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Because of the long history of anti-drug policing in the United States and the criminalization of substance use, clients who use substances are vulnerable to direct and vicarious experiences of police violence. Consequently, those who use substances may face a greater risk of experiencing symptoms of trauma that counselors should address in treatment. We recommend the use of a trauma-informed and abolitionist praxis in clinical and social justice practices as a framework to support clients who use substances and have histories of exposure to police violence.

S100A8/A9 is an endogenous alarmin secreted by myeloid cells during many acute and chronic inflammatory disorders. Despite increasing evidence of the proinflammatory effects of extracellular S100A8/A9, little is known about its intracellular function. Here, we show that cytosolic S100A8/A9 is indispensable for neutrophil post-arrest modifications during outside-in signaling under flow conditions in vitro and neutrophil recruitment in vivo, independent of its extracellular functions. Mechanistically, genetic deletion of S100A9 in mice caused dysregulated Ca2+ signatures in activated neutrophils resulting in reduced Ca2+ availability at the formed LFA-1/F-actin clusters with defective β2 integrin outside-in signaling during post-arrest modifications. Consequently, we observed impaired cytoskeletal rearrangement, cell polarization, and spreading, as well as cell protrusion formation in S100a9-/- compared to wildtype (WT) neutrophils, making S100a9-/- cells more susceptible to detach under flow, thereby preventing efficient neutrophil recruitment and extravasation into inflamed tissue.

Abstract Exposure to nanoparticles (NPs) is frequently associated with adverse cardiovascular effects. In contrast, NPs in nanomedicine hold great promise for precise lung‐specific drug delivery, especially considering the extensive pulmonary capillary network that facilitates interactions with bloodstream‐suspended particles. Therefore, exact knowledge about effects of engineered NPs within the pulmonary microcirculation are instrumental for future application of this technology in patients. To unravel the real‐time dynamics of intravenously delivered NPs and their effects in the pulmonary microvasculature, we employed intravital microscopy of the mouse lung. Only PEG‐amine‐QDs, but not carboxyl‐QDs triggered rapid neutrophil recruitment in microvessels and their subsequent recruitment to the alveolar space and was linked to cellular degranulation, TNF‐α, and DAMP release into the circulation, particularly eATP. Stimulation of the ATP‐gated receptor P2X7R induced expression of E‐selectin on microvascular endothelium thereby mediating the neutrophilic immune response. Leukocyte integrins LFA‐1 and MAC‐1 facilitated adhesion and decelerated neutrophil crawling on the vascular surface. In summary, this study unravels the complex cascade of neutrophil recruitment during NP‐induced sterile inflammation. Thereby we demonstrate novel adverse effects for NPs in the pulmonary microcirculation and provide critical insights for optimizing NP‐based drug delivery and therapeutic intervention strategies, to ensure their efficacy and safety in clinical applications.

O presente artigo, tendo em vista o avanço do direito internacional e a necessidade de efetivação interna das normas da Convenção-Quadro de Controle do Tabaco (CQCT), tem como objeto a análise da competência Para concretizar a regulamentação interna e internacional, com o intuito de se criarem políticas públicas coordenadas de controle do tabaco. Para tanto, foram analisadas as normas internacionais e internas sobre o tema, visitando-se a interpretação a elas dada pela doutrina e pelas decisões judiciais, tanto pela ótica do direito interno quanto internacional e comparado. Nesse sentido, é possível defender que a CQCT abre espaço para regulação internacional por meio das diretrizes, estabelecidas nas Conferências das Partes (COPs), que são, assim, vinculantes a todos os Estados-Membros da convenção. A regulação internacional nasce do chamado direito administrativo internacional, que permite o exercício do poder regulamentar, ou normativo, da administração. Internamente, a regulação deve seguir as diretrizes da COP, havendo espaço para que órgãos, como a Anvisa, no Brasil, concretizem as diretrizes, como a referente aos arts. 9 e 10 da CQCT, que limitou o uso de aditivos de sabores nos produtos de tabaco, sendo uma forma de efetivação das normas internacionais internamente. Também não existe conflito entre a livre iniciativa e o controle do tabaco, pois, como dito pela Corte Constitucional colombiana, no processo em que se discutia a constitucionalidade das restrições à publicidade do tabaco, é um mercado que não deve ser incentivado, apenas tolerado.

Wood fuel from the agroforestry sector is one of the main strategies cited by the EU for reducing energetic dependance on foreign markets. Its sustainability, both economic and environmental, can be improved through the optimization of harvesting and chipping operations. This study was focused on the dynamic and energetic balance of the chipping phase carried out by a chipper operated by the power-take-off (PTO) of a medium-power tractor. Both machines were equipped with sensors for real-time monitoring of fuel consumption, PTO torque and speed, trunk diameter and working time during the comminution of 61 poplar trees grown in a medium rotation coppice system. The data analysis was carried out on the entire dataset (about 29,000 records) without considering their belonging to different trees. By means of proper data ordinations, it has been possible to define all the intervals in which the chipping stopped (e.g., between two trees) and to exclude them from the intervals of actual chipping. This has allowed forcomputation of operative and actual working time, as well as of the basic power required to operate the chipper and the power for actual chipping. Subsequently, the parameter values observed during actual chipping were related to the cutting diameters measured at the same instant. Subsequently, the dataset was divided according to seven diameter classes, and, for each class, the descriptive statistical indices of working time, work productivity, CO2 emissions, energy requirement and fuel consumption were calculated. Eventually, the correlation between the variations in trunk diameter and other parameters was verified both on the whole dataset and based on the class average values. The analysis made it possible to identify the conditions of greatest efficiency for the chipper. More generally, the method could help to increase the accuracy of measurements aimed at characterizing the performance of chippers from the point of view of dynamic energy requirements as well as in relation to different wood species.

ABSTRACT Atypical enteropathogenic Escherichia coli (aEPEC) is a significant cause of diarrhea in low- and middle-income countries. Certain aEPEC strains, including the Brazilian representative strain of serotype O51:H40 called aEPEC 1711-4, can use flagella to attach to, invade, and persist in T84 and Caco-2 intestinal cells. It can also translocate from the gut to extraintestinal sites in a rat model. Although various aspects of the virulence of this strain were studied and the requirement of a type III secretion system for the efficiency of the invasion process was demonstrated, the expression of the locus of enterocyte effacement (LEE) genes during the invasion and intracellular persistence remains unclear. To address this question, the expression of flagella and the different LEE operons was evaluated during kinetic experiments of the interaction of aEPEC 1711-4 with enterocytes in vitro. The genome of the strain was also sequenced. The results showed that flagella expression remained unchanged, but the expression of eae and escJ increased during the early interaction and invasion of aEPEC 1711-4 into Caco-2 cells, and there was no change 24 h post-infection during the persistence period. The number of actin accumulation foci formed on HeLa cells also increased during the 6-h analysis. No known gene related to the invasion process was identified in the genome of aEPEC 1711-4, which was shown to belong to the global EPEC lineage 10. These findings suggest that the LEE components and the intimate adherence promoted by intimin are necessary for the invasion and persistence of aEPEC 1711-4, but the detailed mechanism needs further study.IMPORTANCEAtypical enteropathogenic Escherichia coli (aEPEC) is a major cause of diarrhea, especially in low- and middle-income countries, like Brazil. However, due to the genome heterogeneity of each clonal group, it is difficult to comprehend the pathogenicity of this strain fully. Among aEPEC strains, 1711-4 can invade eukaryotic cells in vitro, cross the gut barrier, and reach extraintestinal sites in animal models. By studying how different known aEPEC virulence factors are expressed during the invasion process, we can gain insight into the commonalities of this phenotype among other aEPEC strains. This will help in developing preventive measures to control infections caused by invasive strains. No known virulence-encoding genes linked to the invasion process were found. Nevertheless, additional studies are still necessary to evaluate the role of other factors in this phenotype.

IntroductionIn adult horses, the development and evaluation of enteral electrolyte solutions containing sodium acetate for correcting hyperchloremic metabolic acidosis are still lacking, although these electrolyte and acid–base imbalances are commonly observed. The objective of this study was to evaluate the alkalinizing effect of two enteral electrolyte solutions containing different concentrations of acetate, administered via nasogastric tube in continuous flow, in adult horses with experimental hyperchloremic metabolic acidosis.MethodsSix mares aged between 3 and 10 years were used in a 6×2 crossover design, with each animal receiving both treatments. The horses were subjected to a protocol to induce hyperchloremic metabolic acidosis. They then received one of two treatments: HighAcetate (81.4 mmol/L) and LowAcetate (22.7 mmol/L) at an infusion rate of 15 mL/kg/h for 12 h. Plasma, serum, and urinary biochemical assessments; hematocrit; urinary volume, pH, and specific gravity; and blood gas analysis were measured at the following time points: T-12 h (beginning of the 12-h fast), T0h (end of fasting and beginning of the acidosis induction phase), every 2 h during the hyperchloremic metabolic acidosis induction phase (Ti2h and Ti4h), every 2 h during the 12-h enteral hydration phase (Tt2h, Tt4h, Tt6h, Tt8h, Tt10h, and Tt12h), with one sample taken at T24h (24 h after the start of acidosis induction) and another at T36h (36 h after the start of acidosis induction). Data were analyzed using descriptive statistics and analysis of variance based on a factorial design of repeated measures, with Tukey’s post-hoc test or the Kruskal-Wallis test with Dunn’s post-hoc test for non-parametric tests.ResultsAt the end of the induction phase, the animals developed moderate to severe hyperchloremic metabolic acidosis. The HighAcetate solution effectively corrected electrolyte and acid–base imbalances before the end of the treatment phase (Tt12h), while the LowAcetate solution was not effective in correcting those changes.ConclusionThe HighAcetate (81.4 mmol/L) solution is deemed an effective and safe alternative for the treatment of hyperchloremic metabolic acidosis in horses.

BackgroundA better understanding of the consequences of the Coronavirus Disease 2019 (COVID-19) pandemic on lifestyle of patients with Chagas disease (ChD) is of paramount importance to facilitate the implementation of intervention strategies tailored to this specific population.ObjectiveThe present study aimed to evaluate the level of physical activity (PA) in Chagas disease (ChD) patients during the Coronavirus Disease 2019 (COVID-19) pandemic and its main associated factors.MethodsThis is a cross-sectional study with 187 patients of both sexes, aged ≥18 years, followed in a national infectious disease center (Rio de Janeiro, Brazil). The level of PA was determined by the International Physical Activity Questionnaire short version and expressed in terms of total volume of physical activity (PA) (MET-minutes per week). Individuals were classified as physically active following the 2020 World Health Organization PA guideline. The exposure variables were age, sex, race, marital status, schooling, income per capita, number of rooms per domicile, number of residents per domicile, body mass index, clinical form of ChD, COVID-19 antibodies, comorbidities, self-reported anxiety, self-reported depression, self-reported fear, and self-reported sadness. The association between the exposure variables with total PA (as a continuous variable) was determined using univariate and multivariate linear regression models.ResultsMean age was 61.1 ± 11.6 years. Most (62%) were women and self-declared their race as mixed (50.8%). The percentage of physically active individuals according to was 52%. The variables independently associated with total PA levels were non-white race (Exp β = 1.39; 95% CI 1.02 to 1.90), dyslipidemia (Exp β = 0.73; 95% CI 0.56 to 0.95) and self-reported depression during quarantine (Exp β = 0.71; 95% CI 0.52 to 0.96).ConclusionNon-white race was positively associated with total levels of PA, while dyslipidemia, and self-reported depression during quarantine were negatively associated with total levels of PA. The identification of associated factors can facilitate the development of tailored strategies to increase PA levels ChD patients.

O veganismo tem como premissa excluir todas as formas de exploração e crueldade contra animais, seja na alimentação, no vestuário ou em qualquer outra finalidade, provocando, por consequência, uma série de desafios ao convívio social. Na prática da comensalidade, posturas alimentares diferentes podem despertar reações tanto de hospitalidade quanto de hostilidade. Este artigo, com base construtivista e de caráter qualitativo, tem como objetivo analisar as relações de comensalidade entre indivíduos veganos e onívoros sob a perspectiva da hospitalidade e da hostilidade na ótica de indivíduos veganos, a partir de uma pesquisa bibliográfica e entrevistas semiestruturadas com 12 indivíduos veganos. Os resultados indicam como principais desafios a aceitação dos novos hábitos por parte de amigos, familiares e colegas de trabalho, bem como eventuais constrangimentos nos momentos de comensalidade, inclusive pela falta de alimentos veganos disponíveis. Evidenciaram também que ações de hospitalidade propiciam reações igualmente hospitaleiras, enquanto ações de hostilidade geram reações igualmente hostis.

Esophagogastric cancers are aggressive malignancies, with poor prognosis despite current standard-of-care therapies. PD-1 inhibitors are a newer class of antitumor agents with the potential to improve outcomes among appropriately selected patients. This review provides an overview of the key trials that have guided the use of PD-1 and PD-L1 inhibitors in the refractory and first-line settings. We highlight recent studies investigating the role of genomic classification in predicting therapeutic activity of PD-1 inhibitors. In addition, there is a discussion of the use of different scoring systems and criteria to determine PD-L1 positivity, the impact on the therapeutic use of immune checkpoint inhibition with anti-PD-1 agents, and the controversies in current methods of PD-L1 testing and their implications in patient selection for anti-PD-1 therapy.

Author(s): Richard Klaus [sup.1] , Teresa K. Barth [sup.2] , Axel Imhof [sup.2] , Franziska Thalmeier [sup.1] , Bärbel Lange-Sperandio [sup.1] Author Affiliations: (1) https://ror.org/05591te55, grid.5252.0, 0000 0004 1936 973X, [...], Background Urinary proteomics identifies the totality of urinary proteins and can therefore help in getting an early and precise diagnosis of various pathological processes in the kidneys. In infants, non-invasive urine collection is most commonly accomplished with a urine bag or clean catch. The influence of those two collection methods on urinary proteomics was assessed in this study. Methods Thirty-two urine samples were collected in infants using urine bag and clean catch within 24 h. Nine boys and seven girls with a mean age of 4.3 ± 2.9 months were included (5 x post-pyelonephritis, 10 x non-kidney disease, 1 x chronic kidney disease (CKD)). Liquid chromatography-mass spectrometry (LC-MS/MS) was performed in data-independent acquisition (DIA) mode. Protein identification and quantification were achieved using Spectronaut. Results A total of 1454 urinary proteins were detected. Albumin and [alpha]-1-microglobulin were detected the most. The 18 top-abundant proteins accounted for 50% of total abundance. The number of proteins was slightly, but insignificantly higher in clean catch (957 ± 245) than in bag urine (876 ± 255). The median intensity was 1.2 x higher in the clean catch. Overall, differential detection of proteins was 29% between the collection methods; however, it diminished to 3% in the 96 top-abundant proteins. Pearson's correlation coefficient was 0.81 ± 0.11, demonstrating a high intraindividual correlation. A principal component analysis and a heat map showed clustering according to diagnoses and patients rather than to the collection method. Conclusion Urinary proteomics shows a high correlation with minor variation in low-abundant proteins between the two urine collection methods. The biological characteristics overrule this variation.

Soybeans, a vital source of protein for animal feed and an essential industrial raw material, are the most traded agricultural commodity worldwide. Accurate price forecasting is crucial for maintaining a resilient global food supply chain and has significant implications for agricultural economics and policymaking. This review examines over 100 soybean price forecast models published in the last decade, evaluating them based on the specific markets they target—futures or spot—while highlighting how differences between these markets influence critical model design decisions. The models are also classified into AI-powered and traditional categories, with an initial aim to conduct a statistical analysis comparing the performance of these two groups. This process unveiled a fundamental gap in best practices, particularly regarding the use of common benchmarks and standardised performance metrics, which limits the ability to make meaningful cross-study comparisons. Finally, this study underscores another important research gap: the lack of models forecasting soybean futures prices in Brazil, the world’s largest producer and exporter. These insights provide valuable guidance for researchers, market participants, and policymakers in agricultural economics.

The biopharmaceutical industry has specificities related to the optimization of its processes, the effectiveness of the maintenance of the productive park in the face of regulatory requirements. and current concepts of modern industry. Current research on the subject points to investments in the health area using the current tools and concepts of Industry 4.0 (I4.0) with the objective of a more assertive production, reduction of maintenance costs, reduction of operating risks, and minimization of equipment idle time. In this context, this study aims to characterize the current knowledge about the challenges of the biopharmaceutical industry in the application of prescriptive maintenance, which derives from predictive maintenance, in the context of I4.0. To achieve this, a systematic review of the literature was carried out in the scientific knowledge bases IEEE Xplore, Scopus, Web of Science, Science Direct, and Google Scholar, considering works such as Reviews, Article Research, and Conference Abstracts published between 2018 and 2023. The results obtained revealed that prescriptive maintenance offers opportunities for improvement in the production process, such as cost reduction and greater proximity to all actors in the areas of production, maintenance, quality, and management. The limitations presented in the literature include a reduced number of models, the lack of a clearer understanding of its construction, lack of applications directly linked to the biopharmaceutical industry, and lack of measurement of costs and implementation time of these models. There are significant advances in this area including the implementation of more elaborate algorithms used in artificial intelligence neural networks, the advancement of the use of decision support systems as well as the collection of data in a more structured and intelligent way. It is concluded that for the adoption of prescriptive maintenance in the pharmaceutical industry, issues such as the definition of data entry and analysis methods, interoperability between “shop floor” and corporate systems, as well as the integration of technologies existing in the world, must be considered for I4.0.

Summary: Background: Mucositis is a common and highly impactful side effect of conventional and emerging cancer therapy and thus the subject of intense investigation. Although common practice, mucositis assessment is heterogeneously adopted and poorly guided, impacting evidence synthesis and translation. The Multinational Association of Supportive Care in Cancer (MASCC) Mucositis Study Group (MSG) therefore aimed to establish expert recommendations for how existing mucositis assessment tools should be used, in clinical care and trials contexts, to improve the consistency of mucositis assessment. Methods: This study was conducted over two stages (January 2022–July 2023). The first phase involved a survey to MASCC-MSG members (January 2022–May 2022), capturing current practices, challenges and preferences. These then informed the second phase, in which a set of initial recommendations were prepared and refined using the Delphi method (February 2023–May 2023). Consensus was defined as agreement on a parameter by >80% of respondents. Findings: Seventy-two MASCC-MSG members completed the first phase of the study (37 females, 34 males, mainly oral care specialists). High variability was noted in the use of mucositis assessment tools, with a high reliance on clinician assessment compared to patient reported outcome measures (PROMs, 47% vs 3%, 37% used a combination). The World Health Organization (WHO) and Common Terminology Criteria for Adverse Events (CTCAE) scales were most commonly used to assess mucositis across multiple settings. Initial recommendations were reviewed by experienced MSG members and following two rounds of Delphi survey consensus was achieved in 91 of 100 recommendations. For example, in patients receiving chemotherapy, the recommended tool for clinician assessment in clinical practice is WHO for oral mucositis (89.5% consensus), and WHO or CTCAE for gastrointestinal mucositis (85.7% consensus). The recommended PROM in clinical trials is OMD/WQ for oral mucositis (93.3% consensus), and PRO-CTCAE for gastrointestinal mucositis (83.3% consensus). Interpretation: These new recommendations provide much needed guidance on mucositis assessment and may be applied in both clinical practice and research to streamline comparison and synthesis of global data sets, thus accelerating translation of new knowledge into clinical practice. Funding: No funding was received.