Bacterial type II toxin-antitoxin (TA) modules encode a toxic protein that downregulates metabolism and a specific antitoxin that binds and inhibits the toxin during normal growth. In non-typeable ...Haemophilus influenzae, a common cause of infections in humans, the vapXD locus was found to constitute a functional TA module and contribute to pathogenicity; however, the mode of action of VapD and the mechanism of inhibition by the VapX antitoxin remain unknown. Here, we report the structure of the intact H. influenzae VapXD complex, revealing an unusual 2:1 TA molecular stoichiometry where a Cas2-like homodimer of VapD binds a single VapX antitoxin. VapX consists of an oligonucleotide/oligosaccharide-binding domain that docks into an asymmetrical cavity on the toxin dimer. Structures of isolated VapD further reveal how a symmetrical toxin homodimer adapts to interacting with an asymmetrical antitoxin and suggest how a primordial TA system evolved to become part of CRISPR-Cas immunity systems.
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•The H. influenzae VapXD toxin-antitoxin complex has an unusual 2:1 stoichiometry•The protein complex forms a circular higher-order structure•The VapD toxin forms a dimer with a central active-site cleft•The VapX antitoxin has an oligonucleotide/oligosaccharide-binding domain
In this paper, Bertelsen et al. present the three-dimensional structure of a toxic protein from the pathogenic bacterium Haemophilus influenzae, which causes a range of diseases in humans. The authors demonstrate that the toxin, which makes the bacterium more virulent, is inactivated by an antitoxin of unusual structure.
The aquatic environment holds a vast source of organisms that provide numerous opportunities to bioprospect new molecules. Notably, fish are producers of an epidermal mucus that offers protection ...against pathogens, making it a promising source of bioactive molecules. This source of molecules, however, has yet to be thoroughly explored, and particularly, optimization of methods for collection and study is needed. This review concentrates on the methods of mucus collection employed to secure high-quality samples, enabling the extraction and characterization of molecules with bioactive potential. A comprehensive search was conducted, and publications were selected based on the following criteria: (i) the mucus has been collected from the external body of the fish, not involving dissection or damage; (ii) mucus crude extracts have undergone a chemical or genetic characterization; (iii) mucus was used in bioactivity assays (e.g., antimicrobial or immune-related). Scraping, bagging, and absorption are the primary methods for collecting fish mucus. They were assessed based on fish handling, sample volume, and processing, including anesthesia and starvation. Scraping with a soft tool, such as cotton balls or sponges, proved most effective and minimized contamination, dilution, and injury risk. This review aids future studies of mucus composition and properties.
Glioblastoma (GBM) is one of the most glycolytic and angiogenic human tumors, characteristics that contribute to the poor prognosis associated with this type of tumor. A lactate shuttle has been ...described between tumor cells and endothelial cells (ECs), with the monocarboxylate transporters (MCTs) acting as important players in this tumor‐EC communication. In this study, we aimed to understand how the tumor microenvironment modulates EC metabolism, and to characterize the role of MCTs in the glioma‐brain EC crosstalk. Exposure of human brain microvascular ECs (HBMEC) to GBM cell‐conditioned media increased the expression of MCT1, which corresponded to activation of oxidative metabolism and an increase in angiogenic capacity, as determined by increased proliferation, migration, and vessel assembly. Lactate depletion from the microenvironment or inhibition of lactate uptake in HBMEC induced an increase in lactate production and a decrease in proliferation, migration, and vessel assembly. Moreover, addition of lactate to HBMEC media promoted activation of AKT and AMPK pathways and increased expression in NFκB, HIF‐1α, and the lactate receptor GPR81. Here, we demonstrate a role for MCT1 as a mediator of lactate signaling between glioma cells and brain ECs. Our results suggest that MCT1 can mediate EC metabolic reprograming, proliferation, and vessel sprouting in response to tumor signaling. Thus, targeting MCT1 in both tumor cells and brain EC may be a promising therapeutic strategy for the treatment of GBM.
Brazilian pine-fruit shells (Araucaria angustifolia) in natural form and as activated carbon were tested as adsorbents for the removal of remazol black B (RB) textile dye from aqueous effluents. The ...effects of shaking time, adsorbent dosage and pH on the adsorption capacity were studied. RB uptake was favorable at pH values ranging from 2.0 to 2.5 and from 2.0 to 7.0 for the biosorbent and the activated carbon, respectively. The contact time required to obtain the equilibrium using the biosorbent and the activated carbon was 12 and 4h at 298K, respectively. The fractionary-order kinetic model provided the best fit to experimental data compared with other models. Equilibrium data were better fit to the Sips isotherm model using the biosorbent as well as the activated carbon. The enthalpy and entropy of adsorption of RB were obtained from adsorption experiments ranging from 298 to 323K. Simulated dyehouse effluents were used to check the applicability of the proposed adsorbents for effluent treatment.
► The PW and AC-PW are good adsorbents to remove RB dye from aqueous solutions. ► AC-PW is an activated carbon prepared from the Brazilian-pine fruit shell. ► PW is the unmodiffied Brazillian pine fruit shell. ► PW maximum sorption capacity was 74.6 mg g–1. ► AC-PW maximum sorption capacity was 446.2 mg g–1. ► AC-PW adsorbent removed 94% of the mixture of dyes in a synthetic dye effluent.
This study aimed to evaluate the performance of the point-of-care circulating cathodic antigen (POC-CCA) test in a highly endemic area in Brazil, comparing it to the Kato-Katz (KK) technique for ...sensitivity, specificity and the intensity of the reaction of the test in relation to the parasitic load. The community in Sergipe, Brazil, participated in the study, providing three stool samples, one of urine (POC-CCA) and fingers tick blood sample was tested by enzyme-linked immunosorbent assay (ELISA). Sensitivity, specificity, positive predictive value, negative predictive value, accuracy, kappa coefficient and Spearman's correlation were calculated for the POC-CCA test using the KK as the reference. The prevalence of schistosomiasis by KK testing was 48.82%; POC-CCA (t+) 66.14%; POC-CCA (t−) 45.24%. ELISA results showed 100% agreement in individuals with high and moderate eggs per gram (EPG). POC-CCA presented good diagnostic performance in individuals with medium and high EPG, but there were a high number of false negatives in individuals with low intensity infections. As observed, POC-CCA-filter test improves accuracy and sensitivity compared to a conventional test.
Objetivo.
Mapear políticas relacionadas à prevenção e ao controle da resistência aos antimicrobianos na perspectiva da saúde humana no Brasil e sistematizar a evolução histórica dessas políticas.
...Método.
Desenvolveu-se uma revisão de escopo conforme as diretrizes do Instituto Joana Briggs e PRISMA. A busca na literatura foi realizada em dezembro de 2020 nas bases de dados LILACS, PubMed e EMBASE. Utilizaram-se os termos “antimicrobial resistance” AND “Brazil” e sinônimos. Uma pesquisa documental com os mesmos termos foi conduzida nos
sites
eletrônicos do governo brasileiro até dezembro de 2021. Foram incluídos estudos de todos os desenhos, sem restrição de idioma ou data. Excluíram-se documentos clínicos, revisões e estudos epidemiológicos que não referenciavam políticas de gestão da resistência aos antimicrobianos no Brasil. Para coleta e análise de dados, estabeleceram-se categorias baseadas em documentos da Organização Mundial da Saúde.
Resultados.
Desde antes da criação do Sistema Único de Saúde, o Brasil possuía políticas relacionadas à resistência aos antimicrobianos, como o Programa Nacional de Imunização e programas de controle de infecção hospitalar. No final das décadas de 1990 e 2000, estabeleceram-se as primeiras políticas específicas sobre resistência aos antimicrobianos (redes e programas de vigilância) e estratégias de educação. Destaca-se o Plano de Ação Nacional de Prevenção e Controle da Resistência aos Antimicrobianos no Âmbito da Saúde Única (PAN-BR), de 2018.
Conclusões.
Apesar do longo histórico de políticas relacionadas à resistência aos antimicrobianos no Brasil, foram identificadas lacunas, sobretudo no monitoramento da utilização de antimicrobianos e na vigilância da resistência aos antimicrobianos. O PAN-BR, primeiro documento de governo elaborado na perspectiva
One Health
, é um marco nas políticas brasileiras.
Perinatal hypoxia-ischemia represents a significant risk to CNS development, leading to high mortality rates, diverse damages, and persistent neurological deficits. Despite advances in neonatal ...medicine in recent decades, the incidence of HIE remains substantial. Motor deficits can manifest early, while cognitive impairments may be diagnosed later, emphasizing the need for extended follow-up. This review aims to explore potential candidates for therapeutic interventions for hypoxic-ischemic encephalopathy (HIE), with a focus on cognitive deficits. We searched randomized clinical trials (RCT) that tested drug treatments for HIE and evaluated cognitive outcomes. The results included studies on erythropoietin, melatonin, magnesium sulfate, topiramate, and a combination of vitamin C and ibuprofen. Although there are several indications of the efficacy of these drugs among animal models, considering neuroprotective properties, the RCTs failed to provide complete effectiveness in the context of cognitive impairments derived from HIE. More robust RCTs are still needed to advance our knowledge and to establish standardized treatments for HIE.
Techniques with high sensitivity and specificity are required for an accurate diagnosis in low-transmission settings, where the conventional parasitological methods are insensitive. We determined the ...accuracy of an up-converting phosphor-lateral flow circulating anodic antigen (UCP-LF CAA) assay in urine and serum for
diagnosis in low-prevalence settings in Ceará, Brazil, before and after praziquantel treatment. Clinical samples of a total of 258 individuals were investigated by UCP-LF CAA, point-of-care-circulating cathodic antigen (POC-CCA), soluble worm antigen preparation (SWAP)-ELISA and Kato-Katz (KK); a selection of 128 stools by real-time PCR technique. Three and 6-weeks after treatment, samples were collected and evaluated by detection
circulating antigens (CAA and CCA). The UCP-LF CAA assays detected 80 positives (31%) with urine and 82 positives (31.8%) with serum. The urine POC-CCA and serum SWAP-ELISA assays detected 30 (11.6%) and 107 (40.7%) positives, respectively. The Kato-Katz technique revealed only 4 positive stool samples (1.6%). Among the 128 individuals with complete data records, 19 cases were identified by PCR (14.8%); Sensitivities and specificities of the UCP-LF CAA assays, determined versus a combined reference standard based on CCA/KK/PCR positivity, ranged from 60-68% to 68-77%, respectively. In addition only for comparative purposes, sensitivities of the different assays were determined vs. a comparative reference based on CAA/KK/PCR positivity, showing the highest sensitivity for the urine CAA assay (80%), followed by the serum CAA (70.9%), SWAP-ELISA (43.6%), PCR (34.5%), POC-CCA (29.1%), whilst triplicate Kato-Katz thick smears had a very low sensitivity (3.6%). CAA concentrations were higher in serum than in urine and were significantly correlated. There was a significant decrease in urine and serum CAA levels 3 and 6-weeks after treatment. The UCP-LF CAA assays revealed 33 and 28
-infected patients at the 3- and 6-week post-treatment follow-up, respectively. The UCP-LF CAA assays show high sensitivity for the diagnosis of
in low-endemicity settings. It detects a considerably higher number of infections than microscopy, POC-CCA or PCR. Also it shows to be very useful for evaluating cure rates after treatment. Hence, the UCP-LF CAA assay is a robust and promising diagnostic approach in low-transmission settings.
We analyzed spatiotemporal patterns of 8,756 schistosomiasis-related deaths in Brazil during 2000-2011 and identified high-risk clusters of deaths, mainly in highly schistosomiasis-endemic areas ...along the coast of Brazil's Northeast Region. Schistosomiasis remains a neglected public health problem with a high number of deaths in disease-endemic and emerging focal areas.
Estimate the reproducibility of hearing screening results using the uHear™ smartphone-based app in two response modes: self-test response and test-operator.
Reliability study conducted with 65 ...individuals aged ≥18 years assisted at the Speech-language and Hearing Therapy clinic of a public higher-education institution. Hearing screening was conducted by a single researcher using the uHear app and earbud headphones in a soundproof booth. Participants responded to sound stimuli in both self-test response mode and test-operator mode. The order in which these two uHear test modes were applied was altered according to the entrance of each participant in the study. The correspondence between the hearing thresholds obtained from each response mode was analyzed and their Intraclass Correlation Coefficient (ICC) was estimated.
A correspondence of ±5 dBHL >75% was observed between these hearing thresholds. The ICC values showed excellent agreement between the two response modes at all frequencies >40 dBHL tested.
The two hearing screening response modes using the uHear app presented high reproducibility, suggesting that the test-operator mode is a viable alternative when the self-test response mode is not recommended.
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