Residual granitic soil improvement for rammed earth construction

This paper describes the research developed to evaluate the performance of stabilised residual granitic soil from the north region of Portugal. It is part of a research project designed to investigate the possibility of using this soil for rammed earth construction. Since its reduced plasticity makes the use of lime less effective, and the increasing environmental concerns with cement production can no longer be ignored, the study was focused on binders made from alkaline activation of low calcium fly ash. Therefore, the aim of this work was to determine, through a parametric analysis using laboratory tests, the optimum fly ash – based alkaline activated binder for improving granitic soil, in terms of mechanical strength. Identification of the key parameters allowed the characterisation of the most effective mixtures, which will be later used in the construction of large rammed earth wall panels that will be tested according to proper specifications

Plasmonic/magnetic liposomes based on nanoparticles with multicore-shell architecture for chemo/thermotherapy

In this work, multicore magnetic nanoparticles (NPs) of manganese ferrite were prepared using carboxymethyl-dextran and melamine as agglutinating agents.Magnetoliposome-like structures containing the multicore NPs exhibit sizes in the range 250 – 400 nm, being suitable for biomedical applications.FCT under Strategic funding of CF-UM-UP (UIDB/04650/2020

Biopolymer films doped with silver(I) coordination polymers against bacterial biofilms

This report describes a template-mediated self-assembly synthesis, full characterization, and structural features of two new silver-based bioactive coordination polymers (CPs) as well their immobilization into acrylated epoxidized soybean oil (ESOA) biopolymer films for antimicrobial applications. The 3D silver(I) CPs [Ag4(8-H2pma)2]n·4nH2O (1) and [Ag5(6-H0.5tma)2(H2O)4]n·2nH2O (2) were generated from AgNO3 and pyromellitic (H4pma) or trimesic (H3tma) acid, also using N,N-dimethylethanolamine (Hdmea) as a template. Both 1 and 2 feature the intricate 3D layer-pillared structures driven by distinct polycarboxylate blocks. Topological analysis revealed binodal nets with the flu and tcj/hc topology in 1 and 2, respectively. These CPs were used to create new hybrid materials, namely by doping the [ESOA]n biopolymer films with very low amounts of 1 and 2 (0.05, 0.1, and 0.5%). Their antimicrobial activity and ability to inhibit bacterial biofilm formation was investigated in detail against both Gram-positive (Staphylococcus epidermidis and Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa and Escherichia coli) bacteria. Both silver(I) coordination polymers and derived biopolymer films showed activity against all the tested bacteria in a concentration dependent manner. Compound 1 was far more active, especially in preventing biofilm formation, with mean bacterial load reductions ranging from 3.7 to 4.3 log against the four bacteria (99.99% bacterial eradication). Thus, the present study expands the antibiofilm applications of CP-doped biopolymers, offering new perspectives and promising results for the design of functional biomaterials (Scheme 1).This work was supported by the Foundation for Science and Technology (FCT) and Portugal 2020 (projects PTDC/QUI-QIN/29697/2017, LISBOA-01-0145-FEDER-029697, UIDB/00100/2020, UIDP/00100/2020, IPL/2020/HyBioPol and REM2013), contracts CEECIND/02725/2018 and CEECIND/00194/2020.info:eu-repo/semantics/publishedVersio

Cancer Theranostic Dyes

Funding Information: This work was financed by national funds from FCT—Fundação para a Ciência e a Tecnologia, I.P., within the scope of the projects of the Ministry of Science Technology and Higher Education: UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences—UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB and, in part, by the Jeanne and J.-Louis Lévesque foundation, Montreal, QC, Canada (J.E.v.L.). J.E.v.L. is a member of the Research Center of the CHUS (CRCHUS), Sherbrooke, QC, Canada, supported by the Fonds de la Recherche du Québec—Santé. C.R.R., A.L. and R.V. were funded by FCT/MCTES, grant numbers SFRH/BPD/124612/2016, SFRH/BD/12161/2022, and SFRH/BD/09845/2022, respectively. Publisher Copyright: © 2023 by the authors.Estradiol-BODIPY linked via an 8-carbon spacer chain and 19-nortestosterone- and testosterone-BODIPY linked via an ethynyl spacer group were evaluated for cell uptake in the breast cancer cell lines MCF-7 and MDA-MB-231 and prostate cancer cell lines PC-3 and LNCaP, as well as in normal dermal fibroblasts, using fluorescence microscopy. The highest level of internalization was observed with 11β-OMe-estradiol-BODIPY 2 and 7α-Me-19-nortestosterone-BODIPY 4 towards cells expressing their specific receptors. Blocking experiments showed changes in non-specific cell uptake in the cancer and normal cells, which likely reflect differences in the lipophilicity of the conjugates. The internalization of the conjugates was shown to be an energy-dependent process that is likely mediated by clathrin- and caveolae-endocytosis. Studies using 2D co-cultures of cancer cells and normal fibroblasts showed that the conjugates are more selective towards cancer cells. Cell viability assays showed that the conjugates are non-toxic for cancer and/or normal cells. Visible light irradiation of cells incubated with estradiol-BODIPYs 1 and 2 and 7α-Me-19-nortestosterone-BODIPY 4 induced cell death, suggesting their potential for use as PDT agents.publishersversionpublishe

Magnetoliposomes containing multicore nanoparticles and a new antitumor thienopyridine compound with potential application in chemo/thermotherapy

Multicore magnetic nanoparticles of manganese ferrite were prepared using carboxymethyl dextran as an agglutinating compound or by an innovative method using melamine as a cross-coupling agent. The nanoparticles prepared using melamine exhibited a flower-shape structure, a saturation magnetization of 6.16 emu/g and good capabilities for magnetic hyperthermia, with a specific absorption rate (SAR) of 0.14 W/g. Magnetoliposome-like structures containing the multicore nanoparticles were prepared, and their bilayer structure was confirmed by FRET (Förster Resonance Energy Transfer) assays. The nanosystems exhibited sizes in the range of 250–400 nm and a low polydispersity index. A new antitumor thienopyridine derivative, 7-[4-(pyridin-2-yl)-1H-1,2,3-triazol-1-yl]thieno[3,2-b]pyridine, active against HeLa (cervical carcinoma), MCF-7 (breast adenocarcinoma), NCI-H460 (non-small-cell lung carcino-ma) and HepG2 (hepatocellular carcinoma) cell lines, was loaded in these nanocarriers, obtaining a high encapsulation efficiency of 98% ± 2.6%. The results indicate that the new magnetoliposomes can be suitable for dual cancer therapy (combined magnetic hyperthermia and chemotherapy).This research was funded by the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding of CF-UM-UP (UIDB/04650/2020) and through the research project PTDC/QUI-QFI/28020/2017 (POCI-01-0145-FEDER-028020), financed by the European Fund of Regional Development (FEDER), COMPETE2020, and Portugal2020. J.M.R. acknowledges FCT, ESF (European Social Fund—North Portugal Regional Operational Program) and HCOP (Human Capital Operational Program) for a PhD grant (SFRH/BD/115844/2016)

The cdh1 c.1901c>t variant: A founder variant in the portuguese population with severe impact in mrna splicing

Hereditary diffuse gastric cancer (HDGC) caused by CDH1 variants predisposes to early-onset diffuse gastric (DGC) and lobular breast cancer (LBC). In Northern Portugal, the unusually high number of HDGC cases in unrelated families carrying the c.1901C>T variant (formerly known as p.A634V) suggested this as a CDH1-founder variant. We aimed to demonstrate that c.1901C>T is a bona fide truncating variant inducing cryptic splicing, to calculate the timing of a potential founder effect, and to characterize tumour spectrum and age of onset in carrying families. The impact in splicing was proven by using carriers’ RNA for PCR-cloning sequencing and allelic expression imbalance analysis with SNaPshot. Carriers and noncarriers were haplotyped for 12 polymorphic markers, and the decay of haplotype sharing (DHS) method was used to estimate the time to the most common ancestor of c.1901C>T. Clinical information from 58 carriers was collected and analysed. We validated the cryptic splice site within CDH1-exon 12, which was preferred over the canonical one in 100% of sequenced clones. Cryptic splicing induced an out-of-frame 37bp deletion in exon 12, premature truncation (p.Ala634ProfsTer7), and consequently RNA mediated decay. The haplotypes carrying the c.1901C>T variant were found to share a common ancestral estimated at 490 years (95% Confidence Interval 445–10,900). Among 58 carriers (27 males (M)–31 females (F); 13–83 years), DGC occurred in 11 (18.9%; 4M–7F; average age 33 ± 12) and LBC in 6 females (19.4%; average age 50 ± 8). Herein, we demonstrated that the c.1901C>T variant is a loss-of-function splice-site variant that underlies the first CDH1-founder effect in Portugal. Knowledge on this founder effect will drive genetic testing of this specific variant in HDGC families in this geographical region and allow intrafamilial penetrance analysis and better estimation of variant-associated tumour risks, disease age of onset, and spectrum.This research and its authors were funded by FEDER—Fundo Europeu de Desenvolvi-mento Regional funds through the COMPETE 2020—Operational Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT—Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274) and LEGOH (PTDC/BTM-TEC/6706/2020). This work was also financed by the projects NORTE-01-0145-FEDER-000003 (DOCnet)—supported by Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF)—project POCI-01-0145-FEDER-016390 (CancelStem) and PTDC/BTM-TEC/30164/2017 (3DChroMe), funded by ERDF, POCI, and FCT

The Portuguese Society of Rheumatology position paper on the use of biosimilars

Biotechnological drugs have become a fundamental resource for the treatment of rheumatic patients. Patent expiry of some of these drugs created the opportunity for biopharmaceutical manufacturers to develop biosimilar drugs intended to be as efficacious as the originator product but with a lower cost to healthcare systems. Due to the complex manufacturing process and highly intricate structure of biologicals, a biosimilar can never be an exact copy of its reference product. Consequently, regulatory authorities issued strict preclinical and clinical guidelines to ensure safety and efficacy equivalence and, in September 2013, the biosimilar of infliximab was the first biosimilar monoclonal antibody to be authorized for use in the European Union. The current document is a position statement of the "Sociedade Portuguesa de Reumatologia" (Portuguese Society of Rheumatology) on the use of biosimilar drugs in rheumatic diseases. Two systematic literature reviews were performed, one concerning clinical trials and the other one concerning international position papers on biosimilars. The results were presented and discussed in a national meeting and a final position document was discussed, written and approved by Portuguese rheumatologists. Briefly, this position statement is contrary to automatic substitution of the originator by the biosimilar, defends either a different INN or the prescription by brand name, supports that switching between biosimilars and the originator molecule should be done after at least 6 months of treatment and based on the attending physician decision and after adequate patient information, recommends the registration of all biosimilar treated patients in Reuma.pt for efficacy, safety and immunogenicity surveillance, following the strategy already ongoing for originators, and opposes to extrapolation of indications approved to the originator to completely different diseases and/or age groups without adequate pre-clinical, safety or efficacy data.info:eu-repo/semantics/publishedVersio

Seasonal Variation in Vitamin D3 Levels Is Paralleled by Changes in the Peripheral Blood Human T Cell Compartment

It is well-recognized that vitamin D3 has immune-modulatory properties and that the variation in ultraviolet (UV) exposure affects vitamin D3 status. Here, we investigated if and to what extent seasonality of vitamin D3 levels are associated with changes in T cell numbers and phenotypes. Every three months during the course of the entire year, human PBMC and whole blood from 15 healthy subjects were sampled and analyzed using flow cytometry. We observed that elevated serum 25(OH)D3 and 1,25(OH)2D3 levels in summer were associated with a higher number of peripheral CD4+ and CD8+ T cells. In addition, an increase in naïve CD4+CD45RA+ T cells with a reciprocal drop in memory CD4+CD45RO+ T cells was observed. The increase in CD4+CD45RA+ T cell count was a result of heightened proliferative capacity rather than recent thymic emigration of T cells. The percentage of Treg dropped in summer, but not the absolute Treg numbers. Notably, in the Treg population, the levels of forkhead box protein 3 (Foxp3) expression were increased in summer. Skin, gut and lymphoid tissue homing potential was increased during summer as well, exemplified by increased CCR4, CCR6, CLA, CCR9 and CCR7 levels. Also, in summer, CD4+ and CD8+ T cells revealed a reduced capacity to produce pro-inflammatory cytokines. In conclusion, seasonal variation in vitamin D3 status in vivo throughout the year is associated with changes in the human peripheral T cell compartment and may as such explain some of the seasonal variation in immune status which has been observed previously. Given that the current observations are limited to healthy adult males, larger population-based studies would be useful to validate these findings