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Advanced Air Mobility (AAM) is an emerging sector that aims to optimise transportation in urban and interurban environments using Unmanned Aerial Vehicles (UAVs). However, these aircraft are particularly susceptible to adverse weather phenomena, such as turbulence or wind gusts. To ensure the safety of operations, high-resolution real-time atmospheric prediction models, such as those based on Computational Fluid Dynamics (CFD), are required. The development of these systems faces challenges as accurate geometric models of navigation environments are needed to simulate the interaction between the wind and the terrain and infrastructure. These models feature complex geometries, so they cannot be manually crafted, requiring automated processing of geospatial data sources. As the main novelty, this work presents a methodology for the automated modelling of interurban environments for CFD simulations using digital elevation models and georeferenced surface semantic classification data. A practical case study was developed in the outskirts of Vigo (Spain), where we demonstrate the effectiveness of our approach and its integration with the open-source CFD software OpenFOAM.

The interest in aluminum-magnesium alloy additive manufacturing through Wire-arc Directed Energy Deposition (DED) technology has substantially grown in recent years. The main challenge in additive manufactured aluminum-magnesium alloys is the occurrence of porosity. In this context, Gas Metal Arc Welding (GMAW) based additive technology is suitable for aluminum printing as it allows high deposition rates and reduces porosity levels through alternative metal transfer modes without adding any extra equipment. Therefore, this research explores the effects of these alternative metal transfer modes, which determine the current signal shape and polarity, on the distribution and morphology of micropores using X-ray computed tomography in both single-bead and double-bead walls. The novelty of this paper lies in the comparison of the porosity obtained using alternative transfer modes, which, unlike CMT (Cold Metal Transfer) modes, have not been exhaustively analyzed. Additionally, to date, there has been no comprehensive comparison of the porosity results obtained in single walls and overlapped walls. The results demonstrate that pulsed-AC transfer mode with a current signal featuring variable polarity yields acceptable porosity fraction values of less than 0.04% in single-bead walls and less than 0.01% in double-bead walls, achieving high productivity.

Invar 36 alloy is of high interest in various industrial sectors, due to its reduced thermal expansion properties. This study aims to validate Wire-Arc Additive Manufacturing (WAAM) technology as a valid method for manufacturing aerospace tooling in Invar 36. The main novelty and the objective of this work is to study the properties of Invar deposited by WAAM technology and to provide guidelines for the manufacture of parts using this technology. To do so, the thermal expansion behaviour of Invar specimens manufactured using Gas Metal Arc Welding (GMAW)-based WAAM technology and Plasma Arc Welding (PAW)-based WAAM technology is analyzed for subsequent comparison with the values obtained from the laminated Invar sample used as the reference specimen. A wall is manufactured with each technology, for comparative purposes, from which specimens were extracted for the dilatometry test and metallographic analysis. The results of these analyses show the advantages of GMAW technology for the manufacture of Invar alloy parts, as it presents the same thermal expansion behaviour as the laminated reference material with less presence of precipitates and no macrostructural failures such as pores, cracks and lacks of fusion. Furthermore, to conclude, an aeronautical tooling that has been manufactured within this work demonstrated the potential of this technology to manufacture specialized aeronautical parts.

The development of biotechnology-based active pharmaceutical ingredients, such as GLP-1 analogs, brought changes in type 2 diabetes treatment options. For better therapeutic efficiency, these active pharmaceutical ingredients require appropriate administration, without the development of adverse effects or toxicity. Therefore, it is required to develop several quantification methods for GLP-1 analogs products, in order to achieve the therapeutic goals, among which ELISA and HPLC arise. These methods are developed, optimized and validated in order to determine GLP-1 analogs, not only in final formulation of the active pharmaceutical ingredient, but also during preclinical and clinical trials assessment. This review highlights the role of ELISA and HPLC methods that have been used during the assessment for GLP-1 analogs, especially for exenatide. Keywords: Type 2 diabetes, Exenatide, Therapeutic drug monitoring, ELISA, HPLC

The association of Comamonas kerstersii with peritonitis resulting from the presence of perforated appendix has previously been described by our research team. In the present study, we describe the isolation of this microorganism from two forms of unusual presentations of C. kerstersii infection not previously described in the literature: localized intra-abdominal infection (psoas abscess) and pelvic peritonitis.

The large-scale industrial use of polysaccharides to obtain energy is one of the most discussed subjects in science. However, modern concepts of biorefinery have promoted the diversification of the use of these polymers in several bioproducts incorporating concepts of sustainability and the circular economy. This work summarizes the major sources of agro-industrial residues, physico-chemical properties, and recent application trends of cellulose, chitin, hyaluronic acid, inulin, and pectin. These macromolecules were selected due to their industrial importance and valuable functional and biological applications that have aroused market interests, such as for the production of medicines, cosmetics, and sustainable packaging. Estimations of global industrial residue production based on major crop data from the United States Department of Agriculture were performed for cellulose content from maize, rice, and wheat, showing that these residues may contain up to 18%, 44%, and 35% of cellulose and 45%, 22%, and 22% of hemicellulose, respectively. The United States (~32%), China (~20%), and the European Union (~18%) are the main countries producing cellulose and hemicellulose-rich residues from maize, rice, and wheat crops, respectively. Pectin and inulin are commonly obtained from fruit (~30%) and vegetable (~28%) residues, while chitin and hyaluronic acid are primarily found in animal waste, e.g., seafood (~3%) and poultry (~4%).

The study analyzes the consistency of future precipitation extremes projected over China under moderate climate scenarios (RCP4.5 and SSP2-4.5) and extreme climate scenarios (RCP8.5 and SSP5-8.5), based on best models' ensembles for each extreme index (best-MME), best models' ensembles regarding all indices (best-rankMME), and multi-model ensembles (MME). To select the best models, the integrated quadratic distance (IQD) combined with the Taylor skill score are used. This evaluation is a practical example of the benefits of using IQD to evaluate the models compared with root mean square error since the former is not sensitive to the similarity of the distribution's averages. All ensembles in each scenario consistently project the decrease of consecutive dry days (CDD) periods in western and northeast China, the increase of the number of days with heavy precipitation (R10mm) over the Qinghai-Tibet Plateau, and the increase of the precipitation intensity (SDII) in most of the Chinese territory. The moderate and extreme scenarios project very similar climate change patterns but more extreme scenarios show greater climate change signal magnitudes. In the case of the moderate scenarios, the most significant uncertainty relies on the CDD projections over southeastern China, where best-rankMME and MME project increasing CDD in the future whilst best-MME project decreasing CDD, although these changes are not statistically significant. Regarding extreme scenarios, the most significant uncertainty relies on the R10mm projections over southeastern China, where the best-MME CMIP5 projects decreasing R10mm (not statistically significant), whilst all the remaining ensembles project increasing values.

The performance of the coupled ocean–atmosphere component of the Brazilian Earth System Model version 2.5 (BESM-OA2.5) was evaluated in simulating the historical period 1850–2005. After a climate model validation procedure in which the main atmospheric and oceanic variabilities were evaluated against observed and reanalysis datasets, the evaluation specifically focused on the mean climate state and the most important large-scale climate variability patterns simulated in the historical run, which was forced by the observed greenhouse gas concentration. The most significant upgrades in the model's components are also briefly presented here. BESM-OA2.5 could reproduce the most important large-scale variabilities, particularly over the Atlantic Ocean (e.g., the North Atlantic Oscillation, the Atlantic Meridional Mode, and the Atlantic Meridional Overturning Circulation), and the extratropical modes that occur in both hemispheres. The model's ability to simulate such large-scale variabilities supports its usefulness for seasonal climate prediction and in climate change studies.

Terpenes are specialized metabolites mainly produced by plants and are highly bioactive [...]

Bacuri (Platonia insignis Mart) is a species from the Clusiaceae genus. Its fruit pulp is commonly used in South America in several food products, such as beverages, ice cream and candies. Only the pulp of the fruit is used, and the peels and seeds are considered waste from these industries. As a trioxygenated xanthone source, this species is of high interest for bioproduct development. This work evaluated the mesocarp and epicarp of bacuri fruits through different extraction methods and experimental conditions (pH, temperature and solvent) in order to determine the most effective method for converting this agro-industrial waste in a value-added bioproduct. Open-column procedures and HPLC and NMR experiments were performed to evaluate the chemical composition of the extracts, along with total phenols, total flavonoids and antioxidant activities (sequestration of the DPPH and ABTS radicals). A factorial design and response surface methodology were used. The best extraction conditions of substances with antioxidant properties were maceration at 50 °C with 100% ethanol as solvent for mesocarp extracts, and acidic sonication in 100% ethanol for epicarp extracts, with an excellent phenolic profile and antioxidant capacities. The main compounds isolated were the prenylated benzophenones garcinielliptone FC (epicarp) and 30-epi-cambogin (mesocarp). This is the first study analysing the performance of extraction methods within bacuri agro-industrial waste. Results demonstrated that shells and seeds of bacuri can be used as phenolic-rich bioproducts obtained by a simple extraction method, increasing the value chain of this fruit.

Small cell bladder cancer (SCBC) is found in 0.5–1.2% of all bladder tumors. Ureteroceles are dilatation of the distal portion of an ectopic ureter, which association with tumors are rare. This article reports the first case described of an SCBC developed into a ureterocele, beyond a literature review. Keywords: Ureterocele, Double ureter, Small-cell, Bladder cancer

BACKGROUND Scedosporium apiospermum is a ubiquitous, emerging and multidrug-resistant fungal pathogen with still rather unknown virulence mechanisms. OBJECTIVES/METHODS The cellular basis of the in vitro interaction between fungi and host cells/tissues is the determinant factor for the development of a successful in vivo infection. Herein, we evaluated the interaction of S. apiospermum conidia with lung epithelial (A549), lung fibroblast (MRC-5) and RAW 264.7 macrophages by light and scanning/transmission electron microscopy. FINDINGS After 4 h of fungi-host cell contact, the percentage of infected mammalian cells and the number of fungi per infected cell was measured by light microscopy, and the following association indexes were calculated for A549, MRC-5 and macrophage cells: 73.2 ± 25.9, 69.7 ± 22.5 and 59.7 ± 11.1, respectively. Both conidia and germinated conidia were regularly observed interacting with the evaluated cells, with a higher prevalence of non-germinated conidia. Interestingly, nests of germinated conidia were evidenced at the surface of lung cells by scanning electron microscopy. Some germination projections and hyphae were seen penetrating/evading the mammalian cells. Furthermore, internalised conidia were seen within vacuoles as visualised by transmission electron microscopy. MAIN CONCLUSIONS The present study contributes to a better understanding of S. apiospermum pathogenesis by demonstrating the first steps of the infection process of this opportunistic fungus.

Onychomycosis is a chronic fungal infection of nails, commonly caused by dermatophyte fungi, primarily species of Trichophyton. Because of the limited drug arsenal available to treat general fungal infections and the frequent failure of onychomycosis treatment, the search for new therapeutic sources is essential, and topical treatment with natural products for onychomycosis has been encouraged. Propolis, an adhesive resinous compound produced by honeybees (Apis mellifera), has shown multiple biological properties including significant antifungal and anti-biofilm activities in vitro. In spite of promising in vitro results, in vivo results have not been reported so far. This study assessed an ethanol propolis extract (PE) as a topical therapeutic option for onychomycosis, including its characterization in vitro and its applicability as a treatment for onychomycosis (from bench to clinic). The in vitro evaluation included analysis of the cytotoxicity and the antifungal activity against the planktonic cells and biofilm formed by Trichophyton spp. We also evaluated the capacity of PE to penetrate human nails. Patients with onychomycosis received topical PE treatments, with a 6-month follow-up period. The results of the in vitro assays showed that PE was non-toxic to the cell lines tested, and efficient against both the planktonic cells and the biofilm formed by Trichophyton spp. The results also showed that PE is able to penetrate the human nail. The results for PE applied topically to treat onychomycosis were promising, with complete mycological and clinical cure of onychomycosis in 56.25% of the patients. PE is an inexpensive commercially available option, easy to obtain and monitor. Our results indicated that PE is a promising natural compound for onychomycosis treatment, due to its ability to penetrate the nail without cytotoxicity, and its good antifungal performance against species such as Trichophyton spp. that are resistant to conventional antifungals, both in vitro and in patients.

Essential oils are natural products with a complex composition. Terpenes are the most common class of chemical compounds present in essential oils. Terpenes and the essential oils containing them are widely used and investigated by their pharmacological properties and permeation-enhancing ability. However, many terpenes and essential oils are sensitive to environmental conditions, undergoing volatilization and chemical degradation. In order to overcome the chemical instability of some isolated terpenes and essential oils, the encapsulation of these compounds in nanostructured systems (polymeric, lipidic, or molecular complexes) has been employed. In addition, nanoencapsulation can be of interest for pharmaceutical applications due to its capacity to improve the bioavailability and allow the controlled release of drugs. Topical drug administration is a convenient and non-invasive administration route for both local and systemic drug delivery. The present review focuses on describing the current status of research concerning nanostructured delivery systems containing isolated terpenes and/or essential oils designed for topical administration and on discussing the use of terpenes and essential oils either for their biological activities or as permeation enhancers in pharmaceutic formulations.

BACKGROUND: Depression is prevalent among women and associated with reduced quality of life, and therefore it is important to determine its incidence in adult women, especially in those with breast cancer. OBJECTIVE: To determine the occurrence of depression in women who underwent conservative surgery for breast cancer with or without breast reconstruction. METHODS: Seventy-five women aged between 18 and 65 years were enrolled. Patients had undergone conservative surgery for breast cancer with immediate breast reconstruction (n = 25) or without breast reconstruction (n = 25) at least one year before the study. The control group consisted of 25 women without cancer, but of similar age and educational level distribution as the other two groups. The Beck Depression Inventory was used to measure depression. The collected data were assessed using analysis of variance and the χ2 test. RESULTS: There were no significant differences between groups in age (p = 0.72) or educational level (p = 0.20). A smaller number of patients had undergone the menopause (p = 0.02) in the control group than in other groups. There were no significant differences in occurrence of depression between groups (χ2=9.97; p = 0.126). CONCLUSÍON: Conservative surgery for breast cancer did not affect the occurrence of depression in women, regardless of whether breast reconstruction was performed.

Plant-derived substances have been considered as important sources of drugs, including antineoplasic agents. Babassu mesocarp is popularly used in Brazil as a food additive, and in popular medicine against several conditions, such as inflammations, menstrual pains and leukaemia. From babassu Orbignya speciosa (Mart.) Barb. Rodr. [Arecaceae (Palmae)] epicarp/mesocarp, an ethanol extract was prepared and named OSEME, which was tested on the viability,morphology and metabolism of several cell lines, such as the leukaemic cell lines, HL-60, K562 and the latter multidrug resistant counterpart K562-Lucena 1, the human breast cancer cell line MCF-7, the mouse fibroblast cell line 3T3-L1 and fresh human lymphocytes. OSEME promoted a dose-dependent decrease on the viability of all cells. This effect was much more pronounced on the tumoral cell lines than on non-tumoral cells, a phenomenon revealed by the dose of OSEME which promotes half of maximal effect (ID50). The decrease on viability was followed by shrinkage of cells, alteration on their morphology, and a markedly nuclear condensation. Curiously, stimulation of 6-phosphofructokinase activity (6.6-times) was observed on HL-60 cells, treated with OSEME, when compared to control treated with ethanol (vehicle). These results support evidences to suggest OSEME as a promising source of novel antineoplasic agents.Substâncias derivadas de plantas têm sido usadas como importante fonte de agentes antineoplásicos. O mesocarpo do babaçu é popularmente usado no Brasil como suplemento alimentar e na medicina popular para o tratamento de várias afecções, tais como: inflamações, cólicas menstruais e leucemia. A partir do epicarpo/mesocarpo do babaçu Orbignya speciosa (Mart.) Barb. Rodr. [Arecaceae (Palmae)] foi preparado um extrato etanólico, denominado OSEME, o qual foi incubado com as seguintes linhagens humanas leucêmicas: HL-60, K562 e a sua derivada resistente a múltiplas drogas, K562-Lucena 1; além destas, foram testadas a linhagem humana de câncer de mama, MCF-7; a linhagem de fibroblastos de camundongo, 3T3-L1 e linfócitos humanos de sangue periférico. OSEME promoveu diminuição da viabilidade em todas as linhagens celulares testadas de maneira dose-dependente. Este efeito foi mais pronunciado sobre as linhagens celulares tumorais quando comparado às não tumorais, o que foi revelado pela dose de OSEME capaz de promover metade do efeito máximo (ID50). A diminuição da viabilidade foi acompanhada por danos sobre a morfologia celular com pronunciada condensação citoplasmática e nuclear. Curiosamente, quando a linhagem HL-60 foi tratada com OSEME, foi detectado um aumento de 6,6 vezes da atividade da enzima 6-fosfofrutoquinase, quando comparado ao grupo controle (células tratadas com o veículo etanol). Esses resultados sugerem que OSEME pode ser uma promissora fonte de novos agentes antineoplásicos.

The antimicrobial activity of copaiba oils was tested against Gram-positive and Gram-negative bacteria, yeast, and dermatophytes. Oils obtained from Copaifera martii, Copaifera officinalis, and Copaifera reticulata (collected in the state of Acre) were active against Gram-positive species (Staphylococcus aureus, methicillin-resistant S. aureus, Staphylococcus epidermidis, Bacillus subtilis, and Enterococcus faecalis) with minimum inhibitory concentrations ranging from 31.3-62.5 µg/ml. The oils showed bactericidal activity, decreasing the viability of these Gram-positive bacteria within 3 h. Moderate activity was observed against dermatophyte fungi (Trichophyton rubrum and Microsporum canis). The oils showed no activity against Gram-negative bacteria and yeast. Scannning electron microscopy of S. aureus treated with resin oil from C. martii revealed lysis of the bacteria, causing cellular agglomerates. Transmission electron microscopy revealed disruption and damage to the cell wall, resulting in the release of cytoplasmic compounds, alterations in morphology, and a decrease in cell volume, indicating that copaiba oil may affect the cell wall.

O gênero Copaifera L. é um dos mais importantes economicamente na Região Amazônica devido, principalmente, à produção dos óleos de copaíba, oléo-resinas com diversas propriedades farmacológicas confirmadas. Apesar disso, os estudos fitoquímicos com as sementes das árvores do gênero Copaifera L.são raros. Copaifera officinalis foi a primeira espécie do gênero Copaifera a ser descrita. Este trabalho descreve a composição dos extratos obtidos em hexano e em acetato de etila das sementes de C. officinalis. No extrato obtido em hexano, a análise por cromatografia em fase gasosa utilizando padrões e através de espectrometria de massas permitiu a identificação de: esqualeno, tetradecano, hexadecano, campesterol, estigmasterol e beta-sitosterol; os ácidos graxos hexadecanóico, 9-octadecenóico e octadecanóico (majoritários); e decanóico, eicosanóico, docosanóico e tetracosanóico (minoritários). Cumarina foi isolada do extrato em acetato de etila e identificada por técnicas de RMN.Copaifera L. is one of the most economically important plant genera in the Amazon Region, since it exudes a resin-oil named copaiba oil possessing several confirmed pharmacological properties. In spite of that, phytochemical studies of the seeds from this genus are rare. Copaifera officinalis L. was the first species in the genus Copaifera to be described. This paper describes the chemical composition of the hexane and ethyl acetate extracts of the seeds from this species. In the hexane extract, gas chromatography and mass spectrometry analyses enabled us to identify squalene, tetradecane, hexadecane, campesterol, stigmasterol and beta-sitosterol; hexadecanoic, 9-octadecenoic and octadecanoic acids (major substances); as well as decanoic, eicosanoic, docosanoic and tetracosanoic (minor substances) acids. Coumarin was detected in the ethyl acetate extract, isolated and identified by NMR.

This review details the history, chemistry and pharmacology of the Copaifera L. genus (Leguminosae - Caesalpinoideae), including copaiba oils.

α-Amyrenone and β-amyrenone are triterpenoid isomers that occur naturally in very low concentrations in several oleoresins from Brazilian Amazon species of Protium (Burseraceae). This mixture can also be synthesized by oxidation of α,β-amyrins, obtained as major compounds from the same oleoresins. Using a very simple, high yield procedure, and using a readily commercially available mixture of α,β-amyrins as substrate, the binary compound α,β-amyrenone was synthesized and submitted to physico-chemical characterization using different techniques such as high-performance liquid chromatography, nuclear magnetic resonance (1H and 13C), mass spectrometry, scanning electron microscopy, differential scanning calorimetry, thermogravimetry and derivative thermogravimetry, and Fourier transform infrared spectroscopy (FTIR). Biological effects were also evaluated by studying the inhibition of enzymes involved in the carbohydrate and lipid absorption process, such as α-amylase, α-glucosidase, lipase, and their inhibitory concentration values of 50% of activity (IC50) were also determined. α,β-Amyrenone significantly inhibited α-glucosidase (96.5% ± 0.52%) at a concentration of 1.6 g/mL. α,β-Amyrenone, at a concentration of 100 µg/mL, showed an inhibition rate on lipase with an IC50 value of 82.99% ± 1.51%. The substances have thus shown in vitro inhibitory effects on the enzymes lipase, α-glucosidase, and α-amylase. These findings demonstrate the potential of α,β-amyrenone for the development of drugs in the treatment of chronic metabolic diseases.