Investigating the origins of Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) comprises 85% of all pancreatic cancers and is characterised by an extremely poor prognosis. It is becoming increasingly obvious that attention has to be focused on early tumour development, when the disease is still manageable. Thus, in this study, I aimed to assess the contribution of adult acinar and duct cells to PDAC development and to identify PDAC tumour-initiating cells (TICs). Our laboratory had previously identified Fbw7 as a potent tumour suppressor in PDAC (unpublished data). Fbw7F/F; KRasLSL-G12D/wt; Pdx1-Cre mice exhibited accelerated PDAC onset compared with KRasLSL-G12D/wt; Pdx1-Cre mice. I confirmed this observation and demonstrated that Fbw7 loss in the pancreatic epithelium had a greater proliferative effect in ductal cells, in the presence and absence of KRasG12D, leading to increased numbers of duct cells positive for phosphorylated histone 3. The selective loss of Fbw7 in adult ductal cells with concomitant KRasG12D expression (Fbw7F/F; KRasLSLG12D/ wt; Ck19-CreER mice) led to PDAC development, which was not preceded by mucinous lesions. These results were confirmed with the loss of p53 with simultaneous KRasG12D expression in adults duct cells (p53F/F; KRasLSL-G12D/wt; Ck19-CreER mice). The absence of mucinous PDAC precursors was not dependent on the genotype, as loss of Fbw7 in KRasG12D-expressing acinar cells allowed the development of mucinous murine pancreatic intraepithelial neoplasia (PanIN). Additionally, I induced bystander PanINs using orthotopic transplantation of PDAC cells. These results provide evidence that ductal cells can originate PDAC and that different pancreatic cells types might adopt different routes to PDAC development. Additionally, the observation of bystander PanINs questioned the sole pre-neoplastic nature of these lesions highlighting the need for a deeper understanding of PDAC biology. In the present work, I have also described a new marker of TICs within PDAC derived from pancreatic progenitors and adult ductal cells. Marker-high PDAC cells exhibited higher in vitro organoid-forming capacity, compared with marker-low cells, isolated from the primary tumour and after long-term cultures. Contrasting with marker-low tumour cells, marker-high cells were capable of forming secondary tumours at low numbers, demonstrating efficient tumour-initiating capacity and recapitulating the histology of the primary tumour source. These results could provide useful information for the development of PDAC targeted therapie

Physicochemical parameters, bioactive components and antioxidant capacity of whey-grape juice beverage.

Food: the tree that sustains life. 872

Dietary intake and macrovascular disease in a Japanese-Brazilian population: a cross-sectional study

OBJETIVO: Descrever o hábito alimentar de nipo-brasileiros com e sem doença macrovascular (DMV). MÉTODOS: Definiu-se DMV, para 1.165 nipo-brasileiros, a partir de escores atribuídos ao histórico de saúde, eletrocardiograma e valores do índice tornozelo-braquial. Determinou-se o consumo alimentar habitual por meio de Questionário de Frequência do Consumo de Alimentos. RESULTADOS: A porcentagem de casos confirmados com DMV foi de 3,2%, sendo semelhante entre os sexos. Observou-se, de forma estatisticamente significante, maior frequência de indivíduos com DMV (confirmados ou suspeitos) entre aqueles de primeira geração, com idade > 60 anos, tabagistas, com hipertensão arterial, hipertrigliceridemia e diabetes. Nipo-brasileiros com DMV (confirmados ou suspeitos) apresentaram menor perímetro do quadril e maior idade, pressão arterial sistólica, triglicérides, glicemia, consumo de alimentos fonte de ferro e menor fonte de fibras de grãos. Encontrou-se diferença estatisticamente significante apenas para o consumo de gordura saturada (análise bruta: segundo terço versus primeiro terço). CONCLUSÕES: programas de educação nutricional devem ser incentivados neste grupo com alta prevalência de doenças crônicas não transmissíveis.OBJECTIVE: To describe the food intake of Japanese-Brazilians with and without macrovascular disease (MVD). METHODS: MVD was defined, for 1,165 Japanese-Brazilians, by scores attributed to the health historical, electrocardiogram and ankle-brachial index values. The usual dietary intake was determined using a food frequency questionnaire. RESULTS: The MVD prevalence was of 3.2%, being similar among genders. Statistically higher frequencies of individuals with MVD were observed among those of first generation, with age > 60 years, tobacco user, with hypertension, hypertriglyceridemia and diabetes. Subjects with MVD were older, with smaller hip circumference, and higher systolic blood pressure levels, triglycerides and glycemia concentration; they informed higher consumption of iron source food and smaller of grains fibers. Statistically significant difference was found to saturated fat (crude analysis: second tercile versus first tercile). CONCLUSIONS: Programs of nutritional education should be stimulated in this group with high prevalence of non-communicable chronic diseases.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Suicide cases in developed and emerging countries: an analysis using wavelets.

Objetivo: Verificar se existe relação de similaridade entre o número de suicídio em países desenvolvidos e emergentes usando a técnica de ondaletas. Métodos: Os dados anuais foram obtidos a partir do relatório da Organização Mundial da Saúde (OMS), no período de 1986 a 2015. Para análise, foi empregada a transformada discreta não decimada de ondaleta (NDWT), a função ondaleta aplicada foi a Daubechies com cinco níveis de decomposição. Com relação ao agrupamento, utilizou-se a energia (variância) para analisar os clusters e, para a visualização do processo de clusterização, trabalhamos com o dendograma, no qual se empregou a distância de Mahalanobis. A quantidade de grupos foi definida por meio da função NbCluster. Resultados: A partir da análise de cluster, verificou-se a formação de quatros grupos. No qual, Japão e Estados Unidos e Brasil localizam-se em grupos distintos e isolados. E os demais países (Áustria, Bélgica, Chile, Israel, México, Itália e Holanda) em um único grupo. Conclusão: Utilizando esse método, foi possível verificar com mais detalhes quais países apresentaram comportamentos semelhantes, mesmo apresentando características bem distintas entre si, tanto socioeconômica, geográfica e climática

Augmented reality-assisted ultrasound breast biopsy

Breast cancer is the most prevalent cancer in the world and the fifth-leading cause of cancer-related death. Treatment is effective in the early stages. Thus, a need to screen considerable portions of the population is crucial. When the screening procedure uncovers a suspect lesion, a biopsy is performed to assess its potential for malignancy. This procedure is usually performed using real-time Ultrasound (US) imaging. This work proposes a visualization system for US breast biopsy. It consists of an application running on AR glasses that interact with a computer application. The AR glasses track the position of QR codes mounted on an US probe and a biopsy needle. US images are shown in the user’s field of view with enhanced lesion visualization and needle trajectory. To validate the system, latency of the transmission of US images was evaluated. Usability assessment compared our proposed prototype with a traditional approach with different users. It showed that needle alignment was more precise, with 92.67 ± 2.32° in our prototype versus 89.99 ± 37.49° in a traditional system. The users also reached the lesion more accurately. Overall, the proposed solution presents promising results, and the use of AR glasses as a tracking and visualization device exhibited good performance.This work was funded by the projects “NORTE-01-0145-FEDER-000045” and “NORTE-01- 0145-FEDER-000059", supported by Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). It was also funded by national funds, through the FCT (Fundação para a Ciência e a Tecnologia) and FCT/MCTES in the scope of the project UIDB/05549/2020, UIDP/05549/2020 and LASI-LA/P/0104/2020. The authors also acknowledge FCT, Portugal and the European Social Found, European Union, for funding support through the “Programa Operacional Capital Humano” (POCH) in the scope of the PhD grants SFRH/BD/136721/2018 (Oliveira B.) and SFRH/BD/136670 (Torres H. R.)