On the Interpretation of subtilisin Carlsberg Time-Resolved Fluorescence Anisotropy Decays: Modeling with Classical Simulations.

In this work, we discuss the challenging time-resolved fluorescence anisotropy of subtilisin Carlsberg (SC), which contains a single Trp residue and is a model fluorescence system. Experimental decay rates and quenching data suggest that the fluorophore should be exposed to water, but the Trp is partially buried in a hydrophobic pocket in the crystallographic structure. In order to study this inconsistency, molecular dynamics simulations were performed to predict the anisotropy decay rates and emission wavelengths of the Trp. We confirmed the inconsistency of the crystallographic structure with the experimentally observed fluorescence data and performed free energy calculations to show that the buried Trp conformation is 2 orders of magnitude (∼3 kcal/mol) more stable than the solvent-exposed one. However, molecular dynamics simulations in which the Trp side chain was restricted to solvent-exposed conformations displayed a maximum Trp emission wavelength shifted toward lower energies and decay rates compatible with the experimentally probed rates. Therefore, if the solvent-exposed conformations are the most important emitters, the experimental anisotropy can be compatibilized with the crystallographic structure. The most likely explanation is that the fluorescence of the most probable conformation in solution, observed in the crystal, is quenched, and this is consistent with the low quantum yield of Trp113 of SC. Additionally, some experiments might have probed denatured or lysed SC structures. SC anisotropy provides an interesting target for the study of fluorescence anisotropy using simulations, which can be used to test and exemplify how modeling can aid the interpretation of experimental data in a system where structure and solution experiments appear to be inconsistent.

Parametric models to compute tryptophan fluorescence wavelengths from classical protein simulations.

Fluorescence spectroscopy is an important method to study protein conformational dynamics and solvation structures. Tryptophan (Trp) residues are the most important and practical intrinsic probes for protein fluorescence due to the variability of their fluorescence wavelengths: Trp residues emit in wavelengths ranging from 308 to 360 nm depending on the local molecular environment. Fluorescence involves electronic transitions, thus its computational modeling is a challenging task. We show that it is possible to predict the wavelength of emission of a Trp residue from classical molecular dynamics simulations by computing the solvent-accessible surface area or the electrostatic interaction between the indole group and the rest of the system. Linear parametric models are obtained to predict the maximum emission wavelengths with standard errors of the order 5 nm. In a set of 19 proteins with emission wavelengths ranging from 308 to 352 nm, the best model predicts the maximum wavelength of emission with a standard error of 4.89 nm and a quadratic Pearson correlation coefficient of 0.81. These models can be used for the interpretation of fluorescence spectra of proteins with multiple Trp residues, or for which local Trp environmental variability exists and can be probed by classical molecular dynamics simulations. © 2018 Wiley Periodicals, Inc.

Tiempo de demora para la hospitalización tras la implantación del ingreso directo a cargo del Servicio de Urgencias / Changes in emergency admission times after the introduction of direct admission from emergency services

ObjetivoValorar el impacto en el tiempo de espera para el ingreso urgente dependiendo del facultativo responsable de éste, el médico de urgencias o el especialista del área médica.Material y métodoTras la autorización al servicio de urgencias hospitalarias para el ingreso directo de pacientes en las especialidades médicas, se definieron dos períodos de estudio: período A (previo al ingreso directo) y período B (tras su implantación). Se analizaron el número de pacientes atendidos, su gravedad, el número y porcentaje de ingresos y el tiempo medio de estancia.ResultadosEn ambos períodos se atendieron 41.917 pacientes (228,07 pacientes/día) y 41.948 (230,48 pacientes/día), respectivamente. El tiempo medio de estancia de los pacientes ingresados directamente desde urgencias disminuyó en 1h y 42m (p=0,001); por el contrario, los ingresos en planta de hospitalización del servicio de medicina interna mantuvieron un tiempo medio de espera similar en los dos períodos analizados.ConclusionesEl traspaso de la competencia del ingreso a los facultativos de urgencias disminuye el tiempo medio de estancia de los pacientes en dicha área, sin modificar el número de ingresos y reduciendo la carga asistencial de los facultativos de la planta de hospitalización(AU)

ObjectiveTo measure the differences of waiting time for the emergency admission depending on which professional is in charge ie. the emergency doctor or the specialist of a specific area.Patients and methodsOnce the Hospital Emergency Service was permitted to admit patients directly to the specialities, two periods of study where taken: Period A (before the direct admission) and Period B (after the implementation of it). The following was analysed: the number of patients taken, the complexity of their problem, the number of admissions and length of their stay.ResultsDuring Period A 41,917 patients were seen (228.07 patients/day) and during Period B 41,948 (230.48 patients/day). The average of the stay for those patients that were admitted directly from Emergencies had decreased by 1h and 42min (p=0.001). The admissions in the Internal Medicine Service kept the same waiting time in both periods.ConclusionsThe transfer of the responsibility of the admissions to emergency doctors has decreased the average waiting time of the patients in this area. The total number of admissions has not increased and has reduced the amount of work the different specialist(AU)

[Changes in emergency admission times after the introduction of direct admission from emergency services]. / Tiempo de demora para la hospitalización tras la implantación del ingreso directo a cargo del Servicio de Urgencias.

OBJECTIVE: To measure the differences of waiting time for the emergency admission depending on which professional is in charge ie. the emergency doctor or the specialist of a specific area. PATIENTS AND METHODS: Once the Hospital Emergency Service was permitted to admit patients directly to the specialities, two periods of study where taken: Period A (before the direct admission) and Period B (after the implementation of it). The following was analysed: the number of patients taken, the complexity of their problem, the number of admissions and length of their stay. RESULTS: During Period A 41,917 patients were seen (228.07 patients/day) and during Period B 41,948 (230.48 patients/day). The average of the stay for those patients that were admitted directly from Emergencies had decreased by 1h and 42 min (p=0.001). The admissions in the Internal Medicine Service kept the same waiting time in both periods. CONCLUSIONS: The transfer of the responsibility of the admissions to emergency doctors has decreased the average waiting time of the patients in this area. The total number of admissions has not increased and has reduced the amount of work the different specialist.

Intoxicación por Nerium oleander / Nerium oleander poisoning

No disponible