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A ocupação intensa e desordenada ocorrida nas últimas décadas na região do Núcleo Rural Lago Oeste (LO), inserida na bacia do ribeirão Tortinho, bem como, o aumento das atividades agrícolas e irrigação, passando a totalizar aproximadamente 22% da bacia, tornou-se um fator preocupante dado que o ribeirão Tortinho contribui para o abastecimento de água para consumo humano em Brasília. Ademais, em face à irregularidade da ocupação urbana, não há abastecimento de água pela companhia local e ocorre a explotação de águas subterrâneas no LO para abastecimento e irrigação. Logo, este trabalho teve como objetivo avaliar o efeito das alterações de uso e cobertura do solo na vazão do ribeirão Tortinho e analisar o impacto devido à exploração de águas subterrâneas sobre o escoamento de base no ribeirão Tortinho. Para avaliar a influência das mudanças ocorridas no uso e cobertura do solo sobre a vazão foi realizada simulação com o modelo de bacia SWAT e aplicado o teste de Kolmogorov-Smirnov nas séries de vazão, enquanto, na avaliação do efeito da retirada de água por poços na região sobre o escoamento de base, foram considerados cenários para a simulação com o modelo acoplado SWAT-MODFLOW. Observou-se que as alterações ocorridas na vazão simulada em face às mudanças de uso e cobertura (1975 e 2013) não foram estatisticamente significantes. Os cenários simulados com maior número de poços, baseados em levantamento de campo, como forma de aproximar mais à situação real, leva a uma extensa área de secamento na região do LO prolongando-se para dentro do Parque Nacional de Brasília, o que afetaria a vegetação nativa e o escoamento de base. Dessa forma, a retirada de águas subterrâneas no LO pode ter impacto significativo no nível freático no domínio poroso e, portanto, verifica-se a importância de hidrometração dos poços na região para que seja realizada a gestão adequada das águas da bacia.

The objective of the study is to evaluate the evolution of the physical and physiological quality of rice seeds throughout the processing process, analyzing the efficiencyof the equipment used in three Seed Processing Units (UBS) to produce certified seeds, located in the region of the inner coastal plain of Lagoa dos Patos. We know that the seed has to be made in the field, starting with the choice of the area, providing a good management and controlling invaders, pests and diseases, but we believe that UBS has a very important role in seed quality, and this is the purpose of this study. Each unit with its equipment on its production line was analyzed. The cultivar IRGA 424 RI was used in the three units, samples were taken at the exit of each equipment, tests for seedling emergence, germination, physical purity and determination of other contaminatingspecies were carried out. A gradual increase in purity and germination was observed along the processing line in the three UBS’s, except for the determination of weedy rice, where equipment was not efficient.

Lung cancer is still the main cause of cancer-related deaths worldwide. Its treatment generally includes surgical resection, immunotherapy, radiotherapy, and chemo-targeted therapies such as the application of tyrosine kinase inhibitors. Gefitinib (GEF) is one of them, but its poor solubility in gastric fluids weakens its bioavailability and therapeutic activity. In addition, like all other chemotherapy treatments, GEF administration can cause damage to healthy tissues. Therefore, the development of novel GEF delivery systems to increase its bioavailability and distribution in tumor site is highly demanded. Herein, an innovative strategy for GEF delivery, by functionalizing PLGA nanoparticles with p28 (p28-NPs), a cell-penetrating peptide derived from the bacterial protein azurin, was developed. Our data indicated that p28 potentiates the selective interaction of these nanosystems with A549 lung cancer cells (active targeting). Further p28-NPs delivering GEF (p28-NPs-GEF) were able to selectively reduce the metabolic activity of A549 cells, while no impact was observed in non-tumor cells (16HBE14o-). In vivo studies using A549 subcutaneous xenograft showed that p28-NPs-GEF reduced A549 primary tumor burden and lung metastases formation. Overall, the design of a p28-functionalized delivery nanosystem to effectively penetrate the membranes of cancer cells while deliver GEF could provide a new strategy to improve lung cancer therapy.

Actinidia arguta (Siebold & Zucc.) Planch. ex Miq. (kiwiberry) leaves are a source of phenolic compounds with pro-health biological effects, such as antioxidant and anti-inflammatory activities. Despite the huge number of studies reporting the composition of A. arguta leaves, no in vitro or in vivo studies explore its potential use as nutraceutical ingredient based on these activities. Therefore, this study aims to characterize the safety profile of kiwiberry leaf extracts using in vitro and in vivo approaches through the assessment of intestinal cell viability (Caco-2 and HT29-MTX), 3D intestinal permeation, and, most important, the redox markers, biochemical profile and liver and kidney function effects after the animal assays. Briefly, wistar rats were orally treated for 7 days with kiwiberry leaf extracts (50 and 75 mg/kg bw), water (negative control), or vitamin C (positive control). The cell viability was above 90% at 1000 μg/mL for both cells. Coumaroyl quinic acid and rutin achieved a permeation higher than 25% in the 3D intestinal model. The animal studies confirmed the extracts’ ability to increase superoxide dismutase, glutathione peroxidase, and catalase content in animals’ livers and kidneys while simultaneously decreasing the triglycerides content. This study highlighted the antioxidant capacity of kiwiberry leaf extracts, ensuring their efficacy and safety as a nutraceutical ingredient, This research was funded by project EXPL/BAA-GR/0663/2021—Kiwi4Health—Exploring the Eco-Innovative Re-Use of Kiwiberry, supported by national funds by FCT/MCTES and by the projects UIDB/50006/2020 and UIDP/50006/2020 through national funds. This work was also financed by national funds from FCT—Fundação para a Ciência e a Tecnologia, I.P., in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences—UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB. The authors are thankful to Minikiwi Land for the samples and all availability during this work. Ana Margarida Silva is thankful for the Ph.D. grant (SFRH/BD/144994/2019) financed by POPH-QREN and subsidized by the European Science Foundation and Ministério da Ciência, Tecnologia e Ensino Superior. Francisca Rodrigues (CEECIND/01886/2020) is thankful for her contract financed by FCT/MCTES—CEEC Individual Program Contract.

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) with mixed-lineage leukemia gene rearrangement (MLL-r) is a poor-prognosis subtype for which additional therapeutic targets are urgently needed. Currently no multi-omics data set for primary MLL r patient cells exists that integrates transcriptomics, proteomics and glycomics to gain an inclusive picture of theranostic targets. Methods: We have integrated transcriptomics, proteomics and glycomics to i) obtain the first inclusive picture of primary patient BCP-ALL cells and identify molecular signatures that distinguish leukemic from normal precursor B-cells and ii) better understand the benefits and limitations of the applied technologies to deliver deep molecular sequence data across major cellular biopolymers. Results: MLL-r cells feature an extensive remodeling of their glycocalyx, with increased levels of Core 2-type O-glycans and complex N-glycans as well as significant changes in sialylation and fucosylation. Notably, glycosaminoglycan remodeling from chondroitin sulfate to heparan sulfate was observed. A survival screen, to determine if glycan remodeling enzymes are redundant, identified MGAT1 and NGLY1, essential components of the N-glycosylation/degradation pathway, as highly relevant within this in vitro screening. OGT and OGA, unique enzymes that regulate intracellular O-GlcNAcylation, were also indispensable. Transcriptomics and proteomics further identified Fes and GALNT7-mediated glycosylation as possible therapeutic targets. While there is overall good correlation between transcriptomics and proteomics data, we demonstrate that a systematic combined multi-omics approach delivers important diagnostic information that is missed when applying a single omics technology. Conclusions: Apart from confirming well-known MLL-r BCP-ALL glycoprotein markers, our integrated multi-omics workflow discovered previously unidentified diagnostic/therapeutic protein targets.

Mixed-lineage Acute Leukemia (MLL) is one of the most high-risk forms of pediatric cancer. Although the long-term survival rates of pediatric acute lymphoblastic leukemia have increased over the past 40 years, the current chemotherapeutic treatment schemes often fail in the treatment of MLL. The biological mechanisms resulting in drug resistance, however, are still not fully understood and there is an urgent need to identify novel diagnostic and therapeutical targets. We have established the first integrated multi-omics investigation of primary patient MLL samples and control precursor B bonemarrow cells from healthy donors, mapping their proteome, transcriptome and glycome. 4–6 million cells from 3 normal bone marrow (BM) and 2 MLL samples were used for analysis on our multi-omics platform. Porous-Graphitised Carbon (PGC) nanoLC-ESIMS/MS was used for Glycomics analyses after the enzymatic and chemical release of N- and O-glycans, respectively. The proteome was explored using RP-LC-ESI-MS/MS analyses, performed after offline high-pH fractionation, in addition to RNA-seq analyses. Overall, 4225 proteins were identified across the patient MLL and control BM cells, of which 216 were overexpressed in MLL (p 2). Preliminary analyses of the RNA-seq data matched well with the proteomics findings, revealing significant alterations in expression of glycoprotein signalling receptors and extracellular matrix proteins as well as various transcription factors. High-pH fractionation also allowed us to identify numerous important glycosyltransferases and expression changes thereof on protein and RNA– seq level. N- and O-glycomics revealed overall lower levels of α2–6 sialylated N- and O-glycans in MLL cells (correlating with ST6Gal1 transcript and ST6Gal1 protein levels) as well as an increase in Core 2 type O-glycans (correlating with GCNT1 transcript level). Patient MLL cells exhibit distinct N- and O-glycan fingerprints, along with specific alterations of receptor tyrosine kinase signalling networks. In addition to wellknown MLL glycoprotein markers, our integrated multiomics workflow identified a number of diagnostic/therapeutic protein candidates that have not previously been described.

Objetivo: analisar produções cientí­ficas de enfermagem dos últimos dez anos que abordem as ações e orientações para o plano de alta de mulheres submetidas í mastectomia. Método: Para a realização da busca de artigos realizou uma revisão sistemática de artigos utilizados - estratégia PICO, nos idiomas Português, Inglês e Espanhol respectivamente. Resultados: Foram utilizadas 19 publicações para a posterior discussão, onde 15 eram de sí­ntese qualitativa e 4 de sí­ntese quantitativa. Conclusão: A maioria dos artigos evidenciou que as intervenções de enfermagem no plano de alta a mulheres submetidas í mastectomia foram baseadas na educação continuada dessas mulheres e também de seus familiares. Essa ferramenta consiste em orientações baseadas na utilização de drenos, apoio emocional, possibilidade de esvaziamento axilar, identificação de sinais de infecções e manejo nos curativos.

Colorectal cancer (CRC) is a heterogeneous disease with high incidence and mortality worldwide. The efficacy of conventional CRC chemotherapy is hampered by poor drug solubility and bioavailability and suboptimal pharmacokinetic profiles. In this work, camptothecin (CPT), a potent anticancer drug, was loaded into an amphiphilic chitosan modified with PEG and oleic acid, to reduce CRC progression after oral administration. While CPT-loaded micelles presented anticancer activity against HCT116, Caco-2 and HT29 CRC cell lines in vitro, empty micelles demonstrated a safe profile when incubated with human blood cells and colorectal cancer cell lines. In a more complex 3D CRC multicellular spheroid model, CPT-loaded micelles also exhibited a significant effect on the spheroid's metabolic activity and size reduction. Remarkably, in vivo studies performed in a HCT116 xenograft model, showed a significant reduction on the tumor growth during and after treatment with CPT-loaded micelles. Moreover, in a more biological relevant in vivo model of chemically-induced CRC, orally administered CPT-loaded micelles demonstrated a significant reduction on tumor incidence and inflammation signs. The findings here reported indicate that CPT-loaded into chitosan-based micelles, by improving drug solubility, alongside its safety profile for normal tissues, may have a promising role CRC chemotherapy.

The objective of this study was to develop zein-casein-lysine nanoparticles to modulate the intestinal permeability of ferulic acid (FA), a bioactive compound with proven antioxidant properties. The nanoparticles were obtained by a liquid-liquid dispersion method and were characterized in terms of mean size, polydispersity index, zeta potential, association efficiency (AE), in vitro drug release, x-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR). The in vitro intestinal permeability of nanoparticles was evaluated through Caco-2 and Caco-2/HT29-MTX monoculture and co-culture models, respectively. Nanoparticles presented a mean size of 199 nm and zeta potential of −26 mV. The AE of FA was 23% evaluated by high-performance liquid chromatography (HPLC). XRD showed amorphization of FA after association and FT-IR showed no changes in chemical structures of the compounds after nanoencapsulation. The cytotoxicity assays demonstrated that multicomposite nanoparticles presented a safe profile against Caco-2 and HT29-MTX cells. In the in vitro permeability assay, free FA exhibited higher permeability compared to FA-loaded nanoparticles, possibly due to prolonged FA release from nanoparticles. These new developed zein-casein-lysine nanoparticles may be used for FA sustained delivery by the oral route.

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) with mixed-lineage leukemia gene rearrangement (MLL-r) is a poor-prognosis subtype for which additional therapeutic targets are urgently needed. Currently no multi omics data set for primary MLL r patient cells exists that integrates transcriptomics, proteomics and glycomics to gain an inclusive picture of theranostic targets.MethodsWe have integrated transcriptomics, proteomics and glycomics to i) obtain the first inclusive picture of primary patient BCP-ALL cells and identify molecular signatures that distinguish leukemic from normal precursor B-cells and ii) better understand the benefits and limitations of the applied technologies to deliver deep molecular sequence data across major cellular biopolymers.ResultsMLL-r cells feature an extensive remodelling of their glycocalyx, with increased levels of Core 2-type O-glycans and complex N-glycans as well as significant changes in sialylation and fucosylation. Notably, glycosaminoglycan remodelling from chondroitin sulfate to heparan sulfate was observed. A survival screen, to determine if glycan remodelling enzymes are redundant, identified MGAT1 and NGLY1, essential components of the N-glycosylation/degradation pathway, as highly relevant within this in vitro screening. OGT and OGA, unique enzymes that regulate intracellular O-GlcNAcylation, were also indispensable. Transcriptomics and proteomics further identified Fes and GALNT7-mediated glycosylation as possible therapeutic targets. While there is overall good correlation between transcriptomics and proteomics data, we demonstrate that a systematic combined multi-omics approach delivers important diagnostic information that is missed when applying a single omics technology.ConclusionsApart from confirming well-known MLL-r BCP-ALL glycoprotein markers, our integrated multi-omics workflow discovered previously unidentified diagnostic/therapeutic protein targets.Graphical abstract

In vitro cell-based models have been used for a long time since they are normally easily obtained and have an advantageous cost-benefit. Besides, they can serve a variety of ends, from studying drug absorption and metabolism to disease modeling. However, some in vitro models are too simplistic, not accurately representing the living tissues. It has been shown, mainly in the last years, that fully mimicking a tissue composition and architecture can be paramount for cellular behavior and, consequently, for the outcomes of the studies using such models. Because of this, 3D in vitro cell models have been gaining much attention, since they are able to better replicate the in vivo environment. In this review we focus on 3D models that contain mucus-producing cells, as mucus can play a pivotal role in drug absorption. Being frequently overlooked, this viscous fluid can have an impact on drug delivery. Thus, the aim of this review is to understand to which extent can mucus affect mucosal drug delivery and to provide a state-of-the-art report on the existing 3D cell-based mucus models.

The use of 3D printing technology in the manufacturing of drug delivery systems has expanded and benefit of a customized care. The ability to create tailor-made structures filled with drugs/delivery systems with suitable drug dosage is especially appealing in the field of nanomedicine. In this work, chitosan-based polymeric micelles loaded with camptothecin (CPT) were incorporated into 3D printing systems (printfills) sealed with an enteric layer, aiming to protect the nanosystems from the harsh environment of the gastrointestinal tract (GIT). Polymeric micelles and printfills were fully characterized and, a simulated digestion of the 3D systems upon an oral administration was performed. The printfills maintained intact at the simulated gastric pH of the stomach and, only released the micelles at the colonic pH. From there, the dissolution media was used to recreate the intestinal absorption and, chitosan micelles showed a significant increase of the CPT permeability compared to the free drug, reaching an apparent permeability coefficient (Papp) of around 9×10-6 cm/s in a 3D intestinal cell-based model. The combination of 3D printing with nanotechnology appears to have great potential for the colon-specific release of polymeric micelles, thereby increasing intestinal absorption while protecting the system/drug from degradation throughout the GIT.

Este estudo busca explorar a consolidação da história da Gerontologia no Brasil, bem como entender as alterações demográficas ocorridas na população brasileira que teve um importante aumento do número de idosos. Por consequência do crescimento da população idosa brasileira, surge o aumento da procura por conhecimento e pesquisa na área do envelhecimento no mundo acadêmico. Baseado nesse movimento crescente, o presente estudo objetivou descrever os motivos e contribuições percebidas por um grupo de profissionais em fase de conclusão de uma pós-graduação em Gerontologia. A pesquisa foi realizada com alunos convidados a participar voluntariamente, e conclui-se que a busca pela formação na área do envelhecimento é um processo permanente que proporciona diversas oportunidades de trabalho e uma grande área de atuação.

The oral administration of drugs remains a challenge due to rapid enzymatic degradation and minimal absorption in the gastrointestinal tract. Mechanical forces, namely hypergravity, can interfere with cellular integrity and drug absorption, and there is no study describing its influence in the intestinal permeability. In this work, it was studied the effect of hypergravity on intestinal Caco-2 cells and its influence in the intestinal permeability of different nanoformulations and molecules. It was shown that the cellular metabolic activity and integrity were maintained after exposure to different gravity-levels (g-levels). Expression of important drug transporters and tight junctions' proteins was evaluated and, most proteins demonstrated a switch of behavior in their expression. Furthermore, paracellular transport of FITC-Dextran showed to significantly increase with hypergravity, which agrees with the decrease of transepithelial electrical resistance and the increase of claudin-2 at higher g-levels. The diffusion of camptothecin released from polymeric micelles revealed a significant decrease, which agrees with the increased expression of the P-gp observed with the increase in g-levels, responsible for pumping this drug out. The neonatal Fc receptor-mediated transport of albumin-functionalized nanoparticles loaded with insulin showed no significant changes when increasing the g-levels. Thus, this study supports the effect of hypergravity on intestinal permeability is dependent on the molecule studied and the mechanism by which it is absorbed in the intestine.

Colorectal cancer (CRC) is a heterogeneous and molecularly complex disease, associated with high mortality worldwide, exposing the urgent need for novel therapeutic approaches. Their development and translation to the clinic have been hampered, partially due to the absence of reliable cellular models that resemble key features of the human disease. While traditional 2D models are not able to provide consistent and predictive responses about the in vivo efficiency of the formulation, animal models frequently fail to recapitulate cancer progression and to reproduce adverse effects. On its turn, multicellular 3D systems, by mimicking key genetic, physical and mechanical cues of the tumor microenvironment, constitute a promising tool in cancer research. In addition, they constitute more physiological and relevant environment for anticancer drugs screening and for predicting patient's response towards personalized approaches, bridging the gap between simplified 2D models and unrepresentative animal models. In this review, we provide an overview of CRC 3D models for translational research, with focus on their potential for nanomedicines screening.

This chapter focuses the challenges of repatriation. Although corporate expatriation has been receiving attention, this chapter seeks to complement this perspective embracing the analysis of the repatriation process. As such, the aim of this chapter is to broaden the knowledge on repatriation exploring previous studies. For this, the authors answer two research questions: Why is the process of expatriation regarded as more relevant than the repatriation process? What do MNEs need to improve to assure a good repatriation process? Regarding the first question, most of repatriation processes are seen by MNEs as the final stage of expatriation which makes companies pay less attention to repatriation as an independent process. Moreover, companies tend to care more with the short-term results of the expatriation experience than the long-term ones, so MNEs disregard the importance of the experience acquired by the repatriate. Regarding the second research question, one concludes that there are four main dimensions: manager feedback; manager network; human resources department and companies.

New types of companies have emerged, known as “Born Globals” (BGs), transitioning and internationalizing early and rapidly. They have attracted scholarly interest because their involvement in international sales from the moment of inception contradicts the more traditional perspectives on internationalization. This chapter explores a gap in the literature on BG micro-enterprises' behavior on their internationalization trajectory. It analyzes the case of a micro-company based in Aveiro, Portugal that follows a passive internationalization path to embrace a BG's typical behavior. The behavior of this micro-company is examined to illustrate how a BG can find new opportunities abroad and take advantage of them, the main entry modes and marketing strategies adopted in the early and rapid internationalization process, the importance of networking and growth strategies, and the role of the CEO in the internationalization process. This chapter adds value by explaining how a micro-enterprise manages to overcome its passive behavior and evolve into a BG company.

Atualmente, as organizações têm no seu capital humano trabalhadores de 3 gerações distintas. Quando associada a comportamentos característicos de cada faixa etária, a idade consiste num elemento distintivo entre grupos de trabalhadores. A multigeracionalidade pode ter impactos positivos e negativos na liderança e na gestão de recursos humanos, na medida em que a identidade geracional pode ser suscetível de determinar o que os indivíduos dessa geração querem do trabalho. Este estudo considera o conceito teórico de gerações e descreve as características distintivas que diferenciam as gerações Baby Boomers, Geração X e Geração Y. O objetivo deste estudo é observar a existência de diferenças nos valores de trabalho com base na segmentação por gerações e nas características comummente associadas a cada geração, no contexto específico da Administração Pública. É, ainda, objetivo deste estudo observar a existência de diferenças na perceção dos valores de trabalho valorizados pelas gerações e identificar quais os aspetos relacionados com o trabalho que cada geração considera como sendo positivos e negativos relativamente à sua e às restantes gerações. O estudo discute os resultados obtidos através da aplicação de 285 inquéritos a trabalhadores da Administração Pública. Os resultados obtidos evidenciam que não existem diferenças geracionais na graduação de valores de trabalho, contudo existem diferenças na perceção dos valores de trabalho valorizados pelas gerações. As diferenças percebidas podem resultar de crenças sobre gerações cabendo aos gestores de recursos humanos e à liderança intervir para desconstruir estereótipos. O estudo das gerações e da diversidade geracional no local de trabalho revela-se de interesse por ser um contributo para a análise das relações de trabalho, facilitando a compreensão de diferentes atitudes, valores e comportamentos dos trabalhadores de cada geração e por fornecer elementos para desenvolvimento de estratégias de trabalho em equipa. Today, organizations have in their human capital workers from 3 distinct generations. When associated with characteristic behaviours of each age group, age is a distinctive element among groups of workers. Multigenerationality can have both positive and negative impacts on leadership and human resource management, as generational identity may be able to determine what individuals in that generation want from work. This study considers the theoretical concept of generations and describes the distinctive characteristics that differentiate the Baby Boomers, Generation X and Generation Y. The aim of this study is to observe the existence of differences in work values based on generational segmentation and characteristics commonly associated with each generation, in the specific context of public administration. It is also the objective of this study to observe the existence of differences in the perception of the work values valued by the generations and to identify which aspects related to the work that each generation considers to be positive and negative in relation to theirs and the other generations. The study discusses the results obtained through the application of 285 surveys to Public Administration workers. The results obtained show that there are no generational differences in the graduation of work values, however there are differences in the perception of work values valued by generations. Perceived differences may result from beliefs about generations and it is important for human resource management and leadership to intervene to deconstruct stereotypes. The study of generations and generational diversity in the workplace is of interest as it contributes to the analysis of labour relations, facilitating the understanding of different attitudes, values and behaviours of the workers of each generation and providing elements for the development of teamwork strategies.