Perillyl Alcohol Promotes Relaxation in Human Umbilical Artery.

BACKGROUND: Perillyl alcohol (POH) is a monoterpenoid found in plant essential oils and has been shown to relax murine vessels, but its effect on human vessels remains poorly studied. OBJECTIVE: The study aimed to characterize the effect of POH on human umbilical arteries (HUA). METHODS: Rings of HUA were obtained from uncomplicated patients and suspended in an organ bath for isometric recording. The vasorelaxant effect of POH in HUA was evaluated on basal tone and electromechanical or pharmacomechanical contractions, and possible mechanisms of action were also investigated. RESULTS: POH (1-1000 µM) altered the basal tone of HUA and completely relaxed HUA rings precontracted with KCl (60 mM) or 5-HT (10 µM), obtaining greater potency in the pharmacomechanical pathway (EC50 110.1 µM), suggesting a complex interference in the mobilization of extra- and intracellular Ca2+. POH (1000 µM) inhibited contractions induced by BaCl2 (0.1-30 mM) in a similar way to nifedipine (10 µM), indicating a possible blockade of L-type VOCC. In the presence of potassium channel blockers, tetraethylammonium (1 mM), 4-aminopyridine (1 mM), or glibenclamide (10 µM), an increase in the EC50 value of the POH was observed, suggesting a modulation of the activity of BKCa, KV, and KATP channels. CONCLUSION: The data from this study suggest that POH modulates Ca2+ and K+ ion channels to induce a relaxant response in HUA.

Molecular mechanism of cellulose depolymerization by the two-domain BlCel9A enzyme from the glycoside hydrolase family 9.

Carbohydrate-active enzymes from the glycoside hydrolase family 9 (GH9) play a key role in processing lignocellulosic biomass. Although the structural features of some GH9 enzymes are known, the molecular mechanisms that drive their interactions with cellulosic substrates remain unclear. To investigate the molecular mechanisms that the two-domain Bacillus licheniformis BlCel9A enzyme utilizes to depolymerize cellulosic substrates, we used a combination of biochemical assays, X-ray crystallography, small-angle X-ray scattering, and molecular dynamics simulations. The results reveal that BlCel9A breaks down cellulosic substrates, releasing cellobiose and glucose as the major products, but is highly inefficient in cleaving oligosaccharides shorter than cellotetraose. In addition, fungal lytic polysaccharide oxygenase (LPMO) TtLPMO9H enhances depolymerization of crystalline cellulose by BlCel9A, while exhibiting minimal impact on amorphous cellulose. The crystal structures of BlCel9A in both apo form and bound to cellotriose and cellohexaose were elucidated, unveiling the interactions of BlCel9A with the ligands and their contribution to substrate binding and products release. MD simulation analysis reveals that BlCel9A exhibits higher interdomain flexibility under acidic conditions, and SAXS experiments indicate that the enzyme flexibility is induced by pH and/or temperature. Our findings provide new insights into BlCel9A substrate specificity and binding, and synergy with the LPMOs.

Historical line of airglow observations at Comandante Ferraz Brazilian Station: measurements of temperature and studies on gravity waves.

The thermal dynamics of the upper atmosphere, especially in the mesosphere, have been improving our understanding about the effects of climate change, as well as how the dynamics and general circulation in the upper atmosphere are driven by different types of waves, such as the atmospheric gravity waves, planetary waves and atmospheric tides. In order to study the upper atmospheric temperature variability and gravity waves, several research groups have been employing the remote technique of observing the airglow emissions originated in the upper mesosphere and lower thermosphere, besides emissions from the ionosphere. INPE's airglow group started the studies on emissions from the upper atmosphere to investigate temperature and dynamics in the mesosphere, thermosphere/ionosphere at the end of 70's. However, only in 2001 this group sent the first airglow experiment to the Brazilian Antarctic Station Comandante Ferraz (EACF) to measure the OH (8-3) emission and temperature. From that year to 2014, several other experiments were carried out at EACF, not only to measure the temperature and airglow intensities, but also to observe gravity waves, winds and other related phenomena. This paper presents airglow experiments at EACF from 2001 to the present, including illustrations, examples of already published results, and unpublished data.

Vasorelaxant effect of (E,E)-farnesol in human umbilical vein ex vivo assays.

(E,E)-farnesol is a sesquiterpene acyclic alcohol produced by bacteria, protozoa, fungi, plants, and animals. The literature describes its applications in food, pharmaceutical, and cosmetic industries, and also in the pharmacological context with a vasorelaxant effect. However, its effects on human umbilical vessels remain poorly investigated. Thus, this study aims to investigate, in a new way, the vasorelaxant effect of (E,E)-farnesol in human umbilical veins (HUV) from healthy donors. Rings obtained from isolated HUV were suspended in an organ bath to record their isometric tension in different experimental sections. (E,E)-farnesol (1 µmol/L to 1 mmol/L) promoted vasorelaxant effect in venous preparations contracted by depolarization (KCl 60 mmol/L) or pharmacological agonism (5-HT 10 µmol/L), with EC50 values of 239.9 µmol/L and 424 µmol/L, respectively. In calcium-free solution, this effect was also observable. (E,E)-farnesol was able to suppress contractions evoked by CaCl2 and BaCl2 suggesting a blockade of voltage-dependent (especially L-type) calcium channels. The vasorelaxant efficacy and potency of (E,E)-farnesol were affected in the presence of tetraethylammonium (1 and 10 mmol/L), glibenclamide (10 µmol/L) and BaCl2 (1 mmol/L) indicating a possible involvement of potassium channels (BKCa, KATP and KIR) in this effect. Our data suggest that (E,E)-farnesol has a promising potential to be applicable as a vasodilator in hypertensive conditions in pregnancy that alter HUV reactivity.

Vasodilation promoted by (E,E)-farnesol involving ion channels in human umbilical arteries.

Background: (E,E)-farnesol is a sesquiterpene alcohol derived from plants and animals that exhibits pharmacological properties in the cardiovascular system. However, its effects on human umbilical vessels remain unknown. Purpose: Thus, this study aims to characterize the vasodilatory effect of (E,E)-farnesol in human umbilical arteries (HUA). Study design: The tissue is obtained from pregnant women over 18 years of age, normotensive, and without prepartum complications. After collected, the tissue was segmented and dissected to remove Wharton's jelly and obtain the umbilical arteries segments. Methods: HUA segments were isolated and sectioned into rings that were subjected to isometric tension recordings in an organ bath. Results: (E,E)-farnesol (1 µmol/L to 1 mmol/L) promoted vasodilatory effect in HUA preparations, affecting basal tone, and inhibiting the electromechanical coupling induced by KCl 60 mmol/L with greater potency (EC50 225.3 µmol/L) than the pharmacomechanical coupling induced by 5-HT 10 µmol/L (EC50 363.5 µmol/L). In the absence of extracellular calcium, pharmacomechanical coupling was also abolished, and contractions induced by CaCl2 or BaCl2 were attenuated by (E,E)-farnesol indicating a possible direct inhibition of L-type VOCC as a mechanism of the vasodilatory effect. The vasodilator efficacy of (E,E)-farnesol on reduction of vasocontraction induced by the presence of tetraethylammonium (1 or 10 mmol/L), 4-aminopyridine (1 mmol/L) and glibenclamide (10 µmol/L) suggesting a possible influence of different potassium channels (BKCa, KV and KATP). Conclusion: These results suggest that (E,E)-farnesol may be a promising pharmacological candidate for obstetric hypertensive disorders.

MDexciteR: Enhanced Sampling Molecular Dynamics by Excited Normal Modes or Principal Components Obtained from Experiments.

Molecular dynamics with excited normal modes (MDeNM) is an enhanced sampling method for exploring conformational changes in proteins with minimal biases. The excitation corresponds to injecting kinetic energy along normal modes describing intrinsic collective motions. Herein, we developed a new automated open-source implementation, MDexciteR (https://github.com/mcosta27/MDexciteR), enabling the integration of MDeNM with two commonly used simulation programs with GPU support. Second, we generalized the method to include the excitation of principal components calculated from experimental ensembles. Finally, we evaluated whether the use of coarse-grained normal modes calculated with elastic network representations preserved the performance and accuracy of the method. The advantages and limitations of these new approaches are discussed based on results obtained for three different protein test cases: two globular and a protein/membrane system.

Contribution to the study of antimicrobial prophylaxis in third molar extraction surgeries / Contribuição ao estudo da profilaxia antimicrobiana em cirurgias de extração dos terceiros molares

ABSTRACT The use of antibiotic prophylaxis in the extraction of third molars is extremely controversial, raising several discussions about the most appropriate clinical protocol to avoid postoperative complications. To review the literature on the subject, describing the evidence for and against antibiotic prophylaxis to prevent surgical site infections in third molar extractions, besides establishing a prophylactic protocol and dosage regimen. A literature review was carried out analyzing scientific evidence from articles on the PubMed and Scielo platforms by searching for the descriptors "antibiotic therapy and infection in third molar extraction surgery", "antimicrobial prophylaxis and infective endocarditis", "antibiotic prophylaxis and adverse effects", "antibiotic therapy in dentistry", "surgical time and incidence of infections in extractions", including original articles and double or triple blind randomized clinical trials, in Portuguese and English, published between 1980 and 2021, separated in chronological order. There is no consensus in the literature on the indication of antimicrobial prophylaxis, but factors as surgeon's skill, time elapsed during the procedure and the patient's general health status directly affect the incidence and severity of infections. Among all the literature analyzed for this study, it is possible to infer that the topic is still extremely questionable and, therefore, it is essential to conduct new experimental studies to obtain more conclusive data on the subject.

RESUMO O emprego da profilaxia antibiótica na exodontia de terceiros molares é extremamente controverso, gerando diversas discussões sobre o protocolo clínico mais adequado para evitar as complicações pós-operatórias. Revisar a literatura referente ao tema, descrevendo as evidências a favor e contra a profilaxia antibiótica para prevenir infecções do sítio cirúrgico nas extrações de terceiros molares, além de firmar um protocolo profilático e regime posológico. Realizou-se uma revisão de literatura analisando evidências científicas através de artigos nas plataformas PubMed e Scielo pela pesquisa de descritores "antibioticoterapia e infecção em cirurgia de extração de terceiros molares", "profilaxia antimicrobiana e endocardite infecciosa", "profilaxia antibiótica e efeitos adversos", "antibioticoterapia em odontologia", "tempo cirúrgico e incidência de infecções em exodontias", sendo incluídos artigos originais e ensaios clínicos duplos ou triplos cegos randomizados, nos idiomas português e inglês, publicados entre 1980 e 2021, separados em ordem cronológica. Não há consenso na literatura sobre a indicação da profilaxia antimicrobiana, porém há fatores como a habilidade do cirurgião, tempo decorrido durante o procedimento e estado de saúde geral do paciente afetam diretamente na incidência e severidade das infecções. Dentre toda a literatura analisada para este estudo, é possível aferir que o tema é ainda extremamente questionável e, portanto, é fundamental que novos estudos de caráter experimental sejam feitos para que se obtenha dados mais contundentes sobre o assunto.

Effects of Standardized Brazilian Green Propolis Extract (EPP-AF®) on Inflammation in Haemodialysis Patients: A Clinical Trial.

Background: Patients on haemodialysis (HD) present a significant inflammatory status, which has a pronounced negative impact on their outcomes. Propolis is a natural resin with anti-inflammatory and immunomodulatory properties. We assessed the safety and impact of a standardized Brazilian green propolis extract (EPP-AF®) on the inflammatory status in patients under conventional HD. Methods: Patients were assigned to receive 200 mg/day of EPP-AF® for 4 weeks followed by 4 weeks without the drug, and changes in plasma levels of interleukins (ILs), interferon gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α), and high-sensitivityc-reactive protein (HsCRP) were measured. A heatmap was used to illustrate trends in data variation. Results: In total, 37 patients were included in the final analysis. Patients presented an exacerbated inflammatory state at baseline. During EPP-AF® use, there was a significant reduction in IFN-γ (p=0.005), IL-13 (p=0.04 2), IL-17 (p=0.039), IL-1ra (p=0.008), IL-8 (p=0.009), and TNF-α (p < 0.001) levels compared to baseline, and significant changes were found in Hs-CRP levels. The heatmap demonstrated a pattern of pronounced proinflammatory status at baseline, especially in patients with primary glomerulopathies, and a clear reduction in this pattern during the use of EPP-AF®. There was a tendency to maintain this reduction after suspension of EPP-AF®. No significant side effects were observed. Conclusion: Patients under haemodialysis presented a pronounced inflammatory status, and EPP-AF® was demonstrated to be safe and associated with a significant and maintained reduction in proinflammatory cytokines in this population. This trial is registered with Clinicaltrials.gov NCT04072341.

Possible mechanisms involved in the neuroprotective effect of Trans,trans-farnesol on pilocarpine-induced seizures in mice.

This study aimed to investigate, through in vivo and in vitro methodologies, the effect of acute trans,trans-farnesol (12.5, 25, 50 or 100 mg/kg, p.o.) administration on behavioral and neurochemical parameters associated with pilocarpine-induced epileptic seizure (300 mg/kg, i.p.) in mice. The initial results showed that the compound in question presents no anxiolytic-like or myorelaxant effects, despite reducing locomotor activity in the animals at all doses tested. In addition, the lowest dose increased the latency to onset of the first epileptic seizure, and the time to death. In addition to decreasing the mortality percentage in mice submitted to the pilocarpine model. In this same model, pretreatment with the lowest dose of the compound decreased the hippocampal concentrations of thiobarbituric acid and nitrite, and partially restored striatal concentrations of noradrenaline, dopamine, and serotonin. Taken together, the results suggest that trans,trans-farnesol presents a central depressant effect which contributes to its antiepileptic action which, in turn, seems to be mediated by the antagonism of muscarinic cholinergic receptors, reduction of oxidative stress. and modulation of noradrenaline, dopamine and serotonin concentrations in the central nervous system.

The C-terminal extension of VgrG4 from Klebsiella pneumoniae remodels host cell microfilaments.

Klebsiella pneumoniae is an opportunistic pathogen, which concerns public health systems worldwide, as multiple antibiotic-resistant strains are frequent. One of its pathogenicity factors is the Type VI Secretion System (T6SS), a macromolecular complex assembled through the bacterial membranes. T6SS injects effector proteins inside target cells. Such effectors confer competitive advantages or modulate the target cell signaling and metabolism to favor bacterial infection. The VgrG protein is a T6SS core component. It may present a variable C-terminal domain carrying an additional effector function. Kp52.145 genome encodes three VgrG proteins, one of them with a C-terminal extension (VgrG4-CTD). VgrG4-CTD is 138 amino acids long, does not contain domains of known function, but is conserved in some Klebsiella, and non-Klebsiella species. To get insights into its function, recombinant VgrG4-CTD was used in pulldown experiments to capture ligands from macrophages and lung epithelial cells. A total of 254 proteins were identified: most of them are ribosomal proteins. Cytoskeleton-associated and proteins involved in the phagosome maturation pathway were also identified. We further showed that VgrG4-CTD binds actin and induces actin remodeling in macrophages. This study presents novel clues on the role of K. pneumoniae T6SS in pathogenesis.

Prediction of hemodynamic tolerance of intermittent hemodialysis in critically ill patients: a cohort study.

The evaluation and management of fluid balance are key challenges when caring for critically ill patients requiring renal replacement therapy. The aim of this study was to assess the ability of clinical judgment and other variables to predict the occurrence of hypotension during intermittent hemodialysis (IHD) in critically ill patients. This was a prospective, observational, single-center study involving critically ill patients undergoing IHD. The clinical judgment of hypervolemia was determined by the managing nephrologists and critical care physicians in charge of the patients on the basis of the clinical data used to calculate the ultrafiltration volume and rate for each dialysis treatment. Seventy-nine (31.9%) patients presented with hypotension during IHD. Patients were perceived as being hypervolemic in 109 (43.9%) of the cases by nephrologists and in 107 (43.1%) by intensivists. The agreement between nephrologists and intensivists was weak (kappa = 0.561). Receiver operating characteristic curve analysis yielded an AUC of 0.81 (95% CI 0.75 to 0.84; P < 0.0001), and a cutoff value of 70 mm for the vascular pedicle width (VPW) had the highest accuracy for the prediction of the absence of hypotension. The clinical judgment of hypervolemia did not predict hypotension during IHD. The high predictive ability of the VPW may assist clinicians with critical thinking.

Unplanned Transfers From Intermediate Care Units to Intensive Care Units: A Cohort Study.

This study evaluated unplanned transfers from the intermediate care unit (IMCU) to the intensive care unit (ICU) among urgent admissions. This retrospective, observational study was conducted in 2 ICUs and 1 IMCU. Three patterns of urgent admission were assessed: admissions to the ICU only, admissions to the IMCU only, and admissions to the IMCU with subsequent transfer to the ICU. Of 5296 admissions analyzed, 1396 patients (26.4%) were initially admitted to the IMCU. Of these, 172 (12.3%) were transferred from the IMCU to the ICU. Mortality was higher in patients transferred from the IMCU to the ICU than in the 3900 ICU-only patients (odds ratio, 3.22; 95% CI, 1.52-6.80). Most transfers from the IMCU to the ICU (135; 78.5%) were due to deterioration of the condition for which the patient was admitted. Patient transfers from the IMCU to the ICU were common, were associated with increased hospital mortality, and were mostly due to deterioration in the condition that was the reason for admission.

Concerted conformational dynamics and water movements in the ghrelin G protein-coupled receptor.

There is increasing support for water molecules playing a role in signal propagation through G protein-coupled receptors (GPCRs). However, exploration of the hydration features of GPCRs is still in its infancy. Here, we combined site-specific labeling with unnatural amino acids to molecular dynamics to delineate how local hydration of the ghrelin receptor growth hormone secretagogue receptor (GHSR) is rearranged upon activation. We found that GHSR is characterized by a specific hydration pattern that is selectively remodeled by pharmacologically distinct ligands and by the lipid environment. This process is directly related to the concerted movements of the transmembrane domains of the receptor. These results demonstrate that the conformational dynamics of GHSR are tightly coupled to the movements of internal water molecules, further enhancing our understanding of the molecular bases of GPCR-mediated signaling.

Efficacy of Brazilian green propolis (EPP-AF®) as an adjunct treatment for hospitalized COVID-19 patients: A randomized, controlled clinical trial.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) promotes challenging immune and inflammatory phenomena. Though various therapeutic possibilities have been tested against coronavirus disease 2019 (COVID-19), the most adequate treatment has not yet been established. Propolis is a natural product with considerable evidence of immunoregulatory and anti-inflammatory activities, and experimental data point to potential against viral targets. We hypothesized that propolis can reduce the negative effects of COVID-19. METHODS: In a randomized, controlled, open-label, single-center trial, hospitalized adult COVID-19 patients were treated with a standardized green propolis extract (EPP-AF®ï¸) as an adjunct therapy. Patients were allocated to receive standard care plus an oral dose of 400 mg or 800 mg/day of green propolis for seven days, or standard care alone. Standard care included all necessary interventions, as determined by the attending physician. The primary end point was the time to clinical improvement, defined as the length of hospital stay or oxygen therapy dependency duration. Secondary outcomes included acute kidney injury and need for intensive care or vasoactive drugs. Patients were followed for 28 days after admission. RESULTS: We enrolled 124 patients; 40 were assigned to EPP-AF®ï¸ 400 mg/day, 42 to EPP-AF®ï¸ 800 mg/day, and 42 to the control group. The length of hospital stay post-intervention was shorter in both propolis groups than in the control group; lower dose, median 7 days versus 12 days (95% confidence interval [CI] -6.23 to -0.07; p = 0.049) and higher dose, median 6 days versus 12 days (95% CI -7.00 to -1.09; p = 0.009). Propolis did not significantly affect the need for oxygen supplementation. In the high dose propolis group, there was a lower rate of acute kidney injury than in the controls (4.8 vs 23.8%), (odds ratio [OR] 0.18; 95% CI 0.03-0.84; p = 0.048). No patient had propolis treatment discontinued due to adverse events. CONCLUSIONS: Addition of propolis to the standard care procedures resulted in clinical benefits for the hospitalized COVID-19 patients, especially evidenced by a reduction in the length of hospital stay. Consequently, we conclude that propolis can reduce the impact of COVID-19.

Realistic simulation is associated with healthcare professionals' increased self-perception of confidence in providing acute stroke care: a before-after controlled study.

BACKGROUND: Simulations are becoming widely used in medical education, but there is little evidence of their effectiveness on neurocritical care. Because acute stroke is a neurological emergency demanding prompt attention, it is a promising candidate for simulation training. OBJECTIVE: To assess the impact of a stroke realistic simulation course on clinicians' self-perception of confidence in the management of acute stroke. METHODS: We conducted a controlled, before-after study. For our intervention, 17 healthcare professionals participated in a stroke realistic simulation course. As controls, participants were chosen from a convenience sample of attendees to the courses Emergency Neurologic Life Support (ENLS) (18 participants) and Neurosonology (20 participants). All participants responded pre- and post-test questionnaires evaluating their self-perception of confidence in acute stroke care, ranging from 10 to 50 points. We evaluated the variation between pre- and post-test results to assess the change on trainees' self-perception of confidence in the management of acute stroke. Multivariate analysis was performed to control for potential confounders. RESULTS: Forty-six (83.63%) subjects completed both questionnaires. The post-test scores were higher than those from the pretests in the stroke realistic simulation course group [pretest median (interquartile range - IQR): 41.5 (36.7-46.5) and post-test median (IQR): 47 (44.7-48); p=0.033], but not in the neurosonology [pretest median (IQR): 46 (44-47) and post-test median (IQR): 46 (44-47); p=0.739] or the ENLS [pretest median (IQR): 46.5 (39-48.2), post-test median (IQR): 47 (40.2-49); p=0.317] groups. Results were maintained after adjustment for covariates. CONCLUSIONS: This stroke realistic simulation course was associated with an improvement on trainees' self-perception of confidence in providing acute stroke care.

Positive fluid balance as an early biomarker for acute kidney injury: a prospective study in critically ill adult patients.

OBJECTIVES: Positive fluid balance is frequent in critically ill patients and has been considered a potential biomarker for acute kidney injury (AKI). This study aimed to evaluate positive fluid balance as a biomarker for the early detection of AKI in critically ill patients. METHODS: This was a prospective cohort study. The sample was composed of patients ≥18 years old who stayed ≥3 days in an intensive care unit. Fluid balance, urinary output and serum creatinine were assessed daily. AKI was diagnosed by the Kidney Disease Improving Global Outcome criteria. RESULTS: The final cohort was composed of 233 patients. AKI occurred in 92 patients (40%) after a median of 3 (2-6) days following ICU admission. When fluid balance was assessed as a continuous variable, a 100-ml increase in fluid balance was independently associated with a 4% increase in the odds of AKI (OR 1.04; 95% CI 1.01-1.08). Positive fluid balance categorized using different thresholds was always significantly associated with subsequent detection of AKI. The mixed effects model showed that increased fluid balance preceded AKI by 4 to 6 days. CONCLUSION: These results suggest that a positive fluid balance might be an early biomarker for AKI development in critically ill patients.

Differential impact of on-site or telepharmacy in the intensive care unit: a controlled before-after study.

BACKGROUND: Clinical pharmacists have an important role in the intensive care unit (ICU) team but are scarce resources. Our aim was to evaluate the impact of on-site pharmacists on medical prescriptions in the ICU. METHODS: This is a retrospective, quasi-experimental, controlled before-after study in two ICUs. Interventions by pharmacists were evaluated in phase 1 (February to November 2016) and phase 2 (February to May 2017) in ICU A (intervention) and ICU B (control). In phase 1, both ICUs had a telepharmacy service in which medical prescriptions were evaluated and interventions were made remotely. In phase 2, an on-site pharmacist was implemented in ICU A, but not in ICU B. We compared the number of interventions that were accepted in phase 1 versus phase 2. RESULTS: During the study period, 8797/9603 (91.6%) prescriptions were evaluated, and 935 (10.6%) needed intervention. In phase 2, there was an increase in the proportion of interventions that were accepted by the physician in comparison to phase 1 (93.9% versus 76.8%, P < 0.001) in ICU A, but there was no change in ICU B (75.2% versus 73.9%, P = 0.845). CONCLUSION: An on-site pharmacist in the ICU was associated with an increase in the proportion of interventions that were accepted by physicians.

Realistic simulation is associated with healthcare professionals' increased self-perception of confidence in providing acute stroke care: a before-after controlled study / Simulação realística é associada a aumento na autopercepção de segurança de profissionais de saúde no atendimento a pacientes com acidente vascular cerebral agudo: um estudo antes-depois controlado

ABSTRACT Background: Simulations are becoming widely used in medical education, but there is little evidence of their effectiveness on neurocritical care. Because acute stroke is a neurological emergency demanding prompt attention, it is a promising candidate for simulation training. Objective: To assess the impact of a stroke realistic simulation course on clinicians' self-perception of confidence in the management of acute stroke. Methods: We conducted a controlled, before-after study. For our intervention, 17 healthcare professionals participated in a stroke realistic simulation course. As controls, participants were chosen from a convenience sample of attendees to the courses Emergency Neurologic Life Support (ENLS) (18 participants) and Neurosonology (20 participants). All participants responded pre- and post-test questionnaires evaluating their self-perception of confidence in acute stroke care, ranging from 10 to 50 points. We evaluated the variation between pre- and post-test results to assess the change on trainees' self-perception of confidence in the management of acute stroke. Multivariate analysis was performed to control for potential confounders. Results: Forty-six (83.63%) subjects completed both questionnaires. The post-test scores were higher than those from the pretests in the stroke realistic simulation course group [pretest median (interquartile range - IQR): 41.5 (36.7-46.5) and post-test median (IQR): 47 (44.7-48); p=0.033], but not in the neurosonology [pretest median (IQR): 46 (44-47) and post-test median (IQR): 46 (44-47); p=0.739] or the ENLS [pretest median (IQR): 46.5 (39-48.2), post-test median (IQR): 47 (40.2-49); p=0.317] groups. Results were maintained after adjustment for covariates. Conclusions: This stroke realistic simulation course was associated with an improvement on trainees' self-perception of confidence in providing acute stroke care.

RESUMO Introdução: Simulações são amplamente utilizadas na educação médica, mas há pouca evidência de sua eficácia no tratamento de pacientes neurocríticos. Como o acidente vascular cerebral agudo (AVC) é uma patologia que requer atendimento imediato, o uso de simulação pode ser uma ferramenta útil no treinamento do manejo desses pacientes. Objetivo: Avaliar o impacto do uso de simulação realística na autopercepção de segurança no atendimento a pacientes vítimas de AVC agudo. Métodos: Estudo antes-depois controlado. No grupo da intervenção, 17 profissionais da área de saúde participaram de um curso de simulação realística de atendimento a pacientes com AVC. Como controles, os participantes foram escolhidos a partir de uma amostra de conveniência composta por 18 participantes do curso Emergency Neurologic Life Support (ENLS) e 20 participantes de um curso de Neurossonologia. Foram respondidos questionários antes e após o curso para avaliar a autopercepção de segurança no atendimento a pacientes vítimas de AVC agudo, variando de 10 a 50 pontos. Foi avaliada a variação entre os resultados pré- e pós-teste, para avaliar a mudança na autopercepção de confiança do trainee no manejo do AVC agudo. Análise multivariada foi realizada para controlar possíveis fatores de confusão. Resultados: Quarenta e seis (83,63%) participantes responderam aos questionários. A pontuação no questionário pós-curso foi maior do que a obtida no questionário pré-curso no grupo de participantes do curso de simulação realística em AVC [mediana do questionário pré-curso: 41,5 (36,7-46,5) e mediana do questionário pós-curso: 47,0 (44,7-48,0); p=0,033]. Essa diferença não foi observada no curso de Neurossonologia [mediana pré-curso (IQR): 46,0 (44,0-47,00), mediana pós-curso (IQR): 46,0 (44,0-47,0); p=0,739] nem no ENLS [mediana pré-curso (IQR): 46,5 (39,0-48,2) mediana pós-curso (IQR): 47,0 (40,2-49,0); p=0,317]. Esses resultados persistiram após ajuste das variáveis. Conclusão: O curso de simulação realística em AVC foi associado a um aumento na autopercepção de segurança dos participantes em atender pacientes vítimas de AVC agudo.

Positive fluid balance as an early biomarker for acute kidney injury: a prospective study in critically ill adult patients

OBJECTIVES: Positive fluid balance is frequent in critically ill patients and has been considered a potential biomarker for acute kidney injury (AKI). This study aimed to evaluate positive fluid balance as a biomarker for the early detection of AKI in critically ill patients. METHODS: This was a prospective cohort study. The sample was composed of patients ≥18 years old who stayed ≥3 days in an intensive care unit. Fluid balance, urinary output and serum creatinine were assessed daily. AKI was diagnosed by the Kidney Disease Improving Global Outcome criteria. RESULTS: The final cohort was composed of 233 patients. AKI occurred in 92 patients (40%) after a median of 3 (2-6) days following ICU admission. When fluid balance was assessed as a continuous variable, a 100-ml increase in fluid balance was independently associated with a 4% increase in the odds of AKI (OR 1.04; 95% CI 1.01-1.08). Positive fluid balance categorized using different thresholds was always significantly associated with subsequent detection of AKI. The mixed effects model showed that increased fluid balance preceded AKI by 4 to 6 days. CONCLUSION: These results suggest that a positive fluid balance might be an early biomarker for AKI development in critically ill patients.