Calcific uraemic arteriolopathy - A mini-review

Calcific Uraemic Arteriolopathy (CUA) or calciphylaxis, is a thrombotic disorder of skin and subcutaneous tissue which typically presents with painful purpuric nodules that may progress to necrotic ulcers, and is a severe, life-threatening condition. CUA is an uncommon clinical entity that affects mostly haemodialysis (HD) patients. Although the process of vascular calcification was initially thought to be the result of a passive deposition of calcium-phosphate crystals, current knowledge suggests a distinct mechanism, including cellular activity with differentiation of vascular smooth muscle cells (VSMCs) into chondrocyte as well as osteoblast-like cellular phenotypes and deficiencies in calcification inhibitors. Although multiple studies suggest a potential relationship between warfarin and CUA, larger prospective studies are needed in order to better evaluate this association, and randomised controlled trials are needed to assess the benefit of distinct interventions in this setting. In this article the topic of CUA is reviewed based on a clinical case of a 65-year-old man undergoing haemodialysis, who underwent an aortic valve replacement one year earlier, receiving a mechanical heart valve, and who has been under warfarin therapy since the

Acesso aos Cuidados de Saúde: um direito em risco?. Relatório Primavera 2015

Em Portugal a saúde tem a dignidade de ser considerada na Constituição da República (CR), no capítulo dos direitos e deveres sociais (Capítulo II). Aí se afirma que “todos têm direito à proteção da saúde e o dever de a defender e promover” (CR, artº 64, nº 1), balanceando-se assim as responsabilidades do Estado, através do dever de proteção, com as responsabilidades individuais, através do dever de defender e promover a saúde. O Estado assume o seu dever garantindo “o acesso de todos os cidadãos, independentemente da sua condição económica” (CR, artº 64, nº3, al. a). O acesso aos cuidados de saúde constitui-se assim como a forma de o Estado garantir aos cidadãos o direito à saúde

O4 - Exploring the biological properties and regenerative potential of biomaterials using cell culture models

Life expectancy has improved signifcantly and, along with the declining birthrate, has contributed to the aging of populations, especially in industrialized countries. Alas, aging is intrinsically associated with the incidence of health problems including bone and tooth loss that require suitable solutions to support the quality of life. To meet these demands, signifcant research eforts have been undertaken to develop novel biomaterials, both orthopedic and dental implants. The feld of biomaterials for bone tissue engineering is increasingly evolving. The most recent generations of biomaterials have increasingly more activity and interaction with the biological environment and stimulate the regeneration of functional tissue. Natural polymers and compounds have been combined with each other to improve workability and are strategically integrated with ceramics or bioactive glasses to reinforce the structure of the fnal system, thus producing composites with a better mechanical performance. Our research group has been focused on the biological characterization of diferent added-value materials and composites, namely by evaluating their antimicrobial, biocompatibility, and regenerative properties. Some of our recent work results allowed us to conclude that marine fungal extracts, as well as sol–gel-derived bioactive glass nanoparticles, have inhibitory efects on the growth of C. albicans and E. faecalis (main pathogens in persistent root canal infections). Additionally, we have characterized cuttlefsh bone powders for endodontic applications. We are also committed to developing strategies for monitoring cell response to these biomaterials at the molecular level that could be used to follow infammation and osteoconduction.info:eu-repo/semantics/publishedVersio

Synthesis and characterization of push-pull bithiophene and thieno[3,2-b]thiophene derivatives bearing an ethyne linker as sensitizers for dye-sensitized solar cells

Five push-pull heterocyclic dyes 4-7, and 9 were synthesized and characterized in order to study the variations in the optical, electronic and photovoltaic properties induced by structural modifications, i.e. different spacer units and anchoring groups. The final push-pull conjugated dyes 6-7 and 9 are formed by a N,N-dimethylaniline donor moiety conjugated with bithiophene, ethynyl-bithiophene or ethynyl-thieno[3,2-b]thiophene spacers and cyanoacetic acid or rhodanine-3-acetic acid as anchoring group. The synthesis of the precursor aldehydes 4-5 was accomplished through a Sonogashira coupling, on the other hand, compound 8 was prepared by Suzuki coupling. Knoevenagel condensation of aldehydes 4, 5 and 8 with cyanoacetic acid or rhodamine-3-acetic acid afforded the final push-pull dyes 6, 7 and 9. Information on conformation, electronic structure and electron distribution was obtained by DFT and TDDFTcalculations. This multidisciplinary study regarding the evaluation of the optical, redox and photovoltaic properties of the dyes reveals that compound 7, bearing an ethynyl-bithiophene spacer conjugated with a cyanoacetic acid anchoring group, has the highest conversion efficiency (3.51 %) as dye sensitizer in nanocrystalline TiO2 solar cells. Co-adsorption studies were also performed for dyes 6-7 with N719 as co-adsorbent, and this enhanced dye efficiencies by 33-45 %. The best cell performance was obtained by co-adsorbing N719 and dye 7 (75/25 vol%) with 4.66 % efficiency.Laboratory for Advanced Computing at the University of CoimbraThanks are due to: Fundaçao para a Ci ~ encia e a Tecnologia for ^ PhD grants to S. S. M. Fernandes (SFRH/BD/87786/2012), and I. Mesquita (PD/BD/105985/2014) and a postdoctoral grant to L.L.G.Justino. (SFRH/BPD/97026/2013); FEDER-COMPETE for financial support through the CQ/UM PEst-C/QUI/UI0686/2013 (FCOMP- 01-0124-FEDER-037302); European Research Council (Contract no: 321315) for funding. H. D. Burrows are grateful for funding from Centro de Química de Coimbra, which is supported by the FC through the programmes UID/QUI/UI0313/2013 and COMPETE. The NMR spectrometer Bruker Avance III 400 is part of the National NMR Network and was purchased within the framework of the National Program for Scientific Re-equipment, contract REDE/1517/ RMN/2005 with funds from POCI 2010 (FEDER) and FCT. The authors also thank the Laboratory for Advanced Computing at the University of Coimbra for providing computing resources that have contributed to the research results reported in this paper (URL http://www.lca.uc.pt). The authors would like also to acknowledge A. I. Pereira for sequential co-adsorption devices and Dr. D. Ivanou for IPCE experiments.info:eu-repo/semantics/publishedVersio

Synthesis and characterization of novel thieno[3,2-b]thiophene based metal-free organic dyes with different heteroaromatic donor moieties as sensitizers for dye-sensitized solar cells

Four novel heterocycle dyes 3a-d were synthesized in order to study the variations produced in the optical, electronic and photovoltaic properties by substitution of different electron-rich heterocyclic groups to the thieno[3,2-b]thiophene system. The final push-pull conjugated dyes 3a-d were synthesized by Suzuki-Miyaura coupling reaction followed by Knoevenagel condensation of the corresponding aldehyde precursors with cyanoacrylic acid 2a-d. These new push-pull systems are based on a thieno[3,2-b]thiophene spacer, a cyanoacetic acid anchoring group and several electron-rich heterocycles (thiophene, pyrrole and furan) as donor groups. The multidisciplinary study concerning the optical, redox and photovoltaic characterization of the dyes reveals that compound 3b bearing a hexyl-bithiophene donor group/heterocyclic spacer exhibits the best overall conversion efficiency (2.49%) as sensitizer in nanocrystalline TiO2 dye sensitized solar cells. Co-adsorption studies between N719 and 3b revealed that upon addition of N719 co-adsorbent, the optimized cell efficiencies were improved by 16–77%. The best efficiency was 4.40%, corresponding to 54% of the photovoltaic performance of the N719-based DSSC fabricated and measured under similar conditions.FCTFEDERQRENEuropean Research Council (Contract no: 321315

Synthesis, structure and antileishmanial evaluation of endoperoxide–pyrazole hybrids

Leishmaniases are among the most impacting neglected tropical diseases. In attempts to repurpose antimalarial drugs or candidates, it was found that selected 1,2,4-trioxanes, 1,2,4,5-tetraoxanes, and pyrazole-containing chemotypes demonstrated activity against Leishmania parasites. This study reports the synthesis and structure of trioxolane–pyrazole (OZ1, OZ2) and tetraoxane–pyrazole (T1, T2) hybrids obtained from the reaction of 3(5)-aminopyrazole with endoperoxide-containing building blocks. Interestingly, only the endocyclic amine of 3(5)-aminopyrazole was found to act as nucleophile for amide coupling. However, the fate of the reaction was influenced by prototropic tautomerism of the pyrazole heterocycle, yielding 3- and 5-aminopyrazole containing hybrids which were characterized by different techniques, including X-ray crystallography. The compounds were evaluated for in vitro antileishmanial activity against promastigotes of L. tropica and L. infantum, and for cytotoxicity against THP-1 cells. Selected compounds were also evaluated against intramacrophage amastigote forms of L. infantum. Trioxolane–pyrazole hybrids OZ1 and OZ2 exhibited some activity against Leishmania promastigotes, while tetraoxane–pyrazole hybrids proved inactive, most likely due to solubility issues. Eight salt forms, specifically tosylate, mesylate, and hydrochloride salts, were then prepared to improve the solubility of the corresponding peroxide hybrids and were uniformly tested. Biological evaluations in promastigotes showed that the compound OZ1•HCl was the most active against both strains of Leishmania. Such finding was corroborated by the results obtained in assessments of the L. infantum amastigote susceptibility. It is noteworthy that the salt forms of the endoperoxide–pyrazole hybrids displayed a broader spectrum of action, showing activity in both strains of Leishmania. Our preliminary biological findings encourage further optimization of peroxide–pyrazole hybrids to identify a promising antileishmanial lead.info:eu-repo/semantics/publishedVersio

P9 - Antimicrobial properties and bioactivity potential of smart nanoparticles for dental applications

Tooth decay is one of the greatest causes of tooth loss in the world. This not only afects the patient’s quality of life but also carries an economic burden associated with the need for multiple reinterventions. Endodontic treatment aims to preserve teeth by cleaning, disinfecting and flling/sealing the root canal. Despite the high success rate of endodontic treatment, failures do occur in a large number of cases. Several new biomaterials for dentistry have been developed, however their bioactivity is often misunderstood. Our work focuses on the biological characterization of novel bioactive glass nanoparticles, including the evaluation of their antimicrobial and biocompatibility properties. Candida albicans (ATCC 11225) and Enterococcus faecalis (ATCC 29212) were included to evaluate the antimicrobial potential by the drop plate method [1]. The cytotoxicity was tested using the MC3T3-E1 cell line, through the resazurin reduction assay. The novel bioactive glass nanoparticles demonstrated antimicrobial activity against C. albicans and E. faecalis, being able to inhibit their growth but also, in some incubation times, decreased the survival of these microorganisms. After 24 h of incubation of MC3T3-E1 osteoblast cells with bioactive glass nanoparticles conditioned medium, around 48% cell viability was achieved. These novel bioactive glass nanoparticles have shown promising properties which may fnd applications on diferent areas of clinical dentistry.info:eu-repo/semantics/publishedVersio

Optical and photovoltaic properties of thieno[3,2-b]thiophene-based push–pull organic dyes with different anchoring groups for dye-sensitized solar cells

The effect of anchoring groups on the optical and electrochemical properties of triphenylamine-thienothiophenes, and on the photovoltaic performance of DSSCs photosensitized with the prepared dyes, was studied using newly synthesized compounds with cyanoacetic acid or rhodanine-3-acetic acid groups. Precursor aldehydes were synthesized through Suzuki cross-coupling, whereas Knoevenagel condensation of these with 2-cyanoacetic acid or rhodanine-3-acetic acid afforded the final push–pull dyes. A comprehensive photophysical study was performed in solution and in the solid state. The femtosecond time-resolved transient absorption spectra for the synthesized dyes were obtained following photoexcitation in solution and for the dyes adsorbed to TiO2 mesoporous films. Information on conformation, electronic structure, and electron distribution was obtained by density functional theory (DFT) and time-dependent DFT calculations. Triphenylamine–thienothiophene functionalized with a cyanoacetic acid anchoring group displayed the highest conversion efficiency (3.68%) as the dye sensitizer in nanocrystalline TiO2 solar cells. Coadsorption studies were performed for this dye with the ruthenium-based N719 dye, and they showed dye power conversion efficiencies enhanced by 20–64%. The best cell performance obtained with the coadsorbed N719 and cyanoacetic dye showed an efficiency of 6.05%.The authors thank Fundacao para a Ciencia e Tecnologia (FCT) for PhD grants to S.S.M.F. (SFRH/BD/87786/2012) and M.C.R.C. (SFRH/BD/78037/2011) and postdoctoral grants to L.L.G.J. (SFRH/BPD/97026/2013) and J.P. (SFRH/BPD/108469/2015). The authors also thank FEDER-COMPETE for the financial support through the CQ/UM PEst-C/QUI/UI0686/2013 (FCOMP-01-0124-FEDER-037302). The NMR spectrometer Bruker AVANCE III 400 is part of the National NMR Network and was purchased within the framework of the National Program for Scientific Re-equipment, contract REDE/1517/RMN/2005 with funds from POCI 2010 (FEDER) and FCT. The group in Coimbra are grateful for funding from "Centro de Quimica de Coimbra," which is supported by the Fundacao para a Ciencia e a Tecnologia (FCT), Portuguese Agency for Scientific Research, through the programs UID/QUI/UI0313/2013 and COMPETE. The authors also thank the Laboratory for Advanced Computing at the University of Coimbra for providing computing resources that have contributed to the research results reported in this paper (URL http://www.lca.uc.pt). This work was performed under the project "SunStorage. harvesting and storage of solar energy,"with reference POCI-01-0145-FEDER-016387, funded by the European Regional Development Fund (ERDF), through COMPETE 2020. Operational Programme for Competitiveness and Internationalization (OPCI), and by national funds through FCT. The research leading to these results has received funding from Laserlab-Europe (grant agreement no. 284464, EC's Seventh Framework Programme). A.I.P. would like to acknowledge the European Commission through the Seventh Framework Programme, the Specific Programme "Ideas" of the European Research Council for research and technological development as part of an Advanced Grant under grant agreement no. 321315, which also partially funded this work. The authors would also like to acknowledge L. Andrade and I. Mesquita for their valuable contribution for the article.info:eu-repo/semantics/publishedVersio

Population genomics of Bombus terrestris reveals high but unstructured genetic diversity in a potential glacial refugium

Ongoing climate change is expected to cause an increase in temperature and a reduction of precipitation levels in the Mediterranean region, which might cause changes in many species distributions. These effects negatively influence species gene pools, decreasing genetic variability and adaptive potential. Here, we use mitochondrial DNA and RADseq to analyse population genetic structure and genetic diversity of the bumblebee species Bombus terrestris (subspecies Bombus terrestris lusitanicus), in the Iberian Peninsula. Although this subspecies shows a panmictic pattern of population structure across Iberia and beyond, we found differentiation between subspecies B. t. lusitanicus and B. t. africanus, probably caused by the existence of barriers to gene flow between Iberia and North Africa. Furthermore, the results revealed that the Iberian Peninsula harbours a large fraction of B. terrestris intraspecific genetic variation, with the highest number of mitochondrial haplotypes found when compared with any other region in Europe studied so far, suggesting a potential role for the Iberian Peninsula as a glacial refugium. Our findings strengthen the idea that Iberia is a very important source of diversity for the global genetic pool of this species, because rare alleles might play a role in population resilience against human- or climate-mediated changes.info:eu-repo/semantics/publishedVersio

Cerebral malaria model applying human brain organoids

Neural injuries in cerebral malaria patients are a significant cause of morbidity and mortality. Nevertheless, a comprehensive research approach to study this issue is lacking, so herein we propose an in vitro system to study human cerebral malaria using cellular approaches. Our first goal was to establish a cellular system to identify the molecular alterations in human brain vasculature cells that resemble the blood–brain barrier (BBB) in cerebral malaria (CM). Through transcriptomic analysis, we characterized specific gene expression profiles in human brain microvascular endothelial cells (HBMEC) activated by the Plasmodium falciparum parasites. We also suggest potential new genes related to parasitic activation. Then, we studied its impact at brain level after Plasmodium falciparum endothelial activation to gain a deeper understanding of the physiological mechanisms underlying CM. For that, the impact of HBMEC-P. falciparum-activated secretomes was evaluated in human brain organoids. Our results support the reliability of in vitro cellular models developed to mimic CM in several aspects. These systems can be of extreme importance to investigate the factors (parasitological and host) influencing CM, contributing to a molecular understanding of pathogenesis, brain injury, and dysfunction.This research was funded by National funds through the Foundation for Science and Technology (FCT) SFRH/BD/131540/2017, SFRH/BD/5813/2020, COVID/BD/152416/2022 and UMINHO/BIM-CNCG/2022/143. This work has been funded by ICVS Scientific Microscopy Platform, member of the national infrastructure PPBI - Portuguese Platform of Bioimaging (PPBIPOCI-01-0145-FEDER-022122; by National funds, through the FCT—project UIDB/50026/2020 and UIDP/50026/2020. Moreover, this work was funded by IF/00143/2015/CP1294/CT0001, PTDC/SAU-PAR/2766/2021 and UIDB/04469/2020. O.M. is funded by the project NORTE-01- 0247-FEDER-045914, supported by POFC–COMPETE and FCT, under the programs PT2020 and NORTE2020. M.I.V. thanks FCT for her contract funding provided through 2020.03113.CEECIND.info:eu-repo/semantics/publishedVersio