ABSTRACT
Liquid chromatography coupled with high-resolution mass spectrometry data-independent acquisition (LC-HRMS/DIA), including MSE, enable comprehensive metabolomics analyses though they pose challenges for data processing with automatic annotation and molecular networking (MN) implementation. This motivated the present proposal, in which we introduce DIA-IntOpenStream, a new integrated workflow combining open-source software to streamline MSE data handling. It provides 'in-house' custom database construction, allows the conversion of raw MSE data to a universal format (.mzML) and leverages open software (MZmine 3 and MS-DIAL) all advantages for confident annotation and effective MN data interpretation. This pipeline significantly enhances the accessibility, reliability and reproducibility of complex MSE/DIA studies, overcoming previous limitations of proprietary software and non-universal MS data formats that restricted integrative analysis. We demonstrate the utility of DIA-IntOpenStream with two independent datasets: dataset 1 consists of new data from 60 plant extracts from the Ocotea genus; dataset 2 is a publicly available actinobacterial extract spiked with authentic standard for detailed comparative analysis with existing methods. This user-friendly pipeline enables broader adoption of cutting-edge MS tools and provides value to the scientific community. Overall, it holds promise for speeding up metabolite discoveries toward a more collaborative and open environment for research.
Subject(s)
Metabolomics , Software , Reproducibility of Results , Workflow , Metabolomics/methods , Mass Spectrometry/methods , Chromatography, Liquid/methodsABSTRACT
Tipping elements are nonlinear subsystems of the Earth system that have the potential to abruptly shift to another state if environmental change occurs close to a critical threshold with large consequences for human societies and ecosystems. Among these tipping elements may be the Amazon rainforest, which has been undergoing intensive anthropogenic activities and increasingly frequent droughts. Here, we assess how extreme deviations from climatological rainfall regimes may cause local forest collapse that cascades through the coupled forest-climate system. We develop a conceptual dynamic network model to isolate and uncover the role of atmospheric moisture recycling in such tipping cascades. We account for heterogeneity in critical thresholds of the forest caused by adaptation to local climatic conditions. Our results reveal that, despite this adaptation, a future climate characterized by permanent drought conditions could trigger a transition to an open canopy state particularly in the southern Amazon. The loss of atmospheric moisture recycling contributes to one-third of the tipping events. Thus, by exceeding local thresholds in forest adaptive capacity, local climate change impacts may propagate to other regions of the Amazon basin, causing a risk of forest shifts even in regions where critical thresholds have not been crossed locally.
Subject(s)
Droughts , Rainforest , Climate Change , TreesABSTRACT
American Trypanosomiasis, also known as Chagas disease, is caused by the protozoan Trypanosoma cruzi and exhibits limited options for treatment. Natural products offer various structurally complex metabolites with biological activities, including those with anti-T. cruzi potential. The discovery and development of prototypes based on natural products frequently display multiple phases that could be facilitated by machine learning techniques to provide a fast and efficient method for selecting new hit candidates. Using Random Forest and k-Nearest Neighbors, two models were constructed to predict the biological activity of natural products from plants against intracellular amastigotes of T. cruzi. The diterpenoid andrographolide was identified from a virtual screening as a promising hit compound. Hereafter, it was isolated from Cymbopogon schoenanthus and chemically characterized by spectral data analysis. Andrographolide was evaluated against trypomastigote and amastigote forms of T. cruzi, showing IC50 values of 29.4 and 2.9 µM, respectively, while the standard drug benznidazole displayed IC50 values of 17.7 and 5.0 µM, respectively. Additionally, the isolated compound exhibited a reduced cytotoxicity (CC50 = 92.8 µM) against mammalian cells and afforded a selectivity index (SI) of 32, similar to that of benznidazole (SI = 39). From the in silico analyses, we can conclude that andrographolide fulfills many requirements implemented by DNDi to be a hit compound. Therefore, this work successfully obtained machine learning models capable of predicting the activity of compounds against intracellular forms of T. cruzi.
Subject(s)
Biological Products , Chagas Disease , Cymbopogon , Diterpenes , Nitroimidazoles , Trypanosoma cruzi , Animals , Chagas Disease/drug therapy , Diterpenes/pharmacology , Diterpenes/metabolism , Biological Products/metabolism , MammalsABSTRACT
This study aimed to assess the antiprotozoal efficacy of dicentrine, an aporphine alkaloid isolated from Ocotea puberula, against amastigote forms of Leishmania (L.) infantum. Our findings reveal that dicentrine demonstrated a notable EC50 value of 10.3 µM, comparable to the positive control miltefosine (EC50 of 10.4 µM), while maintaining moderate toxicity to macrophages (CC50 of 51.9 µM). Utilizing an in silico methodology, dicentrine exhibited commendable adherence to various parameters, encompassing lipophilicity, water solubility, molecule size, polarity, and flexibility. Subsequently, we conducted additional investigations to unravel the mechanism of action, employing Langmuir monolayers as models for protozoan cell membranes. Tensiometry analyses unveiled that dicentrine disrupts the thermodynamic and mechanical properties of the monolayer by expanding it to higher areas and increasing the fluidity of the film. The molecular disorder was further corroborated through dilatational rheology and infrared spectroscopy. These results contribute insights into the role of dicentrine as a potential antiprotozoal drug in its interactions with cellular membranes. Beyond elucidating the mechanism of action at the plasma membrane's external surface, our study sheds light on drug-lipid interface interactions, offering implications for drug delivery and other pharmaceutical applications.
Subject(s)
Antiprotozoal Agents , Antiprotozoal Agents/pharmacology , Antiprotozoal Agents/chemistry , Structure-Activity Relationship , Cell Membrane/drug effects , Aporphines/pharmacology , Aporphines/chemistry , Dose-Response Relationship, Drug , Lauraceae/chemistry , Molecular Structure , Leishmania infantum/drug effects , Parasitic Sensitivity Tests , AnimalsABSTRACT
As part of our continuous research for the discovery of bioactive compounds against Trypanosoma cruzi and Leishmania infantum, the alkaloid (6aS)-dicentrine (1) was oxidized to afford (6aS,6S)- (2) and (6aS,6R)- (3) dicentrine-N-oxides. Evaluation of the cytotoxicity against NCTC cells indicated that 2 and 3 are non-toxic (CC50>200 µM) whereas 1 demonstrated CC50 of 52.0 µM. Concerning T. cruzi activity against amastigotes, derivatives 2 and 3 exhibited EC50 values of 9.9 µM (SI>20.2) and 27.5 µM (SI>7.3), respectively, but 1 is inactive (EC50>100 µM). Otherwise, when tested against L. infantum amastigotes, 1 and 3 exhibited EC50 values of 10.3 µM (SI=5.0) and 12.7 µM (SI>15.7), respectively, being 2 inactive (EC50>100 µM). Comparing the effects of positive controls benznidazol (EC50=6.5 µM and SI>30.7) and miltefosine (EC50=10.2 µM and SI=15.2), it was observed a selective antiparasitic activity to diastereomers 2 and 3 against T. cruzi and L. infantum. Considering stereochemical aspects, it was suggested that the configuration of the new stereocenter formed after oxidation of 1 played an important role in the bioactivity against amastigotes of both tested parasites.
ABSTRACT
INTRODUCTION: Cardiovascular disease represents the foremost cause of death among chronic and non-transmissible diseases. Diagnostic tools commonly used for peripheral and carotid atherosclerosis, such as ankle-brachial index (ABI) and carotid ultrasonography (CU), may contribute as surrogates for the diagnosis of coronary arterial disease (CAD). MATERIAL AND METHODS: We report a cross-sectional study of 50 patients referred to elective invasive coronary angiography (ICA). Patients were submitted to ABI and CU-for carotid intima-media thickness (CIMT) and carotid atherosclerotic plaque screening (CAPS). Clinical and demographic variables were also evaluated. CAD was defined as greater than 50% stenosis in at least one coronary artery. RESULTS: In logistic regression analysis, only CAPS showed a statistically significant area under the curve (AUC) for CAD prediction: 0.812 (95% CI, p <0.001). ABI and CIMT did not show statistically significant performance. For multivariate logistic regression analysis, the model including variables "gender," "dyslipidemia," "smoking," "pack-years," and CAPS predicted CAD better. The AUC for this model was 0.912 (95% CI, p = 0.002). CONCLUSION: The screening for carotid atherosclerotic plaques may enhance traditional risk stratification strategies for CAD. Longitudinal studies and bigger samples of subject are needed to allow extrapolation of our findings.
ABSTRACT
The Amazon rainforest suffers increasing pressure from anthropogenic activities. A key aspect not fully understood is how anthropogenic atmospheric emissions within the basin interact with biogenic emissions and impact the forest's atmosphere and biosphere. We combine a high-resolution atmospheric chemical transport model with an improved emissions inventory and in-situ measurements to investigate a surprisingly high concentration of ozone (O3) and secondary organic aerosol (SOA) 150-200 km downwind of Manaus city in an otherwise pristine forested region. We show that atmospheric dynamics and photochemistry determine a gross production of secondary pollutants seen in the simulation. After sunrise, the erosion of the nocturnal boundary layer mixes natural forest emissions, rich in biogenic volatile organic compounds, with a lofted pollution layer transported overnight, rich in nitrogen oxides and formaldehyde. As a result, O3 and SOA concentrations greater than â¼47 ppbv and 1.8 µg m-3, respectively, were found, with maximum concentrations occurring at 2 pm LT, 150-200 km downwind of Manaus city. These high concentrations affect a large primary forested area of about 11,250 km2. These oxidative areas are under a NOx-limited regime so that changes in NOx emissions from Manaus have a significant impact on O3 and SOA production.
Subject(s)
Air Pollutants , Ozone , Volatile Organic Compounds , Aerosols/analysis , Air Pollutants/analysis , Environmental Monitoring/methods , Forests , Ozone/analysisABSTRACT
The nucleation of atmospheric vapours is an important source of new aerosol particles that can subsequently grow to form cloud condensation nuclei in the atmosphere. Most field studies of atmospheric aerosols over continents are influenced by atmospheric vapours of anthropogenic origin (for example, ref. 2) and, in consequence, aerosol processes in pristine, terrestrial environments remain poorly understood. The Amazon rainforest is one of the few continental regions where aerosol particles and their precursors can be studied under near-natural conditions, but the origin of small aerosol particles that grow into cloud condensation nuclei in the Amazon boundary layer remains unclear. Here we present aircraft- and ground-based measurements under clean conditions during the wet season in the central Amazon basin. We find that high concentrations of small aerosol particles (with diameters of less than 50 nanometres) in the lower free troposphere are transported from the free troposphere into the boundary layer during precipitation events by strong convective downdrafts and weaker downward motions in the trailing stratiform region. This rapid vertical transport can help to maintain the population of particles in the pristine Amazon boundary layer, and may therefore influence cloud properties and climate under natural conditions.
Subject(s)
Aerosols/analysis , Rain , Aerosols/chemistry , Biomass , Brazil , Fires , Particle Size , Volatile Organic Compounds/analysis , Volatile Organic Compounds/chemistryABSTRACT
One new aporphine, dicentrine-ß-N-oxide (1), together with five related known alkaloids dehydrodicentrine (2), predicentrine (3), N-methyllaurotetanine (4), cassythicine (5), and dicentrine (6) were isolated from the leaves of Ocotea puberula (Lauraceae). Antiprotozoal activity of the isolated compounds was evaluated inâ vitro against trypomastigote forms of Trypanosoma cruzi. Among the tested compounds, alkaloid 1 exhibited higher potential with EC50 value of 18.2â µM and reduced toxicity against NCTC cells (CC50 >200â µM - SI>11.0), similar to positive control benznidazole (EC50 of 17.7â µM and SI=10.7). Considering the promising results of dicentrine-ß-N-oxide (1) against trypomastigotes, the mechanism of parasite death caused by this alkaloid was investigated. As observed, this compound reached the plasma membrane electric potential directly after 2â h of incubation and triggered mitochondrial depolarization, which probably leads to trypomastigote death. Therefore, dicentrine-ß-N-oxide (1), reported for the first time in this work, can contribute to future works for the development of new trypanocidal agents.
Subject(s)
Aporphines/pharmacology , Cell Membrane/drug effects , Ocotea/chemistry , Plant Extracts/pharmacology , Trypanocidal Agents/pharmacology , Trypanosoma cruzi/drug effects , Animals , Aporphines/chemistry , Aporphines/isolation & purification , Cell Line , Cell Membrane/metabolism , Membrane Potential, Mitochondrial/drug effects , Mice , Molecular Structure , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Trypanocidal Agents/chemistry , Trypanocidal Agents/isolation & purificationABSTRACT
In the present work, the oxoaporphine alkaloid dicentrinone was isolated, for the first time, from leaves of Ocotea puberula (Lauraceae). This alkaloid exhibited antiparasitic activity against trypomastigote forms of Trypanosoma cruzi (IC50 of 16.4 ± 1.7 µM), similar to the positive control benznidazole (IC50 of 18.7 ± 4.1 µM), reduced mammalian cytotoxicity (CC50 > 200 µM), and a selectivity index (SI) higher than 12. These results were correlated with the effects observed using cellular membrane models, represented by 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE), in Langmuir monolayers. Dicentrinone was incorporated in the films, submitted to lateral compression, and characterized by tensiometry. As observed in compression-decompression and time-stability curves, dicentrinone expanded the lipid monolayers, decreased the compressional modulus of the film, and reduced the stability of the monolayer. Brewster Angle Microscopy and interfacial Infrared Spectroscopy showed that dicentrinone causes the monolayers to be segregated in phases, and to increase the number of gauche/trans conformers ratio for the lipid acyl methylene groups, indicating configurational disorder. As a result, dicentrinone caused a disturbance in the cell membrane models, altering the physicochemical properties of the lipid surface such as thermodynamic, rheological, morphological, and structural aspects. These results can be useful to understand the interactions between dicentrinone and lipid biological surfaces at the molecular level.
Subject(s)
Alkaloids/chemistry , Aporphines/chemistry , Biological Products/therapeutic use , Cell Membrane/drug effects , Lauraceae/chemistry , Plant Leaves/chemistry , Trypanosoma cruzi/drug effects , AnimalsABSTRACT
Quantifying the aerosol/cloud-mediated radiative effect at a global scale requires simultaneous satellite retrievals of cloud condensation nuclei (CCN) concentrations and cloud base updraft velocities (Wb). Hitherto, the inability to do so has been a major cause of high uncertainty regarding anthropogenic aerosol/cloud-mediated radiative forcing. This can be addressed by the emerging capability of estimating CCN and Wb of boundary layer convective clouds from an operational polar orbiting weather satellite. Our methodology uses such clouds as an effective analog for CCN chambers. The cloud base supersaturation (S) is determined by Wb and the satellite-retrieved cloud base drop concentrations (Ndb), which is the same as CCN(S). Validation against ground-based CCN instruments at Oklahoma, at Manaus, and onboard a ship in the northeast Pacific showed a retrieval accuracy of ±25% to ±30% for individual satellite overpasses. The methodology is presently limited to boundary layer not raining convective clouds of at least 1 km depth that are not obscured by upper layer clouds, including semitransparent cirrus. The limitation for small solar backscattering angles of <25° restricts the satellite coverage to â¼25% of the world area in a single day.
ABSTRACT
Vertical architectures for organic electrochemical transistors (OECTs), due to their submicrometer channel lengths, have presented themselves as a straightforward design approach for achieving high gm/τ ratios, a figure of merit that assesses the performance of the devices by virtue of their transconductance (gm = dID/dVGS) and switching time constant (τ). However, as the practical limitations of the geometries are overcome, the influence of parasitic phenomena becomes more dominant and limits the performance of the device. One approach to reduce the detrimental effects of parasitic resistance in the drain-source circuit is to use a four-point sourcing technique. Here, vertical OECTs are fabricated with four-point structures to approach the intrinsic limit of these devices. It is shown that this approach improves the saturation behavior of the devices, closing the gap between measured gm and intrinsic transconductance gmi at their peak values. Overall, the results discussed here provide insight into the effects of parasitic resistance on OECTs, which in contrast to field-effect transistors, are not as extensively documented.
ABSTRACT
This study investigates the interaction between sakuranetin, a versatile pharmaceutical flavonoid, and monolayers composed of unsaturated phospholipids, serving as a surrogate for cell membranes. The phospholipids were 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE). We conducted a series of experiments to comprehensively investigate this interaction, including surface pressure assessments, Brewster angle microscopy (BAM), and polarization-modulated infrared reflection-absorption spectroscopy (PM-IRRAS). Our findings unequivocally demonstrate that sakuranetin interacts with these phospholipids, expanding the monomolecular films. Notably, regarding POPC, the presence of sakuranetin led to a reduction in stability and a decline in surface elasticity, which can likely be attributed to intricate molecular rearrangements at the interface. The visual evidence of aggregations in BAM images reinforces the interactions substantiated by PM-IRRAS, highlighting sakuranetin's interaction with the polar and nonpolar regions of POPC. However, it is worth noting that these aggregations do not appear to contribute significantly to the viscosity of the mixed film, and our investigations did not reveal any substantial hysteresis. In contrast, when examining POPE, we observed a minor reduction in thermodynamic stability, indicative of fewer rearrangements within the monolayer. This notion was further reinforced by the limited presence of aggregations in the BAM images. Sakuranetin also increased the rigidity of the lipid monolayer; nevertheless, the monolayer remained predominantly elastic, facilitating easy re-spreading on the surface, especially for the first lipid. PM-IRRAS analysis unveiled interactions between sakuranetin and POPE's polar and nonpolar segments, compellingly explaining the observed monolayer expansion. Taken together, our data suggest that sakuranetin was more effectively incorporated into the monomolecular layer of POPE, indicating that membranes comprised of POPC might exhibit a greater degree of interaction in the presence of this pharmacologically active compound.
Subject(s)
Phospholipids , Phytoalexins , Water , Water/chemistry , Surface Properties , Phospholipids/chemistry , FlavonoidsABSTRACT
Chagas disease, after more than a century after its discovery, is still a major public health problem. It is estimated that approximately 10 million people worldwide are infected with T. cruzi. However, the situation is more critical in Latin America and other regions where the disease is endemic. The largest number of cases occurs in Brazil, Argentina, and Mexico as more than 100 million people in these regions are located in areas with a high risk of contamination by the vector. The need for new therapeutic alternatives is urgent, as the available drugs have severe limitations such as low efficacy and high toxicity. From this scenario, in this work, we employed the virtual screening technique using cruzain and BDF2 as key biological targets for the survival of the parasite. Our objective was to identify potential inhibitors of T. cruzi trypomastigotes, which could be considered drug candidates against Chagas disease. For this, we employed different in silico methodologies and the obtained results were corroborated using in vitro biological assays. For the VS studies, a database containing synthetic compounds was simulated at the binding site of cruzain and BDF2. In addition, pharmacophoric models were constructed in the initial phases of VS, as well as other advanced analyses (molecular dynamics simulations, calculations of binding free energy, and ADME prediction) were carried out and the results allowed the selection of potential inhibitors of T. cruzi. Based on the obtained data, 32 different compounds commercially available were subjected to biological tests against the trypomastigote form of T. cruzi. As result, 11 of those compounds displayed significant activity against T. cruzi and can be considered potential candidates for the treatment of Chagas disease.
Subject(s)
Chagas Disease , Trypanocidal Agents , Trypanosoma cruzi , Humans , Chagas Disease/drug therapy , Chagas Disease/parasitology , Molecular Dynamics Simulation , Binding Sites , Protein Domains , Trypanocidal Agents/pharmacology , Trypanocidal Agents/therapeutic use , Trypanocidal Agents/chemistryABSTRACT
BACKGROUND: Chagas disease (American Trypanosomiasis) is classified by the World Health Organization (WHO) as one of the seventeen neglected tropical diseases (NTD), affecting, mainly, several regions of Latin America. INTRODUCTION: However, immigration has expanded the range of this disease to other continents. Thousands of patients with Chagas disease die annually, yet no new therapeutics for Chagas disease have been approved, with only nifurtimox and benznidazole available. Treatment with these drugs presents several challenges, including protozoan resistance, toxicity, and low efficacy. Natural products, including the secondary metabolites found in plants, offer a myriad of complex structures that can be sourced directly or optimized for drug discovery. METHODS: Therefore, this review aims to assess the literature from the last 10 years (2012-2021) and present the anti-T. cruzi compounds isolated from plants in this period, as well as briefly discuss computational approaches and challenges in natural product drug discovery. Using this approach, more than 350 different metabolites were divided based on their biosynthetic pathway alkaloids, terpenoids, flavonoids, polyketides, and phenylpropanoids which displayed activity against different forms of this parasite epimastigote, trypomastigote and more important, the intracellular form, amastigote. CONCLUSION: In this aspect, there are several compounds with high potential which could be considered as a scaffold for the development of new drugs for the treatment of Chagas disease-for this, more advanced studies must be performed including pharmacokinetics (PK) and pharmacodynamics (PD) analysis as well as conduction of in vivo assays, these being important limitations in the discovery of new anti-T. cruzi compounds.
Subject(s)
Chagas Disease , Trypanocidal Agents , Trypanosoma cruzi , Humans , Trypanocidal Agents/chemistry , Chagas Disease/drug therapy , Nifurtimox/pharmacology , Nifurtimox/therapeutic use , Drug DiscoveryABSTRACT
The objective was to estimate the prevalence and factors associated with prehypertension and hypertension among health workers who work in high-complexity services for critically-ill and chronic patients. An epidemiological, cross-sectional study was carried out with 490 health workers in the macroregional region of Northern Minas Gerais, Brazil. The dependent variable blood pressure (BP) was categorized as normal BP, prehypertension and hypertension. Multinomial Logistic Regression was used for the multiple analysis. The prevalence of arterial hypertension was 21.8% and that of prehypertension was 25.9%. The chances of developing arterial hypertension and prehypertension were higher in male professionals, aged ≥40 years, in civil servant workers and those who were obese or overweight. The use of continuous medication and night shift work were associated with hypertension and prehypertension, respectively. The prevalence of arterial hypertension in the group of workers was lower than that of the Brazilian population. It is necessary to carry out studies with workers from this group and investments are required in preventive measures that encourage a change to a healthy lifestyle.
Objetivou-se estimar a prevalência e fatores associados à pré-hipertensão e hipertensão arterial entre trabalhadores de saúde que atuam em setores de alta complexidade para pacientes críticos e crônicos. Foi realizado um estudo epidemiológico, transversal com 490 trabalhadores de saúde da macrorregional do norte de Minas Gerais, Brasil. A variável dependente pressão arterial foi categorizada em normal, pré-hipertensão e hipertensão. Para análise múltipla, foi utilizada a Regressão Logística Multinomial. A prevalência da hipertensão arterial foi de 21,8% e da pré-hipertensão foi de 25,9%. As chances de se desenvolver a hipertensão arterial e a pré hipertensão foram maiores nos profissionais do sexo masculino, com idade ≥40 anos, em trabalhadores com vínculo empregatício concursado e naqueles obesos ou com sobrepeso. O uso de medicamento contínuo e o trabalho no turno noturno estiveram associados à hipertensão e pré-hipertensão, respectivamente. A prevalência de hipertensão arterial no grupo de trabalhadores foi menor do que a da população brasileira. São necessários estudos com trabalhadores desse grupo e investimentos em medidas preventivas e que incentivem a mudança para um estilo de vida saudável.
Subject(s)
Hypertension , Prehypertension , Cross-Sectional Studies , Health Personnel , Humans , Hypertension/epidemiology , Male , Prehypertension/epidemiology , Risk FactorsABSTRACT
This study aimed to identify factors associated with the hardy personality in health professionals working in hospital services that treat critically ill patients. This is an epidemiological, cross-sectional, and analytical study conducted with 469 health professionals. We used the Hardiness Scale (HS), coupled with a questionnaire to investigate sociodemographic, occupational, and health conditions. A descriptive and bivariate analysis was performed using the chi-square test and the multiple model through multiple logistic regression, using the Hosmer-Lemeshow and PseudoR2 tests, estimating odds ratios. The classification of total scores in HS showed prevailing moderate hardiness (48.4%). Professionals with a fair or poor fantastic lifestyle (FL) were 74% less likely to show high hardiness than those with very good and excellent FL. Also, professionals who were not on leave, who had high satisfaction with compassion at work, low stress, and low burnout were more likely to show high hardiness. The hardy personality, directly and indirectly, influences the health and well-being of health professionals working in hospital services that treat critically ill patients.
Objetivou-se identificar os fatores associados à personalidade hardiness em profissionais de saúde atuantes em serviços hospitalares que atendem a pacientes críticos. Estudo epidemiológico, transversal e analítico, realizado com 469 profissionais de saúde. Como instrumento, utilizou-se a Escala Hardiness (EH) associada a um questionário para investigar as condições sociodemográficas, ocupacionais e de saúde. Foi realizada a análise descritiva e bivariada por meio do teste qui-quadrado e modelo múltiplo através de regressão logística múltipla, utilizando o teste Hosmer Lemeshow e PseudoR2, estimando razão das chances (odds ratio). A classificação dos escores totais na EH evidenciou preponderância de moderado hardiness (48,4%). A chance de alto hardiness entre profissionais com estilo de vida fantástico regular ou ruim reduziu em 74% quando comparado aos considerados muito bons e excelentes. Também esteve aumentada entre os profissionais que não tiveram licença/afastamento, que apresentavam alta satisfação por compaixão no trabalho, baixo estresse e baixo burnout. A personalidade hardiness influência direta e indiretamente a saúde e o bem-estar do profissional de saúde atuante em serviços hospitalares que atendem a pacientes críticos.
Subject(s)
Adaptation, Psychological , Critical Care , Occupational Stress/psychology , Personality , Personnel, Hospital/psychology , Resilience, Psychological , Adult , Cross-Sectional Studies , Epidemiologic Studies , Female , Humans , Male , Middle Aged , Young AdultABSTRACT
OBJECTIVE: This work describes the isolation of anti-Leishmania amazonensis metabolites from Saururus cernuus (Saururaceae). Additionally, ultrastructural changes in promastigotes were evidenced by electron microscopy. METHODS: The MeOH extract from the leaves of S. cernuus was subjected to bioactivity-guided fractionation. Anti-L. amazonensis activity of purified compounds was performed in vitro against promastigote and amastigote forms. KEY FINDINGS: Bioactivity-guided fractionation of the MeOH extract from the leaves of S. cernuus afforded two related tetrahydrofuran dineolignans: threo,threo-manassantin A (1) and threo,erythro-manassantin A (2). Compounds 1 and 2 displayed activity against promastigotes (EC50 of 35.4 ± 7.7 and 17.6 ± 4.2 µm, respectively) and amastigotes (EC50 of 20.4 ± 1.9 and 16.0 ± 1.1 µm, respectively), superior to that determined for the positive control miltefosine (EC50 of 28.7 ± 3.5 µm). Reduced cytotoxicity for host cells was observed for both compounds. Additionally, ultrastructural changes in promastigotes leading to an alteration of structural morphology were observed, as evidenced by electron microscopy. Furthermore, these compounds altered the morphology and physiology of the plasmatic membrane of L. amazonensis. CONCLUSIONS: The obtained results indicated that dineolignans 1 and 2 could be considered as a scaffold for the design of novel and selective drug candidates for the treatment of leishmaniasis.
Subject(s)
Antiprotozoal Agents/pharmacology , Leishmania/drug effects , Leishmaniasis/drug therapy , Lignans/pharmacology , Saururaceae/chemistry , Animals , Antiprotozoal Agents/chemistry , Antiprotozoal Agents/isolation & purification , Furans/chemistry , Furans/isolation & purification , Furans/pharmacology , Leishmaniasis/parasitology , Lignans/chemistry , Lignans/isolation & purification , Mice , Mice, Inbred BALB C , Microscopy, Electron , Phosphorylcholine/analogs & derivatives , Phosphorylcholine/pharmacology , Plant LeavesABSTRACT
One of the least understood aspects in atmospheric chemistry is how urban emissions influence the formation of natural organic aerosols, which affect Earth's energy budget. The Amazon rainforest, during its wet season, is one of the few remaining places on Earth where atmospheric chemistry transitions between preindustrial and urban-influenced conditions. Here, we integrate insights from several laboratory measurements and simulate the formation of secondary organic aerosols (SOA) in the Amazon using a high-resolution chemical transport model. Simulations show that emissions of nitrogen-oxides from Manaus, a city of ~2 million people, greatly enhance production of biogenic SOA by 60-200% on average with peak enhancements of 400%, through the increased oxidation of gas-phase organic carbon emitted by the forests. Simulated enhancements agree with aircraft measurements, and are much larger than those reported over other locations. The implication is that increasing anthropogenic emissions in the future might substantially enhance biogenic SOA in pristine locations like the Amazon.
ABSTRACT
Organosulfates are formed in the atmosphere from reactions between reactive organic compounds (such as oxidation products of isoprene) and acidic sulfate aerosol. Here we investigated speciated organosulfates in an area typically downwind of the city of Manaus situated in the Amazon forest in Brazil during "GoAmazon2014/5" in both the wet season (February-March) and dry season (August-October). We observe products consistent with the reaction of isoprene photooxidation products and sulfate aerosols, leading to formation of several types of isoprene-derived organosulfates, which contribute 3% up to 42% of total sulfate aerosol measured by aerosol mass spectrometry. During the wet season the average contribution of summed organic sulfate concentrations to total sulfate was 19 ± 10% and similarly during the dry season the contribution was 19 ± 8%. This is the highest fraction of speciated organic sulfate to total sulfate observed at any reported site. Organosulfates appeared to be dominantly formed from isoprene epoxydiols (IEPOX), averaging 104 ± 73 ng m-3 (range 15-328 ng m-3) during the wet season, with much higher abundance 610 ± 400 ng m-3 (range 86-1962 ng m-3) during the dry season. The concentration of isoprene-derived organic sulfate correlated with total inorganic sulfate (R2 = 0.35 and 0.51 during the wet and dry seasons, respectively), implying the significant influence of inorganic sulfate aerosol for the heterogeneous reactive uptake of IEPOX. Organosulfates also contributed to organic matter in aerosols (3.5 ± 1.9% during the wet season and 5.1 ± 2.5% during the dry season). The present study shows that an important fraction of sulfate in aerosols in the Amazon downwind of Manaus consists of multifunctional organic chemicals formed in the atmosphere, and that increased SO2 emissions would substantially increase SOA formation from isoprene.