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This study aimed to evaluate the effects of liposome-encapsulated eugenol-based thiazolic derivatives against efflux pump-carrying bacteria. The Minimum Inhibitory Concentration (MIC) was determined to evaluate the antibacterial activity and antibiotic potentiation against Pseudomonas aeruginosa and Staphylococcus aureus, as well as to analyze the inhibition of efflux pumps in S. aureus strains 1199B and K2068 in the ethidium bromide assay. The direct antibacterial activity analysis showed no clinically relevant results since the compounds presented MICs ≥1024 µg/mL. Regarding the analysis of antibiotic potentiation against multidrug-resistant (MDR) strains of S. aureus, compound LF16 reduced norfloxacin MIC from 128 µg/mL to 64 µg/mL. All associated with gentamicin caused a significant antibiotic MIC reduction. None of the compounds could potentate the activity of norfloxacin against P. aeruginosa. However, all of them potentiated the activity of gentamicin against the same strain. Only the LF 26 caused a significant MIC reduction in the ethidium bromide assay, suggesting efflux inhibition in the S. aureus 1199B strain. Similar results were observed with the K2068 strain. Observing antibiotic MIC reduction S. aureus strains carrying the NorA and MepA proteins brought additional evidence of efflux pump inhibition. Our results indicate that while eugenol-based thiazoles didn’t exhibit direct activity, they can potentiate the antibiotics activity against MDR strains of P. aeruginosa and S. aureus. Among them, compound LF 26 potentiated the inhibitory effects of ethidium bromide and antibiotics against S. aureus strains carrying the NorA and MepA proteins, indicating a potential role of this class of compounds as efflux pump inhibitors.

Abstract Kilohertz‐frequency alternating currents (KFACs) have been indicated to minimize muscle atrophy and weakness. However, the optimal stimulation parameters still need to be determined. Objective This study aimed to investigate the effects of different KFACs on evoked torque, current efficiency, and perceived discomfort. Design KFACs with frequencies of 1 kHz (Aussie current) and 2.5 kHz (Russian current), along with two duty cycles (10% and 20%), were randomly applied to the triceps surae muscle of healthy participants using a crossover design. The NMES intensity, NMES‐evoked torque, NMES efficiency, and NMES discomfort were measured in maximal and submaximal conditions. Statistical analyses were conducted using a two‐way mixed‐model ANOVA with repeated measures. Forty‐four participants were included. Results Aussie currents produced higher evoked torque and efficiency in maximal and submaximal efforts, with higher perceived discomfort in maximal effort. Although the Australian current may cause greater discomfort at maximal efforts, it matches the Russian current in perceived discomfort at submaximal levels. The 20% duty cycle produced the highest efficiency in submaximal efforts. Conclusion In both maximal and submaximal efforts, the Aussie current demonstrated superior NMES efficiency, yielding higher torque with lower amplitude than the Russian current. Clinicians should take these findings into consideration when prescribing KFACs to optimize clinical outcomes.

Resumo: Relato de caso de paciente de 15 anos com Doença Falciforme (DF)de evolução grave, com surgimento de lesão paravertebral evidenciada em exame de ressonância nuclear magnética (RNM), sugerindo hematopoiese extramedular (HEM) e que obteve resolução completa com desaparecimento da lesão após o início do programa de transfusões de troca. Introdução: A HEM é considerada um mecanismo fisiológico compensatório que ocorre quando a medula óssea é incapaz de suprir a demanda de células sanguíneas. Frequentemente, está associada a hemoglobinopatias congênitas ou a desordens de substituição medular adquiridas. Embora qualquer órgão possa estar envolvido, o fígado e o baço são os sítios mais comuns, mas eventualmente acomete torácica como massas lobuladas paravertebrais com densidades de partes moles ao exame de imagem. Relato do caso: Paciente de 15 anos, masculino, pardo, estudante, com diagnóstico de DF S-ßtalassemia realizado pela triagem neonatal, e de osteocondrose múltipla. Menor evoluindo com hipodesenvolvimento e diversas internações por crises vasoclusivas e síndromes torácicas agudas com grande necessidade transfusional. Além disso menor realizou diversas cirurgias ao longo da primeira infância a fim de retirar os osteocondromas. Em junho/23 durante uma internação por crise álgica severa, foi realizada RNM de coluna torácica sendo evidenciada lesões a nível de D4 e D6 descritas inicialmente como hemangiomas, mas que após discussão com radiologista foi aventada a hipótese de HEM. Em julho/23, paciente foi incluído em programa de transfusões de troca manuais mensais no ambulatório transfusional Serum Centro. Em novembro/23 foi instituída a troca por eritracitoaférese, a fim de controlar melhor os níveis de HbS e espaçar os intervalos das trocas, visto que paciente morava em outro município. Após o início das transfusões de troca, houve desaparecimento completo da massa na RNM março/24 e paciente se mantém atualmente no programa de troca automatizada em média a cada 5- 6 semanas. Discussão: : A HEM é um mecanismo compensatório fisiológico, frequentemente associado a hemoglobinopatias, que consiste em áreas microscópicas difusas de tecido hematopoiético que podem ser encontradas diversas partes do corpo. A biópsia por agulha deve ser evitada, em função da alta vascularização deste tecido. O tratamento é o da doença de base e o tecido hematopoiético não deve ser removido, exceto nos casos de haver compressão medular. No nosso relato, com a otimização do tratamento da DF, através da instituição do programa de transfusões de troca automatizada, mantendo Hb basal em torno de 9-10 g/dl e HbS em torno de 30-35% houve desaparecimento da massa torácica confirmada no exame de RNM março/24. Além disso temos que o paciente teve um grande desenvolvimento pondero estatural no período, com melhora da qualidade de vida e da sua autoestima. Conclusão: O achado de massas paravertebrais bilaterais ou não, bem definidas em pacientes com doença falciforme e outras anemias hemolíticas deve alertar para a possibilidade diagnóstica de HEM. Nesses casos o tratamento da doença de base deve ser otimizado às custas de terapia transfusional adequada. A transfusão de troca automatizada – eritrocitaférese garante o manejo seguro e eficaz, mantendo os níveis de HbS adequados.

O mineiro Francisco José Soares, Chico, como prefere ser chamado, nasceu em Conselheiro Lafaiete, uma das cidades mais antigas de Minas Gerais.

Computational strategies to extract meaningful biological information from multiomics data are in great demand for effective clinical use, particularly in complex immune-mediated disorders. Regulatory T cells (Tregs) are essential for immune homeostasis and self-tolerance, controlling inflammatory and autoimmune processes in many diseases with a multigenic basis. Here, we quantify the Transcription Factor (TF) differential occupancy landscape to uncover the Gene Regulatory Modules governing lineage-committed Tregs in the human thymus, and show that it can be used as a tool to prioritise variants in complex diseases. We combined RNA-seq and ATAC-seq and generated a matrix of differential TF binding to genes differentially expressed in Tregs, in contrast to their counterpart conventional CD4 single-positive thymocytes. The gene loci of both established and novel genetic interactions uncovered by the Gene Regulatory Modules were significantly enriched in rare variants carried by patients with common variable immunodeficiency, here used as a model of polygenic-based disease with severe inflammatory and autoimmune manifestations. The Gene Regulatory Modules controlling the Treg signature can, therefore, be a valuable resource for variant classification, and to uncover new therapeutic targets. Overall, our strategy can also be applied in other biological processes of interest to decipher mutational hotspots in individual genomes.

Species diversity depends on the capacity of species to coexist, and when these share similar ecological requirements some degree of partitioning of the ecological niche is expected. Within the order Carnivora, direct and indirect interspecific interactions shape community structure and composition. Although strong negative interactions (e.g., interspecific killing) are expected between large carnivores and subordinate species, mesocarnivores that dominate most human disturbed landscapes can still strongly compete for resources given their similar body size and energy requirements. To identify the mechanisms of coexistence between mesocarnivore species in a Mediterranean landscape we assessed the ecological niche overlap between five species (Vulpes vulpes, Meles meles, Martes foina, Herpestes ichneumon, Genetta genetta), by simultaneously measuring the space, time, and trophic resource use. The multi-species occupancy model fit to camera-trapping data revealed spatial co-occurrence between most species’ pairs and an avoidance pattern between only stone marten and Eurasian badger (78 % probability of a negative effect). Using genetically identified scats, we assessed trophic niche breadth and overlap. Niche breadth was narrow for red fox, Eurasian badger, and stone marten, given these species consumed almost exclusively fruits and arthropods, and so trophic niche overlap was high. For the genet and the mongoose, the consumption of different food resources (e.g., mammals, birds, and reptiles) increased niche breadth and decreased the niche overlap with the other sympatric species. Finally, niche segregation was more significant along the temporal axis, since the mongoose has a diurnal activity pattern and the remaining carnivore species, although mostly nocturnal, had small asynchronies in the activity peaks which could decrease the chance of direct encounters. Therefore, our results suggest that similar habitat preferences and ecological requirements rather than interspecific competition shape the mesocarnivores’ resource use in this landscape. Nonetheless, fine-scale temporal segregation seems the main mechanism to facilitate coexistence, together with small differences in trophic resource use, especially for species with high spatial and temporal overlap.

This paper is a conceptual and interpretative update of a previously published version. The main objective of this study was to understand how target position influences eye movements in navigational and informative tasks. The sample comprised 20 university students (13 females 7 males, aged 18-44). Participants completed a socio-demographic questionnaire and performed two tasks: navigational and informative. Eye movements were recorded during task performance. A 2x2 MANOVA was conducted to analyze linear combinations of dependent variables (blink duration, blink frequency, and fixation duration) across task types and target positions. Results revealed significant differences in eye movement patterns between tasks. The navigational task showed shorter average blink durations (204.236-1656.397 ms) and fewer blinks (1.987-9.786) compared to the informative task (553.598-1864.440 ms; 9.648-20.040 blinks, respectively). Strong interaction effects were observed between average fixation duration and individual position in both navigational (ηp2 = .216) and informative (ηp2 = .176) tasks. We conclude that target position in the navigational task significantly influences university students’ eye movements, while individual position affects eye movements in both navigational and informative tasks. These findings contribute to understanding how task demands modulate visual attention and potentially affect user interface design and educational technology.

This study evaluated the impact of a cognitive stimulation program on older adults diagnosed with dementia. The sample comprised 22 participants aged 73-95, randomly assigned to an experimental group (N = 12) and a control group (N = 10). While no statistically significant decreases were observed in the studied dimensions, clinically relevant gains were noted: 41.70% in cognition, 41.60% in quality of life, and 8.3% in functional skills. Although no therapeutic interventions have successfully reversed dementia, healthcare providers reported improvements in participants’ social interactions, behaviors, and engagement in daily institutional routines. These observations suggest tangible benefits from program participation. It’s important to note that staff working closely with these patients daily observed these improvements despite the lack of statistically significant results. This discrepancy highlights the potential limitations of relying solely on quantitative measures to assess such interventions’ effectiveness. In conclusion, the cognitive stimulation program shows promise as a potential tool for slowing dementia-associated degenerative processes, particularly in areas that standard quantitative assessments may not fully capture. Further research with larger sample sizes and more sensitive measures may be warranted to fully understand the program’s impact.

The main objective of this study is to understand how the target’s position influences eye movement in navigational and informative tasks. The study included 20 university students, 13 females and 7 males, aged between 18 and 44. Participants answered a socio-demographic questionnaire and performed two tasks: navigational and informative. Linear combinations of dependent variables were performed through the MANOVA (2x2) test, which maximized the differences between several conditions of the independent variables. The results indicate that the target’s position in the navigational task significantly influences the eye movement of university students. Additionally, the individual’s position influences eye movement in both navigational and informative tasks. It is concluded that both the target’s position and the individual’s position determine eye movement factors during navigational and informative tasks, highlighting the importance of considering these variables in studies of visual perception and human-computer interaction.

Enquadramento: A exposição dos enfermeiros ao sofrimento e morte dos doentes pode desencadear níveis elevados de sofrimento, dependendo das estratégias de coping utilizadas. Objetivos: Analisar a relação entre o sofrimento e as características sociodemográficas e profissionais identificar as estratégias de coping mais utilizadas; analisar a relação entre o sofrimento e as estratégias de coping. Metodologia: Estudo descritivo, correlacional e transversal. Participaram 26 enfermeiros de uma Unidade Cuidados Intensivos Cardíacos (UCIC). Foi utilizada a Caregiver Grief Scale para avaliar o sofrimento e o Ways of Coping Questionnaire para avaliar as estratégias de coping. Resultados: Não se verifica relação entre o sofrimento e as características sociodemográficas e profissionais. As estratégias de coping mais utilizadas são as centradas no problema (autocontrolo, procura de suporte social). Constata-se uma correlação positiva (r = 0,56) entre o sofrimento e a estratégia de coping distanciamento (p = 0,01). Conclusão: O sofrimento é transversal a todos os enfermeiros de uma UCIC, independentemente das variáveis sociodemográficas e profissionais. Utilizando como estratégia de coping o distanciamento, o sofrimento pode ser maior.

Methyl-eugenol (ME) and eugenol (EUG) are phenylpropanoids with vasodilatory effects. While EUG's vasorelaxant effect in human umbilical artery (HUA) is known, their action in veins is unclear. This study aimed to evaluate ME and EUG in human umbilical vein (HUV). Isolated HUV underwent tension recordings. ME and EUG caused 100 % relaxation in HUV, with EC50 values corresponding to: 174.3 ± 7.3 and 217.3 ± 6.2 µM for ME and EUG respectively in presence of K+; 362.3 ± 5.4 and 227.7 ± 4.9 µM for ME and EUG respectively and in presence of serotonin (5-HT). It was observed that in presence of BaCl2 and CaCl2 evoked contractions, ME (800 and 1000 µM) and EUG (1000 and 1400 µM) prevent the contractions. In presence of K+ channel blockers it was observed that ME promoted relaxation compared to its control, except in presence of 4-AP, suggesting a possible Ca2+-dependent K+ channel activation for this molecule; EUG increased all EC50 in presence of the K+ blockers except in presence of TEA 1 mM. Greater pharmacological potency was observed for ME. This study highlights natural substances' effects on HUV contractile parameters, suggesting ME and EUG as potential vasodilators in maintaining fetal oxygenation and venous flow during gestational hypertensive syndromes.

Accurately predicting spectra for heavy elements, often open-shell systems, is a significant challenge typically addressed using a single cluster approach with a fixed coordination number. Developing a realistic model that accounts for temperature effects, variable coordination numbers, and interprets experimental data is even more demanding due to the strong solute–solvent interactions present in solutions of heavy metal cations. This study addresses these challenges by combining multiple methodologies to accurately predict realistic spectra for highly charged metal cations in aqueous media, with a focus on the electronic absorption spectrum of Ce3+ in water. Utilizing highly correlated relativistic quantum mechanical (QM) wavefunctions and structures from molecular dynamics (MD) simulations, we show that the convolution of individual vertical transitions yields excellent agreement with experimental results without the introduction of empirical broadening. Good results are obtained for both the normalized spectrum and that of absolute intensity. The study incorporates a statistical machine learning algorithm, Gaussian Mixture Models-Nuclear Ensemble Approach (GMM-NEA), to convolute individual spectra. The microscopic distribution provided by MD simulations allows us to examine the contributions of the octa- and ennea-hydrate of Ce3+ in water to the final spectrum. In addition, the temperature dependence of the spectrum is theoretically captured by observing the changing population of these hydrate forms with temperature. We also explore an alternative method for obtaining statistically representative structures in a less demanding manner than MD simulations, derived from QM Wigner distributions. The combination of Wigner-sampling and GMM-NEA broadening shows promise for wide application in spectroscopic analysis and predictions, offering a computationally efficient alternative to traditional methods. [ABSTRACT FROM AUTHOR]