Emerging Cases of Cat-Transmitted Sporotrichosis Driven by Sporothrix brasiliensis in Northeast Brazil.

Cat-transmitted sporotrichosis is caused by the emerging fungal pathogen Sporothrix brasiliensis and constitutes a significant public health issue that affects people living in resource-poor urban centers in Brazil. The lack of knowledge about transmission dynamics makes it difficult to propose public health policies to contain the advance of sporotrichosis. We describe the recent emergence of 1,176 cases of sporotrichosis in cats (2016 to 2021) in the metropolitan region of Recife, Brazil, leading to significant zoonotic transmission and an overwhelming occurrence of S. brasiliensis as the etiological agent. Most cases were from cats in the cities of Olinda (408/1,176; 34.70%), Jaboatão dos Guararapes (332/1,176; 28.23%), and Recife (237/1,176; 20.15%). Molecular typing using amplified fragment length polymorphism (EcoRI-GA/MseI-AG) revealed low polymorphic information content (PIC = 0.2499) and heterozygosity (H = 0.2928), typical of an outbreak scenario. Dendrogram and multivariate cluster analysis revealed that isolates from Pernambuco are closely related to Rio de Janeiro isolates. We report a substantial occurrence of MAT1-2 idiomorphs in the metropolitan region of Recife (0:60 ratio; χ2 = 60.000, P < 0.0001). The limited population differentiation and genetic diversity of the isolates from Pernambuco suggest a recent introduction, possibly via a founder effect, from the parental population in Rio de Janeiro. Our findings emphasize the critical importance of molecular surveillance of S. brasiliensis for outbreak response. A comprehensive one-health strategy is mandatory to control the spread of cat-transmitted sporotrichosis driven by S. brasiliensis, encompassing sanitary barriers, quick diagnosis, and treatment.

Trimethoprim-Based multicomponent solid Systems: Mechanochemical Screening, characterization and antibacterial activity assessment.

In this work, multicomponent trimethoprim-based pharmaceutical solid systems were developed by mechanochemistry, using coformers from the GRAS list and other active pharmaceutical ingredients. The choice of coformers took into account their potential to increase the aqueous solubility/dissolution rate of TMP or its antibacterial activity. All the binary systems were characterized by thermal analysis, powder X-ray diffraction and infrared spectroscopy, and 3 equimolar systems with FTIR pointing to salts, and 4 eutectic mixtures were identified. The intrinsic dissolution rate of TMP in combination with nicotinic acid (a salt) and with paracetamol (eutectic mixture) were 25% and 5% higher than for pure TMP, respectively. For both Gram-positive and -negative strains, the antibacterial activity of TMP with some of the coformers was improved, since the dosage used was lower than the TMP control. A significant increase in antibacterial activity against E. coli was found for the eutectic mixture with curcumin, with the best results being obtained for the eutectic and equimolar mixtures with ciprofloxacin. Combining trimethoprim with coformers offers an interesting alternative to using trimethoprim alone: multicomponent forms with enhanced TMP dissolution rates were identified, as well as combinations showing enhanced antibacterial activity relatively to the pure drug.

Tackling Carbapenem Resistance and the Imperative for One Health Strategies-Insights from the Portuguese Perspective.

Carbapenemases, a class of enzymes specialized in the hydrolysis of carbapenems, represent a significant threat to global public health. These enzymes are classified into different Ambler's classes based on their active sites, categorized into classes A, D, and B. Among the most prevalent types are IMI/NMC-A, KPC, VIM, IMP, and OXA-48, commonly associated with pathogenic species such as Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The emergence and dissemination of carbapenemase-producing bacteria have raised substantial concerns due to their ability to infect humans and animals (both companion and food-producing) and their presence in environmental reservoirs. Adopting a holistic One Health approach, concerted efforts have been directed toward devising comprehensive strategies to mitigate the impact of antimicrobial resistance dissemination. This entails collaborative interventions, highlighting proactive measures by global organizations like the World Health Organization, the Center for Disease Control and Prevention, and the Food and Agriculture Organization. By synthesizing the evolving landscape of carbapenemase epidemiology in Portugal and tracing the trajectory from initial isolated cases to contemporary reports, this review highlights key factors driving antibiotic resistance, such as antimicrobial use and healthcare practices, and underscores the imperative for sustained vigilance, interdisciplinary collaboration, and innovative interventions to curb the escalating threat posed by antibiotic-resistant pathogens. Finally, it discusses potential alternatives and innovations aimed at tackling carbapenemase-mediated antibiotic resistance, including new therapies, enhanced surveillance, and public awareness campaigns.

Sirtuin E deacetylase is required for full virulence of Aspergillus fumigatus.

Aspergillus fumigatus represents a public health problem due to the high mortality rate in immunosuppressed patients and the emergence of antifungal-resistant isolates. Protein acetylation is a crucial post-translational modification that controls gene expression and biological processes. The strategic manipulation of enzymes involved in protein acetylation has emerged as a promising therapeutic approach for addressing fungal infections. Sirtuins, NAD+-dependent lysine deacetylases, regulate protein acetylation and gene expression in eukaryotes. However, their role in the human pathogenic fungus A. fumigatus remains unclear. This study constructs six single knockout strains of A. fumigatus and a strain lacking all predicted sirtuins (SIRTKO). The mutant strains are viable under laboratory conditions, indicating that sirtuins are not essential genes. Phenotypic assays suggest sirtuins' involvement in cell wall integrity, secondary metabolite production, thermotolerance, and virulence. Deletion of sirE attenuates virulence in murine and Galleria mellonella infection models. The absence of SirE alters the acetylation status of proteins, including histones and non-histones, and triggers significant changes in the expression of genes associated with secondary metabolism, cell wall biosynthesis, and virulence factors. These findings encourage testing sirtuin inhibitors as potential therapeutic strategies to combat A. fumigatus infections or in combination therapy with available antifungals.

Desafios do uso da inteligência artificial nos diagnósticos de saúde: uma revisão integrativa / Challenges of using artificial intelligence in health diagnoses: an integrative review / Desafíos del uso de la inteligencia artificial en diagnósticos de salud: una revisión integradora

Objetivo: compreender a participação da IA nos diagnósticos da saúde moderna e definir limites para sua aplicação. Metodologia: Revisão integrativa da literatura. A busca dos estudos se deu nas bases de dados LILACS, MEDLINE e SCIELO e foram selecionados artigos científicos, sem recorte temporal e de idioma. Resultados: A inteligência artificial impacta a medicina em três níveis: otimiza a interpretação de imagens para os médicos, aprimora o fluxo de trabalho reduzindo potenciais erros para os sistemas de saúde e capacita os pacientes a processarem seus próprios dados para promover a saúde. Contudo, é necessária atenção aos dados gerados, pois podem desencadear erros em cascata e expor informações sensíveis dos usuários do sistema de saúde. Conclusão: Atribuir à IA a responsabilidade de escolhas e funções desempenhadas por humanos é intrinsecamente perigoso, apesar de sua contribuição inegável nos processos diagnósticos. Sugere-se a realização de pesquisas robustas para compreender plenamente o impacto dessa nova era tecnológica proporcionada pela IA na área da saúde.

Objective: To understand the role of AI in modern healthcare diagnostics and define boundaries for its application. Methodology:Integrative literature review. Studies were searched in the LILACS, MEDLINE, and SCIELO databases, selecting scientific articles without temporal or language restrictions. Results: Artificial intelligence impacts medicine at three levels: it optimizes image interpretation for physicians, enhances workflow by reducing potential errors for healthcare systems, and empowers patients to process their own data to promote health. However, attention is required regarding the generated data, as it may trigger cascading errors and expose sensitive information of healthcare system users. Conclusion: Assigning AI, the responsibility of choices and functions performed by humans is inherently dangerous, despite its undeniable contribution to diagnostic processes. Robust research is suggested to fully understand the impact of this new technological era provided by AI in healthcare.

Objetivo: Comprender la participación de la IA en los diagnósticos de la salud moderna y definir límites para su aplicación. Metodología:Revisión integrativa de la literatura. Los estudios se buscaron en las bases de datos LILACS, MEDLINE y SCIELO, seleccionando artículos científicos sin restricciones temporales ni lingüísticas. Resultados: La inteligencia artificial impacta la medicina en tres niveles: optimiza la interpretación de imágenes para los médicos, mejora el flujo de trabajo al reducir errores potenciales para los sistemas de salud y capacita a los pacientes para procesar sus propios datos y promover la salud. Sin embargo, se requiere atención respecto a los datos generados, ya que pueden desencadenar errores en cascada y exponer información sensible de los usuarios del sistema de salud. Conclusión: Asignar a la IA la responsabilidad de decisiones y funciones realizadas por humanos es intrínsecamente peligroso, apesar de su contribución innegable a los procesos de diagnóstico. Se sugiere realizar investigaciones sólidas para comprender completamente el impacto de esta nueva era tecnológica proporcionada por la IA en la salud.

Photodynamic inactivation of E. coli with cationic imidazolyl-porphyrin photosensitizers and their synergic combination with antimicrobial cinnamaldehyde.

Bacterial infections are a global health concern, particularly due to the increasing resistance of bacteria to antibiotics. Multi-drug resistance (MDR) is a considerable challenge, and novel approaches are needed to treat bacterial infections. Photodynamic inactivation (PDI) of microorganisms is increasingly recognized as an effective method to inactivate a broad spectrum of bacteria and overcome resistance mechanisms. This study presents the synthesis of a new cationic 5,15-di-imidazolyl porphyrin derivative and the impact of n-octanol/water partition coefficient (logP) values of this class of photosensitizers on PDI efficacy of Escherichia coli. The derivative with logP = -0.5, IP-H-OH2+, achieved a remarkable 3 log CFU reduction of E. coli at 100 nM with only 1.36 J/cm2 light dose at 415 nm, twice as effective as the second-best porphyrin IP-H-Me2+, of logP = -1.35. We relate the rapid uptake of IP-H-OH2+ by E. coli to improved PDI and the very low uptake of a fluorinated derivative, IP-H-CF32+, logP ≈ 1, to its poor performance. Combination of PDI with cinnamaldehyde, a major component of the cinnamon plant known to alter bacteria cell membranes, offered synergic inactivation of E. coli (7 log CFU reduction), using 50 nM of IP-H-OH2+ and just 1.36 J/cm2 light dose. The success of combining PDI with this natural compound broadens the scope of therapies for MDR infections that do not add drug resistance. In vivo studies on a mouse model of wound infection showed the potential of cationic 5,15-di-imidazolyl porphyrins to treat clinically relevant infected wounds.

Dereplication Tools for Rhizophora mangle Extracts from Different Mangrove Areas and their Potential Against Staphylococcus aureus.

Rhizophora extracts have several potential biological activities, and their metabolites can be used in the pharmaceutical industry. Extracts of Rhizophora species obtained from mangroves have shown prospective activity against Staphylococcus aureus. This study aimed to investigate the chemical profile of Rhizophora mangle leaves from fringe, basin, and transition mangrove zones and their bactericidal/bacteriostatic potential against S. aureus. R. mangle leaves were collected monthly in 2018 from litterfall in three different zones of the mangrove of Guaratiba State Reserve: fringe, basin, and transition. Extracts were prepared from the material collected in October and December for LC-HRMS/MS analysis, and dereplication was performed using a molecular library search and the classical molecular networking GNPS platform. The minimum inhibitory concentrations (MICs) of the aqueous extract of R. mangle against S. aureus were determined. No S. aureus growth was observed compared to the control for extracts collected from September to December. Different compounds were annotated in each region, yet a marked presence of phenolic compounds was noted, among them glycosylated flavonoid derivatives of quercetin and kaempferol. The results suggest bactericidal/bacteriostatic activity for extracts of R. mangle leaves collected in 2018 from three mangrove forest zones.

Cardioprotective Effects of Aloysia polystachya Essential Oil on a Rat Model with Multiple Cardiovascular Risk Factors.

Traditional medicine is a frequently utilized method to treat cardiovascular disease and its primary risk factors, including hypertension and dyslipidemia. Aloysia polystachya is a species that is commonly employed to treat various pathological conditions, and it has already been identified as having some cardioprotective effects. This study aimed to investigate the protective effects of the essential oil extracted from the leaves of A. polystachya in a rat model that simulates multiple cardiovascular risk factors. We evaluate the acute toxicity, as well as the cardioprotective effects, by giving different doses of A. polystachya essential oil (1.47 mg/kg, 4.40 mg/kg, and 13.20 mg/kg) over a period of 42 days. The control group was treated with rosuvastatin (5 mg/kg). At the end of the treatments, the renal function, electrocardiography, blood pressure, vascular reactivity, serum biochemical profile, and organ histopathology were evaluated. The main compounds identified in the essential oil of A. polystachya using gas chromatography coupled with mass spectrometry were beta-myrcene (1.08%), limonene (40.13%), and carvone (56.47%). The essential oil of A. polystachya not only lacks acute toxicity but also mitigates the reduction in the excretion of sodium, chloride, and creatinine in urine. Furthermore, it reduces electrocardiographic abnormalities and decreases blood pressure levels. Moreover, this treatment prevents an elevation in markers of inflammation and oxidative stress in the bloodstream. Our findings indicate significant cardioprotective effects of the essential oil of A. polystachya against multiple risk factors for cardiovascular diseases in hypertensive rats.

Access to health and social protection policies by homeless people during the COVID-19 pandemic: a mixed-methods case study on tailored inter-sector care during a health emergency.

Introduction: The article analyzed homeless people's (HP) access to health and social protection policies and tailored inter-sector care, including emergency measures, during the COVID-19 pandemic in Belo Horizonte (BH), capital of Minas Gerais state, Brazil. It intended to provide data on HP and evaluate existing public policies focused on vulnerable populations during this health emergency. Methods: The study adopted a mixed-methods design with triangulation of quantitative and qualitative data. Results: Social cartography showed that in the early months of the pandemic, the health administration had difficulty reordering the health system, which experienced constant updates in the protocols but was nevertheless consolidated over the months. The evidence collected in the study showed that important emergency interventions in the municipality of BH involved activities that facilitated access by HP to the supply of services. Discussion: The existence of national guidelines for inter-sector care for HP cannot be ruled out as a positive influence, although the municipalities are responsible for their implementation. Significantly, a health emergency was necessary to intensify the relationship between health and social protection services. Roving services were among those with the greatest positive evidence, with the least need for infrastructure to be replicated at the local level. In addition, the temporary supply of various inter-sector services, simultaneously with the provision of day shelters by organized civil society, was considered a key factor for expanding and intensifying networks of care for HP during the emergency phase. A plan exists to continue and expand this model in the future. The study concluded that understanding the inter-sector variables that impact HP contributes to better targeting of investments in interventions that work at the root causes of these issues or that increase the effectiveness of health and social protection systems.

Desafios e possibilidades da jurimetria na judicialização em saúde: uma investigação em Minas Gerais do período 2014 a 2020 / Challenges and possibilities of jurimetry in health judicialization: an investigation in Minas Gerais state from 2014 2020 / Desafíos y posibilidades de la jurimetría en la judicialización de la salud: una investigación en Minas Gerais de 2014 a 2020

Objetivo: analisar os processos de saúde, de medicamentos e de medicamentos antineoplásicos em Minas Gerais, em 2014 a 2020, a partir da comparação de diferentes bases de dados. Metodologia: foram utilizadas técnicas de pareamento de bases de dados entre os processos existentes no Tribunal de Justiça do Estado de Minas Gerais e os processos recebidos pela Secretaria Estadual de Saúde de Minas Gerais, descreveram-se as dificuldades encontradas na identificação e quantificação desses processos, e os resultados encontrados foram comparados com informações provenientes de outras fontes. Resultados: nas bases do Tribunal de Justiça de Minas Gerais foram identificados 564.763 processos de saúde. Houve um aumento significativo do número de processos até 2017 e uma estabilização, em patamares altos, a partir de 2017. Ao comparar com os resultados obtidos pelo Instituto Superior de Ensino e Pesquisa e pelo Laboratório de Inovação, Inteligência e Objetivos de Desenvolvimento Sustentável, houve uma importante divergência nos números de processos. Tomando como exemplo a judicialização de saúde contra o estado de Minas Gerais, não foi possível encontrar de forma direta todos os processos recebidos pela Secretaria Estadual de Saúde de Minas Gerais nas diversas bases fornecidas pelo Tribunal de Justiça de Minas Gerais, tendo sido necessária uma integração entre as diferentes bases de dados e uma busca adicional para identificar todos os processos. Conclusão: recomendam-se a padronização e organização dos dados dos processos judiciais em saúde, já na entrada de dados, para facilitar a realização de estudos quantitativos sobre a judicialização da saúde.

Objective: to analyze the health, drug, and antineoplastic drug lawsuits in Minas Gerais, in 2014 to 2020, from the comparison of different databases. Methodology: database pairing techniques were used to link lawsuits from the Minas Gerais State Court of Justice with the processes received by the Minas Gerais Health State Department, the difficulties encountered in identifying and quantifying these processes were described, and the results found were compared with information from other sources. Results: in the Minas Gerais State Court of Justice databases, 564,763 health lawsuits were identified in the studied period. There was a significant increase in the number of processes until 2017 and a stabilization, at high levels, from 2017 onwards. In comparison with the results obtained by the Institute of Higher Education and Research and the Laboratory of Innovation, Intelligence and Sustainable Development Goals there was a great divergence in the number of processes found. Conclusion: taking the health judicialization against Minas Gerais state as an example, it was not possible to directly find all the processes received by Minas Gerais Health State Department in the various databases provided by the Minas Gerais State Court of Justice, requiring integration between the different databases and an additional search to identify all processes.

Objetivo: analizar los juicios de salud, drogas y medicamentos antineoplásicos en Minas Gerais, en 2014 a 2020, a partir de la comparación de diferentes bases de datos. Metodología: técnicas de emparejamiento de bases de datos fueron utilizadas para vincular los juicios existentes en el Tribunal de Justicia del Estado de Minas Gerais con los procesos recibidos por la Secretaría de Estado de Salud de Minas Gerais, las dificultades encontradas en la identificación y cuantificación de esos procesos fueron descritas, y los resultados encontrados fueron comparados con informaciones de otras fuentes. Resultados: en las bases del Tribunal de Justicia del Estado de Minas Gerais se identificaron 564.763 procesos de salud. Hubo un aumento significativo en el número de procesos hasta 2017 y una estabilización, en niveles altos, a partir de 2017. Sin embargo, al comparar con los resultados obtenidos por el Instituto Superior de Educación e Investigación y por el Laboratorio de Innovación, Inteligencia y Objetivos de Desarrollo Sostenible hubo una divergencia importante en el número de procesos. Conclusión: tomando como ejemplo la judicialización de la salud contra el estado de Minas Gerais, no era posible encontrar directamente todos los procesos recibidos por la Secretaría de Estado de Salud de Minas Gerais en las diversas bases de datos proporcionadas por el Tribunal de Justicia del Estado de Minas Gerais, lo que requería una integración entre las diferentes bases de datos y una búsqueda adicional a identificar todos los procesos.

Intuitive eating has reduced the chances of being overweight in university students during the COVID-19 pandemic.

Introduction: University students have been particularly affected during the COVID-19 pandemic, and several sociodemographic and behavioral factors may be associated with the risk of overweight in this population. The aim of this study was to assess the impact of the pandemic on the eating behavior and nutritional status of university students, and the factors associated with these changes, especially the role of intuitive eating in this process. Methods: This is a repeated measures observational study with data collected in the first and third year of the COVID-19 pandemic in Brazil, from students over the age of 18 in the undergraduate programs of a federal university in southeastern Brazil. The survey was conducted using an online form. Eating behavior was assessed using the "Intuitive Eating Scale-2". Results: 251 university students took part, most of them female with a median age of 22. There was an increase in body mass index (BMI) and intuitive eating score between the two periods. In the first year of the pandemic, being female and using tobacco reduced the chances of students being overweight. Living in a marital relationship, worrying about weight gain and body dissatisfaction increased the chances of this outcome. In the third year of the pandemic, it was observed that practicing restrictive diets, having inadequate body perception, worrying about weight gain and living in a marital relationship increased the chances of students being overweight. Being female and eating more intuitively, in line with bodily needs, reduced these odds, demonstrating a protective role in this scenario. Conclusion: There was an increase in BMI and intuitive eating score during the pandemic. Sociodemographic, lifestyle and behavioral variables had both a positive and negative influence on nutritional status. Intuitive eating was shown to be a protective factor during this period, reducing the chances of being overweight in this population. Thus, more intuitive eating may favor greater weight stability, and may, therefore, have helped to reduce the impact of the pandemic on weight gain. In this way, people who ate more intuitively partially resisted the context that favored weight gain (stress, changes in diet and physical inactivity).

O uso do laser de alta e baixa intensidade para o tratamento de hipersensibilidade dentinária: uma revisão integrativa

Objetivo: Determinar as evidências científicas sobre a influência do uso de lasers de baixa e alta intensidade no tratamento da hipersensibilidade da dentina. Revisão de literatura: Foram realizadas buscas na Biblioteca Virtual em Saúde (BVS), incluindo as bases de dados: Literatura Latino Americana e do Caribe em Ciências da Saúde (LILACS); Bibliografia Brasileira de Odontologia (BBO); e National Library of Medicine (MEDLINE). A maioria dos estudos destacam a eficácia dos lasers na redução da HD, com o laser Nd:YAG mostrando-se eficaz na obliteração dos túbulos dentinários e proporcionando alívio a longo prazo. Apesar dos benefícios, alguns estudos alertam para possíveis danos à polpa dentária, especialmente com lasers de alta potência. Considerações finais: Embora os lasers tenham se mostrado eficazes na redução da HD, a escolha do laser deve ser personalizada para cada paciente, destacando a necessidade de aprimorar os protocolos clínicos e adquirir experiência relevante por parte dos profissionais especialistas.

Objective: To determine the scientific evidence on the influence of the use of low and high intensity lasers in the treatment of dentin hypersensitivity. Literature review: Searches were carried out in the Virtual Health Library (VHL), including the databases: Latin American and Caribbean Literature in Health Sciences (LILACS); Brazilian Bibliography of Dentistry (BBO); and National Library of Medicine (MEDLINE). Most studies highlight the effectiveness of lasers in reducing HD, with the Nd:YAG laser proving effective in obliterating dentinal tubules and providing long-term relief. Despite the benefits, some studies warn of possible damage to the dental pulp, especially with high-power lasers. Final considerations: Although lasers have been shown to be effective in reducing HD, the choice of laser must be personalized for each patient, highlighting the need to improve clinical protocols and acquire relevant experience on the part of specialist professionals.

Safety, Efficacy, and Immunogenicity of Therapeutic Vaccines for Patients with High-Grade Cervical Intraepithelial Neoplasia (CIN 2/3) Associated with Human Papillomavirus: A Systematic Review.

Despite the knowledge that HPV is responsible for high-grade CIN and cervical cancer, little is known about the use of therapeutic vaccines as a treatment. We aimed to synthesize and critically evaluate the evidence from clinical trials on the safety, efficacy, and immunogenicity of therapeutic vaccines in the treatment of patients with high-grade CIN associated with HPV. A systematic review of clinical trials adhering to the PRISMA 2020 statement in MEDLINE/PubMed, Embase, CENTRAL Cochrane, Web of Science, Scopus, and LILACS was undertaken, with no data or language restrictions. Primary endpoints related to the safety, efficacy, and immunogenicity of these vaccines were assessed by reviewing the adverse/toxic effects associated with the therapeutic vaccine administration via histopathological regression of the lesion and/or regression of the lesion size and via viral clearance and through the immunological response of individuals who received treatment compared to those who did not or before and after receiving the vaccine, respectively. A total of 1184 studies were identified, and 16 met all the criteria. Overall, the therapeutic vaccines were heterogeneous regarding their formulation, dose, intervention protocol, and routes of administration, making a meta-analysis unfeasible. In most studies (n = 15), the vaccines were safe and well tolerated, with clinical efficacy regarding the lesions and histopathological regression or viral clearance. In addition, eleven studies showed favorable immunological responses against HPV, and seven studies showed a positive correlation between immunogenicity and the clinical response, indicating promising results that should be further investigated. In summary, therapeutic vaccines, although urgently needed to avoid progression of CIN 2/3 patients, still present sparse data, requiring greater investments in a well-designed phase III RCT.

Aortic Thrombosis Associated with Three Types of COVID-19 Vaccine.

Aortic thrombosis has been studied little in patients with COVID-19 and an association has recently been reported with the vaccine for this disease. The aim of the present study is to report five cases of aortic thrombosis at our institution within a three-month period associated with the COVID-19 vaccine. Five cases of aortic thrombosis were evaluated-three women and two men aged 29, 49, 51, 60, and 79 years. Four thrombi involved the thoracic aortic and one involved the abdominal aorta, with embolisms found in the kidneys, spleen, liver, upper limbs, and lower limbs. Embolectomy was performed on the limbs, and anticoagulant therapy was performed for the abdominal arteries. The patients recovered well and anticoagulant therapy was maintained. Aortic thrombosis is uncommon but was associated with the AstraZeneca vaccine in this case series.

Co-regulation of biofilm formation and antimicrobial resistance in Acinetobacter baumannii: from mechanisms to therapeutic strategies.

In recent years, multidrug-resistant Acinetobacter baumannii has emerged globally as a major threat to the healthcare system. It is now listed by the World Health Organization as a priority one for the need of new therapeutic agents. A. baumannii has the capacity to develop robust biofilms on biotic and abiotic surfaces. Biofilm development allows these bacteria to resist various environmental stressors, including antibiotics and lack of nutrients or water, which in turn allows the persistence of A. baumannii in the hospital environment and further outbreaks. Investigation into therapeutic alternatives that will act on both biofilm formation and antimicrobial resistance (AMR) is sorely needed. The aim of the present review is to critically discuss the various mechanisms by which AMR and biofilm formation may be co-regulated in A. baumannii in an attempt to shed light on paths towards novel therapeutic opportunities. After discussing the clinical importance of A. baumannii, this critical review highlights biofilm-formation genes that may be associated with the co-regulation of AMR. Particularly worthy of consideration are genes regulating the quorum sensing system AbaI/AbaR, AbOmpA (OmpA protein), Bap (biofilm-associated protein), the two-component regulatory system BfmRS, the PER-1 ß-lactamase, EpsA, and PTK. Finally, this review discusses ongoing experimental therapeutic strategies to fight A. baumannii infections, namely vaccine development, quorum sensing interference, nanoparticles, metal ions, natural products, antimicrobial peptides, and phage therapy. A better understanding of the mechanisms that co-regulate biofilm formation and AMR will help identify new therapeutic targets, as combined approaches may confer synergistic benefits for effective and safer treatments.

Deacetylation by sirtuins is important for Aspergillus fumigatus pathogenesis and virulence.

Protein acetylation is a crucial post-translational modification that controls gene expression and a variety of biological processes. Sirtuins, a prominent class of NAD + -dependent lysine deacetylases, serve as key regulators of protein acetylation and gene expression in eukaryotes. In this study, six single knockout strains of fungal pathogen Aspergillus fumigatus were constructed, in addition to a strain lacking all predicted sirtuins (SIRTKO). Phenotypic assays suggest that sirtuins are involved in cell wall integrity, secondary metabolite production, thermotolerance, and virulence. AfsirE deletion resulted in attenuation of virulence, as demonstrated in murine and Galleria infection models. The absence of AfSirE leads to altered acetylation status of proteins, including histones and non-histones, resulting in significant changes in the expression of genes associated with secondary metabolism, cell wall biosynthesis, and virulence factors. These findings encourage testing sirtuin inhibitors as potential therapeutic strategies to combat A. fumigatus infections or in combination therapy with available antifungals.

Escherichia coli Phylogenetic and Antimicrobial Pattern as an Indicator of Anthropogenic Impact on Threatened Freshwater Mussels.

Freshwater bivalves are widely used as accumulation indicators and monitoring tools for assessing contaminant effects on different levels of biological integration. This pilot study aimed to explore the phylogenetic diversity of Escherichia coli isolated from freshwater mussels (Margaritifera margaritifera and Potomida littoralis) and characterize their phenotypes and antibiotic resistance profiles. Samples were collected in the Rabaçal and Tua Rivers, in the Douro basin, Portugal-two sites representing different levels of anthropogenic contamination. Antimicrobial susceptibility testing was performed via the disk diffusion method with 21 antibiotics. Results showed that 31% of isolates were multidrug-resistant (MDR). Thus, freshwater mussels provide an effective and time-integrated approach for identifying/quantifying fecal indicators, including MDR bacteria. PCR-based assays were designed for assessing phylogenetic E. coli groups. Among the E. coli isolates, the highest prevalence (44%) was observed in group D or E, followed by group E or Clade I (25%), group A (19%), and group B1 (13%). E. coli isolated from M. margaritifera predominantly exhibited a higher prevalence of phylogroups D or E, whereas E. coli from P. littoralis showed associations with phylogroups E or clade I, B1, A, and D or E. Our results provide new insights into the phylogenetic diversity of E. coli in freshwater bivalves. Additionally, the findings highlight the possible linkage of phylogroups with the host species, the geographical location in the water stream, and human activity. Using E. coli as a bioindicator isolated from freshwater mussels helps us grasp how human activities affect the environment. This study has important implications for those interested in safeguarding water resources, especially in tackling antibiotic resistance in aquatic ecosystems.

An Overview of Cefiderocol's Therapeutic Potential and Underlying Resistance Mechanisms.

Antimicrobial resistance continues to increase globally and treatment of difficult-to-treat (DTT) infections, mostly associated with carbapenem-resistant (CR) Pseudomonas aeruginosa, CR Acinetobacter baumannii, and CR- and third-generation-cephalosporins-resistant Enterobacterales remains a challenge for the clinician. The recent approval of cefiderocol has broaden the armamentarium for the treatment of patients with DTT infections. Cefiderocol is a siderophore cephalosporin that has shown excellent antibacterial activity, in part due to its innovative way of cell permeation. It is relatively stable compared to most commonly found carbapenamases. However, some resistant mechanisms to cefiderocol have already been identified and reduced susceptibility has developed during patient treatment, highlighting that the clinical use of cefiderocol must be rational. In this review, we summarize the current available treatments against the former resistant bacteria, and we revise and discuss the mechanism of action of cefiderocol, underlying the biological function of siderophores, the therapeutic potential of cefiderocol, and the mechanisms of resistance reported so far.

The Acinetobacter baumannii website (Ab-web): a multidisciplinary knowledge hub, communication platform, and workspace.

Acinetobacter baumannii is a Gram-negative bacterium increasingly implicated in hospital-acquired infections and outbreaks. Effective prevention and control of such infections are commonly challenged by the frequent emergence of multidrug-resistant strains. Here we introduce Ab-web (https://www.acinetobacterbaumannii.no), the first online platform for sharing expertise on A. baumannii. Ab-web is a species-centric knowledge hub, initially with 10 articles organized into two main sections, 'Overview' and 'Topics', and three themes, 'epidemiology', 'antibiotic resistance', and 'virulence'. The 'workspace' section provides a spot for colleagues to collaborate, build, and manage joint projects. Ab-web is a community-driven initiative amenable to constructive feedback and new ideas.

Ecotoxicological assessment of guanitoxin-producing cyanobacteria in Danio rerio and Daphnia similis.

Anthropogenic activity has dramatically deteriorated aquatic ecosystems in recent years. Such environmental alterations could change the primary producers' composition, exacerbating the proliferation of harmful microorganisms such as cyanobacteria. Cyanobacteria can produce several secondary metabolites, including guanitoxin, a potent neurotoxin and the only naturally occurring anticholinesterase organophosphate ever reported in the literature. Therefore, this study investigated the acute toxicity of guanitoxin-producing cyanobacteria Sphaerospermopsis torques-reginae (ITEP-024 strain) aqueous and 50% methanolic extracts in zebrafish (Danio rerio) hepatocytes (ZF-L cell line), zebrafish embryos (fish embryo toxicity - FET) and specimens of the microcrustacean Daphnia similis. For this, hepatocytes were exposed to 1-500 mg/L of the ITEP-024 extracts for 24 h, the embryos to 31.25-500 mg/L for 96 h, and D. similis to 10-3000 mg/L for 48 h. Non-target metabolomics was also performed to analyze secondary metabolites produced by the ITEP-024 using LC-MS/MS. Metabolomics indicated the guanitoxin presence just in the aqueous extract of the ITEP-024 and the presence of the cyanopeptides namalides, spumigins, and anabaenopeptins in the methanolic extract. The aqueous extract decreased the viability of zebrafish hepatocytes (EC(I)50(24h) = 366.46 mg/L), and the methanolic extract was not toxic. FET showed that the aqueous extract (LC50(96) = 353.55 mg/L) was more toxic than the methanolic extract (LC50(96) = 617.91 mg/L). However, the methanolic extract had more sublethal effects, such as abdominal and cardiac (cardiotoxicity) edema and deformation (spinal curvature of the larvae). Both extracts immobilized daphnids at the highest concentration analyzed. However, the aqueous extract was nine times more lethal (EC(I)50(48h) = 108.2 mg/L) than the methanolic extract (EC(I)50(48h) = 980.65 mg/L). Our results showed an imminent biological risk for aquatic fauna living in an ecosystem surrounded by ITEP-024 metabolites. Our findings thus highlight the urgency of understanding the effects of guanitoxin and cyanopeptides in aquatic animals.