Development of a chlorhexidine delivery system based on dental reline acrylic resins

Acknowledgements The authors thank the Fundaç˜ao para a Ciˆencia e Tecnologia (FCT), Portugal for the financial support and Centro 2020 through the following projects: UIDB/04138/2020 and UIDP/04138/2020 (iMed. ULisboa), UIDB/05608/2020 and UIDP/05608/2020 (H&TRC), UIDP/ 04044/2020, PAMI - ROTEIRO/0328/2013 (N◦ 022158) and MATIS (CENTRO-01-0145-FEDER-000014 - 3362), L. Gonçalves Principal Researcher grant (CEECIND/03143/2017). Finally, the authors would like to thank VOCO GmbH (Cuxhaven, Germany) for the donation of the Ufi Gel Hard and Prof Alice Nogueira Alves for graphical advice.The high recurrence rate of common denture stomatitis after antifungal treatment is still concerning. This condition is caused by low patient compliance and incomplete local elimination of the main etiological factor — Candida albicans, often associated with other microorganisms, such as Streptococcus species. Impregnating denture materials with antimicrobials for local delivery is a strategy that can overcome the side effects and improve the efficacy of conventional treatments (topical and/or systemic). In this work, we describe the development of three hard autopolymerizing reline acrylic resins (Kooliner, Ufi Gel Hard, and Probase Cold) loaded with different percentages of chlorhexidine (CHX). The novel formulations were characterized based on their antimicrobial activity, mechanical, morphological and surface properties, in-vitro drug release profiles, and cytotoxicity. The addition of CHX in all resins did not change their chemical and mechanical structure. Among all the tested formulations, Probase Cold loaded with 5 wt% CHX showed the most promising results in terms of antimicrobial activity and lack of serious detrimental mechanical, morphological, surface, and biological properties.Fundação para a Ciência e Tecnologia (FCT), PortugalCentro 2020 through the following projects: UIDB/04138/2020 and UIDP/04138/2020 (iMed.ULisboa), UIDB/05608/2020 and UIDP/05608/2020 (H&TRC), UIDP/04044/2020, PAMI - ROTEIRO/0328/2013 (N° 022158)MATIS (CENTRO-01-0145-FEDER-000014 - 3362)Grant (CEECIND/03143/2017

In vitro cytocompatibility evaluation of poly(DL-lactic acid) scaffolds loaded with minocycline and voriconazole addressing osteomyelitis

Purpose: In this work is proposed the cytocompatibility evaluation of an innovative system based on the dual delivery of minocycline (Min) and voriconazole (Vor), aiming for bone infection therapeutics.info:eu-repo/semantics/publishedVersio

¿Entre héroes y deidades? actos de sacrificio de la Edad del Hierro grabados en la roca 6 del monte de Porreiras (Noroeste de Portugal)

El objetivo de este trabajo es publicar los grabados rupestres del Monte das Porreira 6, situado en Paredes de Coura, en el no de Portugal. El estudio se ha basado en un levantamiento fotogramétrico y el posterior contraste con la determinación de la distancia geométrica. Se trata de una roca profusamente decorada con una larga diacronía de grabados. La fase inicial incluye el arte atlántico clásico, integrado en el Calcolítico Reciente. La segunda fase incluye la representación de équidos, jinetes y puñales con mango de antenas. Basándose en los paralelos de dichas armas, es posible integrar estos motivos entre la Edad de Bronce Final y la Edad de Hierro Inicial. También es posible observar el paso de una gramática abstracta, durante la primera fase, a una gramática figurativa, en la que se puede identificar una narrativa relacionada con los sacrificios humanos y de animales, asociada al uso de puñales con mango de antenas. Estas representaciones evocan un simbolismo que recuerda a los textos de Estrabón y objetos de bronce que contienen escenas de sacrificio. La última fase del grabado indica nuevos cambios simbólicos, con la valorización de acciones aisladas perpetradas por un jinete, portando un arma arrojadiza, que pueden representar a una divinidad o a un héroe.The aim of this work is to publish the rock engravings of Monte das Porreira 6, located in the council of Paredes de Coura, in the Northwest of Portugal. The study was based on photogrammetric surveys and subsequent contrast recurring to geometric distance determination. It is a profusely decorated rock with a long diachrony of carving. The initial phase includes Classical Atlantic Art, integrated in the regional Neo-Chalcolithic period. The second phase includes representation of several types of equids, horsemen, and antenna-hilted daggers. Based on parallels for such weapons, it is possible to integrate these motifs between the Late Bronze Age and an Early Iron Age of North-western Iberia. It is also possible to observe a change from an abstract grammar, during the first phase, to a figurative grammar, in which we can identify a narrative related to human and animal sacrifices, associated with the use of antenna-hilted daggers. These depictions recall a symbolism reminiscent of Strabo’s writings, including bronze objects containing sacrificial scenes. The final phase of engraving indicates new symbolic changes, with valorisation of isolated actions perpetrated by horsemen, carrying throwing weapons, which may be a representation of a deity or hero

Release kinetic model and antimicrobial activity of an innovative minocycline and voriconazole co-delivery system

Purpose and Strategy: Development of a new local drug-delivery system aiming at bone infection and the modulation of the polymicrobial activity; simultaneous delivery of minocycline and voriconazole, antibacterial and antifungal agents, respectively; polylactide (PDLLA) scaffolds functionalized with collagen and bioglass, osteogenic enhancers.info:eu-repo/semantics/publishedVersio

Poly(DL-lactic acid) scaffolds adsorbed with minocycline and voriconazole: a new pathway towards infection containment

Bone infection (osteomyelitis): burden as a clinical complication of orthopedic surgeries. Controlled antimicrobial release systems: treat and prevent osteomyelitis. Biomaterials based on porous scaffolds: local administration of high concentration of drugs; no systemic toxicity; extended time. Scaffolds in bone tissue engineering: a combination of bioresorbable polymers with bioactive bioglasses; present biodegradability and biosafety; suitable microenvironment and structure; favor osteogenic differentiation and cell growth. Co-encapsulation of drugs: advantageous means for administration of drugs; novel strategy directed to the co-delivery of two antimicrobials (voriconazole and minocycline).info:eu-repo/semantics/publishedVersio

Investigation of the genotoxicity of digested titanium dioxide nanomaterials in human intestinal cells

Funding: This work was funded by national funds through the FCT - Foundation for Science and Technology, I.P., under the project PTDC/SAUPUB/29481/2017. Research co-funded by UIDB/00009/2020; UIDP/ 00009/2020 (Centre for Toxicogenomics and Human Health – ToxOmics, FCT- Foundation for Science and Technology). NV holds a FCT PhD Scholarship grant (2020.07168.BD). iMed.ULisboa (UIDB/04138/ 2020 and UIDP/04138/2020) principal investigator grants CEECIND/ 03143/2017 (L. M. Gonçalves). The authors thank all the support from the colleagues Paula Alvito, Carla Martins and Ricardo Assunç˜ ao (Food Safety Department, INSA, Lisbon, Portugal) as well from all INGESTnano team members.The widespread use of titanium dioxide nanomaterials (TiO2 NMs) in food and consumer products such as toothpaste or food contact materials, suggests the relevance of human oral exposure to these nanomaterials (NMs) and raises the possibility of adverse effects in the gastrointestinal tract (GIT). We previously showed that the in vitro digestion of TiO2 NMs may increase their toxicity in intestinal cells. In this work, we analyzed the genotoxicity and the intracellular reactive oxygen species induction by physiologically relevant concentrations of three different TiO2 NMs (NM-102, NM-103 and NM-105) in Caco-2 and HT29-MTX-E12 intestinal cells, while considering the potential influence of the digestion process in the NMs’ physiochemical characteristics. The results evidenced a DNA-damaging effect dependent on the NM, more relevant for the rutile/anatase NM-105, possibly due to its lower hydrodynamic size in the cells medium. In addition, the results of the micronucleus assay suggest effects on chromosomal integrity, an indicator of cancer risk, in the HT29-MTX-E12 cells, for all the tested TiO2 NMs, especially after the in vitro digestion. This work supports the evidence for concerns on the use of TiO2 NMs as a food additive, recently reported by EFSA, and for their use in applications in consumer products that may drive human exposure through ingestion.publishersversionpublishe

Novel Machado-Joseph disease-modifying genes and pathways identified by whole-exome sequencing

Funding Information: This work was funded by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020 , and by Portuguese funds through FCT - Fundação para a Ciência e a Tecnologia / Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project PTDC/DTP-PIC/2638/2017 ( POCI-01-0145-FEDER-016592 ); GenomePT ( POCI-01-0145-FEDER-022184 ); ICVS Scientific Microscopy Platform , member of the national infrastructure PPBI - Portuguese Platform of Bioimaging ( PPBI-POCI-01-0145-FEDER-022122 ; by National funds , through the Foundation for Science and Technology (FCT) - project UIDB/50026/2020 and UIDP/50026/2020 ; and by the project NORTE-01-0145-FEDER-000013 , supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) . MR is supported by FCT ( CEECIND/03018/2018 ). ARVM ( SFRH/BD/129547/2017 ) and AFF ( SFRH/BD/121101/2016 ) are supported by a PhD grant financed by FCT . CB is supported by the Multiple System Atrophy Trust and Alzheimer's Research UK . MDC received funding from National Ataxia Foundation (NAF) and from FCT ( SFRH/BPD/101925/2014 ); DV-C received a grant from FCT ( SFRH/BD/147826/2019 ). Publisher Copyright: © 2021Machado-Joseph disease (MJD/SCA3) is a neurodegenerative polyglutamine disorder exhibiting a wide spectrum of phenotypes. The abnormal size of the (CAG)n at ATXN3 explains ~55% of the age at onset variance, suggesting the involvement of other factors, namely genetic modifiers, whose identification remains limited. Our aim was to find novel genetic modifiers, analyse their epistatic effects and identify disease-modifying pathways contributing to MJD variable expressivity. We performed whole-exome sequencing in a discovery sample of four age at onset concordant and four discordant first-degree relative pairs of Azorean patients, to identify candidate variants which genotypes differed for each discordant pair but were shared in each concordant pair. Variants identified by this approach were then tested in an independent multi-origin cohort of 282 MJD patients. Whole-exome sequencing identified 233 candidate variants, from which 82 variants in 53 genes were prioritized for downstream analysis. Eighteen disease-modifying pathways were identified; two of the most enriched pathways were relevant for the nervous system, namely the neuregulin signaling and the agrin interactions at neuromuscular junction. Variants at PARD3, NFKB1, CHD5, ACTG1, CFAP57, DLGAP2, ITGB1, DIDO1 and CERS4 modulate age at onset in MJD, with those identified in CFAP57, ACTG1 and DIDO1 showing consistent effects across cohorts of different geographical origins. Network analyses of the nine novel MJD modifiers highlighted several important molecular interactions, including genes/proteins previously related with MJD pathogenesis, namely between ACTG1/APOE and VCP/ITGB1. We describe novel pathways, modifiers, and their interaction partners, providing a broad molecular portrait of age at onset modulation to be further exploited as new disease-modifying targets for MJD and related diseases.publishersversionpublishe

Novel Machado-Joseph disease-modifying genes and pathways identified by whole-exome sequencing

Machado-Joseph disease (MJD/SCA3) is a neurodegenerative polyglutamine disorder exhibiting a wide spectrum of phenotypes. The abnormal size of the (CAG)n at ATXN3 explains ~55% of the age at onset variance, suggesting the involvement of other factors, namely genetic modifiers, whose identification remains limited. Our aim was to find novel genetic modifiers, analyse their epistatic effects and identify disease-modifying pathways contributing to MJD variable expressivity. We performed whole-exome sequencing in a discovery sample of four age at onset concordant and four discordant first-degree relative pairs of Azorean patients, to identify candidate variants which genotypes differed for each discordant pair but were shared in each concordant pair. Variants identified by this approach were then tested in an independent multi-origin cohort of 282 MJD patients. Whole-exome sequencing identified 233 candidate variants, from which 82 variants in 53 genes were prioritized for downstream analysis. Eighteen disease-modifying pathways were identified; two of the most enriched pathways were relevant for the nervous system, namely the neuregulin signaling and the agrin interactions at neuromuscular junction. Variants at PARD3, NFKB1, CHD5, ACTG1, CFAP57, DLGAP2, ITGB1, DIDO1 and CERS4 modulate age at onset in MJD, with those identified in CFAP57, ACTG1 and DIDO1 showing consistent effects across cohorts of different geographical origins. Network analyses of the nine novel MJD modifiers highlighted several important molecular interactions, including genes/proteins previously related with MJD pathogenesis, namely between ACTG1/APOE and VCP/ITGB1. We describe novel pathways, modifiers, and their interaction partners, providing a broad molecular portrait of age at onset modulation to be further exploited as new disease-modifying targets for MJD and related diseases

Comparison of cadmium binding by humic and fulvic acids extracted from two composts of different origin

Composting has been proven to be an environmentally friendly process for urban organic waste, that can represent an opportunity for new uses under the circular economy framework. The binding of cadmium to fulvic-like and humic-like acids extracted from compost of algae and urban residues were evaluated, and the results show significant differences. The fulvic and humic acids from algae compost bind cadmium more efficiently than those from urban residues compost. Furthermore, data from humic acids from both composts display significantly higher ability to bind to cadmium than both their corresponding fulvic acids and the generic soil extracted humic matter.  Cooperation Program Interreg V-A Spain-Portugal (POCTEP) 2014-2020 and the European Union through the European Regional Development Fund -FEDER within the scope of the project «RES2VALHUM -Valorization of Organic Waste: Production of Humic Substances» (0366_RES2VALHUM_1_P).The authors want to thank LIPOR for the supply of COUR sample. Members of the USC are also grateful to CRETUS Strategic Partnership (ED431E 2018/01) co-funded by FEDER and the Galician Competitive Research Group GRC ED431C/12.Members of the Department of Chemistry are also grateful toCenter of Chemistrythrough projects UID/QUI/00686/2016 and UID/QUI/00686/2019 (CQUM) funded by Foundation for Science and Technology (FCT, Portugal