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Curated scientific databases catalogue and amplify research findings to maximize their reach. Authors should write their papers with this in mind, ensuring that data are accurate, easy to extract, and presented in standardized formats.

COSMIC: a curated database of somatic variants and clinical data for cancer.

The Catalogue Of Somatic Mutations In Cancer (COSMIC), https://cancer.sanger.ac.uk/cosmic, is an expert-curated knowledgebase providing data on somatic variants in cancer, supported by a comprehensive suite of tools for interpreting genomic data, discerning the impact of somatic alterations on disease, and facilitating translational research. The catalogue is accessed and used by thousands of cancer researchers and clinicians daily, allowing them to quickly access information from an immense pool of data curated from over 29 thousand scientific publications and large studies. Within the last 4 years, COSMIC has substantially expanded its utility by adding new resources: the Mutational Signatures catalogue, the Cancer Mutation Census, and Actionability. To improve data accessibility and interoperability, somatic variants have received stable genomic identifiers that are associated with their genomic coordinates in GRCh37 and GRCh38, and new export files with reduced data redundancy have been made available for download.

Identification of purinergic system components in the venom of Bothrops mattogrossensis and the inhibitory effect of specioside extracted from Tabebuia aurea.

Snake bites are a severe problem in the countryside of Brazil and are usually attributed to snakes of the genera Bothrops, Crotalus, and Lachesis. Snake venom can release ectoenzymes and nucleotidases that modulate the purinergic system. In addition to serum therapy against snake poisoning, medicinal plants with anti-inflammatory activities, such as Tabebuia aurea, is empirically applied in accidents that occur in difficult-to-access areas. This study aimed was to verify the presence and activity of nucleotidases in the crude venom of Bothrops mattogrossensis (BmtV) in vitro and characterize the modulation of purinergic components, myeloid differentiation, and inflammatory/oxidative stress markers by BmtV in vivo and in vitro. Moreover, our study assessed the inhibitory activities of specioside, an iridoid isolated from Tabebuia aurea, against the effects of BmtV. Proteomic analysis of venom content and nucleotidase activity confirm the presence of ectonucleotidase-like enzymes in BmtV. In in vivo experiments, BmtV altered purinergic component expression (P2X7 receptor, CD39 and CD73), increased neutrophil numbers in peripheral blood, and elevated oxidative stress/inflammatory parameters such as lipid peroxidation and myeloperoxidase activity. BmtV also decreased viability and increased spreading index and phagocytic activity on macrophages. Specioside inhibited nucleotidase activity, restored neutrophil numbers, and mediate the oxidative/inflammatory effects produced by BmtV. We highlight the effects produced by BmtV in purinergic system components, myeloid differentiation, and inflammatory/oxidative stress parameters, while specioside reduced the main BmtV-dependent effects.

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.

The potential stickiness of pandemic-induced behavior changes in the United States.

Human behavior is notoriously difficult to change, but a disruption of the magnitude of the COVID-19 pandemic has the potential to bring about long-term behavioral changes. During the pandemic, people have been forced to experience new ways of interacting, working, learning, shopping, traveling, and eating meals. A critical question going forward is how these experiences have actually changed preferences and habits in ways that might persist after the pandemic ends. Many observers have suggested theories about what the future will bring, but concrete evidence has been lacking. We present evidence on how much US adults expect their own postpandemic choices to differ from their prepandemic lifestyles in the areas of telecommuting, restaurant patronage, air travel, online shopping, transit use, car commuting, uptake of walking and biking, and home location. The analysis is based on a nationally representative survey dataset collected between July and October 2020. Key findings include that the "new normal" will feature a doubling of telecommuting, reduced air travel, and improved quality of life for some.

Acute exposure of zebrafish (Danio rerio) adults to psychotria carthagenensis leaf extracts: chemical profile, lack of genotoxicity and histological changes.

Psychotria carthagenensis is a shrubby plant, often consumed by traditional populations in religious rituals. Previous studies have shown that this plant's infusion can inhibit the activity of Acetylcholinesterase (AChE) in rats. Despite the therapeutic potential, there is a lack of research regarding its possible toxicological and genotoxic effects. Hence, this study aimed to analyze the chemical profile of the ethanol extract from P. carthagenensis leaves by LC-DAD-MS and assess its possible toxicity and genotoxicity in zebrafish (Danio rerio). Adult zebrafish (N = 9/group) were exposed at different concentrations and the LC50 was calculated. Frequencies of micronucleus (MN) and nuclear abnormalities (NA) were estimated for genotoxic effects, and degree of tissue changes (DTC) was used to assess the liver and gill histopathology. From the LC-DAD-MS analyses, the identified compounds included N-fructosyl valine, ethyl hexoside, 5-O-E-caffeoylquinic acid, N-feruloylagmatime, roseoside, di-O-deoxyhexoyl-hexosyl quercetin, loiolide, and oleamide. The calculated values of LC50 did not vary significantly during the time of exposure. At the concentrations of 1.25, 2.5, 3.75, 5, 7.5, 10 and 15 mg/L, there was no genotoxicity, and only low to moderate toxicity for the tissues was observed, despite mortality of 100% at doses of 20-100 mg/L of P. carthagenensis ethanolic leaf extract. There were changes in cytoplasm of hepatocytes at 1.25 mg/L, and karyorrhexis, karyolysis and megalocytosis at 10 mg/L. In the gills, the alterations were primary lamellar hyperplasia in all concentrations, and at 10 mg/L, secondary lamellar edema and vascular hyperemia were common. Additionally, the chemical composition of P. carthagenensis was expanded.

Prevalence and associated risk factors of post-COVID-19 syndrome in healthcare workers.

Given the global burden of COVID-19 among healthcare workers (HCWs), it is expected that they face an elevated risk of developing post-COVID-19 syndrome. The objectives of this study were to evaluate the prevalence of post-COVID-19 syndrome and associated risk factors in HCWs followed for a median time of 18 months by conducting a retrospective cohort study. All HCWs with confirmed COVID-19 during the period from January 2021 to December 2022 were included in the study. HCWs were regularly assessed after COVID-19 diagnosis, so post-COVID-19 syndrome data could be collected. During the study period, 463 HCWs were included in the study, 227 (49.0%) of which experienced post-COVID-19 syndrome. The most common persistent symptoms were fatigue (n = 147 [32.5%]), memory disorders (n = 98 [21.5%]), dyspnea (n = 73 [16.0%]), anxiety/depression (n = 69 [15.0%]), and cough (n = 43 [9.4%]). Female sex and obesity were statistically associated with the development of post-COVID-19 syndrome. A high prevalence of post-COVID-19 syndrome in HCWs was found. Female sex and obesity appear to be risk factors associated with a higher prevalence of post-COVID-19 syndrome. Special attention should be given to these patients with risk factors during follow-up in the COVID-19 recovery period.

Smoking cessation among tuberculosis patients during the coronavirus disease-2019 pandemic.

Smoking has been recognized as a significant risk factor for COVID-19 and mortality. The World Health Organization (WHO) has recommended smoking cessation to reduce the impact of COVID-19. This study aimed to evaluate the smoking cessation rate of patients starting tuberculosis (TB) treatment at six months using motivational interviewing based on the WHO "five steps to quit" model. In addition, we assessed the knowledge about smoking and the barriers to smoking cessation. We conducted a retrospective cohort study. Outpatients aged >18 years, smokers, and those who are starting TB treatment in two outpatient TB clinics were invited to participate. Patients received information about the importance of smoking cessation, especially in TB patients, and standardized advice based on guidelines. This information was repeated during phone calls during the second and fourth months of treatment. During the study period, 111 patients were included. The primary outcome was the smoking cessation rate at the end of the sixth month of treatment, which was 26.8% (19/71). The barriers to smoking cessation described by the patients were anxiety/depression (47.4%), seeing someone smoking (38.5%), drug use (19.2%), and alcohol abuse (2.6%). The assessment of knowledge about smoking showed that patients had some information gaps. In conclusion, TB smokers who tried to quit smoking during the COVID-19 pandemic faced many challenges. Despite this, we demonstrated a reasonable smoking cessation rate with a nurse-conducted motivational interview.

Long-term outcomes of the global tuberculosis and COVID-19 co-infection cohort.

BACKGROUND: Longitudinal cohort data of patients with tuberculosis (TB) and coronavirus disease 2019 (COVID-19) are lacking. In our global study, we describe long-term outcomes of patients affected by TB and COVID-19. METHODS: We collected data from 174 centres in 31 countries on all patients affected by COVID-19 and TB between 1 March 2020 and 30 September 2022. Patients were followed-up until cure, death or end of cohort time. All patients had TB and COVID-19; for analysis purposes, deaths were attributed to TB, COVID-19 or both. Survival analysis was performed using Cox proportional risk-regression models, and the log-rank test was used to compare survival and mortality attributed to TB, COVID-19 or both. RESULTS: Overall, 788 patients with COVID-19 and TB (active or sequelae) were recruited from 31 countries, and 10.8% (n=85) died during the observation period. Survival was significantly lower among patients whose death was attributed to TB and COVID-19 versus those dying because of either TB or COVID-19 alone (p<0.001). Significant adjusted risk factors for TB mortality were higher age (hazard ratio (HR) 1.05, 95% CI 1.03-1.07), HIV infection (HR 2.29, 95% CI 1.02-5.16) and invasive ventilation (HR 4.28, 95% CI 2.34-7.83). For COVID-19 mortality, the adjusted risks were higher age (HR 1.03, 95% CI 1.02-1.04), male sex (HR 2.21, 95% CI 1.24-3.91), oxygen requirement (HR 7.93, 95% CI 3.44-18.26) and invasive ventilation (HR 2.19, 95% CI 1.36-3.53). CONCLUSIONS: In our global cohort, death was the outcome in >10% of patients with TB and COVID-19. A range of demographic and clinical predictors are associated with adverse outcomes.

Oxidation Products from the Neolignan Licarin A by Biomimetic Reactions and Assessment of in vivo Acute Toxicity.

Licarin A, a dihydrobenzofuranic neolignan presents in several medicinal plants and seeds of nutmeg, exhibits strong activity against protozoans responsible for Chagas disease and leishmaniasis. From biomimetic reactions by metalloporphyrin and Jacobsen catalysts, seven products were determined: four isomeric products yielded by epoxidation from licarin A, besides a new product yielded by a vicinal diol, a benzylic aldehyde, and an unsaturated aldehyde in the structure of the licarin A. The incubation with rat and human liver microsomes partially reproduced the biomimetic reactions by the production of the same epoxidized product of m/z 343 [M + H]+. In vivo acute toxicity assays of licarin A suggested liver toxicity based on biomarker enzymatic changes. However, microscopic analysis of tissues sections did not show any tissue damage as indicative of toxicity after 14 days of exposure. New metabolic pathways of the licarin A were identified after in vitro biomimetic oxidation reaction and in vitro metabolism by rat or human liver microsomes.

Open Targets Platform: supporting systematic drug-target identification and prioritisation.

The Open Targets Platform (https://www.targetvalidation.org/) provides users with a queryable knowledgebase and user interface to aid systematic target identification and prioritisation for drug discovery based upon underlying evidence. It is publicly available and the underlying code is open source. Since our last update two years ago, we have had 10 releases to maintain and continuously improve evidence for target-disease relationships from 20 different data sources. In addition, we have integrated new evidence from key datasets, including prioritised targets identified from genome-wide CRISPR knockout screens in 300 cancer models (Project Score), and GWAS/UK BioBank statistical genetic analysis evidence from the Open Targets Genetics Portal. We have evolved our evidence scoring framework to improve target identification. To aid the prioritisation of targets and inform on the potential impact of modulating a given target, we have added evaluation of post-marketing adverse drug reactions and new curated information on target tractability and safety. We have also developed the user interface and backend technologies to improve performance and usability. In this article, we describe the latest enhancements to the Platform, to address the fundamental challenge that developing effective and safe drugs is difficult and expensive.

Open Targets Genetics: systematic identification of trait-associated genes using large-scale genetics and functional genomics.

Open Targets Genetics (https://genetics.opentargets.org) is an open-access integrative resource that aggregates human GWAS and functional genomics data including gene expression, protein abundance, chromatin interaction and conformation data from a wide range of cell types and tissues to make robust connections between GWAS-associated loci, variants and likely causal genes. This enables systematic identification and prioritisation of likely causal variants and genes across all published trait-associated loci. In this paper, we describe the public resources we aggregate, the technology and analyses we use, and the functionality that the portal offers. Open Targets Genetics can be searched by variant, gene or study/phenotype. It offers tools that enable users to prioritise causal variants and genes at disease-associated loci and access systematic cross-disease and disease-molecular trait colocalization analysis across 92 cell types and tissues including the eQTL Catalogue. Data visualizations such as Manhattan-like plots, regional plots, credible sets overlap between studies and PheWAS plots enable users to explore GWAS signals in depth. The integrated data is made available through the web portal, for bulk download and via a GraphQL API, and the software is open source. Applications of this integrated data include identification of novel targets for drug discovery and drug repurposing.

Health-related quality of life of women with breast cancer being treated with hormone therapy: A scoping review.

OBJECTIVE: To map the evidence available in the literature on the health-related quality of life of women with breast cancer using hormone therapy. DATA SOURCES: This review followed the Joanna Briggs Institute methodological recommendations and Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews reporting guidelines. Searches were performed in nine databases using descriptors, synonyms and keywords; grey literature was also included. The review protocol was registered with the Open Science Framework under doi: http://doi.org/10.17605/OSF.IO/347FM. Inclusion criteria were established according to the Population, Concept, and Context strategy. The selection of studies was performed by two independent reviewers with the aid of RAYYAN software and disagreements were resolved by a third reviewer. The main information from the included articles was grouped into textual categories and presented by means of a narrative synthesis. DATA SUMMARY: A total of 5419 records were identified, of which 42 studies fully met the eligibility criteria. Most were multicenter studies (42.9%) and randomized controlled trials (62%). Most studies addressed anastrozole (39.5%), letrozole (34.2%), and tamoxifen (26.3%), which were studied alone or in combination. The most widely used health-related quality-of-life assessment tool was the EORTC-QLQ-C30. The concomitant use of hormone therapy and cyclin-dependent kinase inhibitors 4 and 6 showed improvement in health-related quality of life. CONCLUSION: In recent years there has been an increase in studies focused on health-related quality of life, and the evidence pointed to relevant information on health-related quality of life and the use of endocrine therapy, tamoxifen in combination with aromatase inhibitors, as well as aromatase inhibitor alone and the use of cyclin-dependent kinase 4 and 6.

Diruthenium(II-III)-ibuprofen-loaded chitosan-based microparticles and nanoparticles systems: encapsulation, characterisation, anticancer activity of the nanoformulations against U87MG human glioma cells.

The aim of this work was to investigate novel formulations containing diruthenium(II-III)-ibuprofen (RuIbp) metallodrug encapsulated into the chitosan (CT) biopolymer. Microparticles (RuIbp/CT MPs, ∼ 1 µm) were prepared by spray-drying, and RuIbp/CT-crosslinked nanoparticles (NPs) by ionic gelation (RuIbp/CT-TPP, TPP = tripolyphosphate (1), RuIbp/CT-TPP-PEG, PEG = poly(ethyleneglycol (2)) or pre-gel/polyelectrolyte complex method (RuIbp/CT-ALG, ALG = alginate (3)). Ru analysis was conducted by energy dispersive x-ray fluorescence or inductively coupled plasma atomic emission spectroscopy, and physicochemical characterisation by powder x-ray diffraction, electronic absorption and FTIR spectroscopies, electrospray ionisation mass spectrometry, thermal analysis, scanning electron, transition electron and atomic force microscopies, and dynamic light scattering. The RuIbp-loaded nanosystems exhibited encapsulation efficiency ∼ 20-37%, drug loading∼ 10-20% (w/w), hydrodynamic diameter (nm): 103.2 ± 7.9 (1), 91.7 ± 12.6 (2), 270.2 ± 58.4 (3), zeta potential (mV): +(47.7 ± 2.8) (1), +(49.2 ± 3.6) (2), -(28.2 ± 2.0) (3). Nanoformulation (1) showed the highest cytotoxicity with increased efficacy in relation to the RuIbp free metallodrug against U87MG human glioma cells.

Poly(lactic acid)/ß-cyclodextrin based nanoparticles bearing ruthenium(II)-arene naproxen complex: preparation and characterisation. Analytical validation for metal determination by microwave-induced plasma optical emission spectrometry.

The objectives of this work are to develop nanocarrier systems for the Ru(II)-p-cymene naproxen antitumor metallodrug, [Ru(η6-p-cymene)(npx)Cl] or Rupcy, based on polymeric nanoparticles (NPs) composed by the biodegradable poly(lactic acid) (PLA) and the hydrophilic polymerised ß-cyclodextrin (PolyCD); to validate an analytical method for determination of Ru incorporated into the metallodrug loaded-NPs. The PolyCD was prepared by single step condensation and polymerisation reaction and incorporated as a polymer blend during the fabrication of PLA/PolyCD blends NPs and also as a core/shell structure built by adsorption of the PolyCD onto the surface of PLA NPs to give PLA(core)/PolyCD(shell) NPs. Three different loaded-systems incorporating the metallodrug (Rupcy-PLA NPs (1), Rupcy-PLA/PolyCD blends (2), and Rupcy-PLA(core)/PolyCD(shell) NPs (3)) were prepared by nanoprecipitation. The characterisation was performed by Proton Nuclear Magnetic Resonance, Matrix Assisted Laser Desorption/Ionization Time-of-Flight, Fourier-Transform Infra-red and UV-VIS Electronic Absorption Spectroscopies, Thermogravimetric Analysis, Differential Scanning Calorimetry, Dynamic Light Scattering, and Electrophoretic Light Scattering. Ru was determined by Microwave Induced Plasma Optical Emission Spectrometry (MIP-OES) with validation of the method. The metallodrug entrapment efficiency was around 90% (w/w) and drug loading was at 3-4% (w/w). The characterised metallodrug-loaded systems exhibited monomodal size distributions and appropriate hydrodynamic diameters [218.3 ± 13.5 (1), 205.4 ± 14.4 (2), 231.5 ± 22.0 (3) nm] and zeta potential values [-31.5 ± 2.2 (1), -26.1 ± 4.5 (2), -28.8 ± 6.1 (3) mV]. The validation of the MIP-OES method by evaluating selectivity, linearity, precision, accuracy, and limits of detection and quantification succeeded. The NPs parameters are compatible with colloidally stable systems. The MIP-OES method showed to be simple, reliable, and feasible to quantify indirectly the amount of the metallodrug-loaded into the PLA NPs.

Path of fear: Experiences of health professionals in the fight against COVID-19.

This study aimed to understand the expressions of fear in the journeys of health professionals who worked in the confrontation of coronavirus disease 2019 (COVID-19), in the city of Manaus, in the Brazilian Western Amazon. This is an exploratory qualitative study that adopts interpretive description as a method to generate informed knowledge responsive to the needs of the practice. We included 56 participants, comprising 23 health managers and 33 health workers (middle and higher level) of different professional categories. The results revealed three circles of experience: (1) knowledge and professional experience in dealing with the disease (unknown-known-experienced); (2) the growing proximity to death and loss (predicted-witnessed-suffered); and (3) the involvement and proximity to whatever affects the individual, their emotions, and personal transformations in the face of the threat (the collective, the neighbor, and oneself). Our results suggest that health professionals who worked during the COVID-19 pandemic in Manaus experienced insecurity, dread, and fear, illustrating the complexity of developing their activities in the front line of care and management during the different phases of the pandemic. A contribution of the study is precisely that of capturing this complexity, which suggests the impossibility of analyzing fear only in its simple manifestation, or in each circle of experience.

Clinical characteristics and outcomes of healthcare workers with COVID-19 pre- and postvaccination.

Vaccines are the most effective strategy to control the spread of coronavirus disease-2019 (COVID-19). Data on COVID-19 among healthcare workers (HCW) pre- and postvaccination are limited. This study aims to evaluate the clinical characteristics and outcomes of HCW with COVID-19 pre- and postvaccination. Retrospective cohort study. All HCWs with suspected COVID-19 were included. Demographic data, occupation, symptoms, work in COVID-19 area, and vaccination status were collected. There were 22 267 HCW visits for suspected COVID-19; 7879 (35.4%) tested positive, and 14 388 (64.6%) tested negative. Fever, cough, fatigue, and dyspnea were positive predictors of COVID-19, and sore throat, headache, coryza, work in a COVID-19 area, and COVID-19 vaccination were negative predictors. Of the total number of visits, 41.2% were from vaccinated HCW and 58.8% were from unvaccinated HCW. Among HCWs with COVID-19, 84 (1.1%) required hospitalization, 11 (0.1%) in an intensive care unit (ICU), with three (0.04%) deaths. Six hospitalizations occurred in vaccinated HCWs, being of short duration, with no need for ICU admission and no deaths. SARS-CoV-2 infection prevalence was high among HCW, and vaccinated HCW had fewer hospitalizations, need for ICU, and deaths. Therefore, vaccines may attenuate COVID-19 severity, and efforts must be concentrated to ensure adequate vaccination for HCW.

Anti-Trichomonas vaginalis activity and chemical analysis of metabolites produced by marine-associated fungi.

Trichomoniasis is the most common non-viral sexually transmitted infection worldwide and it may have serious consequences, especially for women. Currently, 5-nitroimidazole drugs are the treatment of choice for trichomoniasis, although presenting adverse effects and reported cases of drug resistance. Metabolites isolated from marine fungi have attracted considerable attention due to their unique chemical structures with diverse biological activities, including antiprotozoal activity. In this study, we showed the anti-Trichomonas vaginalis activity of fractions obtained from marine fungi and the chemical composition of the most active fraction was determined. Ethyl acetate fractions of the fungus Aspergillus niger (EAE03) and Trichoderma harzianum/Hypocrea lixii complex (EAE09) were active against T. vaginalis. These samples, EAE03 and EAE09, were also effective against the fresh clinical isolate metronidazole-resistant TV-LACM2R, presenting MIC values of 2.0 mg/mL and 1.0 mg/mL, respectively. The same MIC values were found against ATCC 30,236 T. vaginalis isolate. In vitro cytotoxicity revealed only the fraction named EAE03 with no cytotoxic effect; however, the active fractions did not promote a significant hemolytic effect after 1-h incubation. Already, the in vivo toxicity evaluation using Galleria mellonella larvae demonstrated that none of the tested samples caused a reduction in animal survival. The fraction EAE03 was followed for purification steps and analyzed by LC-DAD-MS. Eleven compounds were annotated, including butyrolactone, butanolide, and atromentin. Overall, the range of activities reported confirms the potential of marine fungi to produce bioactive molecules.

Effect of Ylang-Ylang (Cananga odorata Hook. F. & Thomson) Essential Oil on Acute Inflammatory Response In Vitro and In Vivo.

The aim of this study is to evaluate the phytochemical profile, oral acute toxicity, and the effect of ylang-ylang (Cananga odorata Hook. F. & Thomson) essential oil (YEO) on acute inflammation. YEO was analyzed by gas chromatography/mass spectrometry. For in vitro tests, YEO was assessed using cytotoxicity, neutrophil chemotaxis induced by N-formyl methionyl leucyl phenylalanine (fMLP), and phagocytic activity tests. YEO was orally administered in zymosan-induced peritonitis, carrageenan-induced leukocyte rolling, and adhesion events in the in situ microcirculation model and in carrageenan-induced paw edema models. YEO (2000 mg/kg) was also tested using an acute toxicity test in Swiss mice. YEO showed a predominance of benzyl acetate, linalool, benzyl benzoate, and methyl benzoate. YEO did not present in vitro cytotoxicity. YEO reduced the in vitro neutrophil chemotaxis induced by fMLP and reduced the phagocytic activity. The oral treatment with YEO reduced the leukocyte recruitment and nitric oxide production in the zymosan-induced peritonitis model, reduced rolling and adherent leukocyte number induced by carrageenan in the in situ microcirculation model, and reduced carrageenan-induced edema and mechanical hyperalgesia. YEO did not present signs of toxicity in the acute toxicity test. In conclusion, YEO affected the leukocyte activation, and presented antiedematogenic, anti-hyperalgesic, and anti-inflammatory properties.

Tuberculosis in the intensive care unit: alternative treatment regimens and association with mortality.

OBJECTIVES: Adequate anti-tuberculosis (TB) treatment is an important factor that can affect the patient's outcome. Higher mortality is found in patients who do not receive optimal treatment that includes isoniazid and rifampicin. The objective of this study is to evaluate the association of use of alternative TB treatment regimens (without rifampicin and isoniazid) and mortality among patients requiring intensive care. METHODS: Retrospective cohort study, from January 2010 to December 2018. Patients aged > 18 years with a TB diagnosis, admitted to the ICU of a general, tertiary care, university-affiliated hospital (Hospital de Clínicas de Porto Alegre - HCPA) were included. Data on TB treatment used and outcomes of treatment were collected. RESULTS: 462 patients met the inclusion criteria and were included in the analysis; 284 used the usual treatment regimen (rifampicin, isoniazid, pyrazinamide and ethambutol - all orally), and 178 used alternative treatment regimens (IV levofloxacin plus oral ethambutol plus IM streptomycin or IV amikacin, without rifampicin and isoniazid). The mortality was higher among users of alternative treatment regimens (63.5%) than among usual treatment regimen users (51.4%) (P = 0.011). In a multivariate analysis, age, albumin and death were independently associated with alternative treatment regimens use. CONCLUSIONS: TB programmes in which IV rifampicin is not widely available should consider including it, especially for critically ill TB patients, for whom there may be improved survival.

OBJECTIFS: Un traitement antituberculeux (TB) adéquat est un facteur important pouvant influencer les résultats du patient. Une mortalité plus élevée est observée chez les patients qui ne reçoivent pas un traitement optimal comprenant de l'isoniazide et de la rifampicine. L'objectif de cette étude est d'évaluer l'association entre l'utilisation d'autres schémas thérapeutiques anti-TB (sans rifampicine ni isoniazide) et la mortalité chez les patients nécessitant des soins intensifs. MÉTHODES: Etude de cohorte rétrospective, de janvier 2010 à décembre 2018. Les patients âgés de >18 ans avec un diagnostic de TB, admis à l'unité de soins intensifs d'un hôpital général, avec des soins tertiaires, affilié à l'Université (Hôpital de Clínicas de Porto Alegre-HCPA) ont été inclus. Des données sur le traitement anti-TB utilisé et les résultats du traitement ont été collectés. RÉSULTATS: 462 patients répondaient aux critères d'inclusion et ont été inclus dans l'analyse; 284 ont utilisé le schéma thérapeutique habituel (rifampicine, isoniazide, pyrazinamide et éthambutol - tous par voie orale) et 178 ont utilisé des schémas thérapeutiques alternatifs (lévofloxacine IV plus éthambutol oral plus streptomycine IM ou amikacine IV, sans rifampicine ni isoniazide). La mortalité était plus élevée chez les utilisateurs de schémas thérapeutiques alternatifs (63,5%) que chez les utilisateurs de schémas thérapeutiques habituels (51,4%) (P = 0,011). Dans l'analyse multivariée, l'âge, l'albumine et le décès ont été indépendamment associés à l'utilisation de schémas thérapeutiques alternatifs. CONCLUSIONS: Les programmes de lutte contre la TB dans lesquels la rifampicine IV n'est pas largement disponible devraient envisager de l'inclure, en particulier pour les patients atteints de TB et sévèrement malades, pour lesquels la survie peut être améliorée.