CD8+ T-cell Exhaustion Phenotype in Human Asymptomatic and Ocular Toxoplasmosis.

This work analyzed exhaustion markers in CD8+ T-cell subpopulations in 21 samples of peripheral blood mononuclear cells (PBMCs) from individuals with ocular toxoplasmosis (n = 9), chronic asymptomatic toxoplasmosis (n = 7), and non-infected people (n = 5) by using RT-qPCR and flow cytometry techniques. The study found that gene expression of PD-1 and CD244, but not LAG-3, was higher in individuals with ocular toxoplasmosis versus individuals with asymptomatic infection or uninfected. Expression of PD1 in CD8+ central memory (CM) cells was higher in nine individuals with toxoplasmosis versus five uninfected individuals (p = .003). After ex vivo stimulation, an inverse correlation was found between the exhaustion markers and quantitative clinical characteristics (lesion size, recurrence index, and number of lesions). A total exhaustion phenotype was found in 55.5% (5/9) of individuals with ocular toxoplasmosis. Our results suggest that the CD8+ exhaustion phenotype is involved in the pathogenesis of ocular toxoplasmosis.

Stereoselective synthesis of S-norvaline and related amino acids through a common intermediate.

A divergent, enantioselective synthetic strategy is reported to produce the non-proteinogenic, biologically active natural amino acids norvaline, 5-hydroxy-4-oxo-L-norvaline, and ɣ-oxonorvaline. These were synthesized in good yields (45-75%) from the common starting material (S)-allylglycine obtained by asymmetric transfer allylation of glycine Schiff base using the Corey catalyst derived from cinchonidine in more than 97% enantiomeric excess.

Differences in Exudates Between Strains of Chlorella sorokiniana Affect the Interaction with the Microalga Growth-Promoting Bacteria Azospirillum brasilense : Differences in Exudates Between Strains of Chlorella sorokiniana Affect the Interaction with the Microalga Growth-Promoting Bacteria Azospirillum brasilense.

The microalga Chlorella sorokiniana and the microalgae growth-promoting bacteria (MGPB) Azospirillum brasilense have a mutualistic interaction that can begin within the first hours of co-incubation; however, the metabolites participating in this initial interaction are not yet identified. Nuclear magnetic resonance (NMR) was used in the present study to characterize the metabolites exuded by two strains of C. sorokiniana (UTEX 2714 and UTEX 2805) and A. brasilense Cd when grown together in an oligotrophic medium. Lactate and myo-inositol were identified as carbon metabolites exuded by the two strains of C. sorokiniana; however, only the UTEX 2714 strain exuded glycerol as the main carbon compound. In turn, A. brasilense exuded uracil when grown on the exudates of either microalga, and both microalga strains were able to utilize uracil as a nitrogen source. Interestingly, although the total carbohydrate content was higher in exudates from C. sorokiniana UTEX 2805 than from C. sorokiniana UTEX 2714, the growth of A. brasilense was greater in the exudates from the UTEX 2714 strain. These results highlight the fact that in the exuded carbon compounds differ between strains of the same species of microalgae and suggest that the type, rather than the quantity, of carbon source is more important for sustaining the growth of the partner bacteria.

Synthesis, characterization and evaluation of prenylated chalcones ethers as promising antileishmanial compounds.

Drug therapy for leishmaniasis remains a major challenge as currently available drugs have limited efficacy, induce serious side-effects and are not accessible to everyone. Thus, the discovery of affordable drugs is urgently needed. Chalcones present a great potential as bioactive agents due to simple structure and functionalization capacity. The antileishmanial activity of different natural and synthetic chalcones have been reported. Here we report the synthesis of twenty-five novel prenylated chalcones that displayed antiparasitic activity in Leishmania mexicana. All the chalcones were evaluated at 5 µg/mL and eleven compounds exhibited a metabolic inhibition close to or exceeding 50%. Compounds 49, 30 and 55 were the three most active with IC50 values < 10 µM. These chalcones also showed the highest selectivity index (SI) values. Interestingly 49 and 55 possessing a substituent at a meta position in the B ring suggests that the substitution pattern influences antileishmanial activity. Additionally, a tridimensional model of fumarate reductase of L. mexicana was obtained by homology modeling. Docking studies suggest that prenylated chalcones could modulate fumarate reductase activity by binding with good affinity to two binding sites that are critical for the target. In conclusion, the novel prenylated chalcones could be considered as promising antileishmanial agents.

Alteraciones cardiacas y desaturación en pacientes con ventilación mecánica invasiva con sedación intravenosa continua vs interrupción diaria de sedación / Cardiac events and desaturation in patients under invasive mechanical ventilation with continuous intravenous sedation vs daily interruption of sedation / Desordens cardíacas e dessaturação em pacientes com ventilação mecânica invasiva com sedação intravenosa contínua vs interrupção diária da sedação

Resumen: Introducción: la sedación en pacientes críticos que requieren ventilación mecánica es un punto importante para brindarles seguridad y comodidad. En la actualidad el tratamiento del paciente crítico basado en la escala ABCDEF (A [assess]: valorar, prevenir y manejar el dolor. B [both]: protocolos de interrupción diaria de sedación y protocolo de respiración espontánea. C [choice]: elección de analgesia y sedación. D [delirium]: valorar, prevenir y manejar el delirio. E [early]: ejercicio y movilidad temprana. F [family]: inclusión y habilitación familiar) recomienda la interrupción diaria de la sedación y un protocolo diario de respiración espontánea, el cual ha demostrado mejoría en los resultados clínicos (días en ventilación mecánica, delirio). Éste contrasta con el manejo frecuente de sedación intravenosa continua, por lo que en este estudio se comparó la seguridad de estas dos formas de sedación (interrupción diaria versus intravenosa continua). Objetivo: comparar la incidencia de eventos cardiovasculares y desaturación entre un protocolo de interrupción diaria de sedación en pacientes con ventilación mecánica invasiva (VMI) contra sedación intravenosa continua en pacientes con ventilación mecánica invasiva. Material y métodos: tipo de estudio descriptivo comparativo, retrospectivo. Resultados: no se demostró una diferencia estadísticamente significativa en incidencia de eventos cardiacos y desaturación entre pacientes con sedación intravenosa continua y protocolo de interrupción diaria de sedación. Conclusión: la sedación intravenosa continua y el protocolo de interrupción diaria de sedación son igual de seguras en pacientes bajo VMI.

Abstract: Introduction: sedation in the critically patient requiring mechanical ventilation is an important intervention used to provide safety and comfort to the patient. Currently, the management of critically ill patients is based on the ABCDEF bundle (A [assess]: prevent and manage pain. B [both]: protocols for daily interruption of sedation and spontaneous breathing protocol. C [choice]: of analgesia and sedation. D [delirium]: assess, prevent and manage delirium. E [early]: exercise and early mobility. F [family]: inclusion and empowerment) which recommends daily interruption of sedation and a daily spontaneous breathing protocol, it has shown improvement in clinical outcomes (days on mechanical ventilation, delirium). This contrasts with the frequent management of continuous intravenous sedation. Therefore, in this study the safety of these two forms of sedation (daily interruption vs continuous intravenous) will be compared. Objective: to compare the incidence of cardiovascular events and desaturation between a protocol of daily interruption of sedation in patients with invasive mechanical ventilation versus continuous intravenous sedation in patients with invasive mechanical ventilation. Material and methods: retrospective comparative descriptive study. Results: there was no statistically significant difference in the incidence of cardiac events and desaturation between patients with continuous intravenous sedation and daily sedation interruption protocol. Conclusion: continuous intravenous sedation and daily interruption of sedation protocol are equally safe in critically ill patients.

Resumo: Introdução: a sedação em pacientes críticos que necessitam de ventilação mecânica é um ponto importante para proporcionar segurança e conforto ao paciente. Atualmente, o tratamento de pacientes críticos é baseado na escala ABCDEF (A [assess]: avaliar, prevenir e controlar a dor. B [both]: protocolos de interrupção diária da sedação e protocolo de respiração espontânea. C [choice]: escolha da analgesia e sedação. D [delirium]: avaliar, prevenir e controlar delirium. E [early]: exercício e mobilidade precoce. F [family]: inclusão e qualificação da família) recomenda interrupção diária da sedação e protocolo diário de respiração espontânea, que tem mostrado melhora nos desfechos clínicos (dias em ventilação mecânica, delirium). Isso contrasta com o manejo frequente da sedação intravenosa contínua. Portanto, neste estudo foi comparada a segurança dessas duas formas de sedação (interrupção diária vs intravenosa contínua). Objetivo: comparar a incidência de eventos cardiovasculares e dessaturação entre um protocolo diário de interrupção da sedação em pacientes com ventilação mecânica invasiva versus sedação intravenosa contínua em pacientes com ventilação mecânica invasiva. Material e métodos: tipo de estudo comparativo descritivo, retrospectivo. Resultados: não houve diferença estatisticamente significativa na incidência de eventos cardíacos e dessaturação entre pacientes com sedação intravenosa contínua e protocolo de interrupção diária da sedação. Conclusão: a sedação intravenosa contínua e o protocolo diário de interrupção da sedação são igualmente seguros em pacientes submetidos à ventilação mecânica invasiva.

Características tromboelastográficas en pacientes con SARS-CoV-2: reporte de casos / Thromboelastographic characteristics in patients with SARS-CoV-2: case report / Características tromboelatográficas em pacientes com SARS-CoV-2: relatos de casos

Resumen: La frecuencia de eventos tromboembólicos de pacientes con enfermedad por coronavirus es alta, sin embargo aún se desconoce cuál es la manera adecuada de identificar a las personas con mayor riesgo de complicaciones trombóticas y definir quiénes pueden beneficiarse de un tratamiento más agresivo, más allá de la tromboprofilaxis estándar. Una gran proporción de pacientes en estado crítico con coronavirus tienen perfil de tromboelastografía hipercoagulable con daño relacionado a fibrinógeno y a la función plaquetaria, la mayoría de pacientes tiene una máxima amplitud elevada en la tromboelastografía. Se hizo una revisión de tromboelastogramas de 11 pacientes en estado crítico por SARS-CoV-2 para caracterizar su estado de coagulación. Se encontró 36.36% de hipercoagulabilidad en la tromboelastografía principalmente con citrato nativo a pesar del tratamiento con heparina de bajo peso molecular a dosis terapéutica. El perfil predominante hipercoagulable no se asoció a la función plaquetaria, ya que la MA (máxima amplitud) se mantuvo dentro de los límites normales.

Abstract: The frequency of thromboembolic events in patients with coronavirus disease is high, however it is still unknown what is the appropriate way to identify people at higher risk of thrombotic complications and define who can benefit from a more aggressive treatment, beyond the standard thromboprophylaxis. A large proportion of critically ill patients with coronavirus have a hypercoagulable thromboelastography profile with damage related to fibrinogen and platelet function; most patients have a high maximum amplitude on thromboelastography. A review of thromboelastograms of 11 critically ill patients due to SARS-CoV-2 was made to characterize their coagulation status. A 36.36% hypercoagulability was found in thromboelastography, mainly with native citrate, despite treatment with low molecular weight heparin at therapeutic doses. The predominant hypercoagulable profile was not associated with platelet function since the MA (maximum amplitude) remained within normal limits.

Resumo: A frequência de eventos tromboembólicos em pacientes com doença por coronavírus é alta, no entanto, ainda não se sabe qual é a forma adequada de identificar as pessoas com maior risco de complicações trombóticas e definir quem pode se beneficiar de um tratamento mais agressivo, além da tromboprofilaxia padrão. Uma grande proporção de pacientes críticos com coronavírus apresenta um perfil de tromboelastografia hipercoagulável com danos relacionados ao fibrinogênio e função plaquetária, a maioria dos pacientes apresentam uma amplitude máxima elevada na tromboelastografia. Foi feita uma revisão de tromboelastogramas de 11 pacientes en estado crítico devido a SARS-CoV-2 para caracterizar seu estado de coagulação. Encontrou-se hipercoagulabilidade de 36.36% na tromboelastografia, principalmente com citrato nativo, apesar do tratamento com heparina de baixo peso molecular em dose terapêutica. O perfil predominantemente hipercoagulável não foi associado à função plaquetária, uma vez que a AM (amplitude máxima) permaneceu dentro dos limites da normalidade.

Asociación del signo de Godet con la medición por ultrasonido del edema periférico y balance de líquidos. El resurgir de la clínica / Association of the Godet's sign with ultrasound measurement of peripheral edema and fluid balance. The resurrection of the clinic / Associação do sinal de Godet com medida de ultrassom de edema periférico e equilíbrio hidrográfico. O ressurgimento da clínica

Resumen: Introducción: la administración de líquidos representa una intervención terapéutica de primera línea. Sin embargo, con frecuencia esto conduce a sobrecarga de líquidos, lo que se asocia con alta mortalidad. Objetivo: describir la asociación del edema periférico medido por ultrasonido con el balance hídrico acumulado diario y comparar su correlación con el signo de Godet. Material y métodos: pacientes adultos que ingresaron a la unidad de terapia intensiva (UTI) con más de 24 h de estancia y datos clínicos de sobrecarga hídrica. Diseño: es un estudio observacional, prospectivo, longitudinal, simple ciego, piloto. Cálculo de muestra n = 72 pacientes. Resultados: la mediana de edad fue de 45 años, 96.6% estuvo con ventilación mecánica, todos los pacientes presentaron desenlace en el análisis multivariado ajustado y se detectó que hay asociación del signo de Godet con la medición del edema por ultrasonido, observando una fuerte correlación explicada por una R2 87% p = 0.0001. Por último, se realizó otra regresión de los mililitros del balance hídrico acumulado asociada con los milímetros del edema medidos por ultrasonido, encontrando una R2 82% (IC 95% 1.47-3.70 p = 0.0001) interpretado como una fuerte asociación. Conclusiones: el signo de Godet se asoció fuertemente con los milímetros del edema medido por ultrasonido, además tiene una fuerte asociación entre el balance de líquido acumulado por día con los milímetros de edema que se incrementan en el tejido periférico por sobrecarga al día.

Abstract: Introduction: the administration of fluids represents a first-line therapeutic intervention. However, this often leads to fluid overload, which is associated with high mortality. Objective: to describe the association of peripheral edema measured by ultrasound with daily accumulated water balance and to compare its correlation with Godet's sign. Material and methods: adult patients admitted to the intensive care unit with more than 24 hours of stay and clinical data of fluid overload. Design: this is an observational, prospective, longitudinal, single-blind, pilot study. Sample calculation n = 72 patients. Results: the median age was 45 years, 96.6% were on mechanical ventilation, all patients presented their outcome in the adjusted multivariate analysis, and it was found that there is an association of Godet's sign with the measurement of edema by ultrasound, finding a strong correlation explained by an R2 87% p = 0.0001. Finally, another regression of milliliters of accumulated water balance associated with milliliters of edema measured by ultrasound was performed, finding an R2 82% (95% CI 1.47-3.70 p = 0.0001) interpreted as a strong association. Conclusions: Godet's sign was strongly associated with the millimeters of edema measured by ultrasound; it also has a strong association between the balance of fluid accumulated per day with the millimeters of edema that increase in the peripheral tissue due to overload per day.

Resumo: Introdução: a administração de fluidos representa uma intervenção terapêutica de primeira linha. No entanto, isso freqüentemente leva à sobrecarga hidríca, que está associada a alta mortalidade. Objetivo: descrever a associação do edema periférico medido pela ultrassonografia com o balanço hídrico diário acumulado e comparar sua correlação com o sinal de Godet. Material e métodos: pacientes adultos admitidos na unidade de terapia intensiva (UTI) com mais de 24 horas de internação e com quadro clínico de sobrecarga hídrica. Desenho: é um estudo observacional, prospectivo, longitudinal, simples-cego, piloto. Cálculo amostra n = 72 pacientes. Resultados: a idade média foi de 45 anos, 96.6% estavam em ventilação mecânica, todos os pacientes apresentaram seu desfecho na análise multivariada ajustada e constatou-se que há associação do sinal de Godet com a medida do edema pela ultrassonografia, encontrando forte correlação explicado por um R2 87% p = 0.0001. Finalmente, realizou-se outra regressão dos mililitros de balanço hídrico acumulado associado aos milímetros de edema medidos por ultrassom, encontrando um R2 82% (IC 95% 1.47-3.70 p = 0.0001) interpretado como uma forte associação. Conclusões: o sinal de Godet foi fortemente associado com os milímetros de edema medidos por ultrassom, também tem forte associação entre o balanço hídrico acumulado por dia com os milímetros de edema que aumentam nos tecidos periféricos devido à sobrecarga por dia.

Boerhaave syndrome. Case report and literature review.

Spontaneous lesions can affect only a part of the esophageal wall (Mallory-Weiss syndrome) or constitute a full-thickness rupture of the organ, leading to Boerhaave syndrome. Most commonly affecting males between 50 and 70 years of age, Clinically, the Mackler triad is vomiting, severe chest pain, and subcutaneous cervical emphysema. The delay in diagnosis explains the high mortality rate of this pathology up to 40-60% in those treated at 48 hours. The prognosis improves if treatment is established within the first 24 hours.

Las lesiones espontáneas pueden afectar solo una parte de la pared esofágica (síndrome de Mallory-Weiss) o constituir una rotura de espesor total del órgano, dando lugar al síndrome de Boerhaave. Afecta con mayor frecuencia a los varones entre 50 y 70 años de edad. Clínicamente conforma la tríada de Mackler: vómito, dolor torácico intenso y enfisema subcutáneo cervical. El retraso en el diagnóstico explica su alta tasa de mortalidad, de hasta el 40-60% en los pacientes tratados a las 48 horas. El pronóstico mejora si se logra instaurar el tratamiento dentro de las primeras 24 horas.

Perfil tromboelastográfico en pacientes con neumonía por SARS-CoV-2 / Thromboelastographic profile in patients with SARS-CoV-2 pneumonia / Perfil da tromboelastografia em pacientes com pneumonia por SARS-CoV-2

Resumen: Introducción: La enfermedad por coronavirus 2019 (COVID-19) es una enfermedad viral causada por el síndrome agudo respiratorio severo coronavirus 2 (SARS-CoV-2). El riesgo de eventos trombóticos venosos (ETV), que aumenta en pacientes críticamente enfermos, probablemente sea aún mayor en aquéllos con SARS-CoV-2 y enfermedad crítica. Objetivos: Investigar el perfil hemostático mediante tromboelastograma (TEG) en pacientes con neumonía por COVID-19. Material y métodos: Estudio observacional, retrospectivo de un solo centro hospitalario. Se inscribieron retrospectivamente pacientes hospitalizados con diagnóstico de neumonía por COVID-19, se les realizó TEG a las 24 y 72 horas. Se realizó un análisis bivariado, para las variables cuantitativas continuas y discretas se emplearon las pruebas t de Student o U de Mann-Whitney. Para las variables categóricas y nominales se empleó la prueba de χ2 de Pearson. Además, se realizó una curva ROC (característica de funcionamiento del receptor) para determinar el punto de corte del índice de masa corporal (IMC) con mayor sensibilidad y especificidad con relación al desarrollo de alteraciones en el TEG. Después se realizó un análisis multivariado de regresión binaria logística, ajustado para las variables con significancia clínica y estadística. La significancia estadística se estableció como una p < 0.05 o < 5%. Resultados: Se incluyó un total de 66 pacientes, se observó un predominio del perfil hipercoagulable en 28 pacientes (42.4%) a las 24 horas y 20 (30.3%) a las 72 horas a pesar de dosis profiláctica de enoxaparina. Para determinar el punto de corte con mayor asociación entre el IMC y la presencia de trastorno en el TEG, se realizó una curva ROC, obteniendo un ABC de 64.7% (p = 0.003). Encontramos un odds ratio (OR) 1.8 por cada kilogramo de peso por arriba de un IMC > 26.2 kg/m2, para desarrollar hipercoagulabilidad. Conclusión: El alto porcentaje de pacientes con estado hipercoagulable e hiperfibrinogenemia podría condicionar un aumento de la formación y polimerización de fibrina que puede predisponer a la trombosis. La mayoría de la población en nuestro medio cuenta con sobrepeso u obesidad, por lo que probablemente tengan necesidad de un régimen más alto de anticoagulación. Dicho esquema de tromboprofilaxis no debe ser guiado por parámetros como dímero D, sino con una prueba más amplia del perfil hemostático como el TEG.

Abstract: Introduction: Coronavirus disease 2019 (COVID-19) is a viral disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The risk of venous thrombotic events (VTE), which is increased in critically ill patients, is likely to be even higher in those with SARS-CoV-2 and critical illness. Objectives: To investigate the haemostatic profile by TEG in patients with COVID-19 pneumonia. Material and methods: Observational, retrospective study of a single hospital centre. Patients hospitalised with a diagnosis of COVID-19 pneumonia were retrospectively enrolled and underwent thromboelastogram (TEG) at 24 and 72 hours. Bivariate analysis was performed, in which Student's t-tests or Mann-Whitney U-tests were used for continuous and discrete quantitative variables. For categorical and nominal variables, Pearson's χ2 test was used. In addition, a receiver operating characteristic (ROC) curve was performed to determine the body mass index (BMI) cut-off point with the highest sensitivity and specificity in relation to the development of TEG alterations. Subsequently, a multivariate logistic binary regression analysis was performed, adjusted for variables with clinical and statistical significance. Statistical significance was established as a p < 0.05 or < 5%. Results: A total of 66 patients were included, a predominance of hypercoagulable profile was observed in 28 patients (42.4%) at 24 hours and 20 (30.3%) at 72 hours despite prophylactic doses of enoxaparin. To determine the cut-off point with the strongest association between BMI and the presence of TEG disorder, a ROC curve was performed, yielding an ABC of 64.7% (p = 0.003). We found an odds ratio (OR) of 1.8 for each kilogram of weight above a BMI > 26.2 kg/m2, for developing hypercoagulability. Conclusion: The high percentage of patients with hypercoagulable status and hyperfibrinogenemia could lead to an increase in fibrin formation and polymerisation that may predispose to thrombosis. The majority of the population in our setting is overweight or obese and therefore probably requires a higher anticoagulation regimen. Such a thromboprophylaxis scheme should not be guided by parameters such as dimer D but by a broader haemostatic profile test such as TEG.

Resumo: Introdução: A doença de coronavírus 2019 (COVID-19) é uma doença viral causada pelo coronavírus 2 da síndrome respiratória aguda grave (SARS-CoV-2). O risco de eventos trombóticos venosos (ETV), que é aumentado em pacientes críticos, provavelmente será ainda maior naqueles com SARS-CoV-2 e doença crítica. Objetivos: Investigar o perfil hemostático por TEG em pacientes com pneumonia por COVID-19. Material e métodos: Estudo observacional retrospectivo de um único centro hospitalar. Pacientes hospitalizados diagnosticados com pneumonia por COVID-19 foram incluídos retrospectivamente, tromboelastograma (TEG) foi realizado em 24 e 72 horas. Realizou-se análise bivariada, para variáveis ​​quantitativas contínuas e discretas, foram utilizados os testes t de Student ou U de Mann-Whitney. Para variáveis ​​categóricas e nominais, foi utilizado o teste χ2 de Pearson. Além disso, foi realizada uma curva ROC (receiver operating characteristic) para determinar o ponto de corte do índice de massa corporal (IMC) com maior sensibilidade e especificidade em relação ao desenvolvimento de alterações do TEG. Posteriormente, realizou-se análise de regressão binária logística multivariada, ajustada para as variáveis ​​com significância clínica e estatística. A significância estatística foi estabelecida como p < 0.05 ou < 5%. Resultados: Foram incluídos 66 pacientes, sendo observado predomínio do perfil hipercoagulável em 28 pacientes (42.4%) em 24 horas e 20 (30.3%) em 72 horas apesar da dose profilática de enoxaparina. Para determinar o ponto de corte com maior associação entre o IMC e a presença de alteração no TEG, foi realizada uma curva ROC, obtendo-se uma AUC de 64.7% (p = 0.003). Encontramos um Odds Ratio (OR) de 1.8 para cada quilograma de peso acima de um IMC > 26.2 kg/m2, para desenvolver hipercoagulabilidade. Conclusão: O alto percentual de pacientes com estado de hipercoagulabilidade e hiperfibrinogenemia pode condicionar um aumento na formação e polimerização de fibrina que pode predispor à trombose. A maioria da população em nosso meio está acima do peso ou obesa, então eles provavelmente precisam de um regime de anticoagulação mais alto. Esse esquema de tromboprofilaxia não deve ser guiado por parâmetros como o D-dímero, mas sim com um teste mais amplo do perfil hemostático como o TEG.

Predicción de fracaso de las puntas nasales de alto flujo con la escala HACOR, en la insuficiencia respiratoria aguda de pacientes con SARS-CoV-2 / Prediction of failure of the high-flow nasal tips with the HACOR scale, in acute respiratory insufficiency in patients with SARS-CoV-2 / Previsão de falha das pontas nasais de alto fluxo com a escala HACOR, na insuficiência respiratória aguda de pacientes com SARS-CoV-2

Resumen: La insuficiencia respiratoria hipoxémica aguda (IRHA) es una de las principales causas de ingreso en la Unidad de Terapia Intensiva en los pacientes adultos, alrededor de 40% de estos pacientes ameritan intubación endotraqueal. La escala HACOR fue diseñada y validada como una puntuación de predicción clínica para el fracaso de la ventilación no invasiva (VNI) en pacientes con IRHA de diferentes etiologías. Objetivo: Analizar la capacidad predictiva de la escala HACOR en relación al fracaso de las puntas nasales de alto flujo (PNAF). Material y métodos: Se realizó un estudio retrospectivo, observacional en la Terapia Intensiva del Hospital Ángeles Mocel, las PNAF se iniciaron cuando el paciente presentaba IRHA, se calculó la escala HACOR a la hora y a las dos horas de colocación de PNAF, la capacidad de predecir el fracaso de las PNAF de la escala HACOR se determinó calculando el área bajo la curva de «característica operativa del receptor¼ (ROC). Resultados: La escala HACOR con mayor poder discriminatorio se obtuvo a las dos horas de inicio de las PNAF con un punto de corte de 5 puntos con un área bajo la curva (AUC): 0.82 (IC 95% 0.67-0.98), se obtuvo una sensibilidad 84% IC 95% (56.6-89.9%), especificidad 81% IC 95% (40.9-92.9%). Conclusiones: Un puntaje mayor o igual a 5 puntos en la escala HACOR predice fracaso de las PNAF y mayor mortalidad con una sensibilidad y especificidad mayor de 80% en los pacientes con neumonía por COVID-19.

Abstract: Acute hypoxemic respiratory failure (AHRF) is one of the main causes of admission to the intensive care unit in adult patients, around 40% of these patients require endotracheal intubation. The HACOR scale was designed and validated as a clinical prediction score for non-invasive ventilation (NIV) failure in patients with HAI of different etiologies. Objective: To analyze the predictive capacity of the HACOR scale in relation to the failure of the PNAF. Material and methods: A retrospective, observational study was carried out in the Intensive Care Unit at Hospital Ángeles Mocel, the PNAF was started when the patient had AHRF, the HACOR scale was calculated at one hour and 2 hours after the placement of the PNAF, the ability to predict HACOR scale PNAF failure was determined by calculating the area under the «receiver operating characteristic¼ (ROC) curve. Results: The HACOR scale with the highest discriminatory power was obtained 2 hours after the start of the PNAF with a cut-off point of 5 points with an area under the curve (AUC): 0.82 (CI 95% 0.67-0.98), it was obtained a sensitivity 84% CI 95% (56.6-89.9%), specificity 81% CI 95% (40.9-92.9%). Conclusions: A score greater than or equal to 5 points on the HACOR scale predicts failure of the PNAF and higher mortality with a sensitivity and specificity greater than 80% in patients with COVID-19 pneumonia.

Resumo: A insuficiência respiratória hipoxêmica aguda (IRHA) é uma das principais causas de admissão em unidade de Terapia Intensiva em Pacientes Adultos, cerca de 40% desses pacientes requerem intubação endotraqueal. A escala HACOR foi desenhada e validada como um escore de predição clínica para falha da ventilação não invasiva (VNI) em pacientes com IRHA de diferentes etiologias. Objetivo: Analisar a capacidade preditiva da escala HACOR em relação à falha das PNAF. Material e métodos: Foi realizado um estudo retrospectivo e observacional na Unidade de Terapia Intensiva do Hospital Ángeles Mocel, a PNAF foi iniciada quando o paciente tinha IRHA, a escala HACOR foi calculada uma hora e 2 horas após a colocação da PNAF, a capacidade de previsão do fracasso das PNAF da escala HACOR foi determinada pelo cálculo da área sob a curva «receiver operating characteristics¼ (ROC). Resultados: A escala HACOR com maior poder discriminatório foi obtida 2 horas após o início das PNAF com ponto de corte de 5 pontos com área sob a curva (AUC): 0.82 (IC 95% 0.67-0.98), foi obtida uma sensibilidade de 84% IC 95% (56.6%-89.9%), especificidade 81% IC 95% (40.9%-92.9%). Conclusões: Uma pontuação maior ou igual a 5 pontos na escala HACOR prediz falha das PNAF e maior mortalidade com sensibilidade e especificidade maior à 80% em pacientes com pneumonia COVID-19.

Human peripheral blood mononuclear cells as an ex vivo model to study the host parasite interaction in Toxoplasma gondii.

Toxoplasma gondii is a parasite that can invade any cell in the human body. Here, we implemented and described an ex vivo model with human peripheral blood mononuclear cells (PBMCs) without using culture supplements/antibiotics and without cryopreserved cells (EXMOWS) to study the interactions between T. gondii and human cells. To establish the EXMOWS, three independent tests were carried out. Firstly, blood samples from 5 individuals were included to assess the viability and adherence of PBMCs in plate culture. In a second trial, blood samples from three seropositive and two seronegative individuals for T. gondii were used to evaluate human PBMCs cells: parasites, multiplicity of infection (MOI) 1:1, 1:3 and 1:5 at different times post infection (1 h, 6 h and 24 h). The possible immunomodulatory effect of the infection for this EXMOWS were evaluated in a third trial where HFF cells were infected with T. gondii and co-cultured with PBMCs obtained from anti-Toxoplasma IgG positive and IgG negative individuals. One hour was enough time for T. gondii infection of human PBMCs and 2 h was the minimum incubation time to guarantee adherence before carrying out any infection assay. A minimum of 1:3 MOI was necessary to guarantee efficient infection in human PBMCs with T. gondii RH-GFP. All protocols, including PBMCs isolation and stimulation, should be conducted the same day. This EXMOWS can be adapted to study the early stages of interaction with other microorganisms of human interest, without need of using cryopreservation and supplements/antibiotics.

Highly selective Diels-Alder and Heck arylation reactions in a divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles from 2-formylpyrrole.

A highly regio-, chemo- and stereoselective divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles is herein described, starting from 2-formylpyrrole and employing Diels-Alder and Heck arylation reactions. 3-(N-Benzyl-2-pyrrolyl)acrylates and 4-(pyrrol-2-yl)butenones underwent a highly endo-Diels-Alder cycloaddition with maleimides to furnish octahydropyrrolo[3,4-e]indoles, which served as precursors in the regioselective synthesis of aza-polycyclic skeletons via an intramolecular Heck arylation reaction. Through the latter reaction, the 3-(N-benzyl-2-pyrrolyl)acrylates give rise to 3-(pyrrolo[2,1-a]isoindol-3-yl)acrylates. A further oxidative aromatization of the polycyclic intermediates provides the corresponding polycyclic pyrrolo-isoindoles and isoindolo-pyrrolo-indoles. A theoretical study on the stereoselective Diels-Alder reactions, carried out by calculating the endo/exo transition states, revealed the assistance of non-covalent interactions in governing the endo stereocontrol.

Novel prenyloxy chalcones as potential leishmanicidal and trypanocidal agents: Design, synthesis and evaluation.

The available drugs for treating Leishmaniasis and American trypanosomiasis have high toxicity and multiple side effects, among other problems. More effective and less toxic treatments are urgently needed. A series of chalcones that contained a prenyloxy or geranyloxy substituent was synthesized and characterized. Each substituent was attached to the A ring in some compounds and to the B ring in others, with additional substituents placed on the chalcone moiety. The present aim was to evaluate the effect of the substitution pattern on leishmanicidal and trypanocidal activity. When tested at a single concentration, the compounds exerting a metabolic inhibition close to or exceeding 50% for Leishmania mexicana were 11, 17 and 12, and for Trypanosoma cruzi were 11, 17, 15 and 26. Upon determining the selectivity index (SI =IC50/CC50), the values were 80.9, 1.24 and 55.12 for 11, 17 and 12 (respectively) versus L. mexicana, and 75.1, 1.43, 27.36 and 33.52 for 11, 17, 15 and 26 (respectively) versus T. cruzi. Structural isomers 11 and 17 showed activity for both the L. mexicana and T. cruzi strains, though the greater cytotoxic activity of 17 led to a lower SI. Compounds 12, 15 and 26 were species specific. For T. cruzi, the SI was higher for 11, 15 and 26 than for the reference drugs nifurtimox and benznidazole. The examination of promastigote morphology after exposing L. mexicana and T. cruzi to 11 revealed a decrease in cell density. The current findings suggest that 11 could be a useful lead compound for further SAR studies.

Synthesis of exo-Imidazolidin-2-one Dienes, Their Isomerization, and Selectivity in Diels-Alder Cycloadditions.

An efficient and alternative synthesis of exo-imidazolidin-2-one dienes is described. A condensation reaction was carried out with bis-imino derivatives, diacetyl, and triphosgene, affording symmetrically N, N-disubstituted dienes. The use of alkyl methyl α-diketones led to the formation of nonsymmetrical dienes, which underwent isomerization to provide more stable inner-outer-ring dienes under Lewis acid conditions. Evaluation was made of the reactivity as well as regio- and stereoselectivity of these dienes in Diels-Alder reactions. They proved to be highly reactive and selective. DFT calculations of the transition states accounted for their behavior.

Lipase catalyzed epoxidation of fatty acid methyl esters derived from unsaturated vegetable oils in absence of carboxylic acid.

Nowadays the industrial chemistry reactions rely on green technologies. Enzymes as lipases are increasing its use in diverse chemical processes. Epoxidized fatty acid methyl esters obtained from transesterification of vegetable oils have recently found applications as polymer plasticizer, agrochemical, cosmetics, pharmaceuticals and food additives. In this research article, grapeseed, avocado and olive oils naturally containing high percents of mono and poly unsaturations were used as starting materials for the production of unsaturated fatty acid methyl esters. The effect of lauric acid as an active oxygen carrier was studied on epoxidation reactions where unsaturated fatty acid methyl esters were converted to epoxy fatty acid methyl esters using immobilized Candida antarctica Lipase type B as catalyst and hydrogen peroxide as oxygen donor at mild temperature and pressure conditions. After this study it was confirmed by 1H NMR, 13C NMR and GC-MS that the addition of lauric acid to the enzymatic reaction is unnecessary to transform the alkenes in to epoxides. It was found that quantitative conversions were possible in despite of a carboxylic acid absence.

Effect of Laccase-Mediated Biopolymer Grafting on Kraft Pulp Fibers for Enhancing Paper's Mechanical Properties.

High-resistance paper was manufactured by laccase-grafting of carboxymethyl cellulose (CMC) and chitosan (CPX) on Kraft pulp fiber. The reaction was mediated in the presence of laccase by one of the following polyphenols in the presence of air: gallic acid (GA), vanillic acid (VA) and catechol (1,2⁻DHB). Enzyme was added at constant loading (24 kg ton-1), 1% pulp consistency, 0.005% CMC, pH = 6.3 ± 0.5 and 2 mM of mediator. CPX content was assessed at two levels (0% and 0.005%). Treated pulps were analyzed by different mechanical tests (ring crush, mullen, corrugating medium test (CMT) flat crush of corrugating medium test and tension). An improvement in these parameters was obtained by biopolymer coupling and selected mediator. When using GA, three parameters increased more than 40%, while ring crush increased 120%. For the case of VA, properties were enhanced from 74% to 88% when CPX was added. For 1,2⁻DHB, there was not found a statistically significant difference between the results in the presence of CPX. Scanning electron microscopy, confocal microscopy, FTIR and 13C NMR were used in all papers in order to evaluate grafting. Hence, it was possible to correlate polymerization with an improvement of paper's mechanical properties.

Uncovering the lipidic basis for the preparation of functional nicotinic acetylcholine receptor detergent complexes for structural studies.

This study compares the lipid composition, including individual phospholipid molecular species of solubilized nAChR detergent complexes (nAChR-DCs) with those of the bulk lipids from their source, Torpedo californica (Tc) electric tissue. This lipidomic analysis revealed seventy-seven (77) phospholipid species in the Tc tissue. Analysis of affinity-purified nAChR-DCs prepared with C-12 to C-16 phospholipid analog detergents alkylphosphocholine (FC) and lysofoscholine (LFC) demonstrated that nAChR-DCs prepared with FC12, LFC14, and LFC16 contained >60 phospholipids/nAChR, which was more than twice of those prepared with FC14, FC16, and LFC12. Significantly, all the nAChR-DCs lacked ethanolamine and anionic phospholipids, contained only four cholesterol molecules, and a limited number of phospholipid molecular species per nAChR. Upon incorporation into oocytes, FC12 produce significant functionality, whereas LFC14 and LFC16 nAChR-DCs displayed an increased functionality as compared to the crude Tc membrane. All three nAChR-DCs displayed different degrees of alterations in macroscopic activation and desensitization kinetics.

Sustainable application of pecan nutshell waste: Greener synthesis of Pd-based nanocatalysts for electro-oxidation of methanol.

Palladium-based electrocatalysts are widely used in alkaline direct alcohol fuel cells. The synthesis and characterization of carbon-supported bimetallic nanoparticles (NP) of AuPd and AgPd is described using pecan nutshell extract (Carya illinoinensis) which serves as both, reducing and the stabilizing agent. This environmentally friendly route generates bimetallic NP for a wide range of applications, including electrocatalysis; since particularly AuPd NP proved to be a potentially suitable electrode material for alkaline direct methanol fuel cells. The electrocatalytic activity of these nanomaterials was comparable to commercially available Pd/C 1% in the electro-oxidation of methanol in alkaline media.

Chemoenzymatic Kinetic resolution of (R)-malathion in aqueous media.

BACKGROUND: Malathion (R,S)-diethyl-2-[(dimethoxyphosphorothioyl)sulfanyl]butanedioate is a chiral organophosphorus compound used widely as pesticide for suppression of harmful insects such as mosquitoes. It is well known that in biological systems (R)-malathion is the active enantiomer, therefore a sustainable approach could be the use of only the biologically active enantiomer. The resolution of the commercial racemic mixture to obtain the pure active enantiomer combined with a recycling of the undesired enantiomer through a racemization process could be an attractive alternative to reduce the environmental impact of this pesticide. Thus, this work evaluates the use of four commercially available lipases for enantioselective hydrolysis and separation of malathion enantiomers from the commercial racemic mixture. RESULTS: Several lipases were methodologically assessed, considering parameters such as enzyme concentration, temperature and reaction rates. Among them, Candida rugosa lipase exhibited the best performance, in terms of enantioselectivity, E = 185 (selective to the (S)-enantiomer). In this way, the desired unreacted (R)-enantiomer was recovered in a 49.42 % yield with an enantiomeric excess of 87 %. The monohydrolized (S)-enantiomer was recovered and racemized in basic media, followed by esterification to obtain the racemic malathion, which was recycled. In this way, an enantioenriched mixture of (R)-malathion was obtained with a conversion of 65.80 % considering the recycled (S)-enantiomer. CONCLUSION: This work demonstrated the feasibility of exploiting Candida rugosa lipase to kinetically resolve racemic malathion through an environmentally friendly recycling of the undesired (S)-enantiomer. Graphical AbstractLipase catalyzed enantioselective resolution of (R)-malathion in aqueous solvent.

Synthesis of a Functionalized Benzofuran as a Synthon for Salvianolic Acid C Analogues as Potential LDL Antioxidants.

A palladium mediated synthesis of a common synthon for the syntheses of antioxidant analogues of naturally occurring salvianolic acids is presented. The synthetic route may be used to obtain analogues with a balanced lipophilicity/hydrophilicity which may result in potentially interesting LDL antioxidants for the prevention of cardiovascular diseases.