Cancer cells’ metabolism dynamics in renal cell carcinoma patients’ outcome: influence of GLUT-1-Related hsa-miR-144 and hsa-miR-186

The cancer cells’ metabolism is altered due to deregulation of key proteins, including glucose transporter 1 (GLUT-1), whose mRNA levels are influenced by microRNAs (miRNAs). Renal cell carcinoma (RCC) is the most common and lethal neoplasia in the adult kidney, mostly due to the lack of accurate diagnosis and follow-up biomarkers. Being a metabolic associated cancer, this study aimed to understand the hsa-miR-144-5p and hsa-miR-186-3p’s potential as biomarkers of clear cell RCC (ccRCC), establishing their role in its glycolysis status. Using three ccRCC lines, the intra- and extracellular levels of both miRNAs, GLUT-1’s mRNA expression and protein levels were assessed. Glucose consumption and lactate production were evaluated as glycolysis markers. A decrease of intracellular levels of these miRNAs and increase of their excretion was observed, associated with an increase of GLUT-1’s levels and glycolysis’ markers. Through a liquid biopsy approach, we found that RCC patients present higher plasmatic levels of hsa-miR-186-3p than healthy individuals. The Hsa-miR144-5p’s higher levels were associated with early clinical stages. When patients were stratified according to miRNAs plasmatic levels, low plasmatic levels of hsa-miR-144-5p and high plasmatic levels of hsa-miR-186-3p (high-risk group) showed the worst overall survival. Thus, circulating levels of these miRNAs may be potential biomarkers of ccRCC prognosis.M.M. and I.N. are recipients of a research scholarship awarded by LPCC-NRN (Portuguese League Against Cancer—Northern Branch). F.D. is a Ph.D. fellow from the project NORTE-01-0145- FEDER-000027, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This project was also funded by the research Center of the Portuguese Oncology Institute of Porto [CI-IPOP-21-2015]

Holter STAT-ON™ against other tools for detecting MF in advanced Parkinson’s disease: an observational study

BackgroundDifferent screening tools to identify advanced Parkinson’s disease (APD) have emerged in recent years. Among them, wearable medical devices, such as STAT-ON™, have been proposed to help to objectively detect APD.ObjectivesTo analyze the correlation between STAT-ON™ reports and other assessment tools to identify APD and to assess the accuracy of screening tools in APD patients, using the STAT-ON™ as the gold standard.MethodsIn this retrospective, observational study, data from the University Hospital Complex of Pontevedra database on 44 patients with potential APD who wore STAT-ON™ were extracted. Data were collected according to different sources of tools for identifying APD: (1) STAT-ON™, (2) information provided by the patient, (3) questionnaire for advanced Parkinson’s disease (CDEPA), (4) 5-2-1 Criteria, and (5) Making Informed Decisions to Aid Timely Management of Parkinson’s Disease (MANAGE-PD). Considering STAT-ON™ recordings as a reference, the sensitivity, specificity, and positive and negative predictive values for each tool were calculated. The kappa index assessed the degree of agreement between the gold standard and the other instruments.ResultsAlthough no statistically significant association was found between STAT-ON™ recordings and any screening methods evaluated, the CDEPA questionnaire demonstrated the highest sensitivity and VPN values to detect patients with APD candidates for second-line therapy (SLT). According to the correlation analyses, MANAGE-PD demonstrated the highest degree of concordance with STAT-ON™ recordings to identify the SLT indication and to predict the SLT decision.ConclusionSTAT-ON™ device may be a helpful tool to detect APD and to guide treatment decisions

Modelação de redes de gás com vista à deteção e localização de fugas

Tese de Doutoramento em Engenharia Eletrotécnica e de ComputadoresAs condutas são parte integrante das infraestruturas da sociedade atual e são usadas, na indústria de gás natural, para o seu transporte e armazenamento. Uma das problemáticas do uso das condutas é a deteção da ocorrência de fugas. Apesar dos numerosos estudos desenvolvidos, nesta área, persistem ainda questões em aberto e é impreterível atingir resultados equiparáveis aos das redes líquidas, nomeadamente no que respeita à monitorização e ao controlo. A investigação, neste campo, revela-se aliciante, uma vez que não existe, na indústria do gás, um método eficiente de deteção de fugas e se pretende evitar eventuais danos ambientais e para a saúde. A dinâmica do gás, numa conduta, é descrita por um sistema de equações às derivadas parciais e através de modelos de funções de transferência, baseados na solução desse sistema. Usando uma analogia elétrica, a conduta é representada por um quadripolo, tendo por base as medições de pressão/caudal, nas extremidades; é representada também a juncão de condutas, com a obtenção de valores intermédios de pressão/caudal. A obtenção destes perfis de pressão/caudal, ao longo da conduta, apresenta-se como uma mais-valia dado o reduzido número de sensores de caudal existentes nas redes e o elevado custo que acarreta a sua implementação. Consideram-se simplificações dos modelos propostos, que são avaliadas com um caso de estudo composto por dados reais e simulados. Estas simplificações mostram-se precisas e com redução dos custos computacionais, tornando esta técnica economicamente viável. Tendo por base a mesma analogia elétrica, é modelada uma fuga, ao longo de uma conduta com e sem sensores de pressão/caudal. Nesta tese, é proposto um detetor/localizador de fugas, numa conduta de gás natural selada, que visa a inovação e a economia. Assim, através dos modelos supracitados, comparam-se perfis padrão de pressão/caudal e perfis operacionais e a fuga é detetada quando as diferenças entre os perfis ultrapassam os limites estabelecidos. Este detetor mostra-se eficaz, inclusive para fugas inferiores a 1% do caudal médio da conduta e na presença de um elevado nível de ruído nos dados medidos, para além de apontar a localização da fuga e estimar a sua dimensão.Pipeline technology is essential to a modern society infrastructure, and is used to transport and store gas in natural gas industry. One of the key issues faced in pipeline industry is leakage detection. Despite numerous studies in the area, there are still many open questions to be addressed in order to achieve equivalent performance to the one existent in the liquid pipelines, namely in management and control. This area of interest is motivating since there is no efficient method used in the industry and it is crucial to prevent leakage, and therefore avoid potential significant environmental and health consequences. The gas dynamics in the pipeline is described by a system of partial differential equations and transfer functions models are derived from the system solution representation. Using an electrical analogy, the pipeline is represented by a quadripole, depending on the pressure/mass flow at the both ends of the pipeline; also a pipeline junction and intermediate pressure/mass flow values can then be assessed. Thus pressure/mass flow profiles along the pipeline can be determined allowing this methodology to overcome the scarceness of flow measurements and their expensive implementation. The proposed models are simplified and assessed using a case study which is a mix of real and simulated data. This shows important benefits in terms of accuracy and reduction cost of computation, making this methodology to be economically viable. The models for leakage detection purpose are also built based on the same concept, using in some cases pressure/mass flow sensors along the pipeline. In this dissertation an original cost-effective leakage detection method for a closed pipeline is proposed. Using the mentioned models, the operational pressure/mass flow profiles are compared with pre-established profile and a leakage is detected once the difference between those two profiles exceeds the threshold boundaries. This leakage detector can identify leakages of less than 1% even when the measured data has a high level of noise. Furthermore, a way to locate the leakage and estimate its dimension is proposed

Colon microbiota modulation by dairy-derived diet: new strategy for prevention and treatment of colorectal cancer

An unbalanced diet is one of the well-known risk factors for the development of colorectal cancer (CRC). This type of cancer is currently the main cause of cancer-related deaths worldwide, urging the need for new and more effective preventive and therapeutic approaches. It is already known that CRC patients have alterations in the microbial community and metabolism. In this regard, a concept that has been recently attracting the attention of the scientific community is the development of functional food or nutraceuticals, as a new and more effective strategy to overcome CRC patient-associated dysbiosis. Particularly, dairy product enriched diets are the major dairy source of dietary calcium, vitamin D and folate intake, which are well-known to have a protective effect against CRC development. In addition, these products are rich in both pre- and probiotics, constituting a double strategy to modulate both the intestinal microbiota composition and the production of microbial metabolites. Short-chain fatty acids (SCFA), namely, acetate, butyrate, and propionate, are major contributors to colonic homeostasis since they regulate several biological and metabolic processes. In this review, we performed a state of art study concerning the use of dietary patterns, specifically the dairy-derived diet, in the modulation of the human microbiota and their potential use as pre-, pro- or synbiotics for the development of new preventive and therapeutic strategies for CRC.This article is a result of the project EcoAgriFood NORTE-01-0145-FEDER-00009, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). Sara Gomes thanks FCT for her PhD grant SFRH/BD/140965/2018. This work was financed by the Portuguese Foundation for Science and Technology (Fundação para a Ciência e a Tecnologia, FCT) within the scope of project PTDC/QUIQIN/28662/2017. This work was also supported by the strategic programme UID/BIA/04050/2019 funded by national funds through the FCT I.P

Characterisation of microbial attack on archaeological bone

As part of an EU funded project to investigate the factors influencing bone preservation in the archaeological record, more than 250 bones from 41 archaeological sites in five countries spanning four climatic regions were studied for diagenetic alteration. Sites were selected to cover a range of environmental conditions and archaeological contexts. Microscopic and physical (mercury intrusion porosimetry) analyses of these bones revealed that the majority (68%) had suffered microbial attack. Furthermore, significant differences were found between animal and human bone in both the state of preservation and the type of microbial attack present. These differences in preservation might result from differences in early taphonomy of the bones. © 2003 Elsevier Science Ltd. All rights reserved