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Myofibroblastoma of the breast is a benign tumor originated from mesenquimal cells with a very low incidence in breast pathology. Only 80 cases were reported until 2018. Eight histological patterns were described and may mimic a number of other breast diseases. A 55-years old male was diagnosed with an incidental left breast nodule. An ultrasonography with biopsy showed a 27 mm nodule compatible with myofibroblastoma. We performed a lumpectomy via modified Benelli technique. Surgery was curative and the only necessary treatment. Myofibroblastoma could be misdiagnosed and clinical differential diagnosis includes other benign and malignant breast lesions. In the setting of a diagnosis, histology may be confusing as myofibroblastoma may exhibit a wide spectrum of histological features that defines 8 variants. These subgroups can mimic malignant lesions in their histological pattern. Definitive diagnosis depends on histopathological and immunochemical results. Physicians must be aware about heterogeneity in morphological and immunochemical aspects of myofibroblastoma and his variants, as they can lead to erroneous management of the lesion. Surgery is important for a definitive and accurate diagnosis, excluding malignancy and relieving the burden of a close image-based surveillance.

Healthcare-Associated Infections (HAI) affect ~1.7 M people in the USA and 4.1 M in Europe, contributing to 99,000 and 37,000 deaths/year, respectively. Catheter-related infections are the most frequent cause of HAI, leading to life-threatening complications and colossal medical costs. Current prevention/treatment options – sterilization protocols, lock solutions, systemic antibiotic administration – are inefficient and lead to bacterial resistance, a huge threat to public health. This review addresses the existing solutions in the market – mostly catheter caps –, and emerging alternatives, to fight catheter-related infections. Graphene-based biomaterials arise as interesting weapons against these infections, particularly in combination with light: their photothermal and photodynamic properties boost their own antimicrobial action, allowing them to kill bacteria without contributing to bacterial resistance. Healthcare-Associated Infections (HAI) affect ~1.7 M people in the USA and 4.1 M in Europe, contributing to 99,000 and 37,000 deaths/year, respectively. Catheter-related infections are the most frequent cause of HAI, leading to life-threatening complications and colossal medical costs. Current prevention/treatment options – sterilization protocols, lock solutions, systemic antibiotic administration – are inefficient and lead to bacterial resistance, a huge threat to public health. This review addresses the existing solutions in the market – mostly catheter caps –, and emerging alternatives, to fight catheter-related infections. Graphene-based biomaterials arise as interesting weapons against these infections, particularly in combination with light: their photothermal and photodynamic properties boost their own antimicrobial action, allowing them to kill bacteria without contributing to bacterial resistance. Peer Reviewed Award-winning Premio Congreso SIBB 2021

Bacterial adhesion to surfaces is the onset of biofilm formation and a hard problem to tackle, aggravated by the rise in drug-resistant bacteria, responsible for more than 500 000 deaths globally/year. This work reports few-layer graphene (FLG) and few-layer graphene oxide (FLGO) as stand-alone light-responsive platforms to develop smart antibacterial surfaces. Films exposure to low-intensity NIR drastically improve their ability to kill planktonic (up to ∼99%) and adherent (up to ∼85%) methicillin-resistant S. aureus and S. epidermidis. Upon irradiation, a mild photothermal effect is observed in supernatant, with temperature rising from 37.0 °C to 39.0 °C–42.0 °C, while surface temperature of non-oxidized FLG films increases to 51.3 °C versus 56.0 °C for oxidized films. Both films prompt total glutathione oxidation when irradiated, despite FLG films induce higher ROS generation than FLGO, suggesting antioxidants depletion occurs preferentially by ROS-dependent pathway (photodynamic effect) for FLG versus ROS-independent pathway for FLGO films. This proof-of-principle study demonstrates that safe, low-intensity NIR irradiation is a valuable and effective tool to boost graphene surfaces’ antibacterial performance through a synergistic photothermal and photodynamic effect. These stand-alone NIR-activated graphene-based platforms arise as simple and economical disinfection surfaces/systems, with widespread use in medical and non-medical applications.

The lipid mediators platelet-activating factor (PAF) and lysophosphatidylcholine (LPC) play relevant pathophysiological roles in Trypanosoma cruzi infection. Several species of LPC, including C18:1 LPC, which mimics the effects of PAF, are synthesized by T. cruzi. The present study identified a receptor in T. cruzi, which was predicted to bind to PAF, and found it to be homologous to members of the progestin and adiponectin family of receptors (PAQRs). We constructed a three-dimensional model of the T. cruzi PAQR (TcPAQR) and performed molecular docking to predict the interactions of the TcPAQR model with C16:0 PAF and C18:1 LPC. We knocked out T. cruzi PAQR (TcPAQR) gene and confirmed the identity of the expressed protein through immunoblotting and immunofluorescence assays using an anti-human PAQR antibody. Wild-type (WT) and knockout (KO) parasites were also used to investigate the in vitro cell differentiation and interactions with peritoneal mouse macrophages; TcPAQR KO parasites were unable to react to C16:0 PAF or C18:1 LPC. Our data are highly suggestive that PAF and LPC act through TcPAQR in T. cruzi, triggering its cellular differentiation and ability to infect macrophages.

Graphene-based materials (GBMs) have been increasingly explored for biomedical applications. However, interaction between GBMs-integrating surfaces and bacteria, mammalian cells, and blood components, that is, the major biological systems in our body, is still poorly understood. In this study, we systematically explore the features of GBMs that most strongly impact the interactions of GBMs films with plasma proteins and biological systems. Films produced by vacuum filtration of GBMs with different oxidation degree and thickness depict different surface features: graphene oxide (GO) and few-layer GO (FLGO) films are more oxidized, smoother, and hydrophilic, while reduced GO (rGO) and few-layer graphene (FLG) are less or nonoxidized, rougher, and more hydrophobic. All films promote glutathione oxidation, although in a lower extent by rGO, indicating their potential to induce oxidative stress in biological systems. Human plasma proteins, which mediate most of the biological interactions, adsorb less to oxidized films than to rGO and FLG. Similarly, clinically relevant bacteria, Staphylococcus epidermidis, Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, adhere less to GO and FLGO films, while rGO and FLG favor bacterial adhesion and viability. Surface features caused by the oxidation degree and thickness of the GBMs powders within the films have less influence toward human foreskin fibroblasts; all materials allow cell adhesion, proliferation and viability up to 14 days, despite less on rGO surfaces. Blood cells adhere to all films, with higher numbers in less or nonoxidized surfaces, despite none having caused hemolysis (

As we approach the end of the antibiotic era, newer therapeutic options, such as antimicrobial peptides (AMPs), are in urgent demand. AMP surface grafting onto biomaterials has been described as a good strategy to overcome problems associated with their in vivo stability. Helicobacter pylori is among the bacteria that pose greatest threat to human health, being MSI-78A one of the few bactericidal AMPs against this bacterium. Here, we report that MSI-78A grafted onto model surfaces (Self-Assembled Monolayers –SAMs), in a concentration of 30.3 ± 1.2 ng/cm2 determined by quartz crystal microbalance with dissipation (QCM-D), was able to kill, by contact, 98% of planktonic H. pylori in only 2 h. This fact was not verified against the control bacteria (Staphylococcus epidermidis), although the minimal inhibitory concentration (MIC) of MSI-78A in solution is much lower for S. epidermidis (2 µg/mL) than for H. pylori (64 µg/mL). Our results also demonstrated that, in opposite to other bacteria, H. pylori cells were attracted to ethylene glycol terminated (antiadhesive) surfaces, which can explain the high bactericidal potential of grafted MSI-78A. This proof of concept study establishes the foundations for development of MSI-78A grafted nanoparticles for gastric infection management within a targeted nanomedicine concept. This article is a result of the project NORTE-01-0145-FEDER-00012, (NORTE 2020) and FCT/MCTES-through the UID/BIM/04293/2019, PTDC/CTM-BIO/4043/2014, UID/QUI/50006/2013 (LAQV-REQUIMTE) projects. Claudia Monteiro acknowledges FCT for the SFRH/BPD/79439/2011 grant.

Trypanosomatids are protozoan parasites that infect thousands of globally dispersed hosts, potentially affecting their physiology. Several species of trypanosomatids are commonly found in phytophagous insects. Leptomonas wallacei is a gut-restricted insect trypanosomatid only retrieved from Oncopeltus fasciatus. The insects get infected by coprophagy and transovum transmission of L. wallacei cysts. The main goal of the present study was to investigate the effects of a natural infection by L. wallacei on the hemipteran insect O. fasciatus, by comparing infected and uninfected individuals in a controlled environment. The L. wallacei-infected individuals showed reduced lifespan and morphological alterations. Also, we demonstrated a higher infection burden in females than in males. The infection caused by L. wallacei reduced host reproductive fitness by negatively impacting egg load, oviposition, and eclosion, and promoting an increase in egg reabsorption. Moreover, we associated the egg reabsorption observed in infected females, with a decrease in the intersex gene expression. Finally, we suggest alterations in population dynamics induced by L. wallacei infection using a mathematical model. Collectively, our findings demonstrated that L. wallacei infection negatively affected the physiology of O. fasciatus, which suggests that L. wallacei potentially has a vast ecological impact on host population growth.

International audience; Persistent Helicobacter pylori (H. pylori) infection is related to 90% of gastric cancers. With bacterial resistance rising and treatment inefficiency affecting 15% of the patients, alternative treatments urge. Chitosan microspheres (ChMics) have been proposed as an H. pylori-binding system. This work evaluates ChMics biocompatibility, mucopenetration and capacity to treat H. pylori infection in mice after oral administration. ChMics of different size (XL, ∼120 µm and XS, ∼40 µm) and degree of acetylation (6% and 16%) were developed and revealed to be able to adhere both human and mouse-adapted H. pylori strains without cytotoxicity towards human gastric cells. Ex vivo studies showed that smaller (XS) microspheres penetrate further within the gastric foveolae, suggesting their ability to reach deeply adherent bacteria. In vivo assays showed 88% reduction of infection when H. pylori-infected mice (C57BL/6) were treated with more mucoadhesive XL6 and XS6 ChMics. Overall, ChMics clearly demonstrate ability to reduce H. pylori gastric infection in mice, with chitosan degree of acetylation being a dominant factor over microspheres' size on H. pylori removal efficiency. These results evidence the strong potential of this strategy as an antibiotic-free approach to fight H. pylori infection, where microspheres are orally administered, bind H. pylori in the stomach, and remove them through the gastrointestinal tract. STATEMENT OF SIGNIFICANCE: Approximately 90% of gastric cancers are caused by the carcinogenic agent Helicobacter pylori, which infects >50% of the world population. Bacterial resistance, reduced antibiotic bioavailability, and the intricate distribution of bacteria in mucus and within gastric foveolae hamper the success of most strategies to fight H. pylori. We demonstrate that an antibiotic-free therapy based on bare chitosan microspheres that bind and remove H. pylori from stomach can achieve 88% reduction of infection from H. pylori-infected mice. Changing size and mucoadhesive properties, microspheres can reach different areas of gastric mucosa: smaller and less mucoadhesive can penetrate deeper into the foveolae. This promising, simple and inexpensive strategy paves the way for a faster bench-to-bedside transition, therefore holding great potential for clinical application.

The lack of small-diameter vascular grafts (inner diameter

Nanostructured carriers have been widely used in pharmaceutical formulations for dermatological treatment. They offer targeted drug delivery, sustained release, improved biostability, and low toxicity, usually presenting advantages over conventional formulations. Due to its large surface area, small size and photothermal properties, graphene oxide (GO) has the potential to be used for such applications. Nanographene oxide (GOn) presented average sizes of 197.6 ± 11.8 nm, and a surface charge of -39.4 ± 1.8 mV, being stable in water for over 6 months. 55.5 % of the mass of GOn dispersion (at a concentration of 1 mg mL-1) permeated the skin after 6 h of exposure. GOn dispersions have been shown to absorb near-infrared radiation, reaching temperatures up to 45.7 °C, within mild photothermal therapy temperature range. Furthermore, GOn in amounts superior to those which could permeate the skin were shown not to affect human skin fibroblasts (HFF-1) morphology or viability, after 24 h of incubation. Due to its large size, no skin permeation was observed for graphite particles in aqueous dispersions stabilized with Pluronic P-123 (Gt-P-123). Altogether, for the first time, GOn potential as a topic administration agent and for delivery of photothermal therapy has been demonstrated.

Significance: The prevalence and incidence of age-related neurodegenerative diseases (NDDs) tend to increase along with the enhanced average of the world life expectancy. NDDs are a major cause of morbidity and disability, affecting the health care, social and economic systems with a significant impact. Critical Issues and Recent Advances: Despite the worldwide burden of NDDs and the ongoing research efforts to increase the underlying molecular mechanisms involved in NDD pathophysiologies, pharmacological therapies have been presenting merely narrow benefits. On the contrary, absent of detrimental side effects but growing merits, regular physical exercise (PE) has been considered a prone pleiotropic nonpharmacological alternative able to modulate brain structure and function, thereby stimulating a healthier and "fitness" neurological phenotype. Future Directions: This review summarizes the state of the art of some peripheral and central-related mechanisms that underlie the impact of PE on brain plasticity as well as its relevance for the prevention and/or treatment of NDDs. Nevertheless, further studies are needed to better clarify the molecular signaling pathways associated with muscle contractions-related myokines release and its plausible positive effects in the brain. In addition, particular focus of research should address the role of PE in the modulation of mitochondrial metabolism and oxidative stress in the context of NDDs.

We would like to thank Herminia de Lencastre (ITQB-AX NOVA), Adriano Henriques (ITQB-AX NOVA) and PaulaTamagnini (i3S) for the gift of chromosomal DNA, Paulo Tavares (I2BC-CNRS) and Adriano Henriques for the gift of flagellin and anti-sigmaA antibodies, respectively, and Diogo Pereira for carrying out some growth kinetic assays. This work was supported by the FundacAo para a Ciencia e a Tecnologia [Grant Numbers PTDC/BIA-MIC/30696/2017 to ISN and UID/Multi/04378/2019 to Unidade de Ciencias Biomoleculares Aplicadas UCIBIO; and fellowship PD/BD/105737/2014 to F.L.]. ATP-binding cassette (ABC) type I importers are widespread in bacteria and play a crucial role in its survival and pathogenesis. They share the same modular architecture comprising two intracellular nucleotide-binding domains (NBDs), two transmembrane domains (TMDs) and a substrate-binding protein. The NBDs bind and hydrolyze ATP, thereby generating conformational changes that are coupled to the TMDs and lead to substrate translocation. A group of multitask NBDs that are able to serve as the cellular motor for multiple sugar importers was recently discovered. To understand why some ABC importers share energy-coupling components, we used the MsmX ATPase from Bacillus subtilis as a model for biological and structural studies. Here we report the first examples of functional hybrid interspecies ABC type I importers in which the NBDs could be exchanged. Furthermore, the first crystal structure of an assigned multitask NBD provides a framework to understand the molecular basis of the broader specificity of interaction with the TMDs. publishersversion published

The intrinsic properties and versatility of carbon materials (CMs) have recently raised a growing interest in their combination with hydrogels towards the development of advanced materials for biomedical applications. The increasing demand for biomimetic constructs that closely mimic the intricate composition and structure of native tissues has boosted the interest in using three-dimensional (3D) bioprinting technologies for the processing of CMs-containing hydrogels into specialized and more complex constructs capable of steering cell behavior. This review summarizes the progress on the bioprinting of 3D hydrogels containing CMs, focusing on the role of CMs on biomaterial ink design and their impact on both the printing process and the biological function of fabricated constructs. Recent findings demonstrate that CMs are versatile materials that have been mostly used to (1) tune the rheological properties of biomaterial inks, (2) improve the mechanical properties of hydrogels, and/or (3) confer new physical features to hydrogels, such as shape memory, roughness, and thermal and electrical conductivity, which have been shown to modulate the biological response of bioprinted constructs.

A new species of Bessierus Thomas & Orth, formerly a monotypic genus, is described from Amapá State, Brazil. The type species of the genus, B. doloris Thomas & Orth, had only its nymphs described until recently, when its male imago was associated to nymphs mainly based on pigmentation pattern. Bessierus riobranco sp. n. here described has no significant difference on pigmentation pattern from B. doloris, thus the new species could be the male imago of B. doloris, and the putative imago of B. doloris a new species, or even both described imagoes could be new species. Still, a new male imago existence cannot be neglected and we opted to provide a properly description, diagnosis and illustration, hence contributing to the knowledge of mayfly neotropical diversity and future research on the genus. The generic concept of Bessierus and its type species diagnoses are altered to accommodate the new species, and a new record of B. doloris is provided.

Three unusual nymphs of Euthyplociidae, subfamily Euthyplociinae, are described from Ecuador. A new genus and new species are established to accommodate these individuals. The morphologically unique specimens are defined by the following characters: short, stout tusks lacking spine-like setae but densely covered with long, hair-like setae; head almost as long as wide; long, quadrate clypeus with acute apicolateral projections; apex of 3rd segment of labial palp acute; apex of 3rd segment of maxillary palp acute and narrow. The hind wing is small, similar to that of Mesoplocia. An ongoing study of the phylogeny of the family recovers Dasyplocia gen. nov. as closely related to Euthyplocia and Mesoplocia.

Catheter-related infections are a common worldwide health problem, highlighting the need for antimicrobial catheters. Here, antibacterial potential of graphene nanoplatelets (GNP) incorporated in the commonly used polymer for catheter manufacture&mdash, polyurethane (PU)&mdash, is investigated. Two strategies are explored: melt-blending, producing a composite, and dip coating, where a composite layer is deposited on top of PU. GNP with different lateral sizes and oxidation degrees&mdash, GNP-M5, GNP-M15, GNP-M5ox, GNP-M15ox&mdash, are applied in both strategies, and the antimicrobial potential towards Staphylococcus epidermidis of GNP dispersions and GNP-containing PU evaluated. As dispersions, oxidized and smaller GNP powders (GNP-M5ox) inhibit 74% bacteria growth at 128 &micro, g/mL. As surfaces, GNP exposure strongly impacts their antimicrobial profile: GNP absence at the surface of composites yields no significant effects on bacteria, while by varying GNP: PU ratio and GNP concentration, coatings enhance GNP exposure, depicting an antimicrobial profile. Oxidized GNP-containing coatings induce higher antibacterial effect than non-oxidized forms, particularly with smaller GNPox, where a homogeneous layer of fused platelets is formed on PU, leading to 70% reduction in bacterial adhesion and 70% bacterial death. This pioneering work unravels how to turn a polymer clinically used to produce catheters into an antimicrobial surface, crucial to reducing risk of infection associated with catheterization.

This paper has been formally retracted because it has been accidentally published the volume. Request approved by the proceedings Editor and the Publisher on October 24, 2022.

This paper has been formally retracted because it has been accidentally published the volume. Request approved by the proceedings Editor and the Publisher on October 24, 2022.

Although graphene-based materials (GBMs) have been thoroughly explored, their use in antimicrobial surfaces is still a developing field. This review overviews the different methods for fabricating GBMs-containing surfaces (free-standing films, coatings or bulk composites) and their antibacterial properties. The difficulty in controlling the broad number of factors affecting interactions between GBMs and bacteria hampers the establishment of clear cause-effect relations. Nevertheless, it is clear that GBMs size, exposure, oxidation, as well as surface conductivity and roughness are the main surface features influencing the antimicrobial properties. Depending on the production method, GBMs basal planes and/or sharp edges are exposed, having a major impact on bacteria through electron transference, piercing of the membrane or pore formation, amongst others. Each of these effects leads to production of oxidative stress and/or bacterial membrane disruption and, consequently, to bacterial death. While oxidized graphene-containing surfaces are antimicrobial when either basal planes or sharp edges are exposed, graphene-containing surfaces are mainly effective when sharp edges are protruding, except for few studies showing effect due to graphene basal planes when coated over conductive materials. As such, this review enlightens and clarifies the surface features most strongly affecting bacteria, providing researchers the necessary tools to produce antibacterial GBMs-containing surfaces with tuned mechanisms of action.

Helicobacter pylori infection is one of the major risk factors for gastric cancer development. Available antibiotic-based treatments not only fail in around 20% of patients but also have a severe negative impact on the gut microbiota. Recently, we demonstrated that nanostructured lipid carriers (NLC), even without any drug loaded, are bactericidal against H. pylori at low concentrations. This work aims to clarify NLC mode of action and to evaluate if their bactericidal effect is specific to H. pylori without affecting bacteria from microbiota. NLC were produced by hot homogenization followed by ultrasonication method, using Precirol®ATO5 and Miglyol®812 as lipids and Tween®60 as a surfactant. NLC were able to eradicate H. pylori without affecting the other tested bacteria (Lactobacillus, E. coli, S. epidermidis and S. aureus). Bioimaging assays demonstrated that NLC rapidly bind to and cross the H. pylori bacterial membrane, destabilizing and disrupting it, which leads to leakage of the cytoplasmic contents and consequent bacterial death. In an era where efficient alternatives to antibiotics are urgent, NLC are an interesting route to be explored in the quest for new antibiotic-free therapies to fight H. pylori infection.

SUMMARYThe speciesPhytomonas serpensis known to express some molecules displaying similarity to those described in trypanosomatids pathogenic to humans, such as peptidases fromTrypanosoma cruzi(cruzipain) andLeishmaniaspp. (gp63). In this work, a population ofP. serpensresistant to the calpain inhibitor MDL28170 at 70µm(MDLRpopulation) was selected by culturing promastigotes in increasing concentrations of the drug. The only relevant ultrastructural difference between wild-type (WT) and MDLRpromastigotes was the presence of microvesicles within the flagellar pocket of the latter. MDLRpopulation also showed an increased reactivity to anti-cruzipain antibody as well as a higher papain-like proteolytic activity, while the expression of calpain-like molecules cross-reactive to anti-Dm-calpain (fromDrosophila melanogaster) antibody and calcium-dependent cysteine peptidase activity were decreased. Gp63-like molecules also presented a diminished expression in MDLRpopulation, which is probably correlated to the reduction in the parasite adhesion to the salivary glands of the insect vectorOncopeltus fasciatus. A lower accumulation of Rhodamine 123 was detected in MDLRcells when compared with the WT population, a phenotype that was reversed when MDLRcells were treated with cyclosporin A and verapamil. Collectively, our results may help in the understanding of the roles of calpain inhibitors in trypanosomatids.

A morphological comparison of type and non-type material of species of Campylocia, including their junior synonyms, was conducted, in addition to neighbour joining based on K2P distances and Bayesian inference analyses of 376 bp of the mitochondrial gene cytochrome oxidase I (COI) of recently collected specimens. Results revealed the lack of distinguishing characters between C. bocainensis and C. dochmia supported by the molecular analysis, where the overlap of intra- and interspecific genetic divergences suggested genetic flow among individuals. Campylocia burmeisteri is revalidated as a senior synonym of Brazilian south-eastern species C. bocainensis and C. dochmia and of E. guntheri, formerly a synonym of C. anceps. Campylocia burmeisteri is redescribed based on material from its type-locality, Nova Friburgo, Rio de Janeiro State. Two new species, C. demoulini sp. nov. and C. araca sp. nov., are described from the Amazon rain forest and a third species, C. orosi sp. nov., is described from Costa Rica. ...

The biointeractions of graphene-based materials depend on their physico-chemical properties. These properties can be manipulated by polymer adsorption. Graphene nanoplatelets (GNP-C) were modified with PVA, HEC, PEG, PVP, chondroitin, glucosamine, and hyaluronic acid. These materials were characterized by SEM, DLS, XPS, Raman spectroscopy, and TGA. Surface adsorption was confirmed for all polymers. Biocompatibility evaluation showed that all of these materials induced low haemolysis (

This work was financially supported by: Flupol - Surface Engineering S.A., Project POCI-01-0145-FEDER-006939 (Laboratory for Process Engineering, Environment, Biotechnology and Energy - LEPABE funded by FEDER funds through COMPETE2020 - Programa Operacional Competitividade e Internacionalizacao (POCI) - and by national funds through FCT - Fundaccao para a Ciencia e a Tecnologia.Artur Pinto wishes to thank Fundacao para a Ciencia e a Tecnologia (FCT) for PhD grant SFRH/BD/86974/2012, funded by European Social Fund and Portuguese Ministry of Education and Science (MEC) through Programa Operacional Capital Humano (POCH).

Using a one-step thermal reduction and non-covalent chemical functionalization process, PEGylated reduced nanographene oxide (rGOn-PEG) was produced from nanographene oxide (GOn) and characterized in terms of particle size, dispersion stability, chemistry, and photothermal properties, in view of its use for photothermal therapy (PTT) of non-melanoma skin cancer. GOn infrared spectrum presented more intense bands assigned to oxygen containing functional groups than observed for rGOn-PEG. GOn C/O ratio decreased more than 50% comparing with rGOn-PEG and nitrogen was present in the latter (N at % = 20.6) due to introduction of PEG-NH2. Thermogravimetric analysis allowed estimating the amount of PEG in rGOn-PEG to be of about 56.1%. Simultaneous reduction and PEGylation increased the lateral dimensions from 287 &plusmn, 139 nm to 521 &plusmn, 397 nm, as observed by transmission electron microscopy and dynamic light scattering. rGOn-PEG exhibited &asymp, 13-fold higher absorbance in the near-infrared radiation (NIR) region, as compared to unmodified GOn. Low power (150 mW cm&minus, 2) NIR irradiation using LEDs resulted in rGOn-PEG heating up to 47 &deg, C, which is within the mild PTT temperature range. PEGylation strongly enhanced the dispersibility of rGOn in physiological media (phosphate buffered saline, fetal bovine serum, and cell culture medium) and also improved the biocompatibility of rGOn-PEG, in comparison to GOn (25&ndash, 250 &mu, g mL&minus, 1). After a single NIR LED irradiation treatment of 30 min, a decrease of &asymp, 38% in A-431 cells viability was observed for rGOn-PEG (250 &mu, 1). Together, our results demonstrate the potential of irradiating rGOn-PEG using lower energy, cheaper, smaller, and safer LEDs, as alternative to high power lasers, for NIR mild hyperthermia therapy of cancer, namely non-melanoma skin cancer.

Catheter-related infections are a common worldwide health problem, highlighting the need for antimicrobial catheters. Here, antibacterial potential of graphene nanoplatelets (GNP) incorporated in the commonly used polymer for catheter manufacture-polyurethane (PU)-is investigated. Two strategies are explored: melt-blending, producing a composite, and dip coating, where a composite layer is deposited on top of PU. GNP with different lateral sizes and oxidation degrees-GNP-M5, GNP-M15, GNP-M5ox, GNP-M15ox-are applied in both strategies, and the antimicrobial potential towards

Implantable medical devices infection and consequent failure is a severe health issue, which can result from bacterial adhesion, growth, and subsequent biofilm formation at the implantation site. Graphene-based materials, namely graphene oxide (GO), have been described as potential antibacterial agents when immobilized and exposed in polymeric matrices. This work focuses on the development of antibacterial and biocompatible 3D fibrous scaffolds incorporating GO. Poly(e-caprolactone) scaffolds were produced, with and without GO, using wet-spinning combined with additive manufacturing. Scaffolds with different GO loadings were evaluated regarding physical-chemical characterization, namely GO surface exposure, antibacterial properties, and ability to promote human cells adhesion. Antimicrobial properties were evaluated through live/dead assays performed with Gram-positive and Gram-negative bacteria. 2 h and 24 h adhesion assays revealed a time-dependent bactericidal effect in the presence of GO, with death rates of adherent S. epidermidis and E. coli reaching ~80% after 24 h of contact with scaffolds with the highest GO concentration. Human fibroblasts cultured for up to 14 days were able to adhere and spread over the fibers, independently of the presence of GO. Overall, this work demonstrates the potential of GO-containing fibrous scaffolds to be used as biomaterials that hinder bacterial infection, while allowing human cells adhesion.

Designing hydrogels with high-strength and stiffness remains a challenge, limiting their usage in several applications that involve load-bearing. In this work, in situ incorporation of different amounts of graphene oxide (GO) into poly(2-hydroxyethyl methacrylate) (pHEMA) was used to create hydrogels with outstanding stiffness (Young's modulus of up to 6.5 MPa, 8.3x higher than neat pHEMA) and tensile resistance (ultimate tensile strength of up to 1.14 MPa, 7.4x higher than neat pHEMA) without affecting the water absorption capacity, surface wettability and cytocompatibility of pHEMA. Such magnitude of improvement in Young's modulus and ultimate tensile strength was never before described for GO incorporation in hydrogels. Moreover, these stiffness and tensile resistance values are higher than the ones of most hydrogels (few hundred kPa), achieving a stiffness comparable to polydimethylsiloxane (PDMS), cartilage and artery walls and a tensile resistance similar to rigid foams, PDMS and cork. These new materials open a wide range of applications for pHEMA in different fields.

Pleural involvement is the most frequent thoracic complication of rheumatoid arthritis (RA), usually occurring in patients with known RA. Typical rheumatoid pleural effusion is an exudate characterized by low pH and glucose levels and high LDH activity. Rarely, it has features of pseudochylothorax. Other uncommon complications are pneumothorax, hydropneumothorax, empyema, and bronchopleural fistula. The case of a 51-year-oldman with a spontaneous, small, and asymptomatic hydropneumothorax with features of pseudochylothorax is presented. After careful clinical and laboratory evaluation, he was diagnosed with rheumatoid arthritis, and we admitted that the pleural changes were secondary to the connective tissue disease. He started immunosuppressive treatment and maintained stability duringfollow-up,without need of specific pleural treatment. We hypothesized that the pleural nodule found on the chest computed tomography scan was related with the simultaneous occurrence of pleural effusion and pneumothorax. This is a rare presentation and complication of RA, highlighting the utility of a comprehensive clinical and laboratory evaluation and focusing on the importance of pleural rheumatoid nodules in the pathogenesis of RA pleural disease.

Silicone rubber (SR) peritoneal dialysis (PD) catheters are prone to bacterial adhesion and biofilm formation, which contributes to development of infection and associated morbidity in PD patients. We herein evaluate whether surface immobilization of graphene nanoplatelets (GNP) provides antimicrobial properties to SR. Dip and spray coating were used to deposit a dispersion containing SR and GNP-M5 or its oxidized form (GNP-M5ox) on the surface of silicone. The antimicrobial effect of GNP exposure and oxidation towards Staphylococcus epidermidis was assessed. GNP was successfully exposed on the surface, and while dipping provided better adhesion of either GNP, spraying resulted in uniform and higher surface coverage. Spraying led to enhanced bacterial adhesion comparing to dip coated and uncoated SR, which are similar. However, independently of the technique, GNP-M5ox coatings induced higher bacterial death. As such, SR/GNP-M5ox coating performed by dipping revealed to be the most promising approach, preserving bacterial adhesion levels of silicone while increasing bacterial death to around 80%. For the first time, graphene-based materials antimicrobial activity was evaluated by quantification of bacterial adhesion and viability. The high antibacterial effect, associated with a stable and cytocompatible coating which does not delaminate from SR surface, demonstrates its potential use in silicone biomedical industry. (c) 2018 Elsevier Ltd

Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid present in fish oil, has been described as a promising molecule to the treatment of Helicobacter pylori gastric infection. However, due to its highly unsaturated structure, DHA can be easily oxidized loosing part of its bioactivity. This work aims the nanoencapsulation of DHA to improve its bactericidal efficacy against H. pylori. DHA was loaded into nanostructured lipid carriers (NLC) produced by hot homogenization and ultrasonication using a blend of lipids (Precirol AT05 (R), Miglyol-812 (R)) and a surfactant (Tween 60 (R)). Homogeneous NLC with 302 +/- 14 nm diameter,-28 +/- 3 mV surface charge (dynamic and electrophoretic light scattering) and containing 66 +/- 7% DHA (UV/VIS spectroscopy) were successfully produced. Bacterial growth curves, performed over 24 h in the presence of different DHA concentrations (free or loaded into NLC), demonstrated that nanoencapsulation enhanced DHA bactericidal effect, since DHA-loaded NLC were able to inhibit H. pylori growth in a much lower concentrations (25 mu M) than free DHA (>100 mu M). Bioimaging studies, using scanning and transmission electron microscopy and also imaging flow cytometry, demonstrated that DHA-loaded NLC interact with H. pylori membrane, increasing their periplasmic space and disrupting membrane and allowing the leakage of cytoplasmic content. Furthermore, the developed nanoparticles are not cytotoxic to human gastric adenocarcinoma cells at bactericidal concentrations. DHA-loaded NLC should, therefore, be envisaged as an alternative to the current treatments for H. pylori infection. (C) 2017 Elsevier B.V. All rights reserved. FCT/MCTES [POCI-01-0145-FEDER-007274, PTDC/CTM-BIO/4043/2014, PTDC/CTM-BPC/121149/2010, NORTE-01-0145-FEDER-000012] FEDER funds through the COMPETE (POCI), Portugal FCT grant [SFRH/BD/89001/2012] info:eu-repo/semantics/publishedVersion

The analysis of cell-material interactions is a key step in biomaterials development. It is fundamental for designing optimal biomaterial formulations and also required at the final stage of in vitro testing, providing rational criteria for the acceptance or rejection of candidate implant materials and biomedical devices. Cell response to a biomaterial or its leachates can be evaluated at different levels, namely, in terms of cell morphology, viability, metabolic activity, proliferation, migration, and differentiation. Yet, classical cell/molecular biology protocols, originally tailored for measuring events in cells cultured as monolayers, may be inadequate in experimental setups involving, for example, 3D culture on scaffolds. Adjustment, validation, and careful interpretation of obtained data are thus required, as discussed herein. The emergence of new or upgraded assays, advanced bioimaging tools and high-throughput screening platforms has provided important contributions to the field.

Chitosan is a derivative of chitin, obtained by its deacetylation. Chitin is the second most abundant polysaccharide in nature after cellulose. It constitutes the fibrous support of the endo and exoskeleton of many invertebrates. Chitosan is a linear co-polymer of d -glucosamine and N -acetyl d -glucosamine in a β-(1–4) linkage, in which glucosamine is the predominant repeating unit. Chitosan, which is insoluble in water, is soluble in mildly acidic conditions. Acidification causes the protonation of amine functionalities from glucosamine units, which results in the electrostatic repulsions between NH 3 + groups and the destruction of interchain attractive interactions. The sources and the processes of purification, acetylation and deacetylation are described in this chapter, which also provides details on the methods used to measure the degree of acetylation (DA). The structural similarity of chitosan with glicosaminoglycans, which are constituents of the extracellular matrix (ECM), makes it a natural candidate for being a component of ECM-like matrices used for tissue repair/regeneration. The DA is an important property that influences many properties of chitosan, including its ability to support cell attachment, proliferation and differentiation, the inflammatory response and degradation rate. Lysozyme can partially hydrolyze N -acetylated chitosans. Chitosan is easily processed into films, 3D-scaffolds, nanofibres and nanoparticles. It forms polyelectrolyte complexes (PECs) with polysaccharides (eg, alginate, chondroitin sulphate and dextran sulphate), polyamino acids (eg, poly- l -Lysine and poly(aspartic acid)), proteins (eg, collagen) and glycosoaminoglycans (eg, hyaluronic acid). Chitosan is a powerful hemostatic agent and induces blood clotting. Many other applications, including wound healing and tissue repair (eg, bone, cartilage and nerve), drug- and nucleic acid-delivery, have been investigated. Its functionalization, both at the hydroxyl and the amino groups, increases considerably the range of properties that can be obtained and the fields of application.