A quick and low-intensity method for oral administration to large numbers of mice: A possible alternative to oral gavage

Oral administration of medication to experimental animals is a cause of significant stress. When coupled to animals who are already under strenuous circumstances due to the disease being modelled, there is a significant risk for increased morbidity and mortality, thus influencing the results. Faced with these con- straints, a low-intensity method for oral administration was developed, based solely on the natural behaviour of the animals and minimal conditioning, in which precise doses of medication were administered in a locally available, standard wheat cookie fragment, providing both a palatable vehicle and an absorbent matrix for the medication. Fast administration to large numbers of animals was thus achieved, safeguarding the animals’ welfare and ensuring ease of handling. This method is a promising alternative to oral gavage in pre-clinical drug studies with laboratory mice

Systematic Review and Correlations with HPV Status and Patient Survival

Funding: This study was financially supported by the Virology Laboratory from the Pathology Department of the Portuguese Oncology Institute of Lisboa IUIC/1168, with contributions by the Research Center of the Portuguese Oncology Institute of Porto (project no. PI86-CI-IPOP-66-2017), by Base Funding-UIDB/00511/2020 of the Laboratory for Process Engineering, Environment, Biotechnology, and Energy—LEPABE—funded by national funds through the FCT/MCTES (PIDDAC), and Project 2SMART-engineered Smart materials for Smart citizens, with reference NORTE-01- 0145-FEDER-000054, supported by Norte Portugal Regional Operational Programme (NORTE 2020) under the PORTUGAL 2020 Partnership Agreement through the European Regional Development Fund (ERDF).PIK3CA mutations are believed to contribute to the pathogenesis of human papillomavirus (HPV)-associated head and neck squamous cell carcinomas (HNSCC). This study aims to establish the frequency of PIK3CA mutations in a Portuguese HNSCC cohort and to determine their association with the HPV status and patient survival. A meta-analysis of scientific literature also revealed widely different mutation rates in cohorts from different world regions and a trend towards improved prognosis among patients with PIK3CA mutations. DNA samples were available from 95 patients diagnosed with HNSCC at the Portuguese Institute of Oncology in Lisbon between 2010 and 2019. HPV status was established based on viral DNA detected using real-time PCR. The evaluation of PIK3CA gene mutations was performed by real-time PCR for four mutations (H1047L; E542K, E545K, and E545D). Thirty-seven cases were found to harbour PIK3CA mutations (39%), with the E545D mutation (73%) more frequently detected. There were no significant associations between the mutational status and HPV status (74% WT and 68% MUT were HPV (+); p = 0.489) or overall survival (OS) (3-year OS: WT 54% and MUT 65%; p = 0.090). HPV status was the only factor significantly associated with both OS and disease-free survival (DFS), with HPV (+) patients having consistently better outcomes (3-year OS: HPV (+) 65% and HPV (-) 36%; p = 0.007; DFS HPV (+) 83% and HPV (-) 43%; p = 0.001). There was a statistically significant interaction effect between HPV status and PIK3CA mutation regarding DFS (Interaction test: p = 0.026). In HPV (+) patients, PIK3CA wild-type is associated with a significant 4.64 times increase in the hazard of recurrence or death (HR = 4.64; 95% CI 1.02-20.99; p = 0.047). Overall, PIK3CA gene mutations are present in a large number of patients and may help define patient subsets who can benefit from therapies targeting the PI3K pathway. The systematic assessment of PIK3CA gene mutations in HNSCC patients will require further methodological standardisation.publishersversionpublishe

In vivo biocompatibility and biodegradability of dextrin-based hydrogels

The in vivo biocompatibility of dextrin hydrogels obtained by polymerization of dextrin-hydroxyethylmethacrylate (dextrin-HEMA) and dextrin-vinyl acrylate (dextrin-VA) are reported in this work. The histological analysis of subcutaneous implants of these hydrogels, featuring inflammatory and reabsorption events, were carried out over a 16-week period in mice. The dextrin-HEMA hydrogel was quickly and completely degraded and reabsorbed, whereas the dextrin-VA degradation occurred slowly and a thin fibrous capsule surrounded the nondegradable hydrogel. The dextrin-HEMA was degraded after 16 weeks with only mild inflammation and a few detectable foamy macrophages around the implant. These events were followed by complete resorption and no sign of capsule formation or fibrosis associated to the implants. The results indicate that the dextrin hydrogels are biocompatible because no toxicity on the tissues surrounding the implants was found. It may be speculated that a controlled degradation rate of the hydrogels may be obtained by grafting dextrin to HEMA and VA in different proportions.Funding from FCT through POCTI program is acknowledged. The authors Susana Moreira and Rui M. Gil da Costa are recipients of a PhD fellowship from Fundacao para a Ciencia e a Tecnologia (FCT, Portugal)

Science-media online training challenges and opportunities

EuroScitizen COST Action is a research network which aims to identify targeted strategies to raise levels of scientific literacy in Europe using evolution as a model. One of the activities developed by the EuroScitizen Media Working Group (WG4) was a set of Training Schools in Science and Media directed to young scientists and journalists. By uniting scientists and journalists, we aimed to promote better communication between the two groups while giving advanced training in science communication. The training activities were originally planned as one in-person Training School but converted to online events due to the COVID-19 pandemic. This required an adjustment of schedule and contents, and instead of having a training school for three full days, as in the planned in-person school, we developed several shorter sessions. Herein, we present the set of Science and Media training events we organised from June 2021 through February 2022, as well as the main challenges we encountered and what we found to be advantages of the online environment for training. We also share a checklist we developed for the organisation of training schools that may provide a useful tool for people planning other training events. Poster presented at EuroScitizen Sustainability meeting, 20-22 June 2022, Aveiro, Portuga

A aterosclerose nos cuidados de saúde primários: estudo da vida real

Introduction and Objectives: To characterize patients with atherosclerosis, a disease with a high socioeconomic impact, in the Lisbon and Tagus Valley Health Region. Methods: A cross-sectional observational study was carried out through the Lisbon and Tagus Valley Regional Health Administration primary health care database, extracting data on the clinical and demographic characteristics and resource use of adult primary health care users with atherosclerosis during 2016. Different criteria were used to define atherosclerosis (presence of clinical manifestations, atherothrombotic risk factors and/or consumption of drugs related to atherosclerosis). Comparisons between different subpopulations were performed using parametric tests. Results: A total of 318 692 users were identified, most of whom (n=224 845 users; 71%) had no recorded clinical manifestations. The subpopulation with clinical manifestations were older (72.0±11.5 vs. 71.3±11.0 years), with a higher proportion of men (58.0% vs. 45.9%), recorded hypertension (78.3% vs. 73.5%) and dyslipidemia (55.8% vs. 53.5%), and a lower proportion of recorded obesity (18.2% vs. 20.8%), compared to those without clinical manifestations (p<0.001). Mean blood pressure, LDL-C and glycated hemoglobin values were lower in the subpopulation with manifestations (142/74 vs. 146/76 mmHg, 101 vs. 108 mg/dl, and 6.80 vs. 6.84%, respectively; p<0.001). Each user with atherosclerosis attended 4.1±2.9 face-to-face medical consultations and underwent 8.6±10.0 laboratory test panels, with differences in subpopulations with and without clinical manifestations (4.4±3.2 vs. 4.0±2.8 and 8.3±10.3 vs. 8.7±9.8, respectively; p<0.001). Conclusions: About one in three adult primary health care users with atherosclerosis have clinical manifestations. The results suggest that control of cardiovascular risk factors is suboptimal in patients with atherosclerosis.Introdução e objetivos: caracterizar os doentes com aterosclerose, uma doença com elevado impacto socioeconómico, na Região de Saúde de Lisboa e Vale do Tejo. Métodos: Estudo observacional transversal, recorrendo ao Sistema de Informação desta Administração Regional de Saúde, com extração de dados clínico-demográficos e de consumo de recursos dos utilizadores adultos com aterosclerose em 2016. A aterosclerose foi definida pela presença de manifestações clínicas, fatores de risco aterotrombóticos e/ou consumo de medicamentos marcadores de aterosclerose. Foram comparados os resultados para a população com e sem manifestações clínicas (testes paramétricos). Resultados: Identificámos 318 692 utilizadores, a maioria (n=224 845 doentes; 71%) sem registo de manifestações clínicas. A subpopulação com manifestações clínicas era mais idosa (72,0±11,5 versus 71,3±11,0 anos), com maior proporção de homens (58,0% versus 45,9%), registo de hipertensão arterial (78,3% versus 73,5%), dislipidemia (55,8% versus 53,5%) e menor proporção de registo de obesidade (18,2% versus 20,8%), em comparação com a população sem manifestações clínicas (p<0,001). Os valores médios de pressão arterial sistólica/diastólica, C-C-LDL e hemoglobina glicada foram inferiores na subpopulação com manifestações (142/74 versus 146/76 mmHg, 101 versus 108 mg/dL, 6,80 versus 6,84%, respetivamente; p<0,001). Cada utilizador com aterosclerose realizou 4,1±2,9 consultas médicas presenciais e 8,6±10,0 painéis de análises clínicas, com diferenças nas subpopulações com e sem manifestações clínicas (4,4 ± 3,2 versus 4,0 ± 2,8 e 8,3 ± 10,3 versus 8,7±9,8, respetivamente; p<0,001). Conclusões: Cerca de um em cada três utilizadores adultos de cuidados de saúde primários com aterosclerose têm manifestações clínicas. Os resultados sugerem que o controlo dos factores de risco cardiovascular é sub-óptimo em doentes com aterosclerose.info:eu-repo/semantics/acceptedVersio

ESSIM-EA applied to Wildfire Prediction using Heterogeneous Configuration for Evolutionary Parameters

Wildfires devastate thousands forests acres every year around the world. Fire behavior prediction is a useful tool to cooperate in the coordination, mitigation and management of available resources to fight against this type of contingencies. However, the prediction of this phenomenon is usually a difficult task due to the uncertainty in the prediction process. Therefore, several methods of uncertainty reduction have been developed, such as the Evolutionary Statistical System with Island Models based on Evolutionary Algorithms (ESSIM-EA). ESSIMEA focuses its operation on an Evolutionary Parallel Algorithm based on islands, in which the same configuration of evolutionary parameters is used. In this work we present an extension of the ESSIM-EA that allows each island to select an independent configuration of evolutionary parameters. The heterogeneous configuration proposed, at the island level, with the original methodology in three cases of controlled fires has been contrasted. The results show that the proposed ESSIM-EA extension allows to improve the quality of prediction and to reduce processing times.Eje: XVIII Workshop de Agentes y Sistemas Inteligentes (WASI).Red de Universidades con Carreras en Informática (RedUNCI

The burden of atherosclerosis in Portugal

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please [email protected]: This paper sought to estimate the burden of disease attributable to atherosclerosis in mainland Portugal in 2016. Methods and results: The burden of atherosclerosis was measured in disability-adjusted life years (DALY) following the latest 2010 Global Burden of Disease (GBD) methodology. DALYs were estimated as the sum of years of life lost (YLL) with years lived with disability (YLD). The following clinical manifestations of atherosclerosis were included: ischemic heart disease (IHD) (including acute myocardial infarction (AMI), stable angina, and ischemic heart failure (IHF)), ischemic cerebrovascular disease (ICVD) and peripheral arterial disease (PAD). YLL were estimated based on all-cause mortality data for the Portuguese population and mortality due to IHD, ICVD and PAD for the year 2016 sourced from national statistics. Standard life expectancy was sourced from the GBD study. YLD corresponded to the product of the number of prevalent cases by an average disability weight (DW) for all possible combinations of disease. Prevalence data for the different clinical manifestations of atherosclerosis were sourced from epidemiological studies. DW were sourced from the published literature. In 2016, 15,123 deaths were attributable to atherosclerosis, which corresponded to 14.3% of overall mortality in mainland Portugal. DALYs totaled 260,943, 75% due to premature death (196,438 YLL) and 25% due to disability (64,505 YLD). Conclusion: Atherosclerosis entails a high disease burden to society. A large part of this burden would be avoidable if evidence-based effective and cost-effective interventions targeting known risk factors, from prevention to treatment, were implemented.This study was funded by Bayer Portugal, Lda. Funding was independent of the study outcomes.info:eu-repo/semantics/publishedVersio

Anticoagulação Oral e Incidência de Acidente Vascular Cerebral Associado a Fibrilhação Auricular em Portugal Continental: Um Estudo de Modelação

Introdução: A fibrilhação auricular é a disritmia persistente mais prevalente, tendo um importante impacto social e económico. O objetivo principal deste estudo foi avaliar a associação entre a utilização de anticoagulantes orais e a incidência de acidente vascular cerebral associado a fibrilhação auricular, em Portugal continental. Métodos: A base de dados de morbilidade hospitalar foi utilizada para a contabilização dos episódios de internamento com um diagnóstico principal de acidente vascular cerebral e um diagnóstico adicional de fibrilhação auricular, ocorridos durante cada mês do período em análise (janeiro de 2012 a dezembro de 2018), em indivíduos com idade igual ou superior a 18 anos. O número de doentes com registo de fibrilhação auricular presentes nesta base de dados foi utilizado como um proxy da prevalência de fibrilhação auricular conhecida. O número de doentes anticoagulados foi estimado a partir das estatísticas das vendas de antagonistas da vitamina K e novos anticoagulantes orais (apixabano, dabigatrano, edoxabano e rivaroxabano) em Portugal continental. Foi realizada uma análise descritiva das variáveis, construindo-se depois modelos auto-regressivos integrados de médias móveis sazonais (seasonal autoregressive integrated moving average, SARIMA), com recurso ao software R. Resultados: Ocorreram, em média, 522 (± 57) episódios de acidente vascular cerebral por mês. Verificou-se um aumento gradual do número de doentes anticoagulados, passando de 68 943 para 180 389, por mês. A tendência decrescente no número de episódios verificou-se a partir de 2016, a par da maior utilização dos novos anticoagulantes orais, comparativamente aos antagonistas da vitamina K. O modelo final estimado indicou que o aumento do consumo de anticoagulação oral entre 2012 e 2018 em Portugal continental foi associado a um decréscimo do número de acidentes vasculares cerebrais associados a fibrilhação auricular. Estimou-se que, entre 2016 e 2018, a mudança no tipo de anticoagulação se associou a uma redução de 833 episódios de acidentes vascular cerebrais em doentes com fibrilhação auricular (4,2%). Conclusão: A anticoagulação oral associou-se à redução da incidência de acidente vascular cerebral em doentes com fibrilhação auricular, em Portugal continental. Esta redução foi mais relevante no período 2016 a 2018, em provável relação com a introdução dos novos anticoagulantes orais

Machine detector interface for the e+e−e^+e^- future circular collider

The international Future Circular Collider (FCC) study aims at a design of $pp$, $e^+e^-$, $ep$ colliders to be built in a new 100 km tunnel in the Geneva region. The $e^+e^-$ collider (FCC-ee) has a centre of mass energy range between 90 (Z-pole) and 375 GeV (tt_bar). To reach such unprecedented energies and luminosities, the design of the interaction region is crucial. The crab-waist collision scheme has been chosen for the design and it will be compatible with all beam energies. In this paper we will describe the machine detector interface layout including the solenoid compensation scheme. We will describe how this layout fulfills all the requirements set by the parameters table and by the physical constraints. We will summarize the studies of the impact of the synchrotron radiation, the analysis of trapped modes and of the backgrounds induced by single beam and luminosity effects giving an estimate of the losses in the interaction region and in the detector.Comment: 6 pages, 7 figures, 62th ICFA ABDW on High Luminosity Circular $e^+e^-$ Colliders, eeFACT2018, Hong Kong, Chin

A gene expression assay based on chronic lymphocytic leukemia activation in the microenvironment to predict progression

Gene expression; Chronic lymphocytic leukemiaExpresión génica; Leucemia linfocítica crónicaExpressió gènica; Leucèmia limfocítica crònicaSeveral gene expression profiles with a strong correlation with patient outcomes have been previously described in chronic lymphocytic leukemia (CLL), although their applicability as biomarkers in clinical practice has been particularly limited. Here we describe the training and validation of a gene expression signature for predicting early progression in patients with CLL based on the analysis of 200 genes related to microenvironment signaling on the NanoString platform. In the training cohort (n = 154), the CLL15 assay containing a 15-gene signature was associated with the time to first treatment (TtFT) (hazard ratio [HR], 2.83; 95% CI, 2.17-3.68; P < .001). The prognostic value of the CLL15 score (HR, 1.71; 95% CI, 1.15-2.52; P = .007) was further confirmed in an external independent validation cohort (n = 112). Notably, the CLL15 score improved the prognostic capacity over IGHV mutational status and the International Prognostic Score for asymptomatic early-stage (IPS-E) CLL. In multivariate analysis, the CLL15 score (HR, 1.83; 95% CI, 1.32-2.56; P < .001) and the IPS-E CLL (HR, 2.23; 95% CI, 1.59-3.12; P < .001) were independently associated with TtFT. The newly developed and validated CLL15 assay successfully translated previous gene signatures such as the microenvironment signaling into a new gene expression–based assay with prognostic implications in CLL.This work was supported by research funding from the Asociación Española Contra el Cáncer grant [5U01CA157581-05, ECRIN-M3 - A29370] and in part by the Instituto de Salud Carlos III, Fondo de Investigaciones Sanitarias [PI17/00950, M.C., PI17/00943, F.B, PI18/01392, P.A.], and the Spanish Ministry of Economy and Competitiveness [CIBERONC-CB16/12/00233], the Education Council or Health Council of the Junta de Castilla y León [GRS 2036/A/19], and Gilead Sciences [GLD15/00348]. This work was supported by research funding from the Asociación Española Contra el Cáncer grant [5U01CA157581-05, ECRIN-M3 - A29370] and in part by the Instituto de Salud Carlos III, Fondo de Investigaciones Sanitarias [PI17/00950, M.C., PI17/00943, F.B, PI18/01392, P.A.], and the Spanish Ministry of Economy and Competitiveness [CIBERONC-CB16/12/00233], the Education Council or Health Council of the Junta de Castilla y León [GRS 2036/A/19], Gilead Sciences [GLD15/00348] and Gilead Fellowships [GLD16/00144, GLD18/00047, F.B.], and Fundació la Marató de TV3 [201905-30-31 F.B]. All Spanish funding was cosponsored by the European Union FEDER program “Una manera de hacer Europa”. M.C. holds a contract from Ministerio de Ciencia, Innovación y Universidades [RYC-2012-2018]