Search

Tick-transmitted Babesia are a major global veterinary threat and an emerging risk to humans. Unlike their Plasmodium relatives, these erythrocyte-infecting Apicomplexa have been largely overlooked and lack specific treatment. Selective targeting of the Babesia proteasome holds promise for drug development. In this study, we screened a library of peptide epoxyketone inhibitors derived from the marine natural product carmaphycin B for their activity against Babesia. Several of these compounds showed activity against both the asexual and sexual blood stages of Plasmodium falciparum. These compounds inactivate β5 proteasome subunit activity in the lysates of Babesia divergens and Babesia microti in the low nanomolar range. Several compounds were tested with the purified B. divergens proteasome and showed IC50 values comparable to carfilzomib, an approved anticancer proteasome inhibitor. They also inhibited B. divergens growth in bovine erythrocyte cultures with solid EC50 values, but importantly, they appeared less toxic to human cells than carfilzomib. These compounds therefore offer a wider therapeutic window and provide new insights into the development of small proteasome inhibitors as selective drugs for babesiosis.

Abstract Background The rapid spread and increase of chikungunya (CHIKV) and dengue (DENV) cases in Brazilian regions in 2023 has raised concerns about the impact of arboviruses on public health. Epidemiological and genomic surveillance was performed to estimate the introduction and spread of CHIKV and DENV in Brazil. Methods This study obtained results from the Hermes Pardini (HP), a private medical laboratory, and the Health Department of Minas Gerais state (SES-MG). We investigated the positivity rates of CHIKV and DENV by analyzing the results of 139,457 samples tested for CHIKV (44,029 in 2022 and 95,428 in 2023) and 491,528 samples tested for DENV (163,674 in 2022 and 327,854 in 2023) across the five representative geographical regions of Brazil. Genome sequencing was performed on 80 CHIKV and 153 DENV samples that had been positive for RT-PCR tests. Results In our sampling, the data from CHIKV tests indicated that the Northeast region had the highest regional positivity rate in 2022 (58.1%). However, in 2023, the Southeast region recorded the highest positivity rate (40.5%). With regard to DENV, the South region exhibited the highest regional positivity rate in both 2022 (40.8%) and 2023 (22.7%), followed by the Southeast region in both years (34.8% in 2022; 21.4% in 2023). During the first 30 epidemiological weeks of 2023 in the state of Minas Gerais (MG), there was a 5.8-fold increase in CHIKV cases and a 3.5-fold increase in DENV compared to the same period in 2022. Analysis of 151 new DENV-1 and 80 CHIKV genomes revealed the presence of three main clusters of CHIKV and circulation of several DENV lineages in MG. All CHIKV clades are closely related to genomes from previous Brazilian outbreaks in the Northeast, suggesting importation events from this region to MG. We detected the RNA of both viruses in approximately 12.75% of the confirmed positive cases, suggesting an increase of co-infection with DENV and CHIKV during the period of analysis. Conclusions These high rates of re-emergence and co-infection with both arboviruses provide useful data for implementing control measures of Aedes vectors and the urgent implementation of public health politics to reduce the numbers of CHIKV and DENV cases in the country.

Noroviruses are highly contagious and are one of the leading causes of acute gastroenteritis worldwide. Due to a lack of effective antiviral therapies, there is a need to diagnose and surveil norovirus infections to implement quarantine protocols and prevent large outbreaks. Currently, the gold standard of diagnosis uses reverse transcription polymerase chain reaction (RT-PCR), but PCR can have limited availability. Here, we propose a combination of a tunable peptide substrate and gold nanoparticles (AuNPs) to colorimetrically detect the Southampton norovirus 3C-like protease (SV3CP), a key protease in viral replication. Careful design of the substrate employs a zwitterionic peptide with opposite charged moieties on the C- and N- termini to induce a rapid color change visible to the naked eye; thus, this color change is indicative of SV3CP activity. This work expands on existing zwitterionic peptide strategies for protease detection by systematically evaluating the effects of lysine and arginine on nanoparticle charge screening. We also determine a limit of detection for SV3CP of 28.0 nM with comparable results in external breath condensate, urine, and fecal matter for 100 nM of SV3CP. The key advantage of this system is its simplicity and accessibility, thus making it an attractive tool for qualitative point-of-care diagnostics.

The rapid development and introduction of new psychoactive substances (NPS) into illegal markets present an enormous challenge for forensic toxicologists, as there is limited knowledge about their toxicity in humans. To strengthen forensic interpretation of NPS intoxication cases, we have developed a predictive model for estimating human lethal blood concentrations (LBC) of various NPS. This quantitative structure-activity relationship (QSAR) model focuses on opioids, designer benzodiazepines, synthetic cathinones, synthetic cannabinoids, and phenethylamines. Utilising linear regression and multilayer perceptron algorithms, the models was trained using data from the existing literature. A toxicological significance-based approach have been applied to refine the selection of training data. The model demonstrated satisfactory performance metrics through cross-validation (R ≈ 0.8, MAE ≈ 0.6) and comparison with experimental data (R ≈ 0.9). A Python-based web application have been developed to facilite the use of the created model in predicting LBC of NPS. Despite the model's reliability, limitations due to data availability, quality and the complexities of post-mortem toxicology mean that its predictions should be interpreted with caution.

Introdução: É crescente o uso de dispositivos eletrônicos para fumar entre jovens. Objetivo: Descrever a relação entre o uso de cigarro eletrônico e a saúde mental, mais especificamente voltado para o Transtorno de Ansiedade Generalizada, de estudantes de medicina. Método: Coletado o TCLE (Termo de Consentimento Livre e Esclarecido). Parecer CEP: Universidade de Ribeirão Preto, UNAERP, CAAE: 69249523.8.0000.5498. Número do Parecer: 6.187.957. Estudo observacional com amostra de 122 estudantes de Medicina, na faixa etária de 18 a 50 anos. Analisaram-se, principalmente, a saúde mental e a dependência nicotínica de usuários de cigarro eletrônico, através de coleta de dados por meio de um questionário com 28 questões, baseadas na Escala de Ansiedade de Hamilton e no Teste de Fargeström. Realizando-se análise descritiva. Foi feita, também, regressão logística, tendo como variável dependente o uso de cigarro eletrônico e como variáveis independentes: o sexo, a presença de diagnóstico psiquiátrico prévio e a presença de sintomas de ansiedade. Resultados: Dos 122 estudantes que responderam ao questionário, 66,39% são mulheres e 73,33% já tiveram algum diagnóstico psiquiátrico. Além disso, 31,96% da amostra total são fumantes. Destes, 44,26% utilizam cigarro eletrônico. Após a regressão logística, encontramos que ter diagnóstico psiquiátrico prévio aumenta a chance de fazer uso de cigarro eletrônico (odds ratio ajustado = 3,29; intervalo de confiança de 95%: 1,17 – 9,23). Conclusão: O uso de cigarros eletrônicos entre os estudantes de medicina está associado a níveis de ansiedade, destacando os usuários com diagnóstico prévio psiquiátrico, o que aumenta a chance de seu uso, necessitando de prevenção e cessação, para melhor saúde do aluno.

ABSTRACT: For 2160 broilers, were raised from 1 to 42 d of age, was evaluated the consequences of microencapsulated blend of organic acids and bioactive compounds on dietary supplementation in broilers on meat quality and consumer acceptance during 200 d. Broilers were randomly distributed in a completely randomized design with 6 treatments: Negative control (NC): basal diet; Positive control (PC): NC+ Zinc bacitracin 15%; B150: NC+150 g/t of the microencapsulated blend of organic acids and bioactive compounds; B300: NC+300 g/t of the microencapsulated blend of organic acids and bioactive compounds; B450:NC+450 g/t of the microencapsulated blend of organic acids and bioactive compounds; and B600:NC+600 g/t of the microencapsulated blend of organic acids and bioactive compounds. The poultry meat characteristics (thawing loss, cooking loss, shear force, color and microstructure of the meat), oxidative stability (lipid oxidation, antioxidant activity DPPH and ABTS) and consumer acceptance (visual appraisal and willingness to buy) were evaluated. Color parameters (L and b), thawing losses and shear force were not significantly different among the treatments (NC, PC, B150, B300, B450 and B600; P > 0.05). The highest level of a was in the PC. The cooking losses were the greatest in B600. No treatment showed changes in muscle fibers. The antioxidant activity for DPPH was higher for B600. For ABTS, B150 and B300 presented the least lipid oxidation. When evaluating consumers' visual preference, B300 had the greatest in consumer preference and B150 and B300 had the greatest purchase intention on the first day of storage. After 6 d, B300 continued to be the most preferred and B150 and B450 began to show the greatest purchase intention. The B300 treatment showed a protective effect on lipid stability and consumer preference. These results highlight the importance of using a precise additive dosage during animal production to guarantee the meat's quality and satisfy consumers’ demands.

AbstractFrom our roles within international public health organizations, we have collectively witnessed the global challenges presented by outdated health information systems, platforms, and applications. The COVID-19 pandemic has clearly exposed the limitations of our current paper-based vaccine certification methods and highlighted the deficiencies of outdated technological platforms that lack interoperability standards, a situation that underscores the critical need for a digital transformation in how we manage and verify immunization records. Digital vaccination certificates are understood to be secure, electronically stored, and easily accessible records that provide verifiable proof of a person’s immunization status. The Pan American Health Organization (PAHO) envisions leveraging digital technologies to strengthen health systems, enhance data-driven decision-making, and improve health outcomes. The organization’s vision emphasizes the integration of innovative technologies to build resilient and responsive health systems capable of addressing modern public health challenges. In an era of unprecedented technological advancement, our continued reliance on paper-based vaccine certificates is not just anachronistic—it is a significant liability for global public health that impacts the efficiency and effectiveness of our health systems on multiple fronts, limiting our ability to respond to public health crises effectively. With the strategic guidance from its Member States, PAHO has agreed to move toward the digital transformation of the health sector across the entire continent with an initiative that aims to improve health outcomes, ensure equitable access to health services, and enhance the overall efficiency of health systems in the Americas. The roadmap for this digital transformation outlines strategic actions and goals to achieve a connected, efficient, and resilient health sector.

As Tecnologias Digitais de Informação e Comunicação (TDICs) têm transformado as práticas educacionais, oferecendo novas oportunidades para o ensino e a aprendizagem. Este estudo analisa os desafios e as aprendizagens na integração das TDICs no ensino de Geografia, com foco em uma escola pública em Garanhuns-PE. A pesquisa, fundamentada na fenomenologia, investiga as percepções de residentes e alunos sobre a aplicação das TDICs. Os resultados revelam que a falta de infraestrutura adequada, como acesso à internet e recursos digitais, representa um obstáculo significativo para a implementação das TDICs. Contudo, diversas estratégias foram adotadas para contornar essas limitações e promover a participação ativa dos alunos. A pesquisa também destaca a importância da formação continuada dos professores para garantir uma integração efetiva das TDICs, enfatizando a necessidade de habilidades e conhecimentos específicos para utilizar as tecnologias de forma crítica e significativa. Conclui-se que a integração das TDICs no ensino de Geografia requer não apenas a disponibilidade de recursos tecnológicos, mas também uma abordagem pedagógica inovadora e adaptativa, capaz de transformar os desafios em oportunidades de aprendizagem.

In this paper, we present our study into how teaching practices in chemistry are socially stratified under the center-suburban divide in a medium-sized city, located in the State of São Paulo, Brazil. The paper mainly draws upon the Bourdieusian-inspired concepts of institutional habitus and symbolic capital to examine how institutional discourses and norms are embodied and implemented by chemistry teachers in their pedagogical practices, and the way in which this affects the distribution of chemistry knowledge in the classroom. This study is a comparative ethnographic-based investigation which employs multiple qualitative methods to investigate chemistry classes in two public schools in Brazil. The schools were selected based on their achievements in large-scale assessment tests and socioeconomic composition. Based on the results obtained from the analysis of four months of observational data of chemistry classes, school routines, 12 focus groups composed of high school students, and four semi-structured interviews conducted with teachers and staff, we argue that chemistry teaching is partially influenced by two interrelated dimensions of the school's institutional habitus--the schools' reputation and their students' social profile. Students in different schools tend to have unequal opportunities for learning and identification with chemistry. For instance, in the suburban school, students are seen as having learning deficiencies and are given deficit explanations on scientific concepts during classes, while the students from the school in the city center are taught under a pervasive culture centered around academic achievements, intense competition and individuality. The aforementioned factors largely shape chemistry teaching in the two public schools investigated. We conclude by presenting our final considerations on how educational institutions play an influential role in shaping chemistry teaching practices.