Caracterização do receptor peroxissomal PEX5P : Desenvolvimento de um sistema de importação proteica in vitro

Dissertação de Doutoramento em Ciências Biomédicas apresentada ao Instituto de Ciências Biomédicas de Abel Salazar da Universidade do Port

Association between respiratory hospital admissions and air quality in Portugal: a count time series approach

Although regulatory improvements for air quality in the European Union have been made, air pollution is still a pressing problem and, its impact on health, both mortality and morbidity, is a topic of intense research nowadays. The main goal of this work is to assess the impact of the exposure to air pollutants on the number of daily hospital admissions due to respiratory causes in 58 spatial locations of Portugal mainland, during the period 2005-2017. To this end, INteger Generalised AutoRegressive Conditional Heteroskedastic (INGARCH)-based models are extensively used. This family of models has proven to be very useful in the analysis of serially dependent count data. Such models include information on the past history of the time series, as well as the effect of external covariates. In particular, daily hospitalisation counts, air quality and temperature data are endowed within INGARCH models of optimal orders, where the automatic inclusion of the most significant covariates is carried out through a new block-forward procedure. The INGARCH approach is adequate to model the outcome variable (respiratory hospital admissions) and the covariates, which advocates for the use of count time series approaches in this setting. Results show that the past history of the count process carries very relevant information and that temperature is the most determinant covariate, among the analysed, for daily hospital respiratory admissions. It is important to stress that, despite the small variability explained by air quality, all models include on average, approximately two air pollutants covariates besides temperature. Further analysis shows that the one-step-ahead forecasts distributions are well separated into two clusters: one cluster includes locations exclusively in the Lisbon area (exhibiting higher number of one-step-ahead hospital admissions forecasts), while the other contains the remaining locations. This results highlights that special attention must be given to air quality in Lisbon metropolitan area in order to decrease the number of hospital admissions.publishe

Resveratrol Attenuates Copper-Induced Senescence by Improving Cellular Proteostasis

Copper sulfate-induced premature senescence (CuSO 4 -SIPS) consistently mimetized molecular mechanisms of replicative senescence, particularly at the endoplasmic reticulum proteostasis level. In fact, disruption of protein homeostasis has been associated to age-related cell/tissue dysfunction and human disorders susceptibility. Resveratrol is a polyphenolic compound with proved antiaging properties under particular conditions. In this setting, we aimed to evaluate resveratrol ability to attenuate cellular senescence induction and to unravel related molecular mechanisms. Using CuSO 4 -SIPS WI-38 fibroblasts, resveratrol is shown to attenuate typical senescence alterations on cell morphology, senescence-associated beta-galactosidase activity, and cell proliferation. The mechanisms implicated in this antisenescence effect seem to be independent of senescence-associated genes and proteins regulation but are reliant on cellular proteostasis improvement. In fact, resveratrol supplementation restores copperinduced increased protein content, attenuates BiP level, and reduces carbonylated and polyubiquitinated proteins by autophagy induction. Our data provide compelling evidence for the beneficial effects of resveratrol by mitigating CuSO 4 -SIPS stressful consequences by the modulation of protein quality control systems. These findings highlight the importance of a balanced cellular proteostasis and add further knowledge on molecular mechanisms mediating resveratrol antisenescence effects. Moreover, they contribute to identifying specific molecular targets whose modulation will prevent age-associated cell dysfunction and improve human healthspan

The role of the atmospheric aerosol in weather forecasts for the Iberian Peninsula: investigating the direct effects using the WRF-chem model

In the atmosphere, aerosols play an important role in climate change, the Earth’s environment and human health. The purpose of this study is to investigate the direct and semi-direct aerosol effects on weather forecasting, focusing on the Iberian Peninsula (IP). To that end, two Weather Research and Forecasting (WRF)-Chem simulations (with and without aerosol feedback) for an entire year (2015) were performed. The model setup includes two nested domains run in two-way mode, allowing the downscaling for the IP domain at a 5 × 5 km2 high-horizontal resolution. The results were explored through agreement of pairs of time series and their spatial variability in order to analyse the importance of including the online-coupled aerosol radiative effect on the meteorological variables: shortwave (solar) radiation, air temperature and precipitation. Significant variations of agreement were found when capturing both temporal and spatial patterns of the analysed meteorological variables. While the spatial distribution of temperature and precipitation is similar throughout the IP domain, with agreement values ranging from 0.87 up to 1.00, the solar radiation presents a distinct spatial pattern with lower agreement values (0.68–0.75) over ocean and higher agreement (0.75–0.98) over land regions. With regard to the spatial differences between simulations, the aerosol contributed to a considerable decrease in annual mean and maximum radiation (up to 20 and 40 Wm−2, respectively), slightly impacting the temperature variation (up to 0.5 °C). These results suggest that the aerosol feedback effects should be accounted when performing weather forecasts, and not only for purposes of air quality assessment.publishe

Investigating ozone episodes in Portugal: a wavelet-based approach

During the summer season, ozone concentrations regularly exceed the legislation limits in the North of Portugal, namely at Douro Norte monitoring station. The origin of such ozone episodes has been widely reported in several studies although uncertainties regarding its origin still remain. This work intends to investigate how the ozone concentrations measured at the Douro Norte nearest stations, located at west and east directions, are related to those measured at Douro Norte by means of coherence and phase transformations methods. The episodes were selected according to the magnitude of the hourly ozone peaks and the occurrence of exceedances of the threshold value at least in two sites. The results point out that 60 % of the selected episodes highlight significant dependence between Douro Norte station and the other two monitoring sites, with different phase signal and a delay range from 2 to 4 h.The authors wish to thank the financial support of the Comiss˜ao de Coordenac¸ ˜ao e Desenvolvimento Regional do Norte (CCDR-N). Thanks are extended to the Portuguese Foundation for Science and Technology for the financial support through the Project MAPLIA (PTDC/AAG-MAA/4077/2012), and the PhD grant of Carla Gama (SFRH/BD/87468/2012) and the Pos-Doc grant of S. Gouveia (SFRH/-BPD/87037/2012), and CIDMA/UA project PEst- OE/MAT/UI4106/2014 (Centro de Investigac¸ ˜ao e Desenvolvimento em Matem´atica e Aplicac¸ ˜oes, CIDMA/UA, Aveiro, www.cidma.mat. ua.pt), and IEETA/UA project PEst-OE/EEI/-UI0127/2014 (Instituto de Engenharia Electr´onica e Telem´atica de Aveiro, IEETA/UA, Aveiro, www.ieeta.pt).info:eu-repo/semantics/publishedVersio

INTERNAL CAROTID PSEUDOANEURYSM CAUSED BY MIGRATION OF A CORONARY GUIDEWIRE FRAGMENT: A CASE OF A BROKEN ARROW

Introduction: Guidewire fracture is a rare complication of percutaneous coronary intervention (PCI). Retained fragments can cause thrombosis, dissection, perforation of the vessel or embolize. When is impossible to withdraw or to trap the fragment during the procedure, management is debatable between surgical removal or conservative approach. When choosing to leave the fragment in place, the patient remains at risk for all of the aforementioned complications.  Clinical Case: 65-year-old male patient submitted to PCI with stenting of distal right coronary artery in 2017. A proximal optimization technique was performed, with a guidewire placed in the posterior descending artery (PDA). After stenting, the protection guidewire became entrapped and after several retrieval attempts, it fractured. Wire fragment remained within the RCA and ascending aorta with a free mobile distal part in the beginning of the innominate artery. Multiple attempts went in vain for wire retrieval and a conservative approach was adopted. Two and a half years later, the patient felt a sudden chest pain and then collapsed. He was transferred to our Hospital for emergent surgery due to cardiac tamponade. Intra-operatively, cardiac surgeons found the guidewire perforating the posterior descending artery. When trying to pull it out, the guidewire fractured again. Post-intervention CTA revealed migration of the fragmented guidewire now it was entrapped in a tortuous initial portion of the right internal carotid artery and a small pseudoaneurysm was visible at the distal portion of the wire. Surgical approach was performed revealing the presence of the wire within the carotid medial wall, in a subintimal plane. The 7 cm fragment was successfully withdrawn, through a common carotid transverse incision. Pseudoaneurismectomy was performed and carotid artery bifurcation reconstruction with internal carotid artery re-implantation into the bifurcation, end-to-end anastomosis. The patient had an uneventful postoperative course.  Conclusion: Although leaving the wire in place remains an option, coronary guidewire fractured fragments can be associated not only with immediate complications but also with potential adverse events in the long run.

A influência da electrolipólise associada ao exercício físico na atividade metabólica

O excesso de gordura abdominal associa-se a patologias cardiometabólicas. A microcorrente poderá ser coadjuvante ao exercício aeróbio na estimulação da lipólise, prevenindo riscos de saúde. O exercício físico aeróbio constitui uma modalidade capaz de diminuir o tecido adiposo, por estimular a lipólise através da elevação do nível de catecolaminas, resultantes do aumento da actividade do sistema nervoso simpático. O tipo de exercício físico mais adequado para consumo predominante de lípidos é o exercício aeróbio prolongado e de intensidade moderada. No entanto, na prática de exercício físico as fontes lipídicas são globais o que sustenta a utilidade de procedimentos que promovam o gasto de gordura localizada na região abdominal. A electrolipólise, que pode ser realizada pela aplicação de microcorrente de baixa frequência, poderá ser usada com este intuito, uma vez que a activação do sistema nervoso simpático, juntamente com a alteração da polaridade da membrana celular dos adipócitos e o aumento do fluxo sanguíneo, parecem ser os responsáveis pela promoção da lipólise e aumento do metabolismo local. Para além destes mecanismos, a microcorrente favorece a degradação de triglicerídeos ao promover a activação das enzimas triglicerídeo lípase e lípase hormono-sensível. Após a hidrólise de triglicerídeos torna-se fulcral o exercício físico para que os ácidos gordos em circulação sejam utilizados como fonte de energia. Porém não existe evidência científica que comprove os efeitos da electrolipólise associada ao exercício físico bem como consenso nos parâmetros que devem ser utilizados para electrolipólise, neste sentido vários estudos tem sido realizados no âmbito da linha de investigação de sistema tegumentar e metabólico da ESTSP

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

Resveratrol Attenuates Copper-Induced Senescence by Improving Cellular Proteostasis

Copper sulfate-induced premature senescence (CuSO4-SIPS) consistently mimetized molecular mechanisms of replicative senescence, particularly at the endoplasmic reticulum proteostasis level. In fact, disruption of protein homeostasis has been associated to age-related cell/tissue dysfunction and human disorders susceptibility. Resveratrol is a polyphenolic compound with proved antiaging properties under particular conditions. In this setting, we aimed to evaluate resveratrol ability to attenuate cellular senescence induction and to unravel related molecular mechanisms. Using CuSO4-SIPS WI-38 fibroblasts, resveratrol is shown to attenuate typical senescence alterations on cell morphology, senescence-associated beta-galactosidase activity, and cell proliferation. The mechanisms implicated in this antisenescence effect seem to be independent of senescence-associated genes and proteins regulation but are reliant on cellular proteostasis improvement. In fact, resveratrol supplementation restores copper-induced increased protein content, attenuates BiP level, and reduces carbonylated and polyubiquitinated proteins by autophagy induction. Our data provide compelling evidence for the beneficial effects of resveratrol by mitigating CuSO4-SIPS stressful consequences by the modulation of protein quality control systems. These findings highlight the importance of a balanced cellular proteostasis and add further knowledge on molecular mechanisms mediating resveratrol antisenescence effects. Moreover, they contribute to identifying specific molecular targets whose modulation will prevent age-associated cell dysfunction and improve human healthspan