Molecular Docking and Antibacterial Activity of Campesterol Derivatives Against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa multiresistant strains.

This work describes the evaluation the potentiating activity of antibiotics by campesterol (1) and its derivatives (2-11) against multiresistant strains of Staphylococcusaureus 10, Escherichia coli 06 and Pseudomonas aeruginosa 24 employing the microdilution test. When subjected to the in vitro potentiating activity bioassay, all compounds showed a potentiating effect associated with norfloxacin against E. coli and P. aeruginosa with a reduction in the MIC of the antibiotic of up to 75%. These compounds also reduced the MIC of gentamicin by 37% to 87% in S. aureus and E. coli. Additionally, molecular docking studies were conducted to gain a deeper understanding of the interactions between the appropriate proteins and the most effective compounds (2, 4, 9, and 10 against E. coli; 1, 2, 3, 5, 8, and 9 against S. aureus), including antibiotics. This paper registers for the first time the in vitro and in silico studies on the action of compounds 1-11 in antibiotic potentiation.

Assessment In vitro and In silico of the Activity of Thiadiazines as NorA Efflux Pump Inhibitors.

Antimicrobials fight microorganisms, preventing and treating infectious diseases. However, antimicrobial resistance (AMR) is a growing concern due to the inappropriate and excessive use of these drugs. Several mechanisms can lead to resistance, including efflux pumps such as the NorA pump in Staphylococcus aureus, which reduces the effectiveness of fluoroquinolones. Thiadiazines are heterocyclic compounds whose chemical structure resembles that of cephalosporins. Therefore, these compounds and their derivatives have been studied for their potential in combating increased bacterial resistance. To analyze this hypothesis, direct activity assays, antibiotic action-modifying activity, fluorescence assays to evaluate the retention of ethidium bromide inside bacteria, and molecular docking were carried out. These experiments involved serial dilutions in microplates against Staphylococcus aureus strain 1199B under the influence of six thiadiazine derivatives (IJ10, IJ11, IJ21, IJ22, IJ23, and IJ25). The tests revealed that, despite not showing effective direct activity, some thiadiazine derivatives (IJ11, IJ21, and IJ22) inhibited the function of the bromide pump both in microdilution tests and in fluorescence and docking assays. Particularly, the IJ11 compound stood out for its activity similar to efflux inhibitors, as well as its inhibition of the norfloxacin pump of this bacterium. Among the results of this study, it deserves to be highlighted for anchoring future experiments, as it represents the first investigation of this group of thiadiazine derivatives against the NorA pump.

Antibodies against Leptospira spp. in Free-living and Captive Broad-snouted Caiman (Caiman latirostris) and Free-living Yacare Caiman (Caiman yacare) in Brazil.

We evaluated antibodies against Leptospira spp. in both free-living and captive Caiman latirostris from Atlantic Forest, and free-living Caiman yacare from Pantanal, Brazil, by using a microscopic agglutination test. Overall seropositivity was 17%, with rates of 36% in captive C. latirostris (n=4/11) and 18% in free-living C. yacare (n=4/22).

Guanylate-binding protein-5 is involved in inflammasome activation by bacterial DNA but only the cooperation of multiple GBPs accounts for control of Brucella abortus infection.

Introduction: Guanylate-binding proteins (GBPs) are produced in response to pro-inflammatory signals, mainly interferons. The most studied cluster of GBPs in mice is on chromosome 3. It comprises the genes for GBP1-to-3, GBP5 and GBP7. In humans, all GBPs are present in a single cluster on chromosome 1. Brucella abortus is a Gram-negative bacterium known to cause brucellosis, a debilitating disease that affects both humans and animals. Our group demonstrated previously that GBPs present on murine chromosome 3 (GBPchr3) is important to disrupt Brucella-containing vacuole and GBP5 itself is important to Brucella intracellular LPS recognition. In this work, we investigated further the role of GBPs during B. abortus infection. Methods and results: We observed that all GBPs from murine chromosome 3 are significantly upregulated in response to B. abortus infection in mouse bone marrow-derived macrophages. Of note, GBP5 presents the highest expression level in all time points evaluated. However, only GBPchr3-/- cells presented increased bacterial burden compared to wild-type macrophages. Brucella DNA is an important Pathogen-Associated Molecular Pattern that could be available for inflammasome activation after BCV disruption mediated by GBPs. In this regard, we observed reduced IL-1ß production in the absence of GBP2 or GBP5, as well as in GBPchr3-/- murine macrophages. Similar result was showed by THP-1 macrophages with downregulation of GBP2 and GBP5 mediated by siRNA. Furthermore, significant reduction on caspase-1 p20 levels, LDH release and Gasdermin-D conversion into its mature form (p30 N-terminal subunit) was observed only in GBPchr3-/- macrophages. In an in vivo perspective, we found that GBPchr3-/- mice had increased B. abortus burden and higher number of granulomas per area of liver tissue, indicating increased disease severity. Discussion/conclusion: Altogether, these results demonstrate that although GBP5 presents a high expression pattern and is involved in inflammasome activation by bacterial DNA in macrophages, the cooperation of multiple GBPs from murine chromosome 3 is necessary for full control of Brucella abortus infection.

Development of a multivariate predictive model for dapsone adverse drug events in people with leprosy under standard WHO multidrug therapy.

BACKGROUND: The occurrence of adverse drug events (ADEs) during dapsone (DDS) treatment in patients with leprosy can constitute a significant barrier to the successful completion of the standardized therapeutic regimen for this disease. Well-known DDS-ADEs are hemolytic anemia, methemoglobinemia, hepatotoxicity, agranulocytosis, and hypersensitivity reactions. Identifying risk factors for ADEs before starting World Health Organization recommended standard multidrug therapy (WHO/MDT) can guide therapeutic planning for the patient. The objective of this study was to develop a predictive model for DDS-ADEs in patients with leprosy receiving standard WHO/MDT. METHODOLOGY: This is a case-control study that involved the review of medical records of adult (≥18 years) patients registered at a Leprosy Reference Center in Rio de Janeiro, Brazil. The cohort included individuals that received standard WHO/MDT between January 2000 to December 2021. A prediction nomogram was developed by means of multivariable logistic regression (LR) using variables. The Hosmer-Lemeshow test was used to determine the model fit. Odds ratios (ORs) and their respective 95% confidence intervals (CIs) were estimated. The predictive ability of the LRM was assessed by the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 329 medical records were assessed, comprising 120 cases and 209 controls. Based on the final LRM analysis, female sex (OR = 3.61; 95% CI: 2.03-6.59), multibacillary classification (OR = 2.5; 95% CI: 1.39-4.66), and higher education level (completed primary education) (OR = 1.97; 95% CI: 1.14-3.47) were considered factors to predict ADEs that caused standard WHO/MDT discontinuation. The prediction model developed had an AUC of 0.7208, that is 72% capable of predicting DDS-ADEs. CONCLUSION: We propose a clinical model that could become a helpful tool for physicians in predicting ADEs in DDS-treated leprosy patients.

Potentiating-antibiotic activity and absorption, distribution, metabolism, excretion and toxicity properties (ADMET) analysis of synthetic thiadiazines against multi-drug resistant (MDR) strains.

BACKGROUND: Thiadiazines are heterocyclic compounds that contain two nitrogen atoms and one sulfur atom in their structure. These synthetic molecules have several relevant pharmacological activities, such as antifungal, antibacterial, and antiparasitic. OBJECTIVES: The present study aimed to evaluate the possible in vitro and in silico interactions of compounds derived from thiadiazines. METHODS: The compounds were initially synthesized, purified, and confirmed through HPLC methodology. Multi-drug resistant bacterial strains of Staphylococcus aureus 10 and Pseudomonas aeruginosa 24 were used to evaluate the direct and modifying antibiotic activity of thiadiazine derivatives. ADMET assays (absorption, distribution, metabolism, excretion, and toxicity) were conducted, which evaluated the influence of the compounds against thousands of macromolecules considered as bioactive targets. RESULTS: There were modifications in the chemical synthesis in carbon 4 or 3 in one of the aromatic rings of the structure where different ions were added, ensuring a variability of products. It was possible to observe results that indicate the possibility of these compounds acting through the cyclooxygenase 2 mechanism, which, in addition to being involved in inflammatory responses, also acts by helping sodium reabsorption. The amine group present in thiadiazine analogs confers hydrophilic characteristics to the substances, but this primary characteristic has been altered due to alterations and insertions of other ligands. The characteristics of the analogs generally allow easy intestinal absorption, reduce possible hepatic toxic effects, and enable possible neurological and anti-inflammatory action. The antibacterial activity tests showed a slight direct action, mainly of the IJ23 analog. Some compounds were able to modify the action of the antibiotics gentamicin and norfloxacin against multi-drug resistant strains, indicating a possible synergistic action. CONCLUSIONS: Among all the results obtained in the study, the relevance of thiadiazine analogs as possible coadjuvant drugs in the antibacterial, anti-inflammatory, and neurological action with low toxicity is clear. Need for further studies to verify these effects in living organisms is not ruled out.

Synthesis, spectroscopic characterization, and antibacterial activity of chalcone (2E)-1-(3'-aminophenyl)-3-(4-dimethylaminophenyl)-prop-2-en-1-one against multiresistant Staphylococcus aureus carrier of efflux pump mechanisms and ß-lactamase.

BACKGROUND: The bacterium Staphylococcus aureus has stood out for presenting a high adaptability, acquiring resistance to multiple drugs. The search for natural or synthetic compounds with antibacterial properties capable of reversing the resistance of S. aureus is the main challenge to be overcome today. Natural products such as chalcones are substances present in the secondary metabolism of plants, presenting important biological activities such as antitumor, antidiabetic, and antimicrobial activity. OBJECTIVES: In this context, the aim of this work was to synthesize the chalcone (2E)-1-(3'-aminophenyl)-3-(4-dimethylaminophenyl)-prop-2-en-1-one with nomenclature CMADMA, confirm its structure by nuclear magnetic resonance (NMR), and evaluate its antibacterial properties. METHODS: The synthesis methodology used was that of Claisen-Schmidt, and spectroscopic characterization was performed by NMR. For microbiological assays, the broth microdilution methodology was adopted in order to analyze the antibacterial potential of chalcones and to analyze their ability to act as a possible inhibitor of ß-lactamase and efflux pump resistance mechanisms, present in S. aureus strain K4100. RESULTS: The results obtained show that CMADMA does not show direct antibacterial activity, expressing a MIC of ≥1024 µg/mL, or on the enzymatic mechanism of ß-lactamase; however, when associated with ethidium bromide in efflux pump inhibition assays, CMADMA showed promising activity by reducing the MIC of the bromide from 64 to 32 µg/mL. CONCLUSION: We conclude that the chalcone synthesized in this study is a promising substance to combat bacterial resistance, possibly acting in the inhibition of the QacC efflux pump present in S. aureus strain K4100, as evidenced by the reduction in the MIC of ethidium bromide.

Meldrum's acid derivates are MepA efflux pump inhibitors: In vitro and in silico essays.

Efflux pumps are proteins capable of expelling antibiotics from bacterial cells, have emerged as a major mechanism of bacterial resistance. In the ongoing pursuit to overcome and reduce bacterial resistance, novel substances are being explored as potential efflux pump inhibitors. Meldrum's acid, a synthetic molecule widely studied for its role in synthesizing bioactive compounds, holds promise in this regard. Therefore, the objective of this study is to evaluate the antibacterial activity of three derivatives of Meldrum's acid and assess their ability to inhibit efflux mechanisms, employing both in silico and in vitro approaches. The antibacterial activity of the derivatives was assessed using a broth microdilution testing method. Surprisingly, the derivatives did not exhibit direct antibacterial activity on their own. However, they displayed a significant effect in enhancing the efficacy of antibiotics, suggesting a potential role in potentiating their effects. Furthermore, fluorescence emission assays using ethidium bromide indicated that the derivatives could potentially block efflux pumps, as they exhibited fluorescence levels comparable to the positive control. To further investigate their inhibitory capacity, molecular docking studies were conducted in silico, revealing binding interactions similar to ciprofloxacin and carbonyl cyanide 3-chlorophenylhydrazone, known efflux pump inhibitors. These findings highlight the potential of Meldrum's acid derivatives as effective inhibitors of efflux pumps. By targeting these mechanisms, the derivatives offer a promising avenue to enhance the effectiveness of antibiotics and combat bacterial resistance. This study underscores the importance of exploring novel strategies in the fight against bacterial resistance and provides valuable insights into the potential of Meldrum's acid derivatives as efflux pump inhibitors. Further research and exploration in this field are warranted to fully exploit their therapeutic potential.

Current Understanding of Bacillus Calmette-Guérin-Mediated Trained Immunity and Its Perspectives for Controlling Intracellular Infections.

The bacillus Calmette-Guérin (BCG) is an attenuated bacterium derived from virulent Mycobacterium bovis. It is the only licensed vaccine used for preventing severe forms of tuberculosis in children. Besides its specific effects against tuberculosis, BCG administration is also associated with beneficial non-specific effects (NSEs) following heterologous stimuli in humans and mice. The NSEs from BCG could be related to both adaptive and innate immune responses. The latter is also known as trained immunity (TI), a recently described biological feature of innate cells that enables functional improvement based on metabolic and epigenetic reprogramming. Currently, the mechanisms related to BCG-mediated TI are the focus of intense research, but many gaps are still in need of elucidation. This review discusses the present understanding of TI induced by BCG, exploring signaling pathways that are crucial to a trained phenotype in hematopoietic stem cells and monocytes/macrophages lineage. It focuses on BCG-mediated TI mechanisms, including the metabolic-epigenetic axis and the inflammasome pathway in these cells against intracellular pathogens. Moreover, this study explores the TI in different immune cell types, its ability to protect against various intracellular infections, and the integration of trained innate memory with adaptive memory to shape next-generation vaccines.

First Capture of a Jaguar Using a Minimally Invasive Capture System for GPS Tracking in an Isolated Patch of Atlantic Forest in Southern Brazil.

This study presents the first successful capture using GPS tagging of a jaguar (Panthera onca) using a minimally invasive capture system (MICS). We used snare-foot traps and a MICS during two capture campaigns in a fragment of Atlantic Forest in southeastern Brazil. The specimen disarmed snares on different occasions, and capture was only possible with the MICS. The captured jaguar, an estimated 16-year-old adult male, was monitored using a GPS Vertex Plus Iridium collar with an optimal performance of 86% in expected locations. The jaguar's home range (659 km2 by MPC and 174 km2 by 95%K) was within the observed range for the species and the animal was primarily maintained in protected areas. The habitat types most frequently used were native grassland (27.2% of 4798 fixes), marsh (24.8%), and dense lowland forest (24.7%). The use of a MICS for trapping jaguars is a promising technique that shows advantages in terms of efficiency, selectivity, portability, reduced potential risk of injury to animals or trappers, and animal stress compared to other capture methods used for the species.

Chemical composition and antibacterial effects of Etlingera elatior (Jack) R.M. Smith against Staphylococcus aureus efflux pumps.

Multidrug resistance is a significant health problem worldwide, with increasing mortality rates, especially in the last few years. In this context, a consistent effort has been made to discover new antibacterial agents, and evidence points to natural products as the most promising source of bioactive compounds. This research aimed to characterize the antibacterial effect of the essential oil of Etlingera elatior (EOEE) and its major constituents against efflux pump-carrying Staphylococcus aureus strains. The essential oil was extracted from fresh inflorescences by hydrodistillation. Chemical analysis was performed using gas chromatography coupled to mass spectrometry (GC-MS) and gas chromatography equipped with a flame ionization detector (GC-FID). The strains RN-4220, 1199B, IS-58, and 1199 of S. aureus were used to evaluate the antibacterial activity and the inhibition of efflux pumps. A total of 23 compounds were identified, including dodecanal and 1-dodecanol as major compounds. EOEE and dodecanal showed weak activity against the strains, while 1-dodecanol inhibited bacterial growth at low concentrations, indicating strong antibacterial activity. In addition, this compound potentiated the activity of norfloxacin against S. aureus 1199. In conclusion, 1-dodecanol was identified as the most effective compound of EOEE, showing significant potential to be used in antibacterial drug development.

Antibacterial and Toxic Activity of Geopropolis Extracts from Melipona subnitida (Ducke, 1910) (Hymenoptera: Apidae) and Scaptotrigona depilis (Moure, 1942) (Hymenoptera: Apidae).

Bacteria are associated with many infections that affect humans and present antibiotic resistance mechanisms, causing problems in health organisations and increased mortality rates. Therefore, it is necessary to find new antibacterial agents that can be used in the treatment of these microorganisms. Geopropolis is a natural product from stingless bees, formed by a mixture of plant resins, salivary secretions, wax and soil particles, the chemical composition of this natural product is diverse. Thus, this study aimed to evaluate antibacterial activity, antibiotic modulation and the toxicity of geopropolis extracts from the stingless bees, Melipona subnitida (Ducke, 1910) and Scaptotrigona depilis (Moure, 1942) against standard and multi-resistant Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa bacteria. Geopropolis samples were collected in a meliponary located in Camaragibe, Pernambuco, Brazil. To determine the Minimum Inhibitory Concentration (MIC) and antibiotic modulation we performed broth microdilution tests. Mortality tests were used to verify extract toxicity in the model Drosophila melanogaster. The microbiological tests showing that the M. subnitida extracts had better inhibitory effects compared to S. depilis, presenting direct antibacterial activity against standard and multi-resistant strains. The extracts potentialized antibiotic effects, suggesting possible synergy and did not present toxicity in the model used. The information obtained in this study highlights extracts as promising antibacterial agents and is the first study to evaluate bacterial activity in these extracts, in addition to verifying their modulating effects and determining toxicity in the model used.

Bacillus Calmette-Guérin-Trained Macrophages Elicit a Protective Inflammatory Response against the Pathogenic Bacteria Brucella abortus.

The bacillus Calmette-Guérin (BCG) can elicit enhanced innate immune responses against a wide range of infections, known as trained immunity. Brucella abortus is the causative agent of brucellosis, a debilitating disease that affects humans and animals. In this study, we demonstrate that C57BL/6 mouse bone marrow-derived macrophages under BCG training enhance inflammatory responses against B. abortus. BCG-trained macrophages showed increased MHC class II and CD40 expression on the cell surface and higher IL-6, IL-12, and IL-1ß production. The increase in IL-1ß secretion was accompanied by enhanced activation of canonical and noncanonical inflammasome platforms. We observed elevated caspase-11 expression and caspase-1 processing in BCG-trained macrophages in response to B. abortus compared with untrained cells. In addition, these BCG-trained cells showed higher NLRP3 expression after B. abortus infection. From a metabolic point of view, signaling through the Akt/mammalian target of rapamycin/S6 kinase pathway was also enhanced. In addition, BCG training resulted in higher inducible NO synthase expression and nitrite production, culminating in an improved macrophage-killing capacity against intracellular B. abortus. In vivo, we monitored a significant reduction in the bacterial burden in organs from BCG-trained C57BL/6 mice when compared with the untrained group. In addition, previous BCG immunization of RAG-1-deficient mice partially protects against Brucella infection, suggesting the important role of the innate immune compartment in this scenario. Furthermore, naive recipient mice that received BM transfer from BCG-trained donors showed greater resistance to B. abortus when compared with their untrained counterparts. These results demonstrate that BCG-induced trained immunity in mice results in better control of intracellular B. abortus in vivo and in vitro.

Antibiotic-Potentiating Activity of the Schinus terebinthifolius Raddi Essential Oil against MDR Bacterial Strains.

Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus are the primary bacteria that cause clinical infections, such as urinary and intestinal infections, pneumonia, endocarditis, and sepsis. Bacterial resistance is an innate natural occurrence in microorganisms, resulting from mutations or the lateral exchange of genetic material. This serves as evidence for the association between drug consumption and pathogen resistance. Evidence has demonstrated that the association between conventional antibiotics and natural products is a promising pharmacological strategy to overcome resistance mechanisms. Considering the large body of research demonstrating the significant antimicrobial activities of Schinus terebinthifolius Raddi, the present study aimed to evaluate the chemical composition and antibiotic-enhancing effects of Schinus terebinthifolius Raddi essential oil (STEO) against the standard and multidrug-resistant strains of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. The STEO was extracted by hydrodistillation using a Clevenger-type vacuum rotary evaporator. The Minimum Inhibitory Concentration (MIC) of the STEO was assessed by the microdilution method to evaluate the antibacterial activity. The antibiotic-enhancing activity of the essential oil was assessed by determining the MIC of antibiotics in the presence of a sub-inhibitory concentration (MIC/8) of the natural product. The GC-MS analysis revealed alpha-pinene (24.3%), gamma-muurolene (16.6%), and myrcene (13.7%) as major constituents of the STEO. The STEO potentiated the enhanced antibacterial activity of norfloxacin and gentamicin against all the strains and increased the action of penicillin against the Gram-negative strains. Therefore, it is concluded that although the STEO does not exhibit clinically effective antibacterial activity, its association with conventional antibiotics results in enhanced antibiotic activity.

Efflux Pump (QacA, QacB, and QacC) and ß-Lactamase Inhibitors? An Evaluation of 1,8-Naphthyridines against Staphylococcus aureus Strains.

The bacterial species Staphylococcus aureus presents a variety of resistance mechanisms, among which the expression of ß-lactamases and efflux pumps stand out for providing a significant degree of resistance to clinically relevant antibiotics. The 1,8-naphthyridines are nitrogen heterocycles with a broad spectrum of biological activities and, as such, are promising research targets. However, the potential roles of these compounds on bacterial resistance management remain to be better investigated. Therefore, the present study evaluated the antibacterial activity of 1,8-naphthyridine sulfonamides, addressing their ability to act as inhibitors of ß-lactamases and efflux pump (QacA/B and QacC) against the strains SA-K4414 and SA-K4100 of S. aureus. All substances were prepared at an initial concentration of 1024 µg/mL, and their minimum inhibitory concentrations (MIC) were determined by the broth microdilution method. Subsequently, their effects on ß-lactamase- and efflux pump-mediated antibiotic resistance was evaluated from the reduction of the MIC of ethidium bromide (EtBr) and ß-lactam antibiotics, respectively. The 1,8-naphthyridines did not present direct antibacterial activity against the strains SA-K4414 and SA-K4100 of S. aureus. On the other hand, when associated with antibiotics against both strains, the compounds reduced the MIC of EtBr and ß-lactam antibiotics, suggesting that they may act by inhibiting ß-lactamases and efflux pumps such as QacC and QacA/B. However, further research is required to elucidate the molecular mechanisms underlying these observed effects.

Realidade epidemiológica da morbimortalidade hospitalar por acidente vascular cerebral no nordeste brasileiro, de 2015 a 2019 / Epidemiological reality of hospital morbimortality due to cerebral vascular accident in northeast brazil, from 2015 to 2019 / Realidad epidemiológica de la morbimortalidad hospitalaria por accidente vascular cerebral en el noreste de brasil, de 2015 a 2019

Com grande impacto social por alta mortalidade e morbidade no Brasil e no Mundo, o AVC continua em destaque dentre as Doenças Crônicas Não transmissíveis. Visando oferecer subsídios técnico-científicos sobre o perfil epidemiológico desta patologia no Nordeste, este artigo consiste em um estudo de corte transversal, quantitativo, epidemiológico, de série temporal, entre os anos de 2015 a 2019, tendo por base os dados disponibilizados na plataforma DATASUS. Evidenciou-se que o ano de 2019 foi o ano com maior número de internações por esta patologia, predominando em homens. No entanto, as mulheres tiveram mais óbitos. A raça mais acometida foi a parda, com mais de 82% das internações e mais de 83% dos óbitos. Os óbitos ocorreram em todas as faixas etárias, predominando nos mais idosos. O Estado com maior quantitativo de óbitos foi a Bahia, também o mais populoso do estudo. O perfil epidemiológico geral, do paciente acometido por AVC na região Nordeste do Brasil no período avaliado, foi, homem, com idade mais avançada (a partir de 60 anos), pardo, permanecendo cerca de 7,8 dias internados. O custo total desse período, com internações por AVC, foi de R$278.874.426.3, certamente, um custo bastante oneroso ao nosso sistema de saúde. As unidades federativas com maior acometimento são também as mais populosas. Percebendo-se que, por se tratar de uma doença prevenível, com graves sequelas e que causam grandes prejuízos pessoais, sociais e econômicos, torna-se relevante que o sistema público de saúde adote rigorosas medidas para sua prevenção.

With a great social impact due to high mortality and morbidity in Brazil and the world, stroke continues to be highlighted among Chronic Non-communicable Diseases. Aiming to offer technical-scientific support on the epidemiological profile of this pathology in the Northeast, this article consists of a cross-sectional, quantitative, epidemiological, time series study, between the years 2015 and 2019, based on data available on the DATASUS platform . It was evident that 2019 was the year with the highest number of hospitalizations for this pathology, predominantly in men. However, women had more deaths. The most affected race was the mixed race, with more than 82% of hospitalizations and more than 83% of deaths. Deaths occurred in all age groups, predominantly among the elderly. The State with the highest number of deaths was Bahia, also the most populous in the study. The general epidemiological profile of the patient affected by stroke in the Northeast region of Brazil during the period evaluated was male, older (60 years and older), mixed race, and remained hospitalized for approximately 7.8 days. The total cost of this period, with hospitalizations for stroke, was R$278,874,426.3, certainly a very costly cost to our health system. The federative units most affected are also the most populous. Realizing that, as it is a preventable disease, with serious consequences and causing great personal, social and economic losses, it is important that the public health system adopts strict measures for its prevention.

Con gran impacto social debido a la alta mortalidad y morbilidad en Brasil y el mundo, el accidente cerebrovascular sigue destacándose entre las Enfermedades Crónicas No Transmisibles. Con el objetivo de ofrecer soporte técnico-científico sobre el perfil epidemiológico de esta patología en el Nordeste, este artículo consiste en un estudio transversal, cuantitativo, epidemiológico, de series temporales, entre los años 2015 y 2019, con base en datos disponibles en la plataforma DATASUS. . Se evidenció que 2019 fue el año con mayor número de hospitalizaciones por esta patología, predominantemente en hombres. Sin embargo, las mujeres tuvieron más muertes. La raza más afectada fue la mestiza, con más del 82% de las hospitalizaciones y más del 83% de las muertes. Las muertes se produjeron en todos los grupos de edad, predominantemente entre los ancianos. El estado con mayor número de muertes fue Bahía, también el más poblado del estudio. El perfil epidemiológico general del paciente afectado por accidente cerebrovascular en la región Nordeste de Brasil durante el período evaluado fue masculino, mayor (60 años y más), mestizo y permaneció hospitalizado durante aproximadamente 7,8 días. El costo total de este período, con las hospitalizaciones por accidente cerebrovascular, fue de R$ 278.874.426,3, ciertamente un costo muy costoso para nuestro sistema de salud. Las unidades federativas más afectadas son también las más pobladas. Al ser conscientes de que, al tratarse de una enfermedad prevenible, de graves consecuencias y que provoca grandes pérdidas personales, sociales y económicas, es importante que el sistema público de salud adopte medidas estrictas para su prevención. PALABRAS CLAVE: Accidente Cerebrovascular; Epidemiología; Salud Pública.

Terpenes as bacterial efflux pump inhibitors: A systematic review.

Managing antibiotic resistance is a significant challenge in modern pharmacotherapy. While molecular analyses have identified efflux pump expression as an essential mechanism underlying multidrug resistance, the targeted drug development has occurred slower. Thus, considering the verification that terpenes can enhance the activity of antibiotics against resistant bacteria, the present study gathered evidence pointing to these natural compounds as bacterial efflux pump inhibitors. A systematic search for manuscripts published between January 2007 and January 2022 was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol and the following search terms: "Terpene"; AND "Efflux pump"; and "Bacteria." From a total of 101 articles found in the initial search, 41 were included in this review. Seventy-five different terpenes, 63 bacterial strains, and 22 different efflux pumps were reported, with carvacrol, Staphylococcus aureus SA-1199B, and NorA appearing most frequently mentioned terpene, bacterial strain, and efflux pump (EP), respectively. The Chi-Squared analysis indicated that terpenes are significantly effective EP inhibitors in Gram-positive and Gram-negative strains, with the inhibitory frequency significantly higher in Gram-positive strains. The results of the present review suggest that terpenes are significant efflux pump inhibitors and, as such, can be used in drug development targeting the combat of antibacterial resistance.

Silver Trimolybdate (Ag2Mo3O10.2H2O) Nanorods: Synthesis, Characterization, and Photo-Induced Antibacterial Activity under Visible-Light Irradiation.

The present study reports the synthesis, characterization, and antibacterial properties of silver trimolybdate (Ag2Mo3O10.2H2O) nanorods. The synthesis was performed using a conventional hydrothermal method. The sample was characterised by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, UV-Vis-NIR diffuse reflectance, thermogravimetric analysis (TGA), and differential scanning calorimeter (DSC). The direct antibacterial activity was evaluated using the microdilution method to determine the minimum inhibitory concentration (MIC). To assess the ability of Ag2Mo3O10.2H2O nanorods to modulate antibacterial resistance, the MIC of aminoglycosides was established in the presence of a subinhibitory concentration of this substance alone and associated with LED light exposure. The characterization of the sample indicated that the synthesis of silver trimolybdate generated nanometric crystals with rod-like morphology, without secondary phases. The treatment with Ag2Mo3O10.2H2O nanorods alone or combined with visible LED lights exhibited clinically relevant antibacterial activity against both Gram-negative and Gram-positive bacteria. This nanostructure presented a variable antibiotic-modulating action, which was not improved by visible LED light exposure. Nevertheless, LED lights showed promising antibiotic-enhancing activities in the absence of Ag2Mo3O10.2H2O nanorods. In conclusion, silver trimolybdate dihydrate nanorods have antibacterial properties that can be photocatalysed by visible-light exposure. While showing the potential use to combat antibacterial resistance, the simultaneous combination of silver trimolybdate, visible LED lights, and antibacterial drugs should be carefully analysed to avoid antagonist effects that could impair the effectiveness of antibiotic therapy.

Easily purified baculovirus/insect-system-expressed recombinant hepatitis B virus surface antigen fused to the N- or C-terminus of polyhedrin.

Baculoviruses are circular double-stranded DNA viruses that infect insects and are widely used as the baculoviral expression vectors (BEVs), which provide a eukaryotic milieu for heterologous expression. The most frequently used vector is based on Autographa californica multiple nucleopolyhedrovirus (AcMNPV). However, purification of recombinant proteins produced using BEVs is laborious, time-consuming, and often expensive. Numerous strategies have been explored to facilitate purification of heterologous proteins, such as fusion with occlusion body (OBs)-forming proteins like polyhedrin (Polh). Baculoviruses produce OBs in the late stages of infection to protect the virion in the cellular environment, and the main protein responsible for OB formation is Polh. In this study, we investigated the effect of fusing the gene that encodes the surface antigen (S-HBsAg) of hepatitis B virus (HBV) to either the N- or C-terminus of the AcMNPV Polh. The production of recombinant viruses and recombinant proteins was confirmed, and the ability to form chimeric S-HBsAg-containing OBs was accessed by light and scanning electron microscopy of infected cells. The fusion was found to affect the shape and size of the OBs when compared to wild-type OBs, with the N-terminal fusion producing less-amorphous OBs than the C-terminal construct. In addition, the N-terminal construct gave higher levels of expression than the C-terminal construct. Quantitative and qualitative immunoassays with human serum or plasma antibodies against HBsAg showed that the two forms of the antigen reacted differently. Although both reacted with the antibody, the N-terminal fusion protein reacted with more sensitivity (2.27-fold) and is therefore more suitable for quantitative assays than the C-terminal version. In summary, the BEVs represents a promising tool for the production of reagents for the diagnosis of HBV infection.

Inhibition of the MepA efflux pump by limonene demonstrated by in vitro and in silico methods.

Bacterial resistance is a natural process carried out by bacteria, which has been considered a public health problem in recent decades. This process can be triggered through the efflux mechanism, which has been extensively studied, mainly related to the use of natural products to inhibit this mechanism. To carry out the present study, the minimum inhibitory concentration (MIC) tests of the compound limonene were performed, through the microdilution methodology in sterile 96-well plates. Tests were also carried out with the association of the compound with ethidium bromide and ciprofloxacin, in addition to the ethidium bromide fluorimetry, and later the molecular docking. From the tests performed, it was possible to observe that the compound limonene presented significant results when associated with ethidium bromide and the antibiotic used. Through the fluorescence emission, it was observed that when associated with the compound limonene, a greater ethidium bromide fluorescence was emitted. Finally, when analyzing the in silico study, it demonstrated that limonene can efficiently fit into the MepA structure. In this way, it is possible to show that limonene can contribute to cases of bacterial resistance through an efflux pump, so that it is necessary to carry out more studies to prove its effects against bacteria carrying an efflux pump and assess the toxicity of the compound.