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The standard breast cancer therapy still faces major challenges due to non-specific tumor distribution and occurrence of dose-limiting adverse side-effects. Nanomedicine constitutes an appealing approach to improve the therapeutic index of different anti-cancer drugs. Given their biocompatibility, low-cost manufacture and easy surface modification, lipid nanoparticles, such as solid lipid nanoparticles (SLN), have a great potential for drug delivery in cancer therapy. In this work, SLN entrapping the antineoplastic drug Mitoxantrone (Mito) were developed and functionalized with Disteroylphosphatidylethanolamine-poly(ethylene glycol)-folic acid (DSPE-PEG-FA) ligand to improve blood circulation and tumor selectivity and limit the drug systemic side-effects. Nanoparticles presented adequate size and size distribution for intravenous injection and were stable for at least 6 months. Additionally, their hemocompatibility was demonstrated. Moreover, functionalized nanoparticles were able to improve the anti-cancer effect of the free drug, as assessed by the values of IC

TreatingHelicobacter pylori(H. pylori) infections has been a never-ending challenge, which has contributed to the high incidence of gastric cancer. The antibiotics commonly used are not reaching the infection site in its active state and in a concentration high enough to effectively kill the bacteria. In this context, amoxicillin-loaded lipid nanoparticles with carefully chosen materials were developed, namely dioleoylphosphatidylethanolamine (DOPE) as a targeting agent and Tween®80 and linolenic acid as antimicrobial agents. This work shows the ability of these nanoparticles in (i) targeting the bacteria (imaging flow cytometry) and inhibiting their adhesion to MKN-74 cells (bacteria-gastric cells adhesion model); (ii) killing the bacteria even as an antibiotic-free strategy (time-kill kineticstudies, scanning electron microscopy, and bacterial membrane permeability studies); (iii)overcoming gastrointestinal features using a newly developedin vitroinfection model that includes both physical (epithelial cells and mucus) and the chemical (acid medium) barriers; and in (iv) being incorporated in a floating system that can increase the retention time at the stomach. Overall, this work presents an effective nanosystem to deal with the ulcer-bug. Besides, it also provides two innovative tools transferable to other fields-anin vitroinfection model and a floating system to incorporate nanoparticles.

Funding Information: Funding: This work has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme under grant agreement No 804229. iNOVA4Health Research Unit (LISBOA—01–0145—FEDER—007344), which is cofunded by Fundação para a Ciência e Tecnologia (FCT)/Ministério da Ciência e do Ensino Superior, through national funds, and by FEDER under the PT2020 Partnership Agreement, is acknowledged. Authors Aβ—Amyloid beta; CAT—catalase; NF–κB—Nuclear factor kappa–light–chain–enhancer of activated B cell; GSK— Glycogen synthase kinase; GSH—glutathione; APP—Amyloid precursor protein; ROS—Reactive Oxygen Species; TNF— Tumor necrosis factor; JNK—c–Jun N–terminal kinases; SOD—Superoxide Dismutase; Tg—transgenic; PPAR— Peroxisome proliferator–activated receptor alpha; LPS—lipopolysaccharide; MPTP—1—methyl–4—phenyl–1,2,3,6— tetrahydropyridine. 1 (Poly)phenol metabolites are named accordingly the recommendations recently published [32], however the name cited in the original publications where the effect is described is indicated in brackets. ↑—increased ↓— decreased. Funding Information: would like to acknowledge FCT for financial support of D.C (2020.04630.BD), R.M (CEEC/04567/CBIOS/2020) and S.F (UIDP/BD4/04567/2020). Funding Information: This work has received funding from the European Research Council (ERC) under the European Union?s Horizon 2020 research and innovation programme under grant agreement No 804229. iNOVA4Health Research Unit (LISBOA?01?0145?FEDER?007344), which is cofunded by Funda??o para a Ci?ncia e Tecnologia (FCT)/Minist?rio da Ci?ncia e do Ensino Superior, through national funds, and by FEDER under the PT2020 Partnership Agreement, is acknowledged. Authors would like to acknowledge FCT for financial support of D.C (2020.04630.BD), R.M (CEEC/04567/CBIOS/2020) and S.F (UIDP/BD4/04567/2020). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. The rise of neurodegenerative diseases in an aging population is an increasing problem of health, social and economic consequences. Epidemiological and intervention studies have demonstrated that diets rich in (poly)phenols can have potent health benefits on cognitive decline and neurodegenerative diseases. Meanwhile, the role of gut microbiota is ever more evident in modulating the catabolism of (poly)phenols to dozens of low molecular weight (poly)phenol metabolites that have been identified in plasma and urine. These metabolites can reach circulation in higher concentrations than parent (poly)phenols and persist for longer periods of time. However, studies addressing their potential brain effects are still lacking. In this review, we will discuss different model organisms that have been used to study how low molecular weight (poly)phenol metabolites affect neuronal related mechanisms gathering critical insight on their potential to tackle the major hallmarks of neurodegeneration. publishersversion published

Bionanocomposite materials have been designed as a promising route to enhance biopolymer properties, especially for food packaging application. The present study reports the preparation of bionanocomposite films of alginate with different loadings of pure reduced graphene oxide (rGO) or of mixed zinc oxide-rGO (ZnO-rGO) fillers by solvent casting. Sepiolite is used to make compatible rGO with the hydrophilic matrix. The addition of fillers to alginate matrix maintains the low water solubility promoted by the calcium chloride treatment, and, additionally, they demonstrate a weaker mechanical properties, and a slight increase in water vapor permeability and wettability. Due to the properties of ZnO-rGO, the alginate bionanocomposites show an increase of electrical conductivity with the increase of filler content. While the highest electrical conductivity (0.1 S/m) is achieved by the in-plane measurement, it is in the through-plane measurement the remarkable enhancement of almost 30 times greater than the alginate film. With 50% of ZnO-rGO filler, the bionanocomposites present the highest antioxidant and antibacterial activities. The combination of electrical conductivity with bioactive properties makes these films promising not only to extend food shelf-life but also to allow packaged food sterilization at low temperature.

Bacterial biofilms are a major health concern, mainly due to their contribution to increased bacterial resistance to well-known antibiotics. The conventional treatment of biofilms represents a challenge, and frequently, eradication is not achieved with long-lasting administration of antibiotics. In this context, the present work proposes an innovative therapeutic approach that is focused on the encapsulation of N-acetyl-l-cysteine (NAC) into lipid nanoparticles (LNPs) functionalized with d-amino acids to target and disrupt bacterial biofilms. The optimized formulations presented a mean hydrodynamic diameter around 200 nm, a low polydispersity index, and a high loading capacity. These formulations were stable under storage conditions up to 6 months. In vitro biocompatibility studies showed a low cytotoxicity effect in fibroblasts and a low hemolytic activity in human red blood cells. Nevertheless, unloaded LNPs showed a higher hemolytic potential than NAC-loaded LNPs, which suggests a safer profile of the latter. The in vitro antibiofilm efficacy of the developed formulations was tested against Staphylococcus epidermidis (Gram-positive) and Pseudomonas aeruginosa (Gram-negative) mature biofilms. The results showed that the NAC-loaded LNPs were ineffective against S. epidermidis biofilms, while a significant reduction of biofilm biomass and bacterial viability in P. aeruginosa biofilms were observed. In a more complex therapeutic approach, the LNPs were further combined with moxifloxacin, revealing a beneficial effect between the LNPs and the antibiotic against P. aeruginosa biofilms. Both alone and in combination with moxifloxacin, unloaded and NAC-loaded LNPs functionalized with d-amino acids showed a great potential to reduce bacterial viability, with no significant differences in the presence or absence of NAC. However, the presence of NAC in NAC-loaded functionalized LNPs shows a safer profile than the unloaded LNPs, which is beneficial for an in vivo application. Overall, the developed formulations present a potential therapeutic approach against P. aeruginosa biofilms, alone or in combination with antibiotics. ispartof: ACS APPLIED MATERIALS & INTERFACES vol:13 issue:36 pages:42329-42343 ispartof: location:United States status: published

The diversity of zinc oxide (ZnO) particles and derived composites applications is highly dependent on their structure, size, morphology, defect amounts, and/or presence of dopant molecules. In this work, ZnO nanostructures are grown in situ on graphene oxide (GO) sheets by an easily implementable solvothermal method with simultaneous reduction of GO. The effect of two zinc precursors (zinc acetate (ZA) and zinc acetate dihydrate (ZAD)), NaOH concentration (0.5, 1 or 2 M), and concentration (1 and 12.5 mg/mL) and pH (pH = 1, 4, 8, and 12) of GO suspension were evaluated. While the ZnO particle morphology shows to be precursor dependent, the average particle size length decreases with lower NaOH concentration, as well as with the addition of a higher basicity and concentration of GO suspension. A lowered band gap and a higher specific surface area are obtained from the ZnO composites with higher amounts of GO suspension. Otherwise, the low concentration and the higher pH of GO suspension induce more lattice defects on the ZnO crystal structure. The role of the different condition parameters on the ZnO nanostructures and their interaction with graphene sheets was observed to tune the ZnO–rGO nanofiller properties for photocatalytic and antimicrobial activities.

Odontogenic cysts are a heterogeneous group of lesions with varied clinical behavior.To analyze the expression of the epidermal growth factor receptor (EGFR), Cyclin D1, and transcription factor SOX2 in the odontogenic epithelium evaluating the cell cycle control and cystic expansion.This was a cross-sectional study including 40 cases, 20 odontogenic keratocysts (OKC), 10 botryoid odontogenic cysts (BOC), and 10 glandular odontogenic cysts (GOC).All cases of OKC, BOC, and GOC were positive for EGFR in all layers of the cyst lining. The highest expression of nuclear Cyclin D1 was observed in the suprabasal layer of OKCs and in the basal and suprabasal layers of GOC and BOC (p0.001). In addition, SOX2 was only expressed in the suprabasal layer of OKCs.The high expression of EGFR in the cyst membrane suggests that EGF stimulates epithelial proliferation in BOCs, and the high expression of SOX2 in OKCs may be related to the presence of stem cells in the lesion. Cyclin D1 is related to cell cycle disruption in G1-S contributing to stimulates epithelial proliferation of OKCs and GOCs and BOCs.

Several classes of polysaccharides have been described to have hypocholesterolemic potential, namely cholesterol bioaccessibility and bioavailability. This review will highlight the main mechanisms by which polysaccharides are known to affect cholesterol homeostasis at the intestine, namely the effect (i) of polysaccharide viscosity and its influence on cholesterol bioaccessibility; (ii) on bile salt sequestration and its dependence on the structural diversity of polysaccharides; (iii) of bio-transformations of polysaccharides and bile salts by the gut microbiota. Different quantitative structure–hypocholesterolemic activity relationships have been explored depending on the mechanism involved, and these were based on polysaccharide physicochemical properties, such as sugar composition and ramification degree, linkage type, size/molecular weight, and charge. The information gathered will support the rationalization of polysaccharides’ effect on cholesterol homeostasis and highlight predictive rules towards the development of customized hypocholesterolemic functional food.

Chitosan-genipin films have been proposed for preservation of white wine, maintaining their varietal key odorants and organoleptic characteristics of sulfur dioxide treated wines. Nevertheless, these wines showed aroma notes that slightly distinguish them. It is possible that during the contact of films with wine for at least 2 months, after fermentation and prior to bottling, interactions or chemical reactions are promoted. In this work, wine model solutions with volatile compounds in contact with chitosan-genipin films were performed to evaluate their evolution along time. To complement these analyses, the volatile compounds of white and red wines kept in contact with chitosan-genipin films during 2 and 8 months were also studied. The results obtained allowed us to conclude that the contact of chitosan-genipin films with both white and red wines tend to retain long carbon chain volatile compounds, such as ethyl hexanoate and octan-3-one. It also promoted the formation of Maillard reaction products, such as furfural by dehydration of pentoses and Strecker aldehydes, such as 3-methylbutanal and phenylacetaldehyde, by degradation of amino acids. This study reveals that the use of chitosan-genipin films for wine preservation is also able to promote the formation of compounds that can modulate the wines aroma, maintaining the varietal notes.

Staphylococcus aureus (S. aureus) is considered by the World Health Organization as a high priority pathogen for which new therapies are needed. This is particularly important for biofilm implant-associated infections once the only available treatment option implies a surgical procedure combined with antibiotic therapy. Consequently, these infections represent an economic burden for Healthcare Systems. A new strategy has emerged to tackle this problem: for small bugs, small particles. Here, we describe how nanotechnology-based systems have been studied to treat S. aureus biofilms. Their features, drawbacks and potentialities to impact the treatment of these infections are highlighted. Furthermore, we also outline biofilm models and assays required for preclinical validation of those nanosystems to smooth the process of clinical translation., Staphylococcus aureus biofilms are a major cause for implant-associated infections. The lack of an effective treatment and the escalating numbers of antibiotic-resistance events are prompting the research toward alternative nano-based strategies.

This is the first report, to the best of our knowledge, on the degradation of licofelone, a dual cyclooxygenaselipoxygenase inhibitor under development, in phosphatidylcholine bilayers. With the objective of characterizing licofelone-phosphatidylcholine interactions to understand its better gastric tolerability over conventional nonsteroidal anti-inflammatory drugs, our preliminary data showed that the lower the pH, the higher the rate and extent of licofelone degradation in the presence of phosphatidylcholine liposomes. The lipid concentration was another critical factor influencing the rate and extent of licofelone degradation, suggesting that phosphatidylcholine bilayers may act as a catalyst. These data highlight the need of considering lipids in drug development to better predict the drug pharmacokinetics prior to clinical evaluation.

Purpose Amoxicillin is a commonly used antibiotic, although degraded by the acidic pH of the stomach. This is an important limitation for the treatment of Helicobacter pylori infections. The purpose of this work was to encapsulate amoxicillin in lipid nanoparticles, increasing the retention time at the site of infection (gastric mucosa), while protecting the drug from the harsh conditions of the stomach lumen. Materials and methods The nanoparticles were produced by the double emulsion technique and optimized by a three-level Box-Behnken design. Tween 80 and linolenic acid were used as potential therapeutic adjuvants and dioleoylphosphatidylethanolamine as a targeting agent to Helicobacter pylori. Nanoparticles were characterized regarding their physico-chemical features, their storage stability, and their usability for oral administration (assessment of in vitro release, in vitro cell viability, permeability, and interaction with mucins). Results The nanoparticles were stable for at least 6 months at 4°C. In vitro release studies revealed a high resistance to harsh conditions, including acidic pH and physiologic temperature. The nanoparticles have a low cytotoxicity effect in both fibroblasts and gastric cell lines, and they have the potential to be retained at the gastric mucosa. Conclusion Overall, the designed formulations present suitable physico-chemical features for being henceforward used by oral administration to treat Helicobacter pylori infections.

Chitosan is a biopolymer obtained by deacetylation of chitin extracted from sub-products of the food industry and it is rich in nitrogen content. Pyrolyzed chitosan– and chitosan-periodic mesoporous organosilica (PMO)– based porous materials with different pore structures and chemical features are prepared using different dry methods and ensuing pyrolysis at 800 °C, for application in the CO2/CH4 adsorption/separation. The highest CO2 adsorption capacity (1.37 mol·kg−1 at 100 kPa; 1.9 mol·kg−1 at 500 kPa) and the best selectivity for CO2/CH4 separation (95 at 500 kPa) is obtained using 1.5% (m/v) of chitosan solution dried under supercritical CO2. This material combines a good CO2 adsorption capacity with one of the highest selectivities for CO2/CH4 separation of the literature, arising as a promising alternative adsorbent for natural gas or biogas upgrading at reduced cost. The presence of high nitrogen content together with pores of diameter around 2 nm leads to an increase of the CO2 adsorption capacity. In the case of chitosan-PMO-based materials, the activation step using both acid and crushing methods is crucial to increase the CO2 adsorbed amount. Here, the highest CO2 adsorption capacity and the highest selectivity are obtained by the chitosan-PMO crushed adsorbent and the chitosan-PMO material activated with sulfuric acid, respectively. These observations indicate the importance of the controlled attack of the material surface to enhance the diffusion of the target gases within the adsorbent, avoiding the adsorption of other species.

Interest in producing films from renewable and biodegradable polymers, such as polysaccharides, has increased in recent years with the aim of reducing the environmental pollution caused by petroleum-based plastics. Additionally, combining the thermoplastic property of starch with the antioxidant and antimicrobial activities of chitosan is of great interest to develop active materials for food packaging. This study aims the preparation of thermoplastic blended starch-chitosan films mechanically reinforced with reduced graphene oxide (rGO). Blending the starch with chitosan and rGO showed that films had a hydrophobic surface (100°), low water solubility (weight loss less than 10%), and improved antioxidant activity. Furthermore, blended film prepared with 75% starch and 25% chitosan with rGO achieved the maximum value of electrical conductivity (6.51 × 10

Carbonaceous materials derived from biomass have been used as sustainable platforms for the growth of ZnO particles aiming the production of functional composite fillers. Kidney-bean pods were pyrolyzed by applying an experimental design that demonstrates that the specific surface area (SBET) of biochar is improved with increasing pyrolysis temperature combined with a short air-oxidation time. Meanwhile, the graphitization degree and the electrical conductivity (EC) of biochars were negatively affected by increasing the air-oxidation time. The biochar sample with the higher EC and the one with the higher SBET were selected to be functionalized with ZnO particles by a solvothermal methodology, obtaining composites with an EC and SBET properties superior to the ZnO-rGO composite, in addition to a similar antibacterial activity. The developed ZnO-biochar composite structures, which are more ecological and biocompatible than the ZnO composites derived from graphene sheets, can be applied as electrically conductive and active fillers.

Inflammatory bowel disease (IBD) is a group of disabling, destructive and incurable immune-mediated inflammatory diseases comprising Crohn's disease (CD) and ulcerative colitis (UC), disorders that are highly prevalent worldwide and demand a large investment in healthcare. A persistent inflammatory state enables the dysfunction and destruction of healthy tissue, hindering the initiation and endurance of wound healing. Current treatments are ineffective at counteracting disease progression. Further, increased risk of serious side effects, other comorbidities and/or opportunistic infections highlight the need for effective treatment options. Gut microbiota, the key to preserving a healthy state, may, alternatively, increase a patient's susceptibility to IBD onset and development given a relevant bacterial dysbiosis. Hence, the main goal of this review is to showcase the main conventional and emerging therapies for IBD, including microbiota-inspired untargeted and targeted approaches (such as phage therapy) to infection control. Special recognition is given to existing targeted strategies with biologics (via monoclonal antibodies, small molecules and nucleic acids) and stimuli-responsive (pH-, enzyme- and reactive oxygen species-triggered release), polymer-based nanomedicine that is specifically directed towards the regulation of inflammation overload (with some nanosystems additionally functionalized with carbohydrates or peptides directed towards M1-macrophages). The overall goal is to restore gut balance and decrease IBD's societal impact., Portuguese Foundation for Science and Technology (FCT), FEDER funds by means of Portugal 2020 Competitive Factors Operational Program (POCI) and the Portuguese Government (OE) for funding the project PEPTEX with reference PTDC/CTMTEX/28074/2017 (POCI-01-0145-FEDER-028074). Using national funds through FCT/MCTES (Ministry of Science, Technology and Higher Education) the authors are also grateful for the funding associated with the project UID/CTM/00264/2020 of Centre for Textile Science and Technology (2C2T), and UIDB/QUI/50006/2020 of Associated Laboratory for Green Chemistry-Clean Technologies and Processes (LAQV). SCL acknowledges funding from FCT/MEC (Ministry of Education and Science; CEECIND/01620/2017), CN is thankful to FCT for the investigator Grant (IF/00293/2015) and JMD thanks FCT PhD grant 2020.07387.BD

We present pH-responsive phosphorylcholine polymersomes ability to target activated macrophages via scavenger receptors, enter them via endocytosis, and escape from early endosomes enabling the intra-cellular drug delivery. Using an arthritis experimental model and the gold standard disease modifying anti-rheumatic drug, methotrexate, we prove that polymersomes augments therapeutic efficacy, while minimizing the off-target effect. First, we demonstrate the selective accumulation of polymersomes within the inflamed synovial tissues and cells, including macrophages. Second, we show the beneficial therapeutic effect of methotrexate loaded polymersomes in preventing both joint inflammation and further damage. Hence, we prove the therapeutic potential of polymersomes in enhancing the complete prevention of arthritis progression, which makes it a promising nanotherapy for arthritis treatment as well as other inflammatory disorders.TeaserWe show that the effective targeting and delivery of drugs to the main inflammation actors, the macrophages, enhances arthritis therapy.

Cichorium intybus L. or chicory plants are a natural source of health-promoting compounds in the form of supplements such as inulin, as well as other bioactive compounds such as sesquiterpene lactones (SLs). After inulin extraction, chicory roots are considered waste, with most SLs not being harnessed. We developed and optimized a new strategy for SL extraction that can contribute to the conversion of chicory root waste into valuable products to be used in human health-promoting applications. In our work, rich fractions of SLs were recovered from chicory roots using supercritical CO2. A response surface methodology was used to optimize the process parameters (pressure, temperature, flow rate, and co-solvent percentage) for the extraction performance. The best operating conditions were achieved at 350 bar, 40 °C, and 10% EtOH as a co-solvent in a 15 g/min flow rate for 120 min. The extraction with supercritical CO2 revealed to be more selective for the SLs than the conventional solid–liquid extraction with ethyl acetate. In our work, 1.68% mass and a 0.09% sesquiterpenes yield extraction were obtained, including the recovery of two sesquiterpene lactones (8-deoxylactucin and 11β,13-dihydro-8-deoxylactucin), which, to the best of our knowledge, are not commercially available. A mixture of the abovementioned compounds were tested at different concentrations for their toxic profile and anti-inflammatory potential towards a human calcineurin/NFAT orthologue pathway in a yeast model, the calcineurin/Crz1 pathway. The SFE extract obtained, rich in SLs, yielded results of inhibition of 61.74 ± 6.87% with 50 µg/mL, and the purified fraction containing 8-deoxylactucin and 11β,13-dihydro-8-deoxylactucin inhibited the activation of the reporter gene up to 53.38 ± 3.9% at 10 µg/mL. The potential activity of the purified fraction was also validated by the ability to inhibit Crz1 nuclear translocation and accumulation. These results reveal a possible exploitable green technology to recover potential anti-inflammatory compounds from chicory roots waste after inulin extraction.

Apple concentrate juice industry generates a flavored coproduct (apple aroma) recovered in the evaporation process, which is poorly valuated due to the lack of chemical characterization and standardization. In this study, industry apple aroma was characterized, allowing for the identification of 37 compounds, the majority esters (20), alcohols (7), and aldehydes (4). The storage temperature did not affect its volatile composition. Five key compounds were selected and monitored for 10 months of storage, and also compared with other three productions of another season allowing for observation of the same Aroma Index. Apple pomace was also used to produce a hydrodistillate. Contrary to the apple aroma, apple pomace hydrodistillate was unpleasant, reflected in a different volatile composition. Although no additional aroma fraction could be obtained from this wet byproduct, when dried, apple pomace presented 15 volatile compounds with toasted, caramel, sweet, and green notes. The infusions prepared with the dried apple pomace exhibited 25 volatile compounds with a very pleasant (fruity, apple-like, citrus, and spicy notes) and intense aroma. The addition of sugar changed the volatile profile, providing a less intense flavor, with almond, caramel, and sweet notes. These results show that apple aroma and pomace are high-quality flavoring agents with high potential of valuation as food ingredients.

Reduced graphene oxide (rGO) is a promising graphene-based material, with transversal applicability to a wide range of technological fields. Nevertheless, the common use of efficient—but hazardous to environment and toxic—reducing agents prevents its application in biological and other fields. Consequently, the development of green reducing strategies is a requirement to overcome this issue. Herein, a green, simple, and cost-effective one-step reduction methodology is presented. Graphene oxide (GO) was hydrothermally reduced in the presence of caffeic acid (CA), a natural occurring phenolic compound. The improvement of the hydrothermal reduction through the presence of CA is confirmed by XRD, Raman, XPS and TGA analysis. Moreover, CA polymerizes under hydrothermal conditions with the formation of spherical and non-spherical carbon particles, which can be useful for further rGO functionalization. FTIR and XPS confirm the oxygen removal in the reduced samples. The high-resolution scanning transmission electron microscopy (HRSTEM) images also support the reduction, showing rGO samples with an ordered graphitic layered structure. The promising rGO synthesized by this eco-friendly methodology can be explored for many applications.

A Estatística tem marcada importância na Psicologia, pelo que na maioria dos cursos de licenciatura e mestrado em Psicologia são incluídas uma ou duas unidades curriculares sobre Probabilidades e Estatística. No entanto, o ensino da Estatística em Psicologia tem-se mostrado um desafio pedagógico. Os alunos manifestam frequentemente graves dificuldades com vários temas da Estatística, fracas competências matemáticas e uma tendência a desgostar do tema. Esta dissertação revê a história e o papel da Estatística em Psicologia, e explora as competências em Estatística de alunos licenciados em Psicologia, avaliando-as e relacionando-as com as competências matemáticas e a atitude em relação à Estatística (SATS-28). Statistics plays an important role in Psychology, and with that being, many psychology curriculums include one or several Probability and Statistics courses. However, teaching statistics and research methods to psychology students has been a pedagogic challenge. Students often show difficulty and poor knowledge in several statistical fields, lack mathematics skills and a tendency to dislike this discipline. This study reviews the history and role of statistic in psychology, and explores statistical skills on psychology graduate students, while assessing their mathematics skills and attitudes towards statistics (SATS-28). Mestrado em Psicologia da Saúde e Reabilitação Neuropsicológica

The world of (poly)phenols arising from dietary sources has been significantly amplified with the discovery of low molecular weight (LMW) (poly)phenol metabolites resulting from phase I and phase II metabolism and microbiota transformations. These metabolites, which are known to reach human circulation have been studied to further explore their interesting properties, especially regarding neuroprotection. Nevertheless, once in circulation, their distribution to target tissues, such as the brain, relies on their ability to cross the blood-brain barrier (BBB), one of the most controlled barriers present in humans. This represents a key step of an underexplored journey towards the brain. Present review highlights the main findings related to the ability of LMW (poly)phenol metabolites to reach the brain, considering different studies: in silico, in vitro, and in vivo. The mechanisms associated with the transport of these LMW (poly)phenol metabolites across the BBB and possible transporters will be discussed. Overall, the transport of these LMW (poly)phenol metabolites is crucial to elucidate which compounds may exert direct neuroprotective effects, so it is imperative to continue dissecting their potential to cross the BBB and the mechanisms behind their permeation. publishersversion published

Obra ressenyada: Rudolf MUHR; Eugênia DUARTE; Amália MENDES; Carla AMORÓS; Juan A. THOMAS, Pluricentric Languages and Non-Dominant Varieties Worldwide. Part II : The Pluricentricity of Portuguese and Spanish. New Concepts and Descriptions. Frankfurt am Main: Peter Lang, 2016.

This article considers an incumbent’s product innovation decision within an uncertain framework, where the firm decides whether to continue selling the established product. The model being dynamic allows to analyze the trade-off between an early innovation where the new product only slightly improves the existing one, or innovating late with a much better new product. We find that the effect of uncertainty is that it raises the value of the strategy where the firm keeps on producing the old product after innovating. This results in earlier investment if the firm stays active on the established product market after adopting the new product, and that it keeps on producing the established product for a longer time after the product innovation. Limited uncertainty could lead to a non-monotonicity: with a better new product it is not optimal to innovate, whereas innovating is optimal with a worse one.

This paper considers investment problems in real options with non-homogeneous two-factor uncertainty. We derive some analytical properties of the resulting optimal stopping problem and present a finite difference algorithm to approximate the firm’s value function and optimal exercise boundary. An important message in our paper is that the frequently applied quasi-analytical approach underestimates the impact of uncertainty. This is caused by the fact that the quasi-analytical solution does not satisfy the partial differential equation that governs the value function. As a result, the quasi-analytical approach may wrongly advise to invest in a substantial part of the state space.

A levan-type fructooligosaccharide was produced by a Paenibacillus strain isolated from Brazilian crude oil, the purity of which was 98.5% after precipitation with ethanol and dialysis. Characterization by FTIR, NMR spectroscopy, GC-FID and ESI-MS revealed that it is a mixture of linear (26) fructosyl polymers with average degree of polymerization (DP) of 18 and branching ratio of 20. Morphological structure and physicochemical properties were investigated to assess levan microstructure, degradation temperature and thermomechanical features. Thermal Gravimetric Analysis highlighted degradation temperature of 218°C, Differential Scanning Calorimetry (DSC) glass transition at 81.47°C, and Dynamic Mechanical Analysis three frequency-dependent transition peaks. These peaks, corresponding to a first thermomechanical transition event at 86.60°C related to the DSC endothermic event, a second at 170.9°C and a third at 185.2°C, were attributed to different glass transition temperatures of oligo and polyfructans with different DP. Levan showed high morphological versatility and technological potential for the food, nutraceutical, and pharmaceutical industries., São Paulo Research Foundation (FAPESP) within Grants 2020/13271-6 and 2018/25511-1. Additionally, the authors acknowledge the financial support by National Council for Scientific and Technological Development – CNPq and by Coordination for the Improvement of Higher Education Personnel (CAPES), Finance Code 001. In addition, this study was supported by the Portuguese Science Foundation (FCT) under the scope of the strategic funding of UID/BIO/04469/2020 unit and the Project FOSYNBIO (POCI-01-0145-FEDER-029549)., info:eu-repo/semantics/publishedVersion

Cardiovascular (CV) toxicity is nowadays recognized as a class effect of non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs). However, their mechanisms of cardiotoxicity are not yet well understood, since different compounds with similar action mechanisms exhibit distinct cardiotoxicity. For instance, diclofenac (DIC) is among the most cardiotoxic compounds, while naproxen (NAP) is associated with low CV risk. In this sense, this study aimed to unravel the role of drug-lipid interactions in NSAIDs-induced cardiotoxicity. For that, DIC and NAP interactions with lipid bilayers as model systems of cell and mitochondrial membranes were characterized by derivative spectrophotometry, fluorometric leakage assays, and synchrotron X-ray scattering. Both DIC and NAP were found to have the ability to permeabilize the membrane models, as well as to alter the bilayers&rsquo, structure. The NSAIDs-induced modifications were dependent on the lipid composition of the membrane model, the three-dimensional structure of the drug, as well as the drug:lipid molar ratio tested. Altogether, this work supports the hypothesis that NSAIDs-lipid interactions, in particular at the mitochondrial level, may be another key step among the mechanisms underlying NSAIDs-induced cardiotoxicity.

CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior A presente pesquisa visa desvendar o surgimento e as condições de produção de onze edificações em São Luís do Maranhão reconhecidas pelos órgãos do patrimônio como “solares” e analisar seus diálogos com a cultura arquitetônica local. Essas edificações são exemplares do expoente da arquitetura residencial produzida durante a “Idade do Ouro” no Maranhão. Além da excepcionalidade das técnicas construtivas aplicadas, vinculações com fatos e personagens históricos maranhenses que lhes conferiram status de monumento, as dimensões dessas edificações possibilitam um maior número de usos. Todavia, os novos usos que lhes conferem ressignificação cultural, trazem consigo riscos de perda da integridade e autenticidade, riscos esses majorados pela falta de bibliografia especializada que abarque as especificidades das tipologias das casas senhoriais ludovicenses. Isto posto, a presente pesquisa busca reduzir esta lacuna de conhecimento sobre as moradas ludovicenses, apontando as características tipológicas dos solares, distinguindo suas composições materiais arquitetônicas em relação às demais tipologias edilícias das moradas oitocentistas em São Luís, desvendando temporalmente o papel da atribuição da nomenclatura “solar” em relação às arquiteturas respectivas e suas representações sociais, culturais e políticas, verificando também a congruência dessa denominação para o conjunto do casario definido por essa nomenclatura. Ao corrigir essa lacuna, pretende proporcionar um arcabouço teórico robusto sobre os solares ludovicenses, contribuindo para sua interpretação e preservação de sua integridade em futuras intervenções. The present research seeks to unravel the emergence and production conditions of eleven buildings in Sao Luis, Maranhão, recognized as “solares” by heritage protection agencies and their interrelationship with the local architectural culture. These buildings are specimens of the exponent residential architecture produced during the “Golden Age” in Maranhão. Besides the exceptional construction techniques applied, bonds with historic facts and characters from Maranhão, which vested these buildings with monument statuses, their dimensions allow numerous uses. However, the new uses which vest them with cultural resignification put them at risk of losing their integrity and authenticity. These risks are increased by the lack of specialized literature embracing the specificities of São Luis manor houses typologies. Therefore, the present research intends to narrow the knowledge gap on São Luis’s dwellings by pointing up the typological characteristics of solares, distinguishing their architectonic material composition from other 19th-century residential building typologies, unveiling temporally the role of “solar” denomination in relation to respective construction and their social, cultural and political representations, verifying the adequacy of the nomenclature for the buildings called this way. By filling in this gap, it will provide a robust theoretical framework on solares in Sao Luis, contributing to their interpretation and integrity preservation in future interventions.

Submitted by marta feitosa (martaceliafeitosa@yahoo.com.br) on 2021-03-26T18:51:01Z No. of bitstreams: 1 A escrita do gênero diário e o aprend do port c seg lín p surd - Ana Claudia N. do Nascimento.pdf: 284771 bytes, checksum: e72f9d10eebeaae1c477e67fa9796ac5 (MD5) Approved for entry into archive by Josinete Nobrega Araujo (josinete@ifpb.edu.br) on 2021-04-06T23:16:02Z (GMT) No. of bitstreams: 1 A escrita do gênero diário e o aprend do port c seg lín p surd - Ana Claudia N. do Nascimento.pdf: 284771 bytes, checksum: e72f9d10eebeaae1c477e67fa9796ac5 (MD5) Made available in DSpace on 2021-04-06T23:16:02Z (GMT). No. of bitstreams: 1 A escrita do gênero diário e o aprend do port c seg lín p surd - Ana Claudia N. do Nascimento.pdf: 284771 bytes, checksum: e72f9d10eebeaae1c477e67fa9796ac5 (MD5) Previous issue date: 2020-12-15 O presente trabalho faz parte de uma pesquisa que traz em sua temática o aprendizado de Língua Portuguesa como segunda língua para surdos através do gênero diário. Em nossa problemática, buscamos compreender como a escrita do gênero diário pode motivar o aluno surdo no aprendizado do Português como segunda língua. Para responder a essa problemática, traçamos como objetivos compreender a relevância da escrita do gênero diário para o ensino do Português como segunda língua; refletir sobre a importância dos gêneros textuais no aprendizado de uma segunda língua; discutir sobre a relevância da produção do gênero diário para o aprendizado do aluno surdo e compreender a produção do diário como motivação para a escrita. Nossa metodologia pautou-se na pesquisa bibliográfica, visto que realizamos a reflexão sobre dois artigos que abordam o gênero diário. Como aporte teórico, consideramos as discussões de Bakhtin (1997), de Cunha (2007), Bortolazzo (2010), Pozzani e Steffler (2016), Reis (2012), que nos trazem um olhar sobre o gênero diário; Strobel (2009), Fernandes (2006) e demais autores. Ao refletirmos sobre a pesquisa, compreendemos que o gênero diário é de grande valia no aprendizado de Português para o surdo, visto que a escrita desse poderá auxiliar no processo de transição entre a coloquialidade e formalidade, além do desenvolvimento do léxico e a aprendizagem de outros gêneros.

Agrofood byproducts may be exploited as a source of biomolecules suitable for developing bioplastic materials. In this work, the feasibility of using starch, oil, and waxes recovered from potato chips byproducts for films production was studied. The recovered potato starch-rich fraction (RPS) contained an amylopectin/amylose ratio of 2.3, gelatinization temperatures varying from 59 to 71 °C, and a gelatinization enthalpy of 12.5 J/g, similarly to a commercial potato starch (CPS). Despite of its spherical and oval granules identical to CPS, RPS had a more amorphous structure and gave rise to low viscous suspensions, contradicting the typical B-type polymorph crystal structure and sluggish dispersions of CPS, respectively. When used for films production, RPS originated transparent films with lower roughness and wettability than CPS-based films, but with higher stretchability. In turn, when combined with RPS and CPS, oil or waxes recovered from frying residues and potato peels, respectively, allowed to develop transparent yellowish RPS- and CPS-based films with increased surface hydrophobicity, mechanical traction resistance, elasticity, and/or plasticity. Therefore, potato chips industry byproducts revealed to have thermoplastic and hydrophobic biomolecules that can be used to efficiently develop biobased plastics with improved surface properties and flexibility, opening an opportunity for their valorization. published

Chemical characterization before and after gastro-intestinal digestion, and cytotoxicity data.

Crosslinking with genipin increases the acidic stability of chitosan-based materials, opening an opportunity to explore new applications. In this work, the viability of using chitosan-genipin solutions on cellulose-based materials coating was studied. Non-calendered paper and cardboard were used as raw materials. Different number of chitosan-genipin coating layers (1, 3, 6, 20, and 30) were applied and their influence on the materials mechanical, physicochemical, and barrier properties was studied. The small thickness and basis weight of non-calendered paper resulted in an inefficient adhesion of chitosan-genipin coating to the cellulose fibers. However, in cardboard, chitosan-genipin created a dense layer onto the cellulosic-fibers surface without impairing their mechanical properties. It conferred a greenish color, whose intensity increased with the layers number. The chitosan-genipin coating decreased the cardboard air and water vapor permeability up to 71 % and 52 %, respectively, and acted as a physical barrier for cardboard compounds leaching, being suitable for covering cellulose-based materials. published

Impairment of the p53 pathway is a critical event in cancer. Therefore, reestablishing p53 activity has become one of the most appealing anticancer therapeutic strategies. Here, we disclose the p53-activating anticancer drug (3S)-6,7-bis(hydroxymethyl)-5-methyl-3-phenyl-1H,3H-pyrrolo[1,2-c]thiazole (MANIO). MANIO demonstrates a notable selectivity to the p53 pathway, activating wild-type (WT)p53 and restoring WT-like function to mutant (mut)p53 in human cancer cells. MANIO directly binds to the WT/mutp53 DNA-binding domain, enhancing the protein thermal stability, DNA-binding ability, and transcriptional activity. The high efficacy of MANIO as an anticancer agent toward cancers harboring WT/mutp53 is further demonstrated in patient-derived cells and xenograft mouse models of colorectal cancer (CRC), with no signs of undesirable side effects. MANIO synergizes with conventional chemotherapeutic drugs, and in vitro and in vivo studies predict its adequate drug-likeness and pharmacokinetic properties for a clinical candidate. As a single agent or in combination, MANIO will advance anticancer-targeted therapy, particularly benefiting CRC patients harboring distinct p53 status., We thank PT national funds (FCT/MCTES, Fundação para a Ciência e a Tecnologia, and Ministério da Ciência, Tecnologia e Ensino Superior) through grants UIDB/50006/2020, UID/BIO/04469/2019, UIDB/04539/2020, and UIDP/04539/2020 (CIBB); BioTecNorte operation (NORTE-01-0145-FEDER000004) and Porto Neurosciences and Neurologic Disease Research Initiative at I3S (Norte-01-0145-FEDER-000008) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte; Masaryk University (Project MUNI/A/1127/2019) and Ministry of Education, Youth and Sports of the Czech Republic (project nos. LQ1605 and LM2018125); FCT financial support through the fellowships SFRH/BD/119144/2016 (H.R.) and SFRH/BD/117949/2016 (L.R.); Fondazione AIRC (IG#18985, A.I.); and the Programa Operacional Potencial Humano (POCH), specifically the BiotechHealth Programme (Doctoral Programme on Cellular and Molecular Biotechnology Applied to Health Sciences, PD/00016/2012). We thank Dario Rizzotto for assistance in preparing the libraries for RNA sequencing. Funding: This work was supported by PT National Funds (FCT/MCTES, Fundação para a Ciência e Tecnologia, and Ministério da Ciência, Tecnologia e Ensino Superior) via the projects UIDB/50006/2020 (LAQV/REQUIMTE), UIDB/00313/2020, and UIDP/00313/2020, co-funded by COMPETE2020-UE., info:eu-repo/semantics/publishedVersion

The extracellular polysaccharides produced by cyanobacteria have distinctive characteristics that make them promising for applications ranging from bioremediation to biomedicine. In this study, a sulfated polysaccharide produced by a marine cyanobacterial strain and named cyanoflan was characterized in terms of morphology, chemical composition, and rheological and emulsifying properties. Cyanoflan has a 71 % carbohydrate content, with 11 % of sulfated residues, while the protein account for 4 % of dry weight. The glycosidic-substitution analysis revealed a highly branched complex chemical structure with a large number of sugar residues. The cyanoflan high molecular mass fractions (above 1 MDa) and entangled structure is consistent with its high apparent viscosity in aqueous solutions and high emulsifying activity. It showed to be a typical non-Newtonian fluid with pseudoplastic behavior. Altogether, these results confirm that cyanoflan is a versatile carbohydrate polymer that can be used in different biotechnological applications, such as emulsifying/thickening agent in food or cosmetic industries. published

In this work, a process for the extraction and purification of carotenoids from the fruit Bactris gasipaes was developed. Ethanolic and aqueous solutions of ionic liquids (ILs) and surfactants were evaluated on the extraction of these pigments. Thus, we developed an optimized sustainable downstream process mediated by the best solvent with further isolation of the carotenoids and the recyclability of the IL used. The process was characterized not only in terms of efficiency but also regarding its environmental impact. The recyclability of the solvents as well as the high efficiency (maximum yield of extraction of carotenoids = 88.7 ± 0.9 μgcarotenoids·gdried biomass–1) and the low environmental impact of the integrated process developed in this work were demonstrated. In the end, in order to incorporate functional activity for an alternative food-packaging material, carotenoids were successfully applied on the preparation of chitosan-based films with excellent results regarding their mechanical parameters and antioxidant activity. published

This paper presents a novel analysis of two feed-in tariffs (FIT) under market and regulatory uncertainty, namely a sliding premium with cap and floor and a minimum price guarantee. Regulatory uncertainty is modeled with a Poisson process, whereby a jump event may reduce the tariff before the signature of the contract. Using a semi-analytical real options framework, we derive the project value, the optimal investment threshold, and the value of the investment opportunity for these schemes. Taking into consideration the optimal investment threshold, we also compare the two aforementioned FITs with the fixed-price FIT and the fixed-premium FIT, which are policy schemes that have been extensively studied in the literature. Our results show that increasing the likelihood of a jump event lowers the investment threshold for all the schemes; moreover, the investment threshold also decreases when the tariff reduction increases. We also compare the four schemes in terms of the corresponding optimal investment thresholds. For example, we find that the investment threshold of the sliding premium is lower than the minimum price guarantee. This result suggests that the first regime is a better policy than the latter because it accelerates the investment while avoiding excessive earnings for producers or excessive payments for consumers., This work was supported by a PhD scholarship provided by Fundação para a Ciência e a Tecnologia (FCT) through the MIT Portugal program under project SFRH/BD/52086/2013, and was supported by national funds through FCT with references UIDB/50021/2020, UIDB/03182/2020, CEMAT -UIDB/04621/2020, and UIDP/04621/2020. In addition, this material is based upon work supported by the Air Force Office of Scientific Research under award number FA9550-19-1-0020. Claudia Nunes acknowledges support from FCT through project reference FARO_PTDC/EGEECO/30535/2017, through national funds, and the Research Council of Norway through project nr. 268093

Polar lipids from microalgae have aroused greater interest as a natural source of omega-3 (n-3) polyunsaturated fatty acids (PUFA), an alternative to fish, but also as bioactive compounds with multiple applications. The present study aims to characterize the polar lipid profile of cultured microalga Emiliania huxleyi using hydrophilic interaction liquid chromatography coupled with high-resolution mass spectrometry (HILIC&ndash, MS) and fatty acids (FA) analysis by gas chromatography (GC&ndash, MS). The lipidome of E. huxleyi revealed the presence of distinct n-3 PUFA (40% of total FA), namely docosahexaenoic acid (22:6n-3) and stearidonic acid (18:4n-3), which give this microalga an increased commercial value as a source of n-3 PUFA present in the form of polar lipids. A total of 134 species of polar lipids were identified and some of these species, particularly glycolipids, have already been reported for their bioactive properties. Among betaine lipids, the diacylglyceryl carboxyhydroxymethylcholine (DGCC) class is the least reported in microalgae. For the first time, monomethylphosphatidylethanolamine (MMPE) has been found in the lipidome of E. huxleyi. Overall, this study highlights the potential of E. huxleyi as a sustainable source of high-value polar lipids that can be exploited for different applications, namely human and animal nutrition, cosmetics, and pharmaceuticals.

The main objective of this study was to clarify the topical mechanisms underlying diclofenac-induced gastric toxicity by considering for the first time both ionization states of this nonsteroidal anti-inflammatory drug. 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC) liposomes were the model system chosen to mimic the protective phospholipid layers of the gastric mucosa and to describe the interactions with diclofenac, considering the pH gradient found in the gastric mucosa (3 < pH < 7.4). Complementary experimental techniques were combined to evaluate the drug's affinity for DMPC bilayers, as well as to assess the drug's effects on the structural properties of the phospholipid bilayer. The diclofenac-DMPC interactions were clearly dependent on the drug's ionization state. Neutral diclofenac displayed greater affinity for DMPC bilayers than anionic diclofenac. Moreover, the protonated/neutral form of the drug induced more pronounced and/or distinct alterations in the structure of the DMPC bilayer than the deprotonated/ionized form, considering similar membrane concentrations. Therefore, neutral diclofenac-induced changes in the structural properties of the external phospholipid layers of the gastric mucosa may constitute an additional toxicity mechanism of this worldwide-used drug, which shall be considered for the development of safer therapeutic strategies. SIGNIFICANCE STATEMENT: Neutral or anionic diclofenac exerted distinct alterations in phosphatidylcholine bilayers, which are used in this work as models for the protective phospholipid layers of the gastric mucosa. Remarkable changes were induced by neutral diclofenac in the structural properties of the phospholipid bilayer, suggesting that both ionized and neutral states of nonsteroidal anti-inflammatory drugs must be considered to clarify their mechanisms of toxicity and to ultimately develop safer anti-inflammatory drugs.

Cinnamon is a spice widely used as a flavouring agent in foodstuffs. Despite its commercial availability and low cost, C. burmannii aqueous extracts obtained by decoction originate high viscous solutions (1545 cP) when compared with C. verum (51 cP), preventing its broad use by food industry. Following the hypothesis that cinnamon polysaccharides are responsible for this viscosity, in this work, the hot water-soluble polysaccharides from C. burmannii were structurally characterized, using C. verum for comparison. The results showed that C. burmannii had a higher content of branched arabinoxylans in relation to C. verum. The hot water-soluble polysaccharides from C. verum comprised also glucans, arabinogalactans, and pectic polysaccharides. The partial mild acid-hydrolysis performed to C. burmannii allowed to reach a viscosity value near to the C. verum solutions, keeping the characteristic aroma profile of cinnamon by the predominance of cinnamaldehyde and other varietal compounds, namely mono and sesquiterpenoids. Therefore, C. burmannii can be used as flavouring and thickening agent, whereas low viscosity products can be obtained by a partial acid-hydrolysis, contributing to its wide application in food industry.

Background Cell-penetrating peptides (CPPs) have been extensively exploited in gene therapy approaches as vectors for intracellular delivery of bioactive molecules. The ability of CPPs to be internalized into cells and their capacity to complex nucleic acids depend on their molecular structure, both primary and secondary, namely regarding hydrophobicity/hydrophilicity. CPP acylation has been used as a strategy to improve this structural feature. Methods Acyl groups (from 6 to 18 carbon atoms) were attached to the S413-PV peptide and their effects on the peptide competence to complex siRNAs and to mediate gene silencing in glioblastoma (GBM) cells were studied. A systematic characterization of membrane interactions with S413-PV acyl-derivatives was also conducted, using different biophysical techniques (surface pressure-area isotherms in Langmuir monolayers, DSC and 31P NMR) to unravel a relationship between CPP biological activity and CPP effects on membrane stability and lipid organization. Results A remarkable concordance was noticed between acylated-S413-PV peptide competence to promote gene silencing in GBM cells and disturbance induced in membrane models, the lauroyl- and myristoyl-S413-PV peptides being the most effective. A cut-off effect was described for the first time regarding the influence of acyl-chain length on CPP bioactivity. Conclusions C12-S413-PV showed high capacity to destabilize lipid bilayers, to escape from lysosomal degradation and to mediate gene silencing without promoting cytotoxicity. General significance Besides unraveling a new CPP with high potential to be employed as a gene delivery vector, this work emphasizes the benefit from allying biophysical and biological studies towards a proper CPP structural refinement for successful pre-clinical/clinical application.

An adapted methodology for obtaining lipid nanoparticles that only uses the microwave reactor in the synthesis process was developed. The method has the following features: one-pot, one-step, fast, practical, economical, safe, readiness of scaling-up, lack of organic solvents and production of nanoparticles with low polydispersity index (PDI) (below 0.3). This new method was applied for the development of nanostructured lipid carriers (NLC) loaded with a hydrophilic drug, the antiretroviral agent zidovudine (AZT). The aim of the present work was to develop, evaluate and compare optimized NLC formulations produced by two different methods - hot ultrasonication and microwave-assisted method. The development and optimization of the NLC formulations were supported by a Quality by Design (QbD) approach. All formulations were physicochemically characterized by the same parameters. The optimized formulations presented a suitable profile for oral administration (particle size between 100 and 300 nm, PDI 0.3 and negative zeta potential-20 mV). Furthermore, the morphologies assessed by TEM showed spherical shape and confirmed the results obtained by DLS. Both AZT loaded formulations were physically stable for at least 45 days and non-toxic on Jurkat T cells. Drug release studies showed a controlled release of AZT under gastric and plasma-simulated conditions.

This paper analyses the following hitherto understudied feature in real switching options: a firm has a mothballing option and an option to permanently abandon. If the firm finds itself in an operating mode with a price just above the abandonment threshold, it is un-clear whether to exercise the abandonment option or to exercise the mothballing option. If the price goes down, the firm may exit, but, surprisingly, if it goes up, it may mothball. We find that two different strategies could be optimal: one where mothballing is not a viable option and one where mothballing does occur. In the latter case a hysteresis region arises in which the firm produces at a loss, while a further price decrease induces exit and a sufficient price increase results in the firm entering the mothballing stage. Mothballing being optimal requires sufficiently large values of the price trend and the uncertainty parameter. (C) 2018 Elsevier B.V. All rights reserved.

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.

Chitosan-based functional materials are emerging for food applications. The covalent bonding of molecular entities demonstrates to enhance resistance to the typical acidity of food assigning mechanical and moisture/gas barrier properties. Moreover, the grafting to chitosan of some functional molecules, like phenolic compounds or essential oils, gives antioxidant, antimicrobial, among others properties to chitosan. The addition of nanofillers to chitosan and other biopolymers improves the already mentioned required properties for food applications and can attribute electrical conductivity and magnetic properties for active and intelligent packaging. Electrical conductivity is a required property for the processing of food at low temperature using electric fields or for sensors application.

A irradiação de alimentos é um método de conservação utilizado pela indústria na qual determinados tipos de alimentos são expostos à radiação ionizante de maneira controlada e por tempo adequado. Diante do contexto, o objetivo do presente artigo foi analisar as produções científicas sobre a utilização do processo de irradiação em alimentos em relação a sua conservação e aumento da vida útil. Este estudo utilizou como método a revisão bibliográfica, onde por princípio buscou-se publicações indexadas na plataforma Scientific Electronic Library Online (ScIELO), provenientes dos anos de 2011 a 2015 e que possuíssem relação com a área de alimentos e ciências agrárias. O corpus de análise foi composto por 11 artigos, que tiveram seus resumos e conclusões analisados sistematicamente. Eram integralmente brasileiros, escritos em português, majoritariamente publicados no ano de 2011 e resultantes do estado de São Paulo (36,36%). Foram identificados sete periódicos, com destaque para as revistas: Revista Brasileira de Fruticultura e Ciência Rural, que foram responsáveis por 54,54% das produções acerca do assunto analisado. E por fim, foi possível dividir os resultados em duas categorias temáticas, sendo a primeira, vantagens da irradiação de alimentos e a segunda, desvantagens da irradiação de alimentos. A partir de todo o exposto ficou explicito a necessidade e importância de mais pesquisa relacionada a este método de conservação de alimentos, com o intuito de minimizar as desvantagens levantadas neste estudo.

Gastrointestinal (GI) toxicity is a major drawback of the chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs). The NSAIDs topical actions on the protective phospholipid layers of the GI mucosa seem to be a central toxicity mechanism of these pharmaceuticals. This work describes the interactions of acemetacin, a commercialized NSAID, with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayers at pH 3.0, 5.0, and 7.4. This pH range was chosen to mimic the pH gradient found in the gastric mucosa, and to ultimately gain insights into the mechanisms underlying the acemetacin-induced gastric toxicity. Various experimental techniques were combined to characterize the partitioning of acemetacin in DMPC bilayers, and its effects on the phase transition behavior, as well as the structure and dynamics of DMPC bilayers. The acemetacin-DMPC interactions were clearly pH-dependent. The neutral (protonated) form of acemetacin had more affinity for the DMPC bilayer than the negatively charged form. Due to the higher affinity of neutral acemetacin, the drug effects on the phase transition and the structure and dynamics of the DMPC bilayer were more pronounced at lower pH values. In general, acemetacin decreased the temperature and the cooperativity of the lipid phase transition and induced changes in the packing and dynamics of the DMPC bilayer. These results support the hypothesis that acemetacin-induced gastric toxicity may be related to its effects on the protective phospholipid layers of the mucosal barrier.