes de forma a que o fluxo de grupos metil provenientes do folato sejam encaminhados para a enzima TYMS. O polimorfismo de deleção 6pb da TYMS surge como um factor de diagnóstico e de prognóstico de CCR para a população portuguesa. Dos factores nutricionais analisados apenas o folato aparenta ter um papel relevante na modelação do risco de desenvolver CCR. Na doença de Crohn (DC) podemos verificar que a homocisteína e o seu metabolismo poderão contribuir para o aparecimento e desenvolvimento da patologia. O aumento da homocisteína poderá ser o responsável por um aumento da resposta auto-imune do organismo, promovendo o aparecimento da DC. O polimorfismo A2756G MTR desempenha um papel preponderante como factor de diagnóstico da DC, tendo sido associado pela primeira vez a esta patologia. Tem também um papel importante no desenvolvimento da doença, uma vez que está associado a uma idade de diagnóstico mais baixa, sugerindo assim que o desenvolvimento da doença ocorre de forma mais precoce. Concluindo, com este estudo pensamos ter contribuído para um melhor entendimento do papel do ciclo do folato no desenvolvimento de CCR e DC, sendo um ponto de partida para futuras investigações que possam revelar cada vez melhor as complexas interacções metabólicas desta via e a sua influência nas patologias estudadas. Do nosso estudo destacamos a importância de uma análise global das várias etapas do ciclo do folato para que se possa compreender a dinâmica que se estabelece no desenvolvimento destas patologias, podendo diversas alterações, quer a nível genético quer a nível nutricional, exercerem efeitos diferentes consoante o estado dos restantes intervenientes do ciclo do folato. Acreditamos que no futuro este estudo permitirá que o conhecimento do ciclo do folato tenha cada vez mais uma relevância fundamental a nível de diagnóstico e terapêutica destas patologias.------------ ABSTRACT: Colorectal Cancer (CRC) is one of the cancers that have a higher rate of mortality worldwide. In Portugal this pathology is responsible for the deaths of about 3700 people per year, and these numbers increase each year. Over the past few decades the role of genetic changes in the etiology of oncological pathologies has had an increasingly greater emphasis. The number of studies that evaluate the importance of polymorphisms, mutations, changes in gene regulation and gene interactions in the development of these diseases has increased exponentially. With the increased knowledge of how these changes influence the development of cancer, appeared the first means for genetic diagnostic, leading to a change in the way diagnosis is seen and in the prevention of these diseases. In CRC the hereditary forms with clearly identified genetic changes represent only 5% of cases. There are about 25% representing hereditary forms for which the patterns of genetic changes haven’t been established. In this way, studies that will contribute to a greater understanding of the molecular mechanisms responsible for increased susceptibility of individuals to the CRC development are extremely important. CRC is a multifactorial pathology, where genetic factors interact with environmental factors in the emergence and development of the disease.Thus, it is essential to integrate the study of genetic changes in the environmental context of the individuals under study. In the case of this pathology one of the main environmental factors studied is nutrition. Several studies have been conducted over the past few years in order to understand how the intake of nutrients can influence the development of CRC and how nutrients interact with the individual genetic changes. The folate cycle is one of the metabolic processes where the role of nutrition in interaction with genetic alterations has been studied in recent years. This cross between the study of genetic and environmental changes developed Nutrigenetics. The set of studies of this thesis aims to increase awareness of the role of changes in genes of the folate cycle, in interaction with nutritional factors and lifestyle, not only in the development of CRC, but also of another pathology of the gastrointestinal tract, Crohn's disease (CD), an inflammatory disease often associated as a risk factor for the development of CRC. This study dealt mainly in the study of genes thymidylate synthase (TYMS) and methionine synthase (MTR) in populations with CRC and CD, as well as in the nutritional pattern of these populations with particular focus on nutrients involved in the folate cycle (folate, methionine, vitamin B6, vitamin B12). Analyzing the results obtained for the CRC studies we conclude that either the MTR TYMS have a relevant role in susceptibility to develop this pathology, and have an important role in the functioning of the cell cycle during oncogenesis. The results show that the factors that lead to a lower availability of methyl groups in folate cycle (low levels of folate, change the activity of MTR, high expression of TYMS) constitute risk factors, most likely by contribute to a dysregulation of methionine levels available for DNA methylation of the cell. Our results also demonstrate that in tumor cells occur changes in the regulation of the folate cycle in order to promote the synthesis of DNA, to the detriment of methylation of the same by changing the expression of genes so that the methyl groups from folate are forwarded to the TYMS enzyme reaction. The deletion polymorphism 6bp of TYMS emerges as a diagnostic and prognostic factor of CCR for the Portuguese population. Nutritional factors analyzed only folate appears to have a major role in modulating the risk of developing CCR.In Crohn’s disease (CD) we can check that homocysteine and its metabolism may contribute to the emergence and development of this pathology. Increased homocysteine may be responsible for an increase in the body's autoimmune response, promoting the emergence of CD. The polymorphism A2756G MTR plays a leading role as a factor of diagnosis of DC, having been associated with this pathology for the first time. It also has an important role in the development of the disease, since it is associated with a lower diagnostic age, suggesting that the development of the disease occurs earlier. In conclusion, our study has contributed to a better understanding of the role of folate cycle in the development of CRC and CD, being a starting point for future research that may prove increasingly complex metabolic interactions in this via and its influence on the pathologies studied. In our study we highlight the importance of a comprehensive analysis of the various steps of the folate cycle in order to understand the dynamics that settles in the development of these pathologies, and a number of amendments, whether at the genetic level or at the nutritional level, exercise different effects depending on the stage of the remaining participants in the folate cycle. We believe that in the future this study will allow the knowledge of folate cycle to have increasingly a fundamental relevance at the level of diagnosis and treatment of these diseases.

A Classificação Internacional de Funcionalidade, Incapacidade e Saúde : um modelo multidimensional e multideterminado da funcionalidade em idosos assistidos na Rede

RESUMO: Os estudos sobre a funcionalidade da população idosa têm uma representação importante naquilo que é o atual conhecimento da demografia do mundo. Portugal posiciona-se e perspetiva-se como pertencendo aos países mais envelhecidos, possuindo uma rede de cuidados pós-agudos – a Rede Nacional de Cuidados Continuados Integrados (RNCCI)– que assiste uma parcela importante dessa população. Os aspetos conceptuais da funcionalidade de acordo com a OMS e operacionalizados pela Classificação Internacional de Funcionalidade (CIF), não mereceram até agora suficiente aplicabilidade no nosso país, inviabilizando a possibilidade de oferecermos contributos para a sua operacionalização. Da mesma forma, também os Core Sets da Classificação não têm sido sujeitos a processos de validação que contemplem amostras portuguesas, mantendo-se desconhecimento da especificidade dos fatores contextuais na nossa população. O presente estudo tem como objetivos conhecer a evolução da funcionalidade dos idosos assistidos na RNCCI na região do Algarve nas unidades de convalescença e média duração, validar o Core Set Geriátrico da OMS e propor uma versão abreviada da sua modalidade abrangente, no contexto destes cuidados. A amostra constituída por 451 idosos, dos quais 62,1% eram mulheres, revelou na pré-morbilidade níveis favoráveis de funcionalidade, com exceção para as Atividades Domésticas. Contudo, os mais idosos (≥ 85 anos), os indivíduos sem escolaridade, as mulheres e os viúvos/solteiros apresentaram mais casos desfavoráveis quando comparados com os seus pares. Na evolução da funcionalidade observámos melhorias significativas em todos os domínios avaliados, com diferenças relativamente à idade e à escolaridade; apesar dos resultados positivos os mais idosos e os indivíduos sem escolaridade apresentaram níveis inferiores de evolução. No entanto, a funcionalidade alcançada revelou ficar com resultados significativamente inferiores na comparação com aquela que os indivíduos possuíam na pré-morbilidade. Os modelos de regressão revelaram que as Funções Mentais, a Perceção do Estado de Saúde e a atividade Usar o Telefone, foram as variáveis que melhor explicaram os outcomes da funcionalidade alcançada. A validação do Core Set Geriátrico foi possível na maioria das categorias, sendo que foi no componente das Funções do Corpo onde esse processo revelou maior fragilidade. As Funções Neuromusculoesqueléticas e Relacionadas com o Movimento foram aquelas que registaram em ambos os momentos avaliativos frequências mais elevadas de deficiência, enquanto no componente Atividades & Participação isso ocorreu na atividade Utilização dos Movimentos Finos da Mão. Os capítulos Apoios e Relacionamentos e Atitudes foram considerados os Fatores Ambientais mais Facilitadores mas também com maior impacto Barreira. A proposta para o Core Set Geriátrico Abreviado resultou das categorias independentes que explicaram os modelos da funcionalidade alcançada e cujo resultado engloba um conjunto de 27 categorias, com um enfoque importante no componente Atividades/Participação de onde se destacam os domínios da Mobilidade e dos Auto Cuidados. A funcionalidade dos indivíduos e das populações deve ser considerada uma variável incontornável da Saúde Pública, cuja avaliação deve refletir uma abordagem biopsicossocial, apoiada na Classificação Internacional de Funcionalidade. A operacionalização da Classificação a partir dos Core Sets necessita de pesquisa mais aprofundada relativamente às caraterísticas psicométricas dos seus qualificadores e dos seus processos de validação.-----------ABSTRACT: The studies about the functioning of the elderly play an important role on what the present knowledge of the demography in the world is. Portugal figures high on the most aged countries, having a network of post-acute care - the National Network of Integrated Continuous Care (RNCCI) - which assists a large part of that population. The conceptual aspects of functioning according to WHO and operated by the International Classification of Functioning (ICF), have been insufficiently addressed concerning its adequate applicability in our country, hindering the contributions of its operation. In the same way, also the Core Sets of the Classification have not been subjected to validation procedures that include portuguese samples, keeping the unawareness of specificity of the contextual factors in our population. The objectives of the present study were to know the evolution of the functioning of the elderly assisted in the RNCCI in the Algarve region in units of convalescence and average duration, validate the WHO Geriatric Core Set and propose an abridged version of this comprehensive core set in this healthcare context. The sample was composed by 451 elderly people, of which 62.1% were women, they showed favourable levels in functioning in the pre-morbid state, except for Domestic Activities. However, the oldest (≥ 85 years), the individuals with no education, women and widowed/ unmarried showed more unfavourable cases when compared to their peers. In the evolution of functioning we observed significant improvements in all domains assessed, with diferences with respect to age and education. In spite of positive results, the oldest and the individuals with no education showed lower levels of evolution. However, the functioning achieved showed significantly lower results when compared to the those observed in pre-morbidity state. Regression models reveal that Mental Functions, the Perceived Health Status and the Use of the Phone activity, were the variables that better explain the functioning of the outcomes achieved. The validation of the Geriatric Core Set of ICF was possible in most categories, and Body Functions was the component where this process showed greatest weakness. Neuromusculoskeletal and Movement-Related Functions experienced in both evaluation times with higher rates of disability, while in the Activities & Participation component this occurred in the Fine Hand Use activity. The Support and Relationships and Attitudes chapters were considered the Environmental Factors most Facilitators but also with greater impact Barrier. The proposal for the Brief Geriatric Core Set has resulted from the independent categories that explained the regression models of functioning and includes a set of 27 categories, with na important emphasis on Activities & Participation component where we can highlight the areas of Mobility and Self Care domains. The functioning of individuals and populations should be considered as an unavoidable variable of Public Health, of which the assessment should reflect a biopsychosocial approach, based on the International Classification of Functioning. The operationalization of the Classification from the Core Sets requires further research regarding the psychometric characteristics of their qualifiers and their validation procedure.

Dengue: clinical forms and risk groups in a high incidence city in the southeastern region of Brazil

INTRODUCTION: The article describes the epidemiologic profile of dengue cases in Vitória, the capital of Espírito Santo, Brazil, from 2000 to 2009, aimed at identifying risk groups regarding the incidence and severity of the disease. METHODS: Confirmed cases of dengue among city residents during ten years were classified as dengue fever, dengue hemorrhagic fever, dengue shock syndrome and dengue with complications, and analyzed according to sex, age, race-color and education. RESULTS: The proportion of dengue cases was highest among women aged 20 to 29 years-old and similar between whites and blacks. A gradual decrease occurred in the percentage of dengue cases in the population aged 15 years-old or more, in the historical series of 10 years, and a growing increase in individuals less than 15 years-old, showing statistical significance. The fatality rate ranged from zero to 0.3% for all forms of dengue and from 0.2% to 18.2% for severe forms. CONCLUSIONS: The profile of those affected by the disease in the municipality is similar to those affected in Brazil. The increasing number of cases in individuals under 15 years-old corroborates the results of recent studies in other Brazilian municipalities.

S100, CD68, and MHC class II molecule expression in cervical high- and low-grade HPV-induced lesions

INTRODUCTION: Some human papillomavirus (HPV) types are involved in malignant processes in the cervical epithelium, with 99% of cases attributed to oncogenic HPV infection. This study aimed to detect S100, CD68, and major histocompatibility complex class II (MHC-II) molecules in cervical uterine epithelial samples in patients with high- and low-grade lesions induced by HPV. METHODS: Fifty-eight samples from patients who were confirmed positive or negative for high-risk oncogenic HPV DNA, had histopathological diagnosis of cervical intraepithelial neoplasia (CIN) of grades I, II, or III, or were negative for intraepithelial lesion or malignancy were subjected to immunohistochemistry reaction to S100 protein, CD68, and MHC-II (HLA-DR alpha chain). RESULTS: The presence of MHC-II predominated in samples exhibiting histopathological alterations (p < 0.05). S100 detection was more numerous in carcinoma samples (CIN III) (75%). Presence of this protein correlated significantly (p < 0.05) with histopathological findings and viral load. CONCLUSIONS: A small expression of CD68 was observed, which may be explained by the observation in our study having been made on random microscopic fields and not on specific areas. The findings, such as the presence of S100 protein and MHC-II expression in samples with histological alterations, could suggest that the immune system fails to control HPV replication at the early stages of infection. Further studies with larger prospective data are necessary to confirm this result.

High prevalence of HTLV-1 and 2 viruses in pregnant women in São Luis, state of Maranhão, Brazil

INTRODUCTION: Human T cell lymphotropic virus type 1 (HTLV-1) is endemic in the Caribbean, Japan, South America and regions of Africa. HTLV-2 is present in Native American populations and associated with IV drug use in Europe and North America. In Brazil, it is estimated that 1.5 million people are infected with HTLV-1/2. The study objective was to determine HTLV-1/2 prevalence in pregnant women in the prenatal care from three public services in São Luis, State of Maranhão, Brazil, and to counsel seropositive women to reduce viral transmission. METHODS: A cross-sectional study was conducted from February to December 2008; women with age of 18 to 45 years, with low risk for sexually transmitted disease (STD) were invited to participate. Blood samples were collected in filter paper, and HTLV-1/2 immunoenzymatic test (ELISA) was performed as a screening test. Women with reactive results were submitted to peripheral venous blood collection for ELISA repetition, followed by Western blot (WB) and real-time PCR to confirm and discriminate the infection between virus types 1 and 2. RESULTS: Of the 2,044 women tested, seven (0.3%) were ELISA reactive and confirmed positive (four were HTLV-1, and three were HTLV-2). All positive women were oriented not to breastfeed their newborns. CONCLUSIONS: This study showed that the virus is present in high prevalence in that population. Further studies covering other segments of the population are necessary to better characterize the presence of HTLV-1/2 in Maranhão and to elicit measures to prevent its spread.

Carbohydrate-rich high-molecular-mass antigens are strongly recognized during experimental Histoplasma capsulatum infection

INTRODUCTION: During histoplasmosis, Histoplasma capsulatum soluble antigens (CFAg) can be naturally released by yeast cells. Because CFAg can be specifically targeted during infection, in the present study we investigated CFAg release in experimental murine histoplasmosis, and evaluated the host humoral immune response against high-molecular-mass antigens (hMMAg. >150 kDa), the more immunogenic CFAg fraction. METHODS: Mice were infected with 2.2x10(4) H. capsulatum IMT/HC128 yeast cells. The soluble CFAg, IgG anti-CFAg, IgG anti-hMMAg, and IgG-hMMAg circulating immune complexes (CIC) levels were determined by enzymelinked immunosorbent assay, at days 0, 7, 14, and 28 post-infection. RESULTS: We observed a progressive increase in circulating levels of CFAg, IgG anti-CFAg, IgG anti-hMMAg, and IgG-hMMAg CIC after H. capsulatum infection. The hMMAg showed a high percentage of carbohydrates and at least two main immunogenic components. CONCLUSIONS: We verified for the first time that hMMAg from H. capsulatum IMT/HC128 strain induce humoral immune response and lead to CIC formation during experimental histoplasmosis.

A tutela preventiva da responsabilidade civil

The contemporary society is characterized by high risks. Today, the prevention of damages is as important as compensation. This is due to the fact that the potentiality of several damages is not in line with compensation, because often compensation proves to be impossible. Civil law should be at the service of the citizens, which explains that the heart of the institution of non-contractual liability has gradually moved towards the victim's protection. It is requested from Tort law an active attitude that seeks to avoid damages, reducing its dimension and frequency. The imputation by risk proves to be necessary and useful in the present context as it demonstrates the ability to model behaviors, functioning as a warning for agents engaged in hazardous activities. Economically, it seeks to prevent socially inefficient behaviors. Strict liability assumes notorious importance as a deterrent and in the dispersion of damage by society. The paradigm of the imputation founded on fault has proved insufficient for the effective protection of the interests of the citizens, particularly if based in an anachronistic vision of the concept of fault. Prevention arises in several areas, especially in environmental liability, producer liability and liability based on infringement of copyright and rights relating to the personality. To overcome the damage as the gauge for compensation does not inevitably mean the recognition of the punitive approach. Prevention should not be confused with reactive/punitive objectives. The deterrence of unlawful conduct is not subordinated to punishment.

Towards an integrated technology management across the rail supply chain extended to society: building the case study on high-speed trains

The present paper was prepared for the course “Project III”, with the supervision of Prof. António Moniz, reporting on the author speaking notes at the Winter School on Technology Assessment, 6-7 December 2010, as part of the Doctoral Programme on Technology Assessment at FCT-UNL.

Performance analysis of an SRI screen based on employment quality in high and low capital industries: International evidence

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Finance from the NOVA – School of Business and Economics and Maastricht University School of Business and Economics

The impact of talent management practices on employee retention: The moderator effect of leader-member exchange and role modeling

Organizations are undergoing serious difficulties to retain talent. Authors argue that Talent Management (TM) practices create beneficial outcomes for individuals and organizations. However, there is no research on the leaders’ role in the functioning of these practices. This study examines how LMX and role modeling influence the impact that TM practices have on employees’ trust in their organizations and retention. The analysis of two questionnaires (Nt1=175; Nt2=107) indicated that TM only reduced turnover intentions, via an increase in trust in the organization, when role modeling was high and not when it was low. Therefore, we can say that leaders are crucial in the TM context, and in sustaining a competitive advantage for organizations.

Hybrid capture II and PapilloCheck® tests for detection of anal high-risk human papillomavirus

Introduction This study evaluated the level of concordance between hybrid capture II (HCII) and PapilloCheck® for the detection of high-risk human papillomavirus (HPV) in anal samples. Methods Anal cell samples collected from 42 human immunodeficiency virus (HIV)+ patients were analyzed. Results Considering only the 13 high-risk HPV types that are detectable by both tests, HCII was positive for 52.3% of the samples, and PapilloCheck® was positive for 52.3%. The level of concordance was 80.9% (Kappa = 0.61). Conclusions Good concordance was observed between the tests for the detection of high-risk HPV.

Lucuma as an exotic high quality fruit imported into Portugal and the UE

This project has two different goals, one of them is to promote the consumption of exotic fruits with high quality. The other goal of the project is to look for the viability of turning this work project into a real business, focusing in two different channels to diversify its revenues: B2B and B2C. In order to achieve this second goal, this project aims to see the best way to commercialize this product (Lucuma powder and Pulp of Lucuma) and how to make it in an efficient way with right companies. Therefore, the project aims to create a company to commercialize the product between the producers in Peru and possibly small businesses interested in acquire the processed fruit and also individuals interested in own consumption in small quantities. This project, if successful, tries to diversify the consumption into other good organic healthy products in the long-term.

High visceral leishmaniasis mortality rate in Barra Mansa, a new area of visceral leishmaniasis transmission in the State of Rio de Janeiro, Brazil

Introduction Nine cases of visceral leishmaniasis occurred recently in Barra Mansa, State of Rio de Janeiro, with a high mortality rate. Methods We reviewed the medical records of the patients. Results Eight were male; 7 were adults. Patients who died progressed to death quickly and presented with aggravating factors: systemic steroid therapy before diagnosis, bleeding, severe liver involvement, infection, and/or refusal to receive transfusion. Conclusions We warn clinicians to be aware of the emergence of visceral leishmaniasis in new areas and to keep in mind the possibility of atypical clinical pictures and aggravating factors, so timely diagnosis can be made and prompt and adequate treatment can be initiated.

High similarity of Trypanosoma cruzikDNA genetic profiles detected by LSSP-PCR within family groups in an endemic area of Chagas disease in Brazil

IntroductionDetermining the genetic similarities among Trypanosoma cruzi populations isolated from different hosts and vectors is very important to clarify the epidemiology of Chagas disease.MethodsAn epidemiological study was conducted in a Brazilian endemic area for Chagas disease, including 76 chronic chagasic individuals (96.1% with an indeterminate form; 46.1% with positive hemoculture).ResultsT. cruzi I (TcI) was isolated from one child and TcII was found in the remaining (97.1%) subjects. Low-stringency single-specific-primer-polymerase chain reaction (LSSP-PCR) showed high heterogeneity among TcII populations (46% of shared bands); however, high similarities (80-100%) among pairs of mothers/children, siblings, or cousins were detected.ConclusionsLSSP-PCR showed potential for identifying similar parasite populations among individuals with close kinship in epidemiological studies of Chagas disease.

Diagnosing lymphoma in a setting with a high burden of infection: a pediatric case of Epstein-Barr virus-associated aggressive B-cell lymphoma with t(8;14) (q23;q32) and extensive necrosis mimicking tuberculosis

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.