11p15 Epimutations in Pediatric Embryonic Tumors: Insights from a Methylome Analysis.

Embryonic tumors share few recurrent mutations, suggesting that other mechanisms, such as aberrant DNA methylation, play a prominent role in their development. The loss of imprinting (LOI) at the chromosome region 11p15 is the germline alteration behind Beckwith-Wiedemann syndrome that results in an increased risk of developing several embryonic tumors. This study analyzed the methylome, using EPIC Beadchip arrays from 99 sporadic embryonic tumors. Among these tumors, 46.5% and 14.6% presented alterations at imprinted control regions (ICRs) 1 and 2, respectively. Based on the methylation levels of ICR1 and ICR2, four clusters formed with distinct methylation patterns, mostly for medulloblastomas (ICR1 loss of methylation (LOM)), Wilms tumors, and hepatoblastomas (ICR1 gain of methylation (GOM), with or without ICR2 LOM). To validate the results, the methylation status of 29 cases was assessed with MS-MLPA, and a high level of agreement was found between both methodologies: 93% for ICR1 and 79% for ICR2. The MS-MLPA results indicate that 15 (51.7%) had ICR1 GOM and 11 (37.9%) had ICR2 LOM. To further validate our findings, the ICR1 methylation status was characterized via digital PCR (dPCR) in cell-free DNA (cfDNA) extracted from peripheral blood. At diagnosis, we detected alterations in the methylation levels of ICR1 in 62% of the cases, with an agreement of 76% between the tumor tissue (MS-MLPA) and cfDNA methods. Among the disagreements, the dPCR was able to detect ICR1 methylation level changes presented at heterogeneous levels in the tumor tissue, which were detected only in the methylome analysis. This study highlights the prevalence of 11p15 methylation status in sporadic embryonic tumors, with differences relating to methylation levels (gain or loss), location (ICR1 or ICR2), and tumor types (medulloblastomas, Wilms tumors, and hepatoblastomas).

DNA methylation is a comprehensive marker for pediatric adrenocortical tumors.

Children diagnosed with pediatric adrenocortical tumors (pACT) have variable outcomes, and, to date, the disease lacks robust prognostic biomarkers. The prognostic potential of tumor methylation has been demonstrated in several cancers. We aimed to evaluate the pACT methylation profile and its association with disease presentation and survival. In this cross-sectional study, we accessed the DNA methylation (MethylationEPIC Array, Illumina) of 57 primary pACT from Southeastern Brazil and the respective patients' clinicopathological features. We also applied our analysis in an independent 48 pACT methylation dataset. Unsupervised learning whole-methylome analysis showed two groups with distinct methylation signatures: pACT-1 and pACT-2. Compared to pACT-2, pACT-1 tumors were enriched with higher methylation in CpG islands, mainly in gene promoter regions. The topmost hypermethylated gene in these samples was shown to be underexpressed. Patients in the pACT-1 group were older at diagnosis and were more likely to have carcinomas and nonlocalized/advanced and recurrent/metastatic disease. Univariate and bivariate regressions showed that pACT-1 methylation signature confers superior hazard ratio of disease progression and death than known prognostic features. The methylation groups had similar frequencies of germline mutations in the TP53 gene, including the regionally frequent p.R337H. Our analysis replication validated our findings and reproduced those recently described in pACT. We demonstrated the existence of different tumor methylation signatures associated with pACT presentation and clinical evolution, even in the context of germline TP53 mutations. Our data support tumor methylation profiling as a robust and independent prognostic biomarker for pACT and suggest a list of candidate genes for further validation.

Vitamin D receptor hypermethylation as a biomarker for pediatric adrenocortical tumors.

Objective: Pediatric adrenocortical tumors (pACT) display complex genomic backgrounds, lacking robust prognostic markers and targeted therapeutic options. Vitamin D3 receptor (VDR) promoter hypermethylation and underexpression were reported in adrenocortical carcinomas from adult patients. In this study, we aimed to investigate VDR expression levels and methylation status in pACT and their clinical and prognostic significance. Design: Retrospective cross-sectional study enrolling pediatric patients with ACT from two tertiary referral institutions. Methods: We evaluated clinicopathological features, VDR mRNA (qPCR) and protein (immunohistochemistry) expression, and VDR-wide methylation of ACT samples from 108 pediatric patients. Fourteen pediatric and 32 fetal and postnatal normal adrenals were used as controls. Results: Unlike in pre- and post-natal normal adrenals, most pACT lacked nuclear VDR expression and had reduced mRNA levels, especially the carcinomas. Unsupervised analysis of VDR methylation data revealed two groups of pACT with distinct disease features and outcomes. Tumors with high VDR methylation presented lower mRNA levels, and the respective patients presented advanced disease and reduced disease-free and overall survival. Conclusions: VDR has a role in normal adrenocortical development and homeostasis, which is impaired during tumorigenesis. VDR hypermethylation and underexpression may be both predictive and prognostic biomarkers for pACT.

Anatomia radiológica vascular e desenvolvimento de plataformas de ensino interativo / Vascular radiological anatomy and the development of interactive teaching platforms

Anatomia e Radiologia são disciplinas amplamente presentes nas grades curriculares de cursos da área da saúde. A interseção entre a Anatomia Radiológica e as tecnologias recentes, como plataformas de ensino interativo, caracteriza-se como uma tendência a ser seguida na esfera educacional, sendo as implicações desse processo ainda não muito debatidas. O Departamento de Anatomia da Universidade Federal de Juiz de Fora iniciou o desenvolvimento de um atlas de anatomia vascular radiológica, o qual apresenta versões impressa e interativa. Possui imagens de angiotomografias computadorizadas feitas em aparelhos multislice de 16 a 128 canais, sendo as imagens de arquivo pessoal dos organizadores. O atlas promove a identificação das estruturas vasculares em questão e propicia a integração do conhecimento adquirido em salas de aula com a visualização de exames de imagem complementares rotineiros. A indiscutível presença de exames de imagem adicionais na rotina dos profissionais da saúde atuais faz com que seja válida a estratégia de integração entre o método tradicional de ensino e as práticas ativas de aprendizagem, as quais vêm ganhando destaque recentemente, devido a sua efetividade na fixação de conhecimentos.

Anatomy and Radiology are subjects widely present in health courses at universities. The intersection between Radiological Anatomy and recent technologies, such as interactive teaching platforms, is characterized as a tendency to be followed in the educational sphere, and the implications of this process are not much debated. The Department of Anatomy of Juiz de Fora Federal University has begun the development of an atlas of radiological vascular anatomy, which features printed and interactived versions. It presents computed tomography images taken on multislice devices from 16 to 128 channels, and the images are from the personal authors' archives. The Radiologic Vascular Atlas provides the identification of vascular structures in study and makes easier the integration of knowledge acquired in classrooms with the visualization of routine complementary imaging exams. The indisputable presence of complementary imaging examinations in the routine of current health professionals makes valid the strategy of integration between the traditional teaching method and active learning practices, which have recently gained prominence, due to its effectiveness in setting knowledge.

Lepra / hanseníase: passado - presente / Leprosy: past-present

O trabalho apresenta a história da hanseníase, focalizando a doença como uma ameaça à vida individual e coletiva que acompanha o homem desde o passado até o presente. Para realizá-lo, laçamos mão de uma revisão da literatura específica.

Hanseniase e migracao no municipio de Maringa - Parana: 1957-1997 / ?

Este trabalho e um estudo historico-descritivo de natureza qualitativa, cujo o objetivo e estabelecer a relacao entre doenca e o movimento migratorio da hanseniase no municipio de Maringa. Foram entrevistadas 11 pessoas entre portadores e ex-portadores da doenca e profissionais de saude que compartilharam do mesmo problema de forma singular, e vivenciaram a doenca no periodo de 1957-1997. As historias de vida relatadas foram analisadas segundo os seguintes aspectos da hanseniase: os servicos de saude oferecidos, as duas faces da doenca, tratamento, e hanseniase e migracao. Atraves deste estudo, percebemos que um dos motivos da vinda de hansenianos para a regiao foi a tentativa de manter a uniao de sua familia, no que iam de encontro a politica de controle da epoca, do isolamento compulsorio.

Hanseníase e migração no município de Maringá - Paraná: 1957-1997 / ?

Este trabalho é um estudo histórico-descritivo de natureza qualitativa, cujo o objetivo é estabelecer a relação entre a doença e o movimento migratório da hanseníase no município de Maringá. Foram entrevistadas 11 pessoas entre portadores, ex-portadores da doença e profissionais de saúde que compartilharam do mesmo problema de forma singular, e vivenciaram a doença no período de 1957-1997. As histórias de vida relatadas foram analisadas segundo os seguintes aspectos da hanseníase: os serviços de saúde oferecidos, as duas faces da doença, tratamento, e hanseníase e migração. Através deste estudo, percebemos que um dos motivos da vinda de hansenianos para a região foi a tentativa de manter a união de sua família, no que iam de encontro à política de controle da época, do isolamento compulsório. Outro motivo decorre das incapacidades físicas instaladas que o impossibilitava de trabalhar no campo. Concorreram, além disso, a busca da melhoria das condições de vida e recentemente, motivados pela qualidade do atendimento oferecido pela rede do município de Maringá.

Socializando conhecimentos em doenças transmissíveis através do rádio

Trabalho dedicado à complementaçäo da Disciplina Enfermagem em Doenças Transmissíveis. Acreditando que a informaçäo é um mecanismo de socializaçäo do saber, professores da disciplina criaram um trabalho comunitário em saúde que atinge a comunidade de uma grande regiäo, extrapolando a sala de aula e programas desenvolvidos em Instituiçäo de Saúde. Este trabalho informa a problemática bio-socio-econômica das doenças transmissíveis e características epidemiológicas atuais, regionais e locais envolvendo de forma dinâmica ouvintes, professores e alunos da disciplina através de um meio de comunicaçäo, o rádio.

Tendência secular da detecçäo da hanseníase no município de Maringá, PR, 1977/1986 / Temporal tendency in the detection of Hansen's disease in the municipality of Maringá, PR, 1977/1986

Estudo dedicado a analisar o comportamento da hanseníase no município de Maringá - PR. Foram estudadas 348 fichas clínico-epidemiológicas de pacientes portadores de hanseníase no período compreendido entre 1977 e 1986. Verificou-se um maior percentual das formas clínicas Virchowiana + Dimorfa, prevalecendo na faixa etária economicamente ativa, o que näo difere de estudos anteriormente realizados por Belda & Lombardi, por Asseis et al. Säo Apresentadas tabelas e figuras da distribuiçäo da doença segundo sexo, naturalidade, ano de detecçäo, forma clínica, idade na ocasiäo do diagnóstico, tempo do início dos sintomas até diagnóstico com breves comentários, e sua importância para a avaliaçäo epidemiológica da hanseníase neste município