A Nobel Day in Lisbon, Portugal – A Unique Experience for Someone who Loves Science

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Leucemia linfocítica crónica: fisiopatologia, diagnóstico e abordagens terapêuticas

Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2017A leucemia linfocítica crónica (LLC) é uma doença linfoproliferativa caracterizada pela acumulação de células B CD5+ no sangue, medula óssea e gânglios linfáticos. O mecanismo fisiopatológico da doença pode envolver não só a via de sinalização do BCR, como também alterações genéticas e alterações no balanço entre a apoptose e a proliferação celular. O curso clínico da LLC é muito heterogéneo, enquanto que a maior parte dos doentes segue um curso indolente da doença, outros expressam um curso clínico rápido e agressivo, requerendo uma terapia precoce. Nos últimos anos verificou-se uma evolução bastante significativa na compreensão da doença, determinando-se novos fatores de prognóstico (deleções, CD38, ZAP-70), melhorando a classificação do estadiamento da doença e também através da descoberta de novos agentes terapêuticos, que têm como alvo vias de sinalização fundamentais. Muitos destes novos agentes terapêuticos ainda se encontram em fase de ensaios clínicos, mas, no futuro, podem ser o passo necessário para a cura da doença.Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disorder characterized by the accumulation of CD5+ B cells in the blood, bone marrow and lymph nodes. The pathogenesis of CLL may involve not only the signaling pathway of BCR but also genetic alterations and alterations in the balance between apoptosis and cell proliferation. The clinical course of CLL is very heterogeneous: while most patients follow an indolent course of disease, others experience rapid and aggressive clinical course requiring early therapy. The understanding of the disease has considerably evolved in the last years determining new prognostic factors (deletions, CD38, ZAP-70), improving the classification of the disease stage and also through the determination of new therapeutic agents, which target important signaling pathways. Many of these new therapeutic agents are still in clinical trial phase but in the future may be the necessary step for curing the disease

Spin-coated polysaccharide-based multilayered freestanding films with adhesive and bioactive moieties

Freestanding films based on catechol functionalized chitosan (CHI), hyaluronic acid (HA), and bioglass nanoparticles (BGNPs) were developed by spin-coating layer-by-layer assembly (SA-LbL). The catechol groups of 3,4-dihydroxy-l-phenylalanine (DOPA) present in the marine mussels adhesive proteins (MAPs) are the main factors responsible for their characteristic strong wet adhesion. Then, the produced films were cross-linked with genipin to improve their stability in wet state. Overall, the incorporation of BGNPs resulted in thicker and bioactive films, hydrophilic and rougher surfaces, reduced swelling, higher weight loss, and lower stiffness. The incorporation of catechol groups onto the films showed a significant increase in the films’ adhesion and stiffness, lower swelling, and weight loss. Interestingly, a synergetic effect on the stiffness increase was observed upon the combined incorporation of BGNPs with catechol-modified polymers, given that such films were the stiffest. Regarding the biological assays, the films exhibited no negative effects on cellular viability, adhesion, and proliferation, and the BGNPs seemed to promote higher cellular metabolic activity. These bioactive LbL freestanding films combine enhanced adhesion with improved mechanical properties and could find applications in the biomedical field, such as guided hard tissue regeneration membranes.This research was funded by the Portuguese Foundation for Science and Technology (FCT) and the European program FEDER/FEEI (PTDC/BTM-MAT/28123/2017 and PTDC/NAN-MAT/31036/2017) and FCT (MIT-EXPL/BIO/0089/2017).The authors acknowledge the Portuguese Foundation for Science and Technology (FCT) and the European program FEDER/FEEI for the financial support through projects PTDC/BTM-MAT/28123/2017 and PTDC/NAN-MAT/31036/2017. The authors also acknowledge FCT for the financial support through the exploratory project MIT-EXPL/BIO/0089/2017

Comparative analysis of impacted upper canines : panoramic radiograph vs cone beam computed tomography

Background: The use of CBCT exam in the study of IMC is not new. However, it?s still not known in what specific aspects CBCT exam shows a better result than then conventional exams. The aim of this study was to compare and conclude in what way the opinion regarding upper canine impaction differed when observing a panoramic image compared to the observation of a set of CBCT reconstructions. Materials and Methods: Twenty patients (10 males and 10 females) with a total of 28 impacted maxillary canines were identified from the database of the Department of Dentistry, Faculty of Medicine, University of Coimbra. For each canine, two different images were available: a panoramic image and a set of CBCT reconstructions. After a random distribution of both groups images, nine orthodontists completed a questionnaire where they were asked to evaluate ten different questions regarding canine impaction. Statistic analysis was performed using Cronbach?s alpha statistics, Kappa statistics and McNemar test, considering p<0,05 statistically significant. Results: This study showed differences between the two images regarding tooth position. A statistical significant poor agreement was found between the two methods for the mesio-distal position of the apex (k=0,388, p<0,001) and for the labio-palatal tip cusp position (k=0,035, p=0,114). The adjacent root resorption showed a poor and very poor agreement between the two methods. Every other items were scored with an agreement between modalities ranging from moderate to strong. Conclusions: The analyses of panoramic images versus CBCT images reconstructions provided different information regarding tooth position (especially concerning the mesio-distal apex position and the labio-palatal cusp position) but also in the assessment of root resorption. Further investigation should be done to determine in what cases CBCT exam has a clear advantage over conventional 2D exams, justifying its us

Poly(lactic acid)/graphite nanoplatelet nanocomposite filaments for ligament scaffolds

The anterior cruciate ligament (ACL) is one of the most prone to injury in the human body. Due to its insufficient vascularization and low regenerative capacity, surgery is often required when it is ruptured. Most of the current tissue engineering (TE) strategies are based on scaffolds produced with fibers due to the natural ligamentâ s fibrous structure. In the present work, composite filaments based on poly(L-lactic acid) (PLA) reinforced with graphite nanoplatelets (PLA+EG) as received, chemically functionalized (PLA+f-EG), or functionalized and decorated with silver nanoparticles [PLA+((f-EG)+Ag)] were produced by melt mixing, ensuring good filler dispersion. These filaments were produced with diameters of 0.25 mm and 1.75 mm for textile-engineered and 3D-printed ligament scaffolds, respectively. The resulting composite filaments are thermally stable, and the incorporation of graphite increases the stiffness of the composites and decreases the electrical resistivity, as compared to PLA. None of the filaments suffered significant degradation after 27 days. The composite filaments were processed into 3D scaffolds with finely controlled dimensions and porosity by textile-engineered and additive fabrication techniques, demonstrating their potential for ligament TE applications.This research was funded by FCT through the National Funds Reference UIDB/05256/2020 and UIDP/05256/2020, the FCT and European Program FEDER/COMPETE through the project PTDC/BTM-MAT/28123/2017, and the FCT, European Union and European Social Fund (FSE) through the PhD Grant Reference SFRH/BD/138244/2018

3D‐printed cryomilled poly(ε‐caprolactone)/graphene composite scaffolds for bone tissue regeneration

In this study, composite scaffolds based on poly(caprolactone) (PCL) and non-covalently functionalized few-layer graphene (FLG) were manufactured by an extrusion-based system for the first time. For that, functionalized FLG powder was obtained through the evaporation of a functionalized FLG aqueous suspension prepared from a graphite precursor. Cryomilling was shown to be an efficient mixing method, producing a homogeneous dispersion of FLG particles onto the PCL polymeric matrix. Thereafter, fused deposition modeling (FDM) was used to print 3D scaffolds and their morphology, thermal, biodegradability, mechanical, and cytotoxicity properties were analysed. The presence of functionalized FLG demonstrated to induce slight changes in the microstructure of the scaffold, did not affect the thermal stability and enhanced significantly the compressive modulus. The composite scaffolds presented a porosity of around 40% and a mean pore size in the range of 300 μm. The cell viability and proliferation of SaOs-2 cells were assessed and the results showed good cell viability and long-term proliferation onto produced composite scaffolds. Therefore, these new FLG/PCL scaffolds comprised adequate morphological, thermal, mechanical, and biological properties to be used in bone tissue regeneration.The authors acknowledge the Portuguese Foundation for Science and Technology (FCT), the European program FEDER/COMPETE for the financial support through project LA ICVS/3Bs - 2015-2017 and to IPC (UID/CTM/50025/2013 and UID/CTM/50025/2016), and the scholarship SFRH/BD/87214/2012 granted to Eunice Cunha. Daniela Dias acknowledges the mobility grant from the BEAM project- Biomedical Engineering-EU Australian cooperation at master level, ICIECP Education Cooperation Programme (388414-EM-January 1, 2014-IT-ERA MUNDUS-ICIJMP). We also acknowledge Prof. Dietmar W. Hutmacher that kindly hosts Daniela Dias in the IHBI laboratory

Dilemas da Sialoadenite Esclerosante Crónica: Um Caso Clínico e Revisão da Literatura

Reporta-se um caso clínico de sialoadenite esclerosante crónica focando aspetos clínicos, laboratoriais e histológicos, e realiza-se uma revisão da literatura com discussão da abordagem clínica multidisciplinar desta patologia. A sialoadenite esclerosante crónica é uma doença inflamatória crónica, incomum, que se integrou recentemente no espectro de doenças associadas à IgG4. Esta patologia simula patologia neoplásica cervical e o seu diagnóstico definitivo é difícil. A sua etiologia, tratamento e evolução são na atualidade temas de debate científico

An antisense transcript mediates MALAT1 response in human breast cancer

© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: Long non-coding RNAs (lncRNAs) represent a substantial portion of the human transcriptome. LncRNAs present a very stringent cell-type/tissue specificity being potential candidates for therapeutical applications during aging and disease. As example, targeting of MALAT1, a highly conserved lncRNA originally identified in metastatic non-small cell lung cancer, has shown promising results in cancer regression. Nevertheless, the regulation and specificity of MALAT1 have not been directly addressed. Interestingly, MALAT1 locus is spanned by an antisense transcript named TALAM1. Methods: Here using a collection of breast cancer cells and in vitro and in vivo migration assays we characterized the dynamics of expression and demonstrated that TALAM1 regulates and synergizes with MALAT1 during tumorigenesis. Results: Down-regulation of TALAM1 was shown to greatly impact on the capacity of breast cancer cells to migrate in vitro or to populate the lungs of immunocompromised mice. Additionally, we demonstrated that TALAM1 cooperates with MALAT1 in the regulation of the properties guiding breast cancer aggressiveness and malignancy. Conclusions: By characterizing this sense/anti-sense pair we uncovered the complexity of MALAT1 locus regulation, describing new potential candidates for cancer targeting.This work was supported by Fundação para a Ciência e Tecnologia (FCT) (PTDC/BIM-MED/0032/2014); UID/BIM/50005/2019, project funded by Fundação para a Ciência e a Tecnologia (FCT)/ Ministério da Ciência, Tecnologia e Ensino Superior (MCTES) through Fundos do Orçamento de Estado; LISBOA-01-0145-FEDER-016394, projeto cofinanciado pelo FEDER através POR Lisboa 2020 - Programa Operacional Regional de Lisboa, do PORTUGAL 2020 e pela Fundação para a Ciência e a Tecnologia; LISBOA-01-0145-FEDER-028534, projeto cofinanciado pelo FEDER através POR Lisboa 2020 - Programa Operacional Regional de Lisboa, do PORTUGAL 2020 e pela Fundação para a Ciência e a Tecnologia. B.B.J. was an FCT Investigator (IF/00166/2014). C.V. was a Gulbenkian Foundation Fellow. S.N.-P. was recipient of an individual FCT postdoctoral fellowship (SFRH/BPD/91159/2012).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