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Abstract Background Ischemia/reperfusion injury is the leading cause of acute kidney injury (AKI). The current standard of care focuses on supporting kidney function, stating the need for more efficient and targeted therapies to enhance repair. Mesenchymal stromal cells (MSCs) and their secretome, either as conditioned medium (CM) or extracellular vesicles (EVs), have emerged as promising options for regenerative therapy; however, their full potential in treating AKI remains unknown. Methods In this study, we employed an in vitro model of chemically induced ischemia using antimycin A combined with 2-deoxy-d-glucose to induce ischemic injury in proximal tubule epithelial cells. Afterwards we evaluated the effects of MSC secretome, CM or EVs obtained from adipose tissue, bone marrow, and umbilical cord, on ameliorating the detrimental effects of ischemia. To assess the damage and treatment outcomes, we analyzed cell morphology, mitochondrial health parameters (mitochondrial activity, ATP production, mass and membrane potential), and overall cell metabolism by metabolomics. Results Our findings show that ischemic injury caused cytoskeletal changes confirmed by disruption of the F-actin network, energetic imbalance as revealed by a 50% decrease in the oxygen consumption rate, increased oxidative stress, mitochondrial dysfunction, and reduced cell metabolism. Upon treatment with MSC secretome, the morphological derangements were partly restored and ATP production increased by 40–50%, with umbilical cord-derived EVs being most effective. Furthermore, MSC treatment led to phenotype restoration as indicated by an increase in cell bioenergetics, including increased levels of glycolysis intermediates, as well as an accumulation of antioxidant metabolites. Conclusion Our in vitro model effectively replicated the in vivo-like morphological and molecular changes observed during ischemic injury. Additionally, treatment with MSC secretome ameliorated proximal tubule damage, highlighting its potential as a viable therapeutic option for targeting AKI.

Afforestation affects Mediterranean farmland biodiversity due to loss and fragmentation of grassland habitats. While the influence of landscape context and plantation edges on farmland bird responses to afforestation is well-documented, less is known about the influence of grassland vegetation height and how it interacts with afforestation to influence bird communities. Here, we examined how changes in grassland vegetation height affect bird responses to afforestation in a farmland region in southern Portugal, and how these are affected by plantation type and edge. This region has experienced afforestation with eucalyptus, pine and oak stands, agricultural intensification, and frequent dry periods. To capture local and landscape-level changes, we collected data in two periods (2005 and 2014–15). Grassland vegetation height varied between sampling periods, emerging as a key factor affecting changes observed. Ground-nesting and cereal-associated species increased in abundance with taller vegetation in 2014–15, while in 2005, with drier weather and shorter vegetation, the species associated with ploughed fields were more abundant. Vegetation height effects on bird assemblages depended on plantation type and distance to plantation edges. Farmland bird abundance, including ground-nesting and cereal crops-associated species, increased with taller vegetation, particularly near oak and pine plantations. Conversely, species associated with ploughed fields declined with taller vegetation, especially near eucalyptus plantations. Results highlight complex interactions between vegetation height, plantation type, and edge proximity shaping avian assemblages. This study supports the importance of field and landscape-level management with special focus on grassland vegetation height and landscape heterogeneity for preserving open-farmland birds in fast-changing Mediterranean farmland landscapes.

This work was done on 1996 and 1997, and presents an extremely valuable baseline to compare the recent and future changes on the insular shallow habitats of the Azorean islands. We examined the structure of the molluscan communities of the macroalgae Halopteris scoparia in São Miguel Island (Azores, Portugal). This island was chosen because it is the largest and the most populated of the archipelago, with polluted sites which are not common in the Azores. The relationship between the epifaunal assemblages and a set of environmental factors – geographical location (orientation), seawater temperature, depth, algal volume, degree of disturbance, and degree of exposure to the wave action – was investigated using distance-based redundancy analysis and significant variation in the distribution of richness of assemblages was found. Four environmental predictors were common to all the four analyses implemented (richness and assemblage structure using both AIC and BIC): algal volume (that correlates with algal dry weight), seawater temperature, coastal orientation and depth. Finally, the application in the Azores of this methodology favours a sampling program in Spring-Summer (when disturbance seems to be more susceptible to detection), and the use of H. scoparia in the subtidal zone, as the target alga is recommended due to its large covering of rocky shore substrates.

Currently, fertilization decisions in apple orchards are based on soil and leaf analyses while the leaf material is sampled after the growing season, usually in June–July (90–110 days after full bloom). This approach is inefficient, as the information becomes available later than the growing season and is therefore only useful in supporting fertilization decisions for the next year, not the current one. To establish a method that provides useful information for fertilization decisions earlier in the growth cycle, our research focused on the assessment of the nutrient content of petiole sap using different methods, the standard method and the rapid method using a reflectometer. For this study, in 2021, four ‘Gala’ orchards were fertilized with different N–P–K levels. Macro and micronutrients were determined in leaves and petiole sap at 45 and 90–110 days after full bloom (DAFB) using standard laboratory methods and the reflectometer. When leaf analysis at 45 and 90–110 DAFB was compared with petiole sap analysis at the same time point, no significant correlations were found between the nutrient contents in leaf material and petiole sap, with the exception of calcium. However, positive results were obtained regarding the correlation between reflectometer determination and standard laboratory analyses. The regression analysis revealed high determination coefficients for N-NO3− (R2 = 0.703), K+ (R2 = 0.705), Ca2+ (R2 = 0.715), and Mg2+ (R2 = 0.780) between standard laboratory methods and the reflectometer. These results suggest that the reflectometer enables a real-time diagnostic tool for monitoring nutrient status throughout the growth cycle, particularly key nutrients related to fruit quality. The N–P–K fertilization strategies had no influence on the nutrient content of leaves or petiole sap. The nutrient content of both sample types varied depending on the orchard.

Renewable energy communities have gained popularity as a means of reducing carbon emissions and enhancing energy independence. However, determining the optimal sizing for each production and storage unit within these communities poses challenges due to conflicting objectives, such as minimizing costs while maximizing energy production. To address this issue, this paper employs a Multi-Objective Particle Swarm Optimization (MOPSO) algorithm with multiple swarms. This approach aims to foster a broader diversity of solutions while concurrently ensuring a good plurality of nondominant solutions that define a Pareto frontier. To evaluate the effectiveness and reliability of this approach, four case studies with different energy management strategies focused on real-world operations were evaluated, aiming to replicate the practical challenges encountered in actual renewable energy communities. The results demonstrate the effectiveness of the proposed approach in determining the optimal size of production and storage units within renewable energy communities, while simultaneously addressing multiple conflicting objectives, including economic viability and flexibility, specifically Levelized Cost of Energy (LCOE), Self-Consumption Ratio (SCR) and Self-Sufficiency Ratio (SSR). The findings also provide valuable insights that clarify which energy management strategies are most suitable for this type of community.

This paper presents an optimization approach for Micro-cogeneration systems with internal combustion engines integrated into residential grids, addressing power demand failures caused by intermittent renewable energy sources. The proposed method leverages machine learning techniques, control strategies, and grid data to improve system flexibility and efficiency in meeting electricity and domestic hot water demands. Historical residential grid data were analysed to develop a machine learning-based demand prediction model for electricity and hot water. Thermal energy storage was integrated into the Micro-cogeneration system to enhance flexibility. An optimization model was created, considering efficiency, emissions, and cost while adapting to real-time demand changes. A control strategy was designed for the flexible operation of the Micro-cogeneration system, addressing excess thermal energy storage and resource allocation. The proposed solution’s effectiveness was validated through simulations, with results demonstrating the Micro-cogeneration system’s ability to efficiently address high electricity and hot water demand periods while mitigating power demand failures from renewable energy sources. The research presents a novel approach with the potential to significantly improve grid resilience, energy efficiency, and renewable energy integration in residential grids, contributing to more sustainable and reliable energy systems.

Liver diseases affect hundreds of millions of people worldwide; most often the hepatocytes or cholangiocytes are damaged. Diseases of the biliary tract cause severe patient burden, and cholangiocytes, the cells lining the biliary tract, are sensitive to numerous drugs. Therefore, investigations into proper cholangiocyte functions are of utmost importance, which is restricted, in vitro, by the lack of primary human cholangiocytes allowing such screening. To investigate biliary function, including transepithelial transport, cholangiocytes must be cultured as three-dimensional (3D) ductular structures. We previously established murine intrahepatic cholangiocyte organoid-derived cholangiocyte-like cells (CLCs) and cultured them onto polyethersulfone hollow fiber membranes (HFMs) to generate 3D duct structures that resemble native bile ducts at the structural and functional level. Here, we established an efficient, stepwise method for directed differentiation of human intrahepatic cholangiocyte organoids (ICOs) into CLCs. Human ICO-derived CLCs showed key characteristics of cholangiocytes, such as the expression of structural and functional markers, formation of primary cilia, and P-glycoprotein-mediated transport in a polarized fashion. The organoid cultures exhibit farnesoid X receptor (FXR)-dependent functions that are vital to liver bile acid homeostasis in vivo. Furthermore, human ICO-derived CLCs cultured on HFMs in a differentiation medium form tubular architecture with some tight, confluent, and polarized monolayers that better mimic native bile duct characteristics than differentiated cultures in standard 2D or Matrigel-based 3D culture plates. Together, our optimized differentiation protocol to obtain CLC organoids, when applied on HFMs to form bioengineered bile ducts, will facilitate studying cholangiopathies and allow developing therapeutic strategies.

Assessing a plant’s nutritional status and fertilizer rates and types that can optimize fruit quality and yield are critical in intensive apple orchards. The aim of this work was to identify correlations between nutrients in the different organs that allow the early diagnosis of the nutritional status and to assess the impact on the optimal nutrient content in apple leaves, as well as in the yield and quality of chemical and organic fertilization. Five orchards of ‘Gala’ were fertilized with different levels of NPK over a period of four years. Macro and micronutrients of buds, flowers, 45 and 90–110 days after full bloom (DAFB) leaves and 60 DAFB and 15 days before harvest (DBH) fruits were determined. Boron was the only element for which strong correlations, 0.7 < r < 0.9, were observed between all organ pairs. The fertilization treatments did not affect the nutrient concentrations in the leaves of 90–110 DAFB other than P, Ca and Mg and did not affect the macronutrients in the fruit. In one of the five orchards, the yield increased by 26% with double fertilization compared to standard fertilization and, for the other four orchards, the impact depended on the year. Fruit size was more related to crop load than to fertilization and TSS and firmness were not affected by the type or amount of fertilizers. Replacing part of the chemical fertilizer with organic materials did not affect productivity or fruit quality.

Mariana Bourgeois, a Viúva Mallen, foi uma mulher invulgar que, no século XVIII, aproveitando-se da sua condição social, fundou a sua própria oficina de impressão no Porto. Neste trabalho procura-se, através de pesquisas nos arquivos, traçar uma biografia (familiar, social e profissional) de Mariana e de suas muitas companhias (Francisco Mallen, seu marido; João Roberto Bourgeois, seu irmão; entre outros) e expor a complexa rede familiar e comercial que une todos estes. Deste modo, pretende-se contribuir para futuras investigações sobre a história dos livreiros franceses em Portugal, com ainda tantas personagens por explorar.

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Introduction: Breast cancer is the second most common oncological disease worldwide. To analyse the new disease specific funding programme (breast cancer) implemented at the Francisco Gentil Portuguese Institute of Oncology, Lisbon Center (Instituto Português de Oncologia de Lisboa Francisco Gentil), the actual costs of the patients were examined using activity-based costing as a costing methodology. This study addresses the following question: “How much does it cost to treat breast cancer per ‘patient-month’ compared to the monthly fixed ‘funding envelope’?”. Materials and Methods: The study cohort consisted of 807 patients, corresponding to all the patients eligible for the new disease specific funding programme and who were enrolled during the first year of implementation. Activity-based costing was used to calculate the total real costs per stage of disease and per ‘patient-month’ as well as the deviation from the monthly fixed ‘funding envelope’. Results: The total costs were 6.6 M€, whereas the total funding was 5.2 M€ for a total of 5648 ‘patient-months’. In 2014, the balance difference between the funding obtained and the actual costs was -1.4 €M for the cohort of 807 patients. Discussion: The extreme cases of differences in cost per ‘patient-month’ compared to the monthly fixed ‘funding envelope’ were (i) stage 0/Tis, with higher funding at 415.23 € per ‘patient-month’, and (ii) stage IIIC, with lower funding at 1062.79 € per ‘patient-month’. Conclusion: The ‘patient-month’ cost, regardless of disease stage was 1170.29 €. The median deviation per ‘patient-month’ was negative (241.21 €) compared to the monthly fixed ‘funding envelope’ of 929.08 € in the first year. Establishing activity-based costing - funding models will be crucial for the future sustainability of the healthcare sector.

Background. The long-term prognosis and transition towards sustained ambulatory hypertension (SHT) of white-coat hypertension (WCHT) remain uncertain particularly in those with both normal nighttime and daytime blood pressure (BP) values. Different classification criteria and the use of antihypertensive drugs may contribute to conflicting results. Patients and Methods. We prospectively evaluated for a 7.1 year transition to SHT in 899 nondiabetic subjects free from cardiovascular (CV) events: normotensive (NT) (n = 344; 52, 9% female; ageing 48 ± 14 years); untreated WCHT (UnWCHT n = 399; 50, 1% female; ageing 51 ± 14 years); and treated WCHT with antihypertensive drugs after baseline (TxWCHT n = 156; 54, 4% female; ageing 51 ± 15 years). All underwent 24 h ambulatory BP monitoring (24 h-ABPM) at baseline, at 30 to 60 months, and at 70 to 120 months thereafter. WCHT was at baseline (with no treatment) as office BP ≥ 140/or 90 mm·Hg, daytime BP

Population growth and climate change lead agricultural cultures to face environmental degradation and rising of resistant diseases and pests. These conditions result in reduced product quality and increasing risk of harmful toxicity to human health. Thus, the prediction of the occurrence of diseases and pests and the consequent avoidance of the erroneous use of phytosanitary products will contribute to improving food quality and safety and environmental land protection. This study presents the design and construction of a low-cost IoT sensor mesh that enables the remote measurement of parameters of large-scale orchards. The developed remote monitoring system transmits all monitored data to a central node via LoRaWAN technology. To make the system nodes fully autonomous, the individual nodes were designed to be solar-powered and to require low energy consumption. To improve the user experience, a web interface and a mobile application were developed, which allow the monitored information to be viewed in real-time. Several experimental tests were performed in an olive orchard under different environmental conditions. The results indicate an adequate precision and reliability of the system and show that the system is fully adequate to be placed in remote orchards located at a considerable distance from networks, being able to provide real-time parameters monitoring of both tree and the surrounding environment.

In chronic kidney disease (CKD), the secretion of uremic toxins is compromised leading to their accumulation in blood, which contributes to uremic complications, in particular cardiovascular disease. Organic anion transporters (OATs) are involved in the tubular secretion of protein-bound uremic toxins (PBUTs). However, OATs also handle a wide range of drugs, including those used for treatment of cardiovascular complications and their interaction with PBUTs is unknown. The aim of this study was to investigate the interaction between commonly prescribed drugs in CKD and endogenous PBUTs with respect to OAT1-mediated uptake. We exposed a unique conditionally immortalized proximal tubule cell line (ciPTEC) equipped with OAT1 to a panel of selected drugs, including angiotensin-converting enzyme inhibitors (ACEIs: captopril, enalaprilate, lisinopril), angiotensin receptor blockers (ARBs: losartan and valsartan), furosemide and statins (pravastatin and simvastatin), and evaluated the drug-interactions using an OAT1-mediated fluorescein assay. We show that selected ARBs and furosemide significantly reduced fluorescein uptake, with the highest potency for ARBs. This was exaggerated in presence of some PBUTs. Selected ACEIs and statins had either no or a slight effect at supratherapeutic concentrations on OAT1-mediated fluorescein uptake. In conclusion, we demonstrate that PBUTs may compete with co-administrated drugs commonly used in CKD management for renal OAT1 mediated secretion, thus potentially compromising the residual renal function.

This paper proposes a new method for the simultaneous determination of the optimal control parameters of proportional resonant controllers and the optimal design of the output filter of a grid-tied three-phase inverter. The proposed method, based on the grey wolf optimization (GWO) algorithm, addresses both optimization problems as a single process to achieve a better system frequency response. It optimizes the unknown parameters by using a fitness function to find the best trade-off between the following fundamental terms: the harmonic attenuation rate; the power loss, through the damping resistor; and the current tracking error in the stationary frame, ensuring the system and grid stability. To validate the proposed optimization methodology, two case studies are considered with different output filter topologies with passive damping methods. The results obtained from the proposed optimization procedure were analyzed and discussed according to the fitness function terms.

Standalone microgrids with photovoltaic (PV) solutions could be a promising solution for powering up off-grid communities. However, this type of application requires the use of energy storage systems (ESS) to manage the intermittency of PV production. The most commonly used ESSs are lithium-ion batteries (Li-ion), but this technology has a low lifespan, mostly caused by the imposed stress. To reduce the stress on Li-ion batteries and extend their lifespan, hybrid energy storage systems (HESS) began to emerge. Although the utilization of HESSs has demonstrated great potential to make up for the limitations of Li-ion batteries, a proper power management strategy is key to achieving the HESS objectives and ensuring a harmonized system operation. This paper proposes a novel power management strategy based on an artificial neural network for a standalone PV system with Li-ion batteries and super-capacitors (SC) HESS. A typical standalone PV system is used to demonstrate and validate the performance of the proposed power management strategy. To demonstrate its effectiveness, computational simulations with short and long duration were performed. The results show a minimization in Li-ion battery dynamic stress and peak current, leading to an increased lifespan of Li-ion batteries. Moreover, the proposed power management strategy increases the level of SC utilization in comparison with other well-established strategies in the literature.

Apesar do aumento no número de casos de infecção humana por Rhodococcus equi (R. equi) registado nas últimas décadas, sobretudo em indivíduos infectados pelo vírus da imunodeficiência humana (VIH), esse diagnóstico permanece uma raridade. Os autores apresentam um caso de infecção pulmonar por R. equi num homem de 36 anos com síndrome de imunodeficiência adquirida (SIDA). A doença manifestou-se de forma insidiosa, apresentando-se radiologicamente sob a forma de lesão pulmonar esquerda com cavitação e nível hidroaéreo, tendo sido inicialmente colocada a hipótese diagnóstica de tuberculose pulmonar (TP) dada a pesquisa de bacilos álcool-ácido resistentes (BAAR) na expectoração ter sido positiva. Posteriormente, foi possível isolar o R. equi nas culturas de expectoração e lavado broncoalveolar (LBA). O estudo anátomo-patológico confirmou a presença concomitante de malacoplaquia pulmonar. O doente cumpriu antibioterapia dirigida ao agente e teve boa evolução clínica, analítica e radiológica. A propósito deste caso, os autores fazem uma revisão teórica do tema à luz dos conhecimentos actuais.

Apresenta-se o caso de um doente do sexo masculino, com 83 anos de idade, que no decurso de investigação de quadro de suboclusão intestinal realizou uma tomografia axial computadorizada (TAC), que revelou a presença de duas veias cavas inferiores (setas brancas), unindo-se imediatamente na porção pré-hepática (variante do normal). Pode observar-se a artéria aorta, com calcificações, entre ambas as veias cavas inferiores. O desenvolvimento da veia cava ocorre entre a 6ª e 10ª semanas de gestação, a partir da veia supracardinal direita, enquanto que a veia supracardinal esquerda involui. A sua duplicação ocorre como resultado da persistência de ambas as veias supracardinais (direita e esquerda) e tem uma prevalência estimada de 0.2-0.3%. Geralmente, é uma anomalia assintomática, detectada acidentalmente em exames imagiológicos. Contudo, o seu diagnóstico é importante, uma vez que a sua presença tem implicações clínicas relevantes, nomeadamente no tratamento de doenças tromboembólicas.

Apresentam-se dois casos de quisto pericárdico diagnosticados acidentalmente em exames de imagem de rotina. Ambos os doentes, uma mulher de 18 anos (fig. A y B) e um homem de 83 anos (fig. 2 A y B), não apresentavam qualquer sintoma relacionável com a presença de quisto pericárdico. Realizaram em consulta de rotina uma telerradiografia de tórax, que em ambos os casos mostrou uma imagem hiperdensa, arredondada e homogénea, no ângulo cardiofrénico direito. Para esclarecimento das referidas imagens, ambos os doentes realizaram Tomografia axial computorizada (TAC). Em ambos os casos a TAC confirmou a presença de uma massa homogénea no ângulo cardiofrénico direito, de densidade hídrica, não captante de contraste, a traduzir quisto pericárdico.Os quistos pericárdicos são uma anomalia rara (com uma incidência de 1/100000), benigna, e na maioria dos casos congénita. Em 75% dos casos, são encontrados de forma acidental em exames de imagem de rotina de doentes assintomáticos. Os quistos assintomáticos devem ser abordados conservadoramente

We define a four-dimensional spin-foam perturbation theory for the BF-theory with a B∧B potential term defined for a compact semi-simple Lie group G on a compact orientable 4-manifold M. This is done by using the formal spin foam perturbative series coming from the spin-foam generating functional. We then regularize the terms in the perturbative series by passing to the category of representations of the quantum group U_q(g) where g is the Lie algebra of G and q is a root of unity. The Chain-Mail formalism can be used to calculate the perturbative terms when the vector space of intertwiners Λ⊗Λ→A, where A is the adjoint representation of g, is 1-dimensional for each irrep Λ. We calculate the partition function Z in the dilute-gas limit for a special class of triangulations of restricted local complexity, which we conjecture to exist on any 4-manifold M. We prove that the first-order perturbative contribution vanishes for finite triangulations, so that we define a dilute-gas limit by using the second-order contribution. We show that Z is an analytic continuation of the Crane-Yetter partition function. Furthermore, we relate Z to the partition function for the F∧F theory.

Foi efetuado o levantamento das espécies ocorrentes na Serra de Itabirito, Município de Itabirito, Minas Gerais, em áreas de cerrado e campo-rupestre. Nesta primeira etapa foram coletadas e identificadas 366 espécies, pertencentes a 209 gêneros, agrupadas em 78 famílias. Compositae é a família mais representativa, com cerca de 57 espécies e 22 gêneros, vindo a seguir Leguminosae com 37 espécies e 14 gêneros e Gramineae com 14 espécies e 13 gêneros.This study is a survey of species occuring in the "cerrado" and "campo-rupreste" of Itabirito Hills, County of Itabirito, State of Minas Gerais, Brazil. In this first stage we collected and identified 366 species, belonging to 209 genera, grouped into 78 families. Compositae was the most representative family having 57 species and 22 genera, followed by Leguminosae with 37 species and 14 genera, and Gramineae with 14 species and 13 genera.