Bio-guided isolation of a new sesquiterpene from Artemisia cina with anthelmintic activity against Haemonchus contortus L3 infective larvae.

Haemonchus contortus is a blood-feeding gastrointestinal parasite that impacts grazing sheep, causing economic losses in animal production. Due to its anthelmintic resistance, alternative antiparasitic treatments like plant-based anthelmintics are necessary to explore. Artemisia cina (Asteraceae) is a plant whose n-hexane extract and ethyl acetate extract exhibit anthelmintic activity against H. contortus, the n-hexane more active. To discover additional bioactive metabolites, a chemical analysis was performed on ethyl acetate extract, which presented an LC90 of 3.30 mg/mL and allowed the isolation of 11-[(1R,5S,7R,8R,10S,)-1,8-dihydroxy-5,10-dimethyl-4-oxodecahydroazulen-7-yl] acrylic acid. This new sesquiterpene was identified through one and two-dimensional NMR. The compound was named cinic acid and displayed an LC50 of 0.13 (0.11-0.14) mg/mL and LC90 of 0.40 (0.37-0.44) mg/mL, which, compared with ethyl acetate extract larvicidal activity, was 256-fold more active at LC50 and 15.71-fold at LC90. In this study, a new sesquiterpene with larvicidal activity against H. contortus L3 infective larvae was isolated from the ethyl acetate extract of Artemisia cina.

Understanding Artemisia cina Ethyl Acetate Extract's Anthelmintic Effect on Haemonchus contortus Eggs and L3 Larvae: The Synergism of Peruvin Binary Mixtures.

Haemonchus contortus, a blood-feeding parasite in grazing sheep, causes economic losses. Drug resistance necessitates exploring plant-based anthelmintics like Artemisia cina (Asteraceae). The plant, particularly its ethyl acetate extract, shows anthelmintic activity against H. contortus. However, there is limited information on pharmacodynamic interactions in ethyl acetate compounds. The study aims to identify pharmacodynamic interactions in the ethyl acetate extract of A. cina with anthelmintic effects on H. contortus eggs and L3 larvae using binary mixtures. Bioactive compounds were isolated via chromatography and identified using spectroscopic techniques. Pharmacodynamic interactions were assessed through binary mixtures with a main compound. Four bioactive compounds were identified: 1-nonacosanol, hentriacontane, peruvin, and cinic acid. Binary mixtures, with peruvin as the main compound, were performed. Peruvin/1-nonacosanol-hentriacontane and peruvin/cinic acid mixtures demonstrated 1.42-fold and 4.87-fold increased lethal effects in H. contortus L3 infective larvae, respectively, at a 0.50LC25/0.50LC25 concentration. In this work, we determined the synergism between bioactive compounds isolated from the ethyl acetate extract of A. cina and identified unreported compounds for the specie.

Biochemical parameters, oxidative stress biomarkers, and anatomopathological changes in Wistar rats treated with 3'-demethoxy-6-O-demethylisoguaiacin and norisoguaiacin.

Artemisia cina (Ac) is a plant with anthelmintic compounds such as 3'-demethoxy-6-O-demethylisoguaiacin (D) and norisoguaiacin (N). Three major objectives were proposed: (1) To evaluate biochemical parameters in blood (2) to determine the tissue oxidative stress by biomarkers as TBARS and glutathione peroxidase activity, and (3) to evaluate anatomopathological changes in organs such as the brain, liver, kidney, and lung after oral administration of n-hexane extract of Ac and D and N. D and N were administrated following the OECD guides for acute oral toxicity evaluation (Guide 420). Fifty Wistar rats were distributed into ten groups as follows: Group 1 (G1): 4 mg/Kg; G2: 40 mg/Kg; G3: 240 mg/Kg; G4: 1600 mg/Kg of n-hexane extract of Ac. G5: 2 mg/Kg; G6: 20 mg/Kg; G7: 120 mg/Kg; G8: 800 mg/Kg of D and N, G9: water and G10: polyvinylpyrrolidone at 2000 mg/Kg. At 14 days, the rats were euthanized, and the blood, liver, brain, kidney, and lung were taken for biochemical analysis, anatomopathological changes, and TBARS and GSH evaluation. Glucose, cholesterol, and phosphorus were altered. Histopathological analysis showed multifocal neuronal degeneration in the brain (G2). The kidney and lungs had changes in G7. The GSH and TBARS increased in G6 and G7. The TBARS activity was higher in G1 and G2. In conclusion, extract and D and N of Ac did not have damage at therapeutic doses. D, N, and n-hexane extract of A. cina do not cause histopathological damage at pharmaceutical doses. Still, the brain, kidney, and liver are related to biochemical parameters at higher doses. However, compounds are proposed as antioxidant agents.

Computational Prediction of Amino Acid Preferences of Potentially Multispecific Peptide-Binding Domains Involved in Protein-Protein Interactions.

Many protein-protein interactions involve the binding of short protein segments to peptide-binding domains. Usually, such interactions require the recognition of linear motifs with variable conservation. The combination of highly conserved and more variable regions in the same ligands often contributes to the multispecificity of binding, a common property of enzymes and cell signaling proteins. Characterization of amino acid preferences of peptide-binding domains is important for the design of mediators of protein-protein interactions (PPIs). Computational methods are an efficient alternative to the often costly and cumbersome experimental techniques, enabling the design of potential mediators that can be later validated in downstream experiments. Here, we described a methodology using the Pepspec application of the Rosetta molecular modeling package to predict the amino acid preferences of peptide-binding domains. This methodology is useful when the structure of the receptor protein and the nature of the peptide ligand are both known or can be inferred. The methodology starts with a well-characterized anchor from the ligand, which is extended by randomly adding amino acid residues. The binding affinity of peptides generated this way is then evaluated by flexible-backbone peptide docking in order to select the peptides with the best predicted binding scores. These peptides are then used to calculate amino acid preferences and to optionally compute a position-weight matrix (PWM) that can be used in further studies. To illustrate the application of this methodology, we used the interaction between subunits of human interferon regulatory factor 5 (IRF5), previously known to be multispecific but globally guided by a short conserved motif called pLxIS. The estimated amino acid preferences were consistent with previous knowledge about the IRF5 binding surface. Positions occupied by phosphorylatable serine residues exhibited a high frequency of aspartate and glutamate, likely because their negatively charged side chains are similar to phosphoserine.

Junctions and Superconducting Symmetry in Twisted Bilayer Graphene.

Junctions provide a wealth of information on the symmetry of the order parameter of superconductors. We analyze junctions between a scanning tunneling microscope (STM) tip and superconducting twisted bilayer graphene (TBG) and TBG Josephson junctions (JJs). We compare superconducting phases that are even or odd under valley exchange (s- or f-wave). The critical current in mixed (s and f) JJs strongly depends on the angle between the junction and the lattice. In STM-TBG junctions, due to Andreev reflection, the f-wave leads to a prominent peak in subgap conductance, as seen in experiments.

[Ethiology, risk factors and Whole blood viscosity index in thromboembolic venous disease]. / Etiología, factores de riesgo e Índice de viscosidad sanguíneo total en enfermedad tromboembólica venosa.

Backround: Venous thromboembolic disease (VTED) is a frequent cause of hospitalization and mortality. Whole blood viscosity (WBV) participates in the pathogenesis of thrombosis. Objective: To identify the most frequent etiologies and their association with WBV index (WBVI) in hospitalized patients with VTED. Material and methods: Observational, cross-sectional, retrospective, analytical study, Group 1: cases (patients diagnosed with VTED) and Group 2: controls without thrombosis. Risk factors for VTED were described and WBVI was calculated from total proteins and hematocrit. Descriptive and inferential statistics were used with Chi-squared test, Fisher's exact test, Mann Whitney U test, bivariate and multivariate logistic regression analysis. Results: We included 146 patients and 148 controls, age 46.3 ±17.7 vs. 58 ± 18.2 years, of both sexes (female, 65.1%). The most frequent etiology was neoplastic (23.3%), followed by diseases with cardiovascular risk (17.8%). Independent risk factors for VTED were age, chronic kidney disease, presence of liver disease or solid neoplasia. WBVI was similar in patients with VTED as in those without thrombosis. We found an association of the presence of deep vein thrombosis and diseases with cardiovascular risk (p = 0.040). Conclusions: The presence of chronic kidney disease, liver disease, and solid neoplasia are independent risk factors for VTED. The WBVI is a simple and rapid diagnostic tool in the evaluation of patients with VTED.

Introducción: la enfermedad tromboembólica venosa (ETEV) es causa frecuente de hospitalización y mortalidad. La viscosidad sanguínea participa en la patogénesis de la trombosis. Objetivo: analizar los factores de riesgo y el índice de viscosidad sanguíneo total (IVTS) en pacientes con ETEV. Material y métodos: estudio observacional, transversal, retrospectivo, analítico. Grupo 1: casos (pacientes con diagnóstico de ETEV), y grupo 2: controles sin trombosis. Se describieron los factores de riesgo para ETEV y se calculó el IVTS a partir de proteínas totales y hematocrito. Se utilizó estadística descriptiva e inferencial con prueba de Chi cuadrada, prueba exacta de Fisher, U de Mann Whitney, análisis de regresión logística bivariado y multivariado. Resultados: incluimos 146 pacientes y 148 controles, edad 46.3 ± 17.7 frente a 58 ± 18.2 años, de ambos sexos, femenino (65.1%). La etiología más frecuente fue la neoplásica (23.3%), seguida de la enfermedad con riesgo cardiovascular (17.8%). Los factores de riesgo independientes para ETEV fueron: edad, enfermedad renal crónica, presencia de hepatopatía o neoplasia sólida. El IVTS fue similar en los pacientes con ETEV que en aquellos sin trombosis. Se encontró asociación de la presencia de trombosis venosa profunda y enfermedades con riesgo cardiovascular (p = 0.040). Conclusiones: la presencia de ERC, hepatopatía y neoplasia sólida son factores de riesgo independientes para ETEV. El IVTS es un instrumento diagnóstico sencillo y rápido en la evaluación de los pacientes con ETEV.

Definición de la presión arterial normal a las 11-14 semanas de gestación según riesgo / Definition of normal blood pressure at 11 to 14 weeks' gestation according to risk

Resumen Objetivo: Definir la presión arterial normal en el primer trimestre de la gestación según el desempeño para predecir preeclampsia. Método: Estudio de cohorte en embarazos de feto único, según el modelo de riesgos en competencia para preeclampsia. La presión arterial se midió de manera estandarizada entre las 11 y 14 semanas de gestación. Resultados: En 797 embarazos incluidos hubo 40 (5.0%, intervalo de confianza del 95% [IC 95%]: 3.6-6.4) partos con preeclampsia. Las presiones arteriales sistólica, diastólica y media fueron respectivamente de 101 (9), 68 (8) y 79 (8) mmHg en las embarazadas que no desarrollaron preeclampsia, frente a 109 (10), 75 (8) y 86 (8) mmHg en las que sí (p < 0.001, prueba t de Student). Las áreas bajo la curva fueron 0.707 (0.637-0.777), 0.728 (0.661-0.795) y 0.738 (0.673-0.803). A 3% de falsos positivos, los puntos de corte fueron 119, 83 y 94 mmHg con valores predictivos negativos del 95.6%. Conclusiones: Es factible definir normalidad para la presión arterial en el embarazo con base bioestadística y clínica.

Abstract Objective: To define normal blood pressure at first trimester of pregnancy by performance for pre-eclampsia prediction. Method: A cohort study in singleton pregnancies, according to the competing risks model for pre-eclampsia. Blood pressure was measured according to a standardized method at 11 to 14 weeks' gestation. Results: Among 797 pregnancies included, there were 40 (5.0%, IC95 3.6; 6.4) deliveries with pre-eclampsia. The systolic, diastolic, and mean arterial blood pressures were respectively of 101(9), 68(8) and 79(8) mmHg in pregnant women who did not develop pre-eclampsia, against 109(10), 75(8) and 86(8) in those who did (p < 0.001, t-test). The areas under the curves were 0.707 (0.637; 0.777), 0.728 (0.661; 0.795), and 0.738 (0.673; 0.803). At a 3% of false positive rate, the cut-off points were 119, 83 and 94 mmHg with predictive values of negative of 95.6%. Conclusions: It is feasible to define the normal values for blood pressure in pregnancy on biostatistic and clinical basis.

3'-Demethoxy-6-O-Demethylisoguaiacin and Norisoguaiacin Nematocidal Lignans from Artemisia cina against Haemonchus contortus Infective Larvae.

Artemisia cina is a plant used in traditional Chinese medicine as a remedy for parasitic diseases. This study describes the isolation and chemical characterization of anthelmintic compounds of A. cina against Haemonchus contortus infective larvae (L3) through lethal testing. Previously, three extracts-n-hexane (HexAc), ethyl acetate (EtOAc) and methanol (MeOAc)-were evaluated at concentrations of 4 to 0.5 mg/mL, resulting in the HexAc extract with the greatest effect of 76.6% mortality of the larvae at 4 mg/mL. Then, this was chemically fractioned by polarity, obtaining seven fractions (C1F1-C1F7), and, when evaluated at concentrations from 2 to 0.25 mg/mL, the 2 mg/mL C1F5 fraction produced an effect against the nematode H. contortus of 100% mortality of the larvae. Thus, this fraction was fractionated again by column chromatography, obtaining twelve subfractions (C2F1-C2F12) which were evaluated from 1 to 0.125 mg/mL, with the C2F5 subfraction causing a nematicidal effect of 100% mortality. NMR analysis of one (1H, 13C and DEPT) and two dimensions (COSY, HSQC and HMBC) and mass spectrometry of this fraction allowed us to identify the mixture of 3'-demethoxy-6-O-demethylisoguaiacin and norisoguaiacin. Therefore, it can be assumed that the mixture of these compounds is responsible for the anthelmintic effect. These results indicate that A. cina containing anthelmintic compounds and might be used as an antiparasitic drug against H. contortus.

Definition of normal blood pressure at 11 to 14 weeks' gestation according to risk.

OBJECTIVE: To define normal blood pressure at first trimester of pregnancy by performance for pre-eclampsia prediction. METHOD: A cohort study in singleton pregnancies, according to the competing risks model for pre-eclampsia. Blood pressure was measured according to a standardized method at 11 to 14 weeks' gestation. RESULTS: Among 797 pregnancies included, there were 40 (5.0%, IC95 3.6; 6.4) deliveries with pre-eclampsia. The systolic, diastolic, and mean arterial blood pressures were respectively of 101(9), 68(8) and 79(8) mmHg in pregnant women who did not develop pre-eclampsia, against 109(10), 75(8) and 86(8) in those who did (p < 0.001, t-test). The areas under the curves were 0.707 (0.637; 0.777), 0.728 (0.661; 0.795), and 0.738 (0.673; 0.803). At a 3% of false positive rate, the cut-off points were 119, 83 and 94 mmHg with predictive values of negative of 95.6%. CONCLUSIONS: It is feasible to define the normal values for blood pressure in pregnancy on biostatistic and clinical basis.

OBJETIVO: Definir la presión arterial normal en el primer trimestre de la gestación según el desempeño para predecir preeclampsia. MÉTODO: Estudio de cohorte en embarazos de feto único, según el modelo de riesgos en competencia para preeclampsia. La presión arterial se midió de manera estandarizada entre las 11 y 14 semanas de gestación. RESULTADOS: En 797 embarazos incluidos hubo 40 (5.0%, intervalo de confianza del 95% [IC 95%]: 3.6-6.4) partos con preeclampsia. Las presiones arteriales sistólica, diastólica y media fueron respectivamente de 101 (9), 68 (8) y 79 (8) mmHg en las embarazadas que no desarrollaron preeclampsia, frente a 109 (10), 75 (8) y 86 (8) mmHg en las que sí (p < 0.001, prueba t de Student). Las áreas bajo la curva fueron 0.707 (0.637-0.777), 0.728 (0.661-0.795) y 0.738 (0.673-0.803). A 3% de falsos positivos, los puntos de corte fueron 119, 83 y 94 mmHg con valores predictivos negativos del 95.6%. CONCLUSIONES: Es factible definir normalidad para la presión arterial en el embarazo con base bioestadística y clínica.

Reference values for uterine artery mean pulsatility index throughout pregnancy customized by parity, transvaginal measurement and blood pressure.

INTRODUCTION: Population-specific reference ranges for uterine artery (UtA) mean pulsatility index (PI) throughout pregnancy have been shown to be of value in antenatal care. OBJECTIVE: To construct reference values for UtA mean PI throughout pregnancy, customized by maternal characteristics, transvaginal measurement and blood pressure in a Mexican population. METHODS: Cross-sectional study in 2286 normal singleton pregnancies in Mexico City. Blood pressure and UtA mean PI were measured using standardized methodology. Reference ranges by gestation were constructed. The effects of independent variables were tested by multiple linear regression. RESULTS: UtA mean PI median value between 11 and 41 weeks decreased from 1.714 to 0.523. The 95th percentile decreased from 2.600 to 0.653. Previous parity without preeclampsia had the main effect on UtA mean PI. Mean blood pressure had an effect on UtA mean PI by interaction with parity. Previous preeclampsia had an effect on UtA mean PI by interaction with maternal characteristics. A correction factor was obtained for transvaginal measurement. CONCLUSIONS: UtA mean PI usually decreases according to placentation and maternal adaptation to pregnancy. The effects of parity on blood pressure and UtA mean PI might reflect cardiovascular remodeling after gestation.

INTRODUCCIÓN: Los rangos de referencia de población específica para el índice de pulsatilidad medio de la arteria uterina (IPmAUt) durante el embarazo han demostrado valor en el cuidado prenatal. OBJETIVO: Construir valores de referencia para el IPmAUt durante el embarazo, personalizados por características maternas, medición transvaginal y presión arterial en una población mexicana. MÉTODOS: Estudio transversal de 2286 embarazos normales de feto único en la Ciudad de México. La presión arterial y el IPmAUt se midieron mediante metodología estandarizada. Se construyeron rangos de referencia por gestación. Los efectos de las variables independientes se probaron mediante regresión lineal múltiple. RESULTADOS: La mediana del IPmAUt entre las 11 y 41 semanas disminuyó de 1.714 a 0.523. El percentil 95 disminuyó de 2.600 a 0.653. La paridad sin preeclampsia previa representó el principal efecto sobre el IPmAUt. La presión arterial media tuvo efecto sobre el IPmAUt por interacción con la paridad. La preeclampsia previa tuvo efecto sobre el IPmAUt por interacción con las características maternas. Se obtuvo un factor de corrección para medición transvaginal. CONCLUSIONES: El IPmAUt disminuye normalmente según la placentación y adaptación materna al embarazo. Los efectos de la paridad sobre la presión arterial y el IPmAUt podrían reflejar remodelación cardiovascular posterior a la gestación.

An Artemisia cina n-hexane extract reduces the Haemonchus contortus and Teladorsagia circumcincta fecal egg count in naturally infected periparturient goats.

The objective of this study was to evaluate an n-hexane extract of Artemisia cina (Acn-h) as a natural anthelmintic treatment for periparturient goats naturally infected with the nematodes Haemonchus contortus and Teladorsagia circumcincta. A total of 200 periparturient Alpine and Nubian goats were used. Deworming criteria were based on the following parameters: fecal egg account (epg), ocular mucosa color (OMC), and body condition (BC). A previous analysis using coprocultures of the flock revealed the presence of H. contortus (80%) and T. circumcincta (20%). The Acn-h contained two new compounds identified by mass spectrometry data as isoguaiacin and norisoguaiacin at 284.14 and 315 m/z. The lethal effects of Acn-h at 0.5, 1, 2, and 4 mg/mL on H. contortus adult stages were 31.6, 66.5, 81.3, and 86.9%, respectively (p < 0.05), showing similar efficacy at 2 and 4 mg/mL with albendazole (positive control group). Then, two experimental groups, with 100 goats in peripartum in each, were distributed randomly and treated at day 0 as follows: group 1 = 4 mg/kg of Acn-h as single oral dose, and group 2 = control group, treated with water (as a placebo). The epg, OMC, and BC parameters were recorded at 0 (periparturient period), 7 (birth period), and 23 (postpartum) days and analyzed using a completely randomized design with Duncan's test for comparison of means and analysis of variance. The following epg reductions were recorded in the Acn-h-treated group as follows: 20.1 ± 34.4 and 31.7 ± 38.2% at days 7 and 23 compared to the control group. During the whole experiment, no significant differences in OMC or BC were observed in relation to the control group, excepting at day 23 (p < 0.05) for BC in the group treated with A. cina. Thus, Acn-h can be a useful natural alternative tool for the control of the nematodes H. contortus and T. circumcincta in periparturient goat flocks.

Valores de referencia personalizados para el índice de pulsatilidad medio de la arteria uterina durante el embarazo según paridad, medición transvaginal y presión arterial / Reference values for uterine artery mean pulsatility index throughout pregnancy customized by parity, transvaginal measurement and blood pressure

Resumen Introducción: Los rangos de referencia de población específica para el índice de pulsatilidad medio de la arteria uterina (IPmAUt) durante el embarazo han demostrado valor en el cuidado prenatal. Objetivo: Construir valores de referencia para el IPmAUt durante el embarazo, personalizados por características maternas, medición transvaginal y presión arterial en una población mexicana. Métodos: Estudio transversal de 2286 embarazos normales de feto único en la Ciudad de México. La presión arterial y el IPmAUt se midieron mediante metodología estandarizada. Se construyeron rangos de referencia por gestación. Los efectos de las variables independientes se probaron mediante regresión lineal múltiple. Resultados: La mediana del IPmAUt entre las 11 y 41 semanas disminuyó de 1.714 a 0.523. El percentil 95 disminuyó de 2.600 a 0.653. La paridad sin preeclampsia previa representó el principal efecto sobre el IPmAUt. La presión arterial media tuvo efecto sobre el IPmAUt por interacción con la paridad. La preeclampsia previa tuvo efecto sobre el IPmAUt por interacción con las características maternas. Se obtuvo un factor de corrección para medición transvaginal. Conclusiones: El IPmAUt disminuye normalmente según la placentación y adaptación materna al embarazo. Los efectos de la paridad sobre la presión arterial y el IPmAUt podrían reflejar remodelación cardiovascular posterior a la gestación.

Abstract Introduction: Population-specific reference ranges for uterine artery (UtA) mean pulsatility index (PI) throughout pregnancy have been shown to be of value in antenatal care. Objective: To construct reference values for UtA mean PI throughout pregnancy, customized by maternal characteristics, transvaginal measurement and blood pressure in a Mexican population. Methods: Cross-sectional study in 2286 normal singleton pregnancies in Mexico City. Blood pressure and UtA mean PI were measured using standardized methodology. Reference ranges by gestation were constructed. The effects of independent variables were tested by multiple linear regression. Results: UtA mean PI median value between 11 and 41 weeks decreased from 1.714 to 0.523. The 95th percentile decreased from 2.600 to 0.653. Previous parity without preeclampsia had the main effect on UtA mean PI. Mean blood pressure had an effect on UtA mean PI by interaction with parity. Previous preeclampsia had an effect on UtA mean PI by interaction with maternal characteristics. A correction factor was obtained for transvaginal measurement. Conclusions: UtA mean PI usually decreases according to placentation and maternal adaptation to pregnancy. The effects of parity on blood pressure and UtA mean PI might reflect cardiovascular remodeling after gestation.

Möbius Strip Microlasers: A Testbed for Non-Euclidean Photonics.

We report on experiments with Möbius strip microlasers, which were fabricated with high optical quality by direct laser writing. A Möbius strip, i.e., a band with a half twist, exhibits the fascinating property that it has a single nonorientable surface and a single boundary. We provide evidence that, in contrast to conventional ring or disk resonators, a Möbius strip cavity cannot sustain whispering gallery modes (WGM). Comparison between experiments and 3D finite difference time domain (FDTD) simulations reveals that the resonances are localized on periodic geodesics.

Presión arterial en embarazos normales de la Ciudad de México / Blood pressure in normal pregnancies from Mexico City

Resumen Objetivo: Determinar la presión arterial (PA) normal en embarazadas en la Ciudad de México. Método: Estudio transversal descriptivo de la PA en embarazos normales de feto único en la Ciudad de México. Las mediciones siguieron un método estandarizado con uso de dispositivos electrónicos automatizados. Se construyeron valores de referencia de las presiones sistólica (PS), diastólica (PD) y arterial media (PAM). Se probaron los efectos de las características maternas y de la gestación sobre la PA. Los intervalos de referencia de la PA se ajustaron para las variables significativas. Resultados: En 1,056 mujeres con edad media de 33 años y 160 cm medios de estatura se realizaron 1,915 mediciones entre las 5 y 41 semanas de edad gestacional (EG) con peso medio de 65 kg. La PA durante el embarazo fue de 102.7/67.2 ± 9.3/7.4 DE mmHg y 79.0 ± 7.4 DE mmHg la PAM. La PA tuvo una relación cuadrática con la EG, la más baja en el segundo trimestre. La PS y la PD mostraron una correlación lineal (r = 0.71). El peso materno tuvo el efecto más significativo sobre PS y PAM; la estatura sobre la PD. La edad, etnia, paridad, consumo de tabaco y antecedente familiar ejercieron efectos diferentes en cada PA. La gestación no tuvo efecto significativo en el modelo multivariado de la PS. Conclusiones: La PA se halló por debajo de la norma convencional en embarazadas. Los criterios diagnósticos para hipertensión en el embarazo deben revisarse; los valores de referencia pueden ajustarse a características maternas y gestacionales.

Abstract Objective: To determine the normal blood pressure (BP) in pregnancy, Mexico City. Methods: A cross-sectional observational study was carried out of BP on singleton normal pregnancies in Mexico City. Measurements followed a standardised methodology using automated electronic devices. Reference values of systolic (SBP), diastolic (DBP) and mean arterial pressure (MAP) were constructed. Maternal and gestation characteristics effects on BP were tested. The reference ranges of BP were adjusted for significant variables. Results: On 1,056 women of 33 years old mean age and 160.0 cm mean height, 1,915 measurements were made between 5 and 41 weeks of gestational age (GA) with 65.0 kg of mean weight. The median BP throughout pregnancy was 102.7/67.2 ± 9.3/7.4 SD mmHg, and 79.0 ± 7.4 SD mmHg the MAP. BP had a quadratic relationship with GA, being the lowest in 2nd trimester. SBP and DBP had a r = 0.71 linear correlation. Maternal weight had the most significant effect on SBP and MAP; height, on DBP. Maternal age, ethnic origin, parity, tobacco habit and family history had differential effects on BP. Gestation had no significant effect on SBP multivariate model. Conclusions: BP resulted lower than conventional standard for pregnant women. Diagnostic criteria for hypertension in pregnancy must be revised; reference values can be adjusted by maternal and gestation characteristics.

Presión arterial en embarazos normales de la Ciudad de México.

OBJECTIVE: To determine the normal blood pressure (BP) in pregnancy, Mexico City. METHODS: A cross-sectional observational study was carried out of BP on singleton normal pregnancies in Mexico City. Measurements followed a standardised methodology using automated electronic devices. Reference values of systolic (SBP), diastolic (DBP) and mean arterial pressure (MAP) were constructed. Maternal and gestation characteristics effects on BP were tested. The reference ranges of BP were adjusted for significant variables. RESULTS: On 1,056 women of 33 years old mean age and 160.0 cm mean height, 1,915 measurements were made between 5 and 41 weeks of gestational age (GA) with 65.0 kg of mean weight. The median BP throughout pregnancy was 102.7/67.2 ± 9.3/7.4 SD mmHg, and 79.0 ± 7.4 SD mmHg the MAP. BP had a quadratic relationship with GA, being the lowest in 2nd trimester. SBP and DBP had a r = 0.71 linear correlation. Maternal weight had the most significant effect on SBP and MAP; height, on DBP. Maternal age, ethnic origin, parity, tobacco habit and family history had differential effects on BP. Gestation had no significant effect on SBP multivariate model. CONCLUSIONS: BP resulted lower than conventional standard for pregnant women. Diagnostic criteria for hypertension in pregnancy must be revised; reference values can be adjusted by maternal and gestation characteristics.

OBJETIVO: Determinar la presión arterial (PA) normal en embarazadas en la Ciudad de México. MÉTODO: Estudio transversal descriptivo de la PA en embarazos normales de feto único en la Ciudad de México. Las mediciones siguieron un método estandarizado con uso de dispositivos electrónicos automatizados. Se construyeron valores de referencia de las presiones sistólica (PS), diastólica (PD) y arterial media (PAM). Se probaron los efectos de las características maternas y de la gestación sobre la PA. Los intervalos de referencia de la PA se ajustaron para las variables significativas. RESULTADOS: En 1,056 mujeres con edad media de 33 años y 160 cm medios de estatura se realizaron 1,915 mediciones entre las 5 y 41 semanas de edad gestacional (EG) con peso medio de 65 kg. La PA durante el embarazo fue de 102.7/67.2 ± 9.3/7.4 DE mmHg y 79.0 ± 7.4 DE mmHg la PAM. La PA tuvo una relación cuadrática con la EG, la más baja en el segundo trimestre. La PS y la PD mostraron una correlación lineal (r = 0.71). El peso materno tuvo el efecto más significativo sobre PS y PAM; la estatura sobre la PD. La edad, etnia, paridad, consumo de tabaco y antecedente familiar ejercieron efectos diferentes en cada PA. La gestación no tuvo efecto significativo en el modelo multivariado de la PS. CONCLUSIONES: La PA se halló por debajo de la norma convencional en embarazadas. Los criterios diagnósticos para hipertensión en el embarazo deben revisarse; los valores de referencia pueden ajustarse a características maternas y gestacionales.

Validation of a preeclampsia early screening test in a Mexican population.

BACKGROUND: No preeclampsia screening test has been validated in our country. OBJECTIVE: To assess the fit and performance of the FMF 4.0 Bayesian algorithm in a Mexican population. METHOD: Cohort study in singleton pregnancies, according to the competing risks model for preeclampsia. A priori risk was calculated based on medical history. Mean blood pressure (MBP), uterine artery mean pulsatility index (UtAmPI) and pregnancy-associated plasma protein A (PAPP-A) were measured at 11-14 weeks of gestation using standardized methodology. The value of each marker was transformed into multiples of the median (MoM) by the originala algorithm and by population-correctionb. Multivariate normal distribution and Bayes theorem were applied to obtain post-test probabilities. RESULTS: There was 5.0% (40/807) of preeclampsia. Distributions in women without preeclampsia were MBP = 0.927a vs. 0.991b, UtAmPI = 0.895a vs. 1.030b and PAPP-A = 0.815a vs. 0.963b (p < 0.001). The AUC was 0.821a vs. 0.823b. For a detection rate of 69 %, cutoff points were 1 in 240a and 1 in 120b, with false positive rates of 31 %a and 29 %b. CONCLUSIONS: The model has to be adjusted to the target population.

ANTECEDENTES: Ninguna prueba de tamiz de preeclampsia ha sido validada en nuestro país. OBJETIVO: Evaluar el ajuste y rendimiento del algoritmo bayesiano FMF 4.0 en una población mexicana. MÉTODO: Estudio de cohorte en embarazos de feto único, según el modelo de riesgos en competencia para preeclampsia. El riesgo a priori se calculó por historia clínica. La presión arterial media (PAM), el índice de pulsatilidad medio de la arteria uterina (IPmAUt) y la proteína plasmática A asociada al embarazo (PAPP-A) se midieron a las 11-14 semanas de gestación con metodología estandarizada. El valor de cada marcador se transformó en múltiplos de la mediana (MoM) por el algoritmo originala y el corregidob a la población. Se aplicaron la distribución normal multivariante y el teorema de Bayes para las probabilidades posprueba. RESULTADOS: Hubo un 5.0% (40/807) de preeclampsia. Las distribuciones sin preeclampsia fueron PAM 0.927a vs. 0.991b, UtAmPI 0.895a vs. 1.030b y PAPP-A 0.815a vs. 0.963b (p < 0.001). El área bajo la curva fue 0.821a vs. 0.823b. Para una detección del 69%, los puntos de corte fueron 1 en 240a y 1 en 120b, a falsos positivos del 31%a y 29%b. CONCLUSIONES: El modelo debe ajustarse a la población diana.

Validación de la calculadora de la Fundación de Medicina Fetal para tamiz de preeclampsia adaptada a población mexicana / Validation of the Fetal Medicine Foundation calculator for pre-eclampsia screening test adapted to a Mexican population

Resumen OBJETIVO: Validar el rendimiento de la calculadora de la Fundación de Medicina Fetal 4.0 adaptada a población mexicana. MATERIALES Y MÉTODOS: Estudio de cohorte efectuado en embarazos con feto único, según el modelo de riesgos en competencia para preeclampsia en un centro de medicina fetal de la Ciudad de México. El riesgo a priori se calculó de acuerdo con la historia clínica. La presión arterial media, el índice de pulsatilidad medio de la arteria uterina y la proteína plasmática A asociada al embarazo se midieron a las 11 a 14 semanas de gestación con metodología estandarizada. El valor de cada marcador se transformó en múltiplos de la mediana adaptados a la población local. Se aplicaron la distribución normal multivariante y el teorema de Bayes para obtener las probabilidades posprueba individuales, que se utilizaron como clasificadores para el área bajo la curva de característica receptor-operador. RESULTADOS: La incidencia de preeclampsia fue del 5.0% (54/1078). El área bajo la curva de característica receptor-operador fue de 0.784 (0.712; 0.856) para preeclampsia a menos de 37 semanas y de 0.807 (0.762; 0.852) para preeclampsia global. CONCLUSIONES: La calculadora FMF 4.0 adaptada a población mexicana resultó válida. Si bien tuvo menor rendimiento al esperado para preeclampsia a menos de 37 semanas, el rendimiento para preeclampsia global fue satisfactorio. Se justifica desarrollar la calculadora local.

Abstract OBJECTIVE: To validate the performance of the Fetal Medicine Foundation 4.0 calculator adapted to the Mexican population. MATERIALS AND METHODS: Cohort study performed in singleton pregnancies, according to the competing risk model for preeclampsia in a fetal medicine center in Mexico City. The a priori risk was calculated according to the clinical history. Mean arterial pressure, mean uterine artery pulsatility index and pregnancy-associated plasma protein A were measured at 11 to 14 weeks of gestation with standardized methodology. The value of each marker was transformed into multiples of the median adapted to the local population. Multivariate normal distribution and Bayes' theorem were applied to obtain individual posttest probabilities, which were used as classifiers for the area under the receiver-operator characteristic curve. RESULTS: The incidence of preeclampsia was 5.0% (54/1078). The area under the receiver-operator characteristic curve was 0.784 (0.712; 0.856) for preeclampsia at less than 37 weeks and 0.807 (0.762; 0.852) for global preeclampsia. CONCLUSIONS: The FMF 4.0 calculator adapted to Mexican population proved valid. Although it had lower performance than expected for preeclampsia at less than 37 weeks, the performance for global preeclampsia was satisfactory. The development of the local calculator is justified.

A Computational Approach to Explore the Interaction of Semisynthetic Nitrogenous Heterocyclic Compounds with the SARS-CoV-2 Main Protease.

In the context of the ongoing coronavirus disease 2019 (COVID-19) pandemic, numerous attempts have been made to discover new potential antiviral molecules against its causative agent, SARS-CoV-2, many of which focus on its main protease (Mpro). We hereby used two approaches based on molecular docking simulation to explore the interaction of four libraries of semisynthetic nitrogenous heterocyclic compounds with Mpro. Libraries L1 and L2 contain 52 synthetic derivatives of the natural compound 2-propylquinoline, whereas libraries L3 and L4 contain 65 compounds synthesized using the natural compound physostigmine as a precursor. Validation through redocking suggested that the rigid receptor and flexible receptor approaches used for docking were suitable to model the interaction of this type of compounds with the target protein, although the flexible approach seemed to provide a more realistic representation of interactions within the active site. Using empirical energy score thresholds, we selected 58 compounds from the four libraries with the most favorable energy estimates. Globally, favorable estimates were obtained for molecules with two or more substituents, putatively accommodating in three or more subsites within the Mpro active site. Our results pave the way for further experimental evaluation of the selected compounds as potential antiviral agents against SARS-CoV-2.

A Marine Diterpenoid Modulates the Proteasome Activity in Murine Macrophages Stimulated with LPS.

The proteasome is an intracellular complex that degrades damaged or unfolded proteins and participates in the regulation of several processes. The immunoproteasome is a specialized form that is expressed in response to proinflammatory signals and is particularly abundant in immune cells. In a previous work, we found an anti-inflammatory effect in a diterpenoid extracted from the octocoral Pseudopterogorgia acerosa, here called compound 1. This compound prevented the degradation of inhibitor κB α (IκBα) and the subsequent activation of nuclear factor κB (NFκB), suggesting that this effect might be due to inhibition of the ubiquitin-proteasome system. Here we show that compound 1 inhibits the proteasomal chymotrypsin-like activity (CTL) of murine macrophages in the presence of lipopolysaccharide (LPS) but not in its absence. This effect might be due to the capacity of this compound to inhibit the activity of purified immunoproteasome. The compound inhibits the cell surface expression of major histocompatibility complex (MHC)-I molecules and the production of proinflammatory cytokines induced by LPS in vitro and in vivo, respectively. Molecular docking simulations predicted that compound 1 selectively binds to the catalytic site of immunoproteasome subunits ß1i and ß5i, which are responsible for the CTL activity. Taken together these findings suggest that the compound could be a selective inhibitor of the immunoproteasome, and hence could pave the way for its future evaluation as a candidate for the treatment of inflammatory disorders and autoimmune diseases.

Long-term spatial memory in humans trained in a virtual maze / Memória espacial de longo prazo em humanos treinados num labirinto virtual / Memoria espacial a largo plazo en humanos entrenados en un laberinto virtual

Abstract In this study we evaluated the long-term spatial memory in humans. A quasiexperimental design was used in which three groups of undergraduate students were trained in a virtual water maze to locate a hidden platform whose location was indicated by a set of cues. A pre-test without platform was performed prior to the training, and a post-test was conducted immediately after this (Group 0h), or after a retention interval of two (Group 48h) or seven days (Group 168h). For the pre-test, there was no evidence of preference for any area of the maze. Throughout the training trials, the time to find the goal decreased without differences between groups. During the post-test, all groups showed a preference for the reinforced quadrant, although the spent time, swimming distance, and accuracy of the search behavior in that area was equivalent between Group 0 h and Group 48 h, but higher than that shown by the Group 168 h. These data indicate changes in long-term spatial memory in humans, occurring after an interval of 48 h after its acquisition. The results are discussed on the basis of general memory processes and specific processes proposed by particular spatial memory theories. The clinical and comparative psychology implications are also addressed.

Resumo Neste estudo, avaliou-se a memória espacial de longo prazo em humanos. Para isso, empregou-se um desenho quase-experimental no qual se treinou três grupos de estudantes de graduação num labirinto virtual de água para localizar uma plataforma oculta cuja posição era sinalizada por um conjunto de chaves. Realizou-se um pré-teste sem plataforma antes do treinamento, e imediatamente depois se conduziu um pós-teste (Grupo 0 h), assim como depois de um intervalo de retenção de dois dias (Grupo 48 h) e de sete dias (Grupo 168 h). No pré-teste, não se encontrou evidência de preferência por alguma área do labirinto. Ao longo dos ensaios de treinamento, o tempo para encontrar a meta diminuiu sem diferenças entre grupos. Durante o pós-teste, todos os grupos mostraram uma preferência pelo quadrante reforçado, contudo o tempo de permanência, a distância de nado e a precisão do comportamento de busca nessa área foi equivalente entre o Grupo 0 h e o Grupo 48 h, embora maior à amostragem pelo Grupo 168 h. Esses dados indicam mudanças ocorridas 48 h depois da aquisição na memória espacial de longo prazo em humanos. Discutem-se os resultados a partir de processos gerais de memória e de processos específicos propostos por teorias particulares de memória espacial; ao final, abordam-se as implicações clínicas e pertinentes ao campo da psicologia comparada.

Resumen En este estudio se evaluó la memoria espacial a largo plazo en humanos. Para ello, se empleó un diseño cuasiexperimental en el que se entrenó a tres grupos de estudiantes de pregrado en un laberinto virtual de agua para localizar una plataforma oculta cuya ubicación era señalada por un conjunto de claves. Se realizó un pretest sin plataforma antes del entrenamiento, e inmediatamente después se condujo un postest (Grupo 0 h), así como después de un intervalo de retención de dos días (Grupo 48 h) y siete días (Grupo 168 h). En el pretest no se encontró evidencia de preferencia por alguna zona del laberinto. A lo largo de los ensayos de entrenamiento, el tiempo para encontrar la meta disminuyó sin diferencias entre grupos. Durante el postest, todos los grupos mostraron una preferencia por el cuadrante reforzado, sin embargo, el tiempo de permanencia, la distancia de nado y la precisión de la conducta de búsqueda en dicha zona fue equivalente entre el Grupo 0 h y el Grupo 48 h, aunque mayor a la mostrada por el Grupo 168 h. Estos datos indican cambios ocurridos 48 h después de la adquisición en la memoria espacial a largo plazo en humanos. Se discuten los resultados a partir de procesos generales de memoria y procesos específicos propuestos por teorías particulares de memoria espacial; y al final se abordan las implicaciones clínicas y pertinentes al campo de la psicología comparada.