Fostering innovation in the treatment of chronic polymicrobial cystic fibrosis-associated infections exploring aspartic acid and succinic acid as ciprofloxacin adjuvants

Cystic fibrosis (CF) disease provokes the accumulation of thick and viscous sputum in the lungs, favoring the development of chronic and polymicrobial infections. Pseudomonas aeruginosa is the main bacterium responsible for these chronic infections, and much of the difficulty involved in eradicating it is due to biofilm formation. However, this could be mitigated using adjuvant compounds that help or potentiate the antibiotic action. Therefore, the main goal of this study was to search for substances that function as adjuvants and also as biofilm-controlling compounds, preventing or dismantling P. aeruginosa biofilms formed in an in vitro CF airway environment. Dual combinations of compounds with subinhibitory (1 and 2 mg/L) and inhibitory concentrations (4 mg/L) of ciprofloxacin were tested to inhibit the bacterial growth and biofilm formation (prophylactic approach) and to eradicate 24-h-old P. aeruginosa populations, including planktonic cells and biofilms (treatment approach). Our results revealed that aspartic acid (Asp) and succinic acid (Suc) restored ciprofloxacin action against P. aeruginosa. Suc combined with 2 mg/L of ciprofloxacin (Suc-Cip) was able to eradicate bacteria, and Asp combined with 4 mg/L of ciprofloxacin (AspCip) seemed to eradicate the whole 24-h-old populations, including planktonic cells and biofilms. Based on biomass depletion data, we noted that Asp induced cell death and Suc seemed somehow to block or reduce the expression of ciprofloxacin resistance. As far as we know, this kind of action had not been reported up till now. The presence of Staphylococcus aureus and Burkholderia cenocepacia did not affect the efficacy of the AspCip and SucCip therapies against P. aeruginosa and, also important, P. aeruginosa depletion from polymicrobial communities did not create a window of opportunity for these species to thrive. Rather the contrary, Asp and Suc also improved ciprofloxacin action against B. cenocepacia. Further studies on the cytotoxicity using lung epithelial cells indicated toxicity of SucCip caused by the Suc. In conclusion, we provided evidences that Asp and Suc could be potential ciprofloxacin adjuvants to eradicate P. aeruginosa living within polymicrobial communities. AspCip and SucCip could be promising therapeutic options to cope with CF treatment failures.This work was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/04469/2020 unit and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020— Programa Operacional Regional do Norte. The authors acknowledge COMPETE2020 and FCT for the project POCI-01-0145-FEDER-029841 and for Scientific Employment Stimulus 2017 (CEECIND/01507/2017) provided to ASinfo:eu-repo/semantics/publishedVersio

Matemática na hora do conto

Este artigo procura realçar que, através da conexão entre a literatura e a matemática, se podem criar situações em que as crianças abordem conceitos matemáticos de uma forma significativa permitindo que as habilidades matemáticas e as de linguagem se desenvolvam em conjunto. Uma das formas mais significativas de se construir conhecimento matemático é resolver problemas e desafios, tão comuns nos contos infantis. Apresentamos duas situações, que se enquadram nesta perspetiva pedagógica. Em ambas as situações foi usado um conto como ponto de partida para a construção de atividades matemáticas e tendo presente uma visão construtivista do ensino da matemática.This article seeks to highlight that, through the connection between literature and mathematics, can create situations where children addressing mathematical concepts in a meaningful way allowing mathematical skills and language develop together. One of the most significant ways to construct mathematical knowledge is to solve problems and challenges, so common in children stories. Here are two situations that fall into this pedagogical perspective. In both cases we used a short story as a starting point for the construction of mathematical activities and bearing a constructivist view of teaching mathematics

Antimicrobial resistance three ways: healthcare crisis, major concepts, and the relevance of biofilms

Worldwide, infections are resuming their role as highly effective killing diseases, as current treatments are failing to respond to the growing problem that is antimicrobial resistance (AMR). The social and economical burden of AMR seems ever rising, with health- and research-related organizations rushing to collaborate on a worldwide scale to find effective solutions. Resistant bacteria are spreading even in first-world nations, being found not only in healthcare-related settings, but also in food and in the environment. In this mini-review, the impact of AMR in healthcare systems and the major bacteria behind it are highlighted. Ecological aspects of AMR evolution and the complexity of its molecular mechanisms are explained. Major concepts, such as intrinsic, acquired, and adaptive resistance, as well as tolerance and heteroresistance, are also clarified. More importantly, the problematic of biofilms and their role in AMR, namely its main resistance and tolerance mechanisms, is elucidated. Finally, some of the most promising anti-biofilm strategies being investigated are reviewed. Much is still to be done regarding the study of AMR and the discovery of new anti-biofilm strategies. Gladly, considerable research on this topic is generated every day and increasingly concerted actions are being engaged globally to try and tackle this problem.This work was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2019 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684) and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte. The authors also acknowledge COMPETE2020 and FCT for the project POCI-01-0145-FEDER-029841, and FCT for the PhD Grants of Andreia Magalhães [grant number SFRH/BD/132165/2017] and Tânia Grainha [grant number SFRH/BD/136544/2018].info:eu-repo/semantics/publishedVersio

Measuring adherence to inhaled control medication in patients with asthma: Comparison among an asthma app, patient self‐report and physician assessment

Background Previous studies have demonstrated the feasibility of using an asthma app to support medication management and adherence but failed to compare with other measures currently used in clinical practice. However, in a clinical setting, any additional adherence measurement must be evaluated in the context of both the patient and physician perspectives so that it can also help improve the process of shared decision making. Thus, we aimed to compare different measures of adherence to asthma control inhalers in clinical practice, namely through an app, patient self-report and physician assessment. Methods This study is a secondary analysis of three prospective multicentre observational studies with patients (≥13 years old) with persistent asthma recruited from 61 primary and secondary care centres in Portugal. Patients were invited to use the InspirerMundi app and register their inhaled medication. Adherence was measured by the app as the number of doses taken divided by the number of doses scheduled each day and two time points were considered for analysis: 1-week and 1-month. At baseline, patients and physicians independently assessed adherence to asthma control inhalers during the previous week using a Visual Analogue Scale (VAS 0–100). Results A total of 193 patients (72% female; median [P25–P75] age 28 [19–41] years old) were included in the analysis. Adherence measured by the app was lower (1 week: 31 [0–71]%; 1 month: 18 [0–48]%) than patient self-report (80 [60–95]) and physician assessment (82 [51–94]) (p 0.05). There was a moderate correlation between patient self-report and physician assessment (ρ = 0.596, p < 0.001). Conclusions Adherence measured by the app was lower than that reported by the patient or the physician. This was expected as objective measurements are commonly lower than subjective evaluations, which tend to overestimate adherence. Nevertheless, the low adherence measured by the app may also be influenced by the use of the app itself and this needs to be considered in future studies.info:eu-repo/semantics/publishedVersio

Patient-physician discordance in assessment of adherence to inhaled controller medication: a cross-sectional analysis of two cohorts

We aimed to compare patient's and physician's ratings of inhaled medication adherence and to identify predictors of patient-physician discordance.(SFRH/BPD/115169/2016) funded by Fundação para a Ciência e Tecnologia (FCT); ERDF (European Regional Development Fund) through the operations: POCI-01-0145-FEDER-029130 ('mINSPIRERS—mHealth to measure and improve adherence to medication in chronic obstructive respiratory diseases—generalisation and evaluation of gamification, peer support and advanced image processing technologies') cofunded by the COMPETE2020 (Programa Operacional Competitividade e Internacionalização), Portugal 2020 and by Portuguese Funds through FCT (Fundação para a Ciência e a Tecnologia).info:eu-repo/semantics/publishedVersio

Ser ou não ser praxado? A teoria da ação planeada como modelo para compreender a participação dos caloiros na praxe académica

The main goal of this study was to investigate the predictors of the freshmen’s intentions to participate in academic hazing. With this goal, we used the theory of planned behavior (Azjen, 1991) which allows an analysis of the relative weight of attitudes, subjective norm, and perceived behavioral control in the intentions to participate in academic hazing. The freshmen who participated in this study (N = 353) filled in a questionnaire. The results supported the theory of planned behavior predictive power, with the attitude and perceived behavioral control as significant predictors of the freshmen’s intentions to participate in academic hazing. The subjective norm was not a significant predictor. The theoretical and social implications of these results are discussed.Com este estudo pretendemos investigar quais são os preditores da intenção de participação dos caloiros na praxe académica. Para tal, recorremos à teoria da ação planeada (Ajzen, 1991) que permite analisar o peso relativo das atitudes, da norma subjetiva, e do controlo comportamental percebido nas intenções de ser praxado. Os participantes, estudantes universitários (N = 353) a frequentar o 1º ano de uma Licenciatura, preencheram um questionário. Os resultados confirmaram o valor preditivo da teoria, tendo sido a atitude e o controlo comportamental percebido preditores significativos da intenção dos caloiros em serem praxados. A norma subjetiva não se mostrou um preditor significativo. As implicações teóricas e sociais destes resultados são discutidas

Identification of clusters of asthma control: A preliminary analysis of the inspirers studies

This work was funded by ERDF (European Regional Development Fund) through the operations: POCI- -01-0145-FEDER-029130 (“mINSPIRERS—mHealth to measure and improve adherence to medication in chronic obstructive respiratory diseases - generalisation and evaluation of gamification, peer support and advanced image processing technologies”) co-funded by the COMPETE2020 (Programa Operacional Competitividade e Internacionalização), Portugal 2020 and by Portuguese Funds through FCT (Fundação para a Ciência e a Tecnologia).© 2020, Sociedade Portuguesa de Alergologia e Imunologia Clinica. All rights reserved. Aims: To identify distinct asthma control clusters based on Control of Allergic Rhinitis and Asthma Test (CARAT) and to compare patients’ characteristics among these clusters. Methods: Adults and adolescents (≥13 years) with persistent asthma were recruited at 29 Portuguese hospital outpatient clinics, in the context of two observational studies of the INSPIRERS project. Demographic and clinical characteristics, adherence to inhaled medication, beliefs about inhaled medication, anxiety and depression, quality of life, and asthma control (CARAT, >24 good control) were collected. Hierarchical cluster analysis was performed using CARAT total score (CARAT-T). Results: 410 patients (68% adults), with a median (percentile 25–percentile 75) age of 28 (16-46) years, were analysed. Three clusters were identified [mean CARAT-T (min-max)]: cluster 1 [27(24-30)], cluster 2 [19(14-23)] and cluster 3 [10(2-13)]. Patients in cluster 1 (34%) were characterised by better asthma control, better quality of life, higher inhaler adherence and use of a single inhaler. Patients in clusters 2 (50%) and 3 (16%) had uncontrolled asthma, lower inhaler adherence, more symptoms of anxiety and depression and more than half had at least one exacerbation in the previous year. Further-more, patients in cluster 3 were predominantly female, had more unscheduled medical visits and more anxiety symp-toms, perceived a higher necessity of their prescribed inhalers but also higher levels of concern about taking these inhalers. There were no differences in age, body mass index, lung function, smoking status, hospital admissions or specialist physician follow-up time among the three clusters. Conclusion: An unsupervised method based on CARAT--T, identified 3 clusters of patients with distinct, clinically meaningful characteristics. The cluster with better asthma control had a cut-off similar to the established in the validation study of CARAT and an additional cut-off seems to distinguish more severe disease. Further research is necessary to validate the asthma control clusters identified.publishersversionpublishe

Morphological and Postural changes in the foot during pregnancy and puerperium : a longitudinal study

The aim of this study is to observe the morphological and postural changes to the foot that take place during pregnancy and the puerperium. Method: In this descriptive, observational, longitudinal study, we analysed 23 pregnant women, with particular attention to morphological and postural aspects of the foot, at three time points during and after pregnancy: in weeks 9-13 of gestation, weeks 32-35 of gestation and weeks 4-6 after delivery. The parameters considered were changes in foot length, the Foot Posture Index (FPI) and the Hernández Corvo Index, which were analysed using a pedigraph and taking into account the Body Mass Index (BMI). The same procedure was conducted in each review. Results: The statistical analyses obtained for each foot did not differ significantly between the three measurement times. A pronator-type footprint was most frequently observed during the third trimester of pregnancy; it was predominantly neutral during the postpartum period. Statistically significant differences between the measurement times were obtained in the right foot for cavus vs. neutral foot type (between the first and third trimesters and also between the first trimester and the puerperium) (in both cases, p < 0.0001). Conclusions: Foot length increases in the third trimester and returns to normal in the puerperium. According to FPI findings, the third trimester of pregnancy is characterised by pronation, while the posture returns to neutrality during the postpartum period. During pregnancy, the plantar arch flattens, and this persists during the puerperium. The incidence of cavus foot increases significantly in the third trimester and in the puerperium

SARS-CoV-2 introductions and early dynamics of the epidemic in Portugal

Genomic surveillance of SARS-CoV-2 in Portugal was rapidly implemented by the National Institute of Health in the early stages of the COVID-19 epidemic, in collaboration with more than 50 laboratories distributed nationwide. Methods By applying recent phylodynamic models that allow integration of individual-based travel history, we reconstructed and characterized the spatio-temporal dynamics of SARSCoV-2 introductions and early dissemination in Portugal. Results We detected at least 277 independent SARS-CoV-2 introductions, mostly from European countries (namely the United Kingdom, Spain, France, Italy, and Switzerland), which were consistent with the countries with the highest connectivity with Portugal. Although most introductions were estimated to have occurred during early March 2020, it is likely that SARS-CoV-2 was silently circulating in Portugal throughout February, before the first cases were confirmed. Conclusions Here we conclude that the earlier implementation of measures could have minimized the number of introductions and subsequent virus expansion in Portugal. This study lays the foundation for genomic epidemiology of SARS-CoV-2 in Portugal, and highlights the need for systematic and geographically-representative genomic surveillance.We gratefully acknowledge to Sara Hill and Nuno Faria (University of Oxford) and Joshua Quick and Nick Loman (University of Birmingham) for kindly providing us with the initial sets of Artic Network primers for NGS; Rafael Mamede (MRamirez team, IMM, Lisbon) for developing and sharing a bioinformatics script for sequence curation (https://github.com/rfm-targa/BioinfUtils); Philippe Lemey (KU Leuven) for providing guidance on the implementation of the phylodynamic models; Joshua L. Cherry (National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health) for providing guidance with the subsampling strategies; and all authors, originating and submitting laboratories who have contributed genome data on GISAID (https://www.gisaid.org/) on which part of this research is based. The opinions expressed in this article are those of the authors and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government. This study is co-funded by Fundação para a Ciência e Tecnologia and Agência de Investigação Clínica e Inovação Biomédica (234_596874175) on behalf of the Research 4 COVID-19 call. Some infrastructural resources used in this study come from the GenomePT project (POCI-01-0145-FEDER-022184), supported by COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation (POCI), Lisboa Portugal Regional Operational Programme (Lisboa2020), Algarve Portugal Regional Operational Programme (CRESC Algarve2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and by Fundação para a Ciência e a Tecnologia (FCT).info:eu-repo/semantics/publishedVersio

MAMMALS IN PORTUGAL : A data set of terrestrial, volant, and marine mammal occurrences in P ortugal

Mammals are threatened worldwide, with 26% of all species being includedin the IUCN threatened categories. This overall pattern is primarily associatedwith habitat loss or degradation, and human persecution for terrestrial mam-mals, and pollution, open net fishing, climate change, and prey depletion formarine mammals. Mammals play a key role in maintaining ecosystems func-tionality and resilience, and therefore information on their distribution is cru-cial to delineate and support conservation actions. MAMMALS INPORTUGAL is a publicly available data set compiling unpublishedgeoreferenced occurrence records of 92 terrestrial, volant, and marine mam-mals in mainland Portugal and archipelagos of the Azores and Madeira thatincludes 105,026 data entries between 1873 and 2021 (72% of the data occur-ring in 2000 and 2021). The methods used to collect the data were: live obser-vations/captures (43%), sign surveys (35%), camera trapping (16%),bioacoustics surveys (4%) and radiotracking, and inquiries that represent lessthan 1% of the records. The data set includes 13 types of records: (1) burrowsjsoil moundsjtunnel, (2) capture, (3) colony, (4) dead animaljhairjskullsjjaws, (5) genetic confirmation, (6) inquiries, (7) observation of live animal (8),observation in shelters, (9) photo trappingjvideo, (10) predators dietjpelletsjpine cones/nuts, (11) scatjtrackjditch, (12) telemetry and (13) vocalizationjecholocation. The spatial uncertainty of most records ranges between 0 and100 m (76%). Rodentia (n=31,573) has the highest number of records followedby Chiroptera (n=18,857), Carnivora (n=18,594), Lagomorpha (n=17,496),Cetartiodactyla (n=11,568) and Eulipotyphla (n=7008). The data setincludes records of species classified by the IUCN as threatened(e.g.,Oryctolagus cuniculus[n=12,159],Monachus monachus[n=1,512],andLynx pardinus[n=197]). We believe that this data set may stimulate thepublication of other European countries data sets that would certainly contrib-ute to ecology and conservation-related research, and therefore assisting onthe development of more accurate and tailored conservation managementstrategies for each species. There are no copyright restrictions; please cite thisdata paper when the data are used in publications.info:eu-repo/semantics/publishedVersio