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BACKGROUND: The function of polymorphonuclear neutrophils (PMNs) decreases with age, which results in infectious and inflammatory complications in older individuals. The underlying causes are not fully understood. ATP release and autocrine stimulation of purinergic receptors help PMNs combat microbial invaders. Excessive extracellular ATP interferes with these mechanisms and promotes inflammatory PMN responses. Here, we studied whether dysregulated purinergic signaling in PMNs contributes to their dysfunction in older individuals. RESULTS: Bacterial infection of C57BL/6 mice resulted in exaggerated PMN activation that was significantly greater in old mice (64 weeks) than in young animals (10 weeks). In contrast to young animals, old mice were unable to prevent the systemic spread of bacteria, resulting in lethal sepsis and significantly greater mortality in old mice than in their younger counterparts. We found that the ATP levels in the plasma of mice increased with age and that, along with the extracellular accumulation of ATP, the PMNs of old mice became increasingly primed. Stimulation of the formyl peptide receptors of those primed PMNs triggered inflammatory responses that were significantly more pronounced in old mice than in young animals. However, bacterial phagocytosis and killing by PMNs of old mice were significantly lower than that of young mice. These age-dependent PMN dysfunctions correlated with a decrease in the enzymatic activity of plasma ATPases that convert extracellular ATP to adenosine. ATPases depend on divalent metal ions, including Ca2+, Mg2+, and Zn2+, and we found that depletion of these ions blocked the hydrolysis of ATP and the formation of adenosine in human blood, resulting in ATP accumulation and dysregulation of PMN functions equivalent to those observed in response to aging. CONCLUSIONS: Our findings suggest that impaired hydrolysis of plasma ATP dysregulates PMN function in older individuals. We conclude that strategies aimed at restoring plasma ATPase activity may offer novel therapeutic opportunities to reduce immune dysfunction, inflammation, and infectious complications in older patients.

The operating room demands well-functioning workflows and optimized communication. Based on the formalization of specific surgical interventions via BPMN, intraoperative checklists can automatically be generated to support the surgical team by the provision of relevant clinical information and situation-dependent assistive functions. While focusing on the surgeon, other actors have not yet been considered. The aim of this work is therefore the extension of the intraoperative checklist to enable role-specific support and improved communication between the actors. The BPMN approach is adapted to depict role-specific surgical steps and clinical information to realize the collaborative, multi-role usage of the checklist. The proof of concept demonstrates the automatic generation of intraoperative checklists which provide relevant information depending on the role. An initial evaluation of the checklist based on the cochlea implantation use case shows promising results.

This paper describes how automatic speech recognition (ASR) can be used to explore electronic patient records (EPR) in a sterile environment. As an information display, we used a system that was developed for the presentation of patient data and for supporting surgical hand disinfection. The speech recognition was performed using the Mozilla Web Speech API. A room microphone, a Jabra Box, and a directional microphone, a RØDE NT-USB Mini, were tested at various positions. Interactions with the EPR are triggered with a list of commands. The interaction was working as indented and test persons reported the system as intuitive.

BackgroundATP enhances neutrophil responses, but little is known about the role of ATP in influenza infections.MethodsWe used a mouse influenza model to study if ATP release is associated with neutrophil activation and disease progression.ResultsInfluenza infection increased pulmonary ATP levels 5-fold and plasma ATP levels 3-fold over the levels in healthy mice. Adding ATP at those concentrations to blood from healthy mice primed their neutrophils and enhanced CD11b and CD63 expression, CD62L shedding, and reactive oxygen species production in response to formyl peptide receptor (FPR) stimulation. Influenza infection also primed neutrophils in vivo, resulting in FPR-induced CD11b expression and CD62L shedding up to 3-times higher than that of uninfected mice. In infected mice, large numbers of neutrophils entered the lungs. These cells were significantly more activated than peripheral neutrophils of infected and pulmonary neutrophils of healthy mice. Plasma ATP levels of infected mice and influenza disease progression corresponded with the numbers and activation level of their pulmonary neutrophils.ConclusionOur findings suggest that ATP release from the lungs of infected mice promotes influenza disease progression by priming peripheral neutrophils that become strongly activated and cause pulmonary tissue damage after their recruitment to the lungs.

Fibrosis resulting from pathological repair secondary to recurrent or persistent tissue damage often leads to organ failure and mortality. Biliary fibrosis is a crucial but easily neglected pathological feature in hepatobiliary disorders, which may promote the development and progression of benign and malignant biliary diseases through pathological healing mechanisms secondary to biliary tract injuries. Elucidating the etiology and pathogenesis of biliary fibrosis is beneficial to the prevention and treatment of biliary diseases. In this review, we emphasized the importance of biliary fibrosis in cholangiopathies and summarized the clinical manifestations, epidemiology, and aberrant cellular composition involving the biliary ductules, cholangiocytes, immune system, fibroblasts, and the microbiome. We also focused on pivotal signaling pathways and offered insights into ongoing clinical trials and proposing a strategic approach for managing biliary fibrosis-related cholangiopathies. This review will offer a comprehensive perspective on biliary fibrosis and provide an important reference for future mechanism research and innovative therapy to prevent or reverse fibrosis.

Abstract Background The function of polymorphonuclear neutrophils (PMNs) decreases with age, which results in infectious and inflammatory complications in older individuals. The underlying causes are not fully understood. ATP release and autocrine stimulation of purinergic receptors help PMNs combat microbial invaders. Excessive extracellular ATP interferes with these mechanisms and promotes inflammatory PMN responses. Here, we studied whether dysregulated purinergic signaling in PMNs contributes to their dysfunction in older individuals. Results Bacterial infection of C57BL/6 mice resulted in exaggerated PMN activation that was significantly greater in old mice (64 weeks) than in young animals (10 weeks). In contrast to young animals, old mice were unable to prevent the systemic spread of bacteria, resulting in lethal sepsis and significantly greater mortality in old mice than in their younger counterparts. We found that the ATP levels in the plasma of mice increased with age and that, along with the extracellular accumulation of ATP, the PMNs of old mice became increasingly primed. Stimulation of the formyl peptide receptors of those primed PMNs triggered inflammatory responses that were significantly more pronounced in old mice than in young animals. However, bacterial phagocytosis and killing by PMNs of old mice were significantly lower than that of young mice. These age-dependent PMN dysfunctions correlated with a decrease in the enzymatic activity of plasma ATPases that convert extracellular ATP to adenosine. ATPases depend on divalent metal ions, including Ca2+, Mg2+, and Zn2+, and we found that depletion of these ions blocked the hydrolysis of ATP and the formation of adenosine in human blood, resulting in ATP accumulation and dysregulation of PMN functions equivalent to those observed in response to aging. Conclusions Our findings suggest that impaired hydrolysis of plasma ATP dysregulates PMN function in older individuals. We conclude that strategies aimed at restoring plasma ATPase activity may offer novel therapeutic opportunities to reduce immune dysfunction, inflammation, and infectious complications in older patients.

One of the easiest ways to improve everyone’s physical and mental health is to choose appropriate physical activity (PA). Its general decline in recent decades has triggered an increase in civilisation-related diseases. Female college students neglect PA more than males. We compared the PA of female undergraduates at the University of P.J. Šafárik in Košice (UPJŠ) to their actual aerobic endurance based on our research. The study comprised 268 female students from four UPJŠ faculties. PA data were gathered using a short version of the International Physical Activity Questionnaire (IPAQ). Aerobic endurance capacity was determined using the results of a 20m beep-test, which was then converted to estimated VO2 max values. The results were comparable to other studies when converted to MET-min/week, but undergraduate students’ self-reported PA did not differ between faculties. A correlation exists between total (r = 0.24; p

The levee effect poses a challenge for flood risk management. While there is research on the consequences of the levee effect in general, a detailed understanding of policies addressing residual risk is lacking. The aim of this research is to understand how coercive and cooperative policy designs are applied in spatial planning provisions dealing with residual flood risk and which context conditions influence planning authorities when deciding on a certain policy design. We applied a qualitative research approach, including expert interviews and examining relevant documents. The results show that coercive planning policies can regulate the use of areas with residual risk either by limiting the extension of building land or by prescribing flood adaptation of buildings. However, the formulation of such regulations is connected to the spatial context, the actors involved, past flood events and risk awareness. Cooperative planning policies address residual risk either as recommendations or by providing local authorities scope for decision-making when it comes to land use planning in residual risk areas. The interview partners also discussed possibilities that go beyond spatial planning, such as emergency management. The research shows the variety of policies that can offer ways of dealing with flooding beyond the expected level.

Introduction: During processing, a large amount of by-products is produced from tamarillo fruits in the form of stalks, outer skins, and pomace (residual seeds and inner skins). This material is a renewable source of bioactive compounds with high economic value and positive effects on human health. Previous reviews have focused on the ethnobotanical, traditional uses, and phytochemistry of the tamarillo fruit. This report aims to compile production and cultivation data, as well as the valorization of this agro-industrial residue, green extraction methods used for extracting the bioactive compounds, and their biological activity. Method: In this study, a literature search was conducted in five scientific databases: Web of Science, ScienceDirect, Scopus, PubMed, and Google Scholar to retrieve research published in English, Spanish, or Portuguese between 2009 and 2024, which mentions the composition and extraction methods of bioactive compounds from tamarillo wastes and by-products and the health benefits associated with these compounds. The data extracted was compiled and shown in this scoping review. Results: Tamarillo wastes and by products have a rich nutritional and bioactive composition, including high protein, vitamins A and C, minerals, dietary fiber, sugars, terpenes, flavonoids, carotenoids, anthocyanins, and other phytochemicals. Green methods have been effective, yielding high amounts of these compounds while preserving their integrity. Natural polyphenols have shown antioxidant, anticholinesterase, anti-inflammatory, antimicrobial, anti-diabetic, and anti-obesity properties. The antioxidant fibers, mucilage, and pectin of the pomace contribute to improved intestinal health. Conclusion: Therefore, these wastes and by-products have potential uses as natural colorant, antioxidants, supplements, functional foods, active biobased films, and in pharmaceutical and cosmeceutical sectors due to their effective bioactive molecules. Future research should focus on the use of tamarillo by-products as a source of functional ingredients in several other formulations that are still little explored, as well as their use as a natural colorant and antioxidant. More studies are necessary on the composition-activity relationship, physiological mechanisms, and clinical response.

Biliary complications are still a major cause for morbidity and mortality after liver transplantation (LT). Ischemia/reperfusion injury (IRI) leads to disruption of the biliary epithelium. We introduce a novel model to study the effect of IRI on human cholangiocytes using extrahepatic cholangiocyte organoids (ECOs). Extrahepatic bile duct tissue was collected during LT at static cold storage and after reperfusion (n = 15); gallbladder tissue was used for controls (n = 5). ECOs (n = 9) were cultured from extrahepatic biliary tissue, with IRI induced in an atmosphere of 95% air (nitrogen), 1% O2 and 5% CO2for 48 h, followed by 24 h of reoxygenation. Qualitative and quantitative histology and qRT-PCR were performed to discern phenotype, markers of hypoxia, programmed cell death and proliferation. ECOs self-organized into circular structures resembling biliary architecture containing cholangiocytes that expressed EpCAM, CK19, LGR5 and SOX-9. After hypoxia, ECOs showed increased expression of VEGF A (p < 0.0001), SLC2A1 (p < 0.0001) and ACSL4 (p < 0.0001) to indicate response to hypoxic damage and subsequent programmed cell death. Increase in cyclin D1 (p < 0.0001) after reoxygenation indicated proliferative activity in ECOs. Therefore, ECO structure and response to IRI are comparable to that found in-vivo, providing a suitable model to study IRI of the bile duct in-vitro.

Purslane (Portulaca oleracea) and spinach (Spinacea oleracea) are species with elevated levels of oxalic acid, an antinutrient that interferes in the bioaccessibility of minerals such as calcium and iron. Evaluating methods to determine oxalic acid content with reduced matrix interference, such as employing Flame Atomic Absorption Spectrometry (FAAS), can enhance the specificity of determinations. The different matrices of purslane (whole plant, leaves, and juice) and spinach (whole plant) were tested using three extraction methods (M1, M2, and M3). The oxalic acid content was evaluated by UV-vis spectrophotometry and FAAS (Flame Atomic Absorption Spectrometry). The absence of the precipitation step in M1 resulted in high levels of oxalic acid in the investigated matrices. The quantification of oxalic acid by FAAS for M2 (6M HCl for 1 hour at 100°C) and M3 (0.25N HCl for 15 minutes at 100°C) in the samples of purslane leaves and spinach whole plants yielded statistically similar results. However, the analysis by UV-vis spectrophotometry for M2 and M3 showed significant discrepancies in all evaluated samples, suggesting interference from colored compounds in the food matrix. • Comparison of methods of extraction • Comparison of UV-vis spectrophotometer and FAAS in the quantification of oxalic acid • Analysis of antinutrients in plant matrices

In the FCTRAC project, a fuel cell electric tractor is developed based on the existing diesel vehicle STEYR 4130 Expert CVT. After the FCTRAC project is presented, the paper introduces the developed fuel cell electric powertrain architecture designed to deliver comparable working performance to the donor vehicle. The description of the thermal system focuses on the challenging heat dissipation of the fuel cell stack. The design of the 700-bar hydrogen storage system is discussed, considering vehicle framework conditions. Finally, the paper addresses the test bench validation of the FCTRAC powertrain. It confirms the simulative development approach and demonstrates operation comparable to the donor vehicle with 95 kW constant load at 35 °C ambient temperature without derating.

Resumo: O objetivo deste estudo foi desenvolver metodologia para estimar a incidência de câncer no Brasil e regiões. A partir de dados dos registros de câncer de base populacional (RCBP) e do Sistema de Informações sobre Mortalidade (SIM) foram calculadas razões de incidência e mortalidade (I/M) anuais, tipo de câncer, faixa etária e sexo em cada RCBP. Para estimar as razões I/M por região em 2018, foram aplicados modelos multiníveis longitudinais de Poisson. A estimativa de casos novos de câncer, em 2018, foi calculada aplicando-se as razões I/M estimadas ao número de óbitos corrigidos do SIM ocorridos naquele ano. Norte e Nordeste concentraram as menores razões I/M. Os cânceres de pâncreas, pulmão, fígado e esôfago tiveram as menores razões I/M, enquanto as maiores razões I/M foram estimadas para câncer de tireoide, testículo, próstata e mama feminina. Para 2018, foram estimados 506.462 casos novos de câncer no Brasil. Mama feminina e próstata foram os dois principais tipos de câncer em todas as regiões. No Norte e no Nordeste, destacaram-se os cânceres do colo do útero e de estômago. Diferenças nas razões I/M entre as regiões foram observadas e podem estar relacionadas ao desenvolvimento socioeconômico e ao acesso a serviços de saúde.

Liver transplantation is the only curative option for many liver diseases that end up in liver failure, and cholangiopathy remains a challenging complication post-liver transplant, associated with significant morbidity and potential graft loss. The low availability of organs and high demand for transplantation motivate scientists to find novel interventions. Organoids, as three-dimensional cell cultures derived from adult cells or induced pluripotent cells, may help to address this problem. Different types of organoids have been described, from which cholangiocyte organoids offer a high level of versatility and plasticity for a deeper study of liver disease mechanisms. Cholangiocytes can be obtained from different segments of the biliary tree and have shown a remarkable capacity to adapt to new environments, presenting an effective system for studying cholangiopathies. Studies using cholangiocyte organoids show promising results for disease modeling, where organoids offer fundamental features to recapitulate the complexities of tissues in vitro and uncover fundamental pathological pathways to potentially reveal therapeutic strategies for personalized medicine. Organoids could hold the potential for regeneration of injured livers, representing tools of clinical impact in regenerative medicine when tissue damage is already present.

Laser beam butt welding is often the technique of choice for a wide range of industrial tasks. To achieve high quality welds, manufacturers often rely on heavy and expensive clamping systems to limit the sheet movement during the welding process, which can affect quality. Jiggless welding offers a cost-effective and highly flexible alternative to common clamping systems. In laser butt welding, the process-induced joint gap has to be monitored in order to counteract the effect by means of an active position control of the sheet metal. Various studies have shown that sheet metal displacement can be detected using inductive probes, allowing the prediction of weld quality by ML-based data analysis. The probes are dependent on the sheet metal geometry and are limited in their applicability to complex geometric structures. Camera systems such as long-wave infrared (LWIR) cameras can instead be mounted directly behind the laser to overcome a geometry dependent limitation of the jiggles system. In this study we will propose a deep learning approach that utilizes LWIR camera recordings to predict the remaining welding process to enable an early detection of weld interruptions. Our approach reaches 93.33% accuracy for time-wise prediction of the point of failure during the weld.