Dynamics of the heme-binding bacterial gas-sensing dissimilative nitrate respiration regulator (DNR) and activation barriers for ligand binding and escape.

DNR (dissimilative nitrate respiration regulator) is a heme-binding transcription factor that is involved in the regulation of denitrification in Pseudomonas aeruginosa. In the ferrous deoxy state, the heme is 6-coordinate; external NO and CO can replace an internal ligand. Using fluorescence anisotropy, we show that high-affinity sequence-specific DNA binding occurs only when the heme is nitrosylated, consistent with the proposed function of DNR as NO sensor and transcriptional activator. This role is moreover supported by the NO "trapping" properties revealed by ultrafast spectroscopy that are similar to those of other heme-based NO sensor proteins. Dissociated CO-heme pairs rebind in an essentially barrierless way. This process competes with migration out of the heme pocket. The latter process is thermally activated (Ea ∼ 7 kJ/mol). This result is compared with other heme proteins, including the homologous CO sensor/transcription factor CooA, variants of the 5-coordinate mycobacterial sensor DosT and the electron transfer protein cytochrome c. This comparison indicates that thermal activation of ligand escape from the heme pocket is specific for systems where an external ligand replaces an internal one. The origin of this finding and possible implications are discussed.

Oral microbial biomap in the drought environment: Sjogren's syndrome.

Sjogren's syndrome (SS) is an autoimmune disease that affects primarily the salivary glands, making perturbations in the oral ecosystem and potential factors of salivary flow that influence the onset and development of the disease. The oral cavity contains diverse microorganisms that inhabit various niches such as the oral microbial "biomap." It does not seem specific enough to establish a characteristic microbiome, given the diversity of clinical manifestations, variable rates of salivary secretion, and influential risk factors in patients with SS. This review discusses the biogeography of the oral microbiome in patients with SS such as saliva, tongue, tooth, mucosa, and gum. The microorganisms that were more abundant in the different oral niches were Gram-positive species, suggesting a higher survival of cell wall bacteria in this arid oral environment. Reduced salivary flow appears not to be linked to the cause of dysbiosis alone but influences host-associated risk factors. However, much work remains to be done to establish the role of the microbiome in the etiopathogenesis of autoimmune diseases such as SS. Future studies of the microbiome in autoimmunity will shed light on the role of specific microorganisms that have never been linked before with SS.

Maternal-fetal outcomes of pregnancies in women treated at an inborn errors of metabolism unit.

INTRODUCTION: Intermediate Inborn Errors of Metabolism (IEM) are a group of inherited diseases that include phenylketonuria (PKU), tyrosinemia II (TSII), organic acidaemias and ornithine transcarbamylase deficiency (OTCD), among others. They are increasingly more common in adults due to improved management. This has allowed more affected women to consider having children with good prospects. However, pregnancy may worsen metabolic control and/or increase maternal-fetal complications. The objective is to analyse the characteristics and outcomes of pregnancies of our patients with IEM. METHODS: Retrospective descriptive study. Pregnancies of women with IEM attended to at the adult IEM referral unit of the Hospital Universitario Virgen del Rocío were included. The qualitative variables were described as n(%) and the quantitative as P50 (P25-P75). RESULTS: 24 pregnancies were recorded: 12 newborns were healthy, 1 inherited their mother's disease, 2 had maternal phenylketonuria syndrome, 1 was stillborn (gestational week 31 + 5), 5 were spontaneous abortions and 3 were voluntarily terminated. The gestations were divided into metabolically controlled and uncontrolled. CONCLUSIONS: Pregnancy planning and multidisciplinary management through to postpartum is essential to ensure maternal and fetal health. The basis of treatment in PKU and TSII is a strict protein-limited diet. Events that increase protein catabolism in organic acidaemias and DOTC should be avoided. Further investigation of pregnancy outcomes in women with IEM is needed.

[Predictive variables of serious victims, critical or deceased in traffic accidents in Extremadura, Spain]. / Variables predictoras de víctimas graves, críticas o fallecidas en los accidentes de tráfico en Extremadura.

OBJECTIVE: Traffic accidents constitute a public health problem and are the leading cause of accidental death in the world. Analyze if the type of accident, the age of the victim or the attention provided by the emergency medicalized units (UME) are related to the morbidity and mortality due to traffic accidents in Extremadura (Spain) during the years 2012, 2013, 2014 and 2015. METHODS: Descriptive study of the information in the records of the emergency response coordination center 112. A multivariate analysis was carried out. The prognostic status was introduced as a dependent variable and the type of accident, the age of the accident. RESULTS: The type of accident [odds ratio (OR)=1.745; 95% confidence interval (95% CI=1.488-2.045), the victim's age (OR=1.016; 95% CI=1.013-1.020), UME 4-3 (OR=4.304; 95% CI=2.158-8.587), UME 4-1 (OR=2.463; 95% CI=1.414-4.291) and UME 1-4 (OR=1.990; 95% CI=1.052-3.762) are related to the prognostic status of the victims. CONCLUSIONS: Inter-urban traffic accidents, the victim's age and three UME influence the prognostic status of the victims.

OBJETIVO: Los accidentes de tráfico constituyen un problema de salud pública y son la principal causa de muerte accidental en el mundo. El objetivo de este trabajo fue analizar si el tipo de accidente, la edad de la víctima o la atención prestada por las unidades medicalizadas de emergencia (UME) estaban relacionados con la morbimortalidad por accidentes de tráfico en Extremadura durante los años 2012, 2013, 2014 y 2015. METODOS: Se elaboró un estudio descriptivo de la información registrada en el Centro Coordinador de Urgencias y Emergencias-112. Se realizó un análisis multivariante, considerándose como variable dependiente el estado pronóstico y como variables independientes el tipo de accidente, la edad de los accidentados y las UME. RESULTADOS: El tipo de accidente (odds ratio (OR)=1,745; intervalo de confianza al 95% (IC95%)=1,488-2,045], la edad de la víctima (OR=1,016; IC95%=1,013-1,020), la UME 4-3 (OR=4,304; IC95%= 2,158-8,587), la UME 4-1 (OR=2,463; IC95%=1,414-4,291) y la UME 1-4 (OR=1,990; IC95%=1,052-3,762) tuvieron relación con el estado pronóstico de las víctimas. CONCLUSIONES: Los accidentes interurbanos, la edad de la víctima y tres UME influyen en el estado pronóstico de las víctimas.

Analysis of mobile emergency response unit times in attending traffic accidents in Extremadura, Spain. / Análisis de tiempos de las unidades medicalizadas de emergencia en la atención a los accidentes de tráfico en Extremadura.

OBJECTIVES: To analyze the time mobile emergency response units took to attend casualties due to traffic accidents in Extremadura from 2012 to 2015. MATERIAL AND METHODS: Retrospective descriptive study of information in the records of the emergency response coordination center 112 (ERCC-112) related to traffic accidents attended by mobile units. We compared care times in different situations, taking into consideration the seriousness of casualties. RESULTS: The ERCC-112 mobile units attended 5572 traffic accidents, with 113 deaths. Half the accidents required the attendance of a mobile response unit (activation rate of 0.51). There was an inverse relationship between intervention duration and the population of the city or town where the accident took place. The shortest times were recorded in the 2 provincial capitals of Extremadura. The longest times were recorded in less densely populated areas. The mean (SD) duration required for interventions recorded for the fleet of units overall was longer in fatal accidents (45.5 [21.5] minutes) than in nonfatal accidents (28.6 [15.9] minutes) (P<.001). Likewise times were longer in critical cases with poorer prognosis (35.6 [20.2] minutes) than in less serious ones (27.3 [14.5] minutes) (P<.001). CONCLUSION: Mobile emergency unit attendance at traffic accidents took longer in less densely populated geographic areas. Units also took longer to attend accidents that caused serious casualties or deaths.

OBJETIVO: Analizar los intervalos temporales de las unidades medicalizadas de emergencia (UME) en la atención prestada a los accidentes de tráfico en Extremadura durante el periodo 2012-2015. METODO: Estudio descriptivo retrospectivo de la información registrada en el Centro Coordinador de Urgencias y Emergencias-112 (CCU-112) relativa a la asistencia prestada por las UME en los accidentes de tráfico. Se realizó un análisis comparativo de los diferentes intervalos temporales empleados por las UME, incluyendo el pronóstico de las víctimas. RESULTADOS: Un total de 5.572 accidentes de tráfico requirieron atención al CCU-112 con un total de 113 muertes. La tasa de activación de las UME por accidentes de tráfico fue de 0,51 (uno de cada dos accidentes). Los tiempos de intervención presentaron una relación inversa con el volumen de población del núcleo donde se ubica cada UME, con tiempos medios de intervención menores en las dos capitales de provincia y mayores en las áreas más extensas, con mayor dispersión geográfica y menor densidad de población. El tiempo de actuación del conjunto de las UME fue mayor en la asistencia a accidentes con víctimas mortales (45,5 ± 21,5 frente a 28,6 ± 15,9 minutos, p < 0,001) y con pronóstico grave o crítico (35,6 ± 20,2 frente a 27,3 ±14,5 minutos, p < 0,001). CONCLUSIONES: Los intervalos temporales empleados por las UME fueron más prolongados en las áreas con menor densidad de población, mayor dispersión geográfica y en accidentes con víctimas graves o mortales.

Ultrafast Spectroscopy Evidence for Picosecond Ligand Exchange at the Binding Site of a Heme Protein: Heme-Based Sensor YddV.

An important question for the functioning of heme proteins is whether different ligands present within the protein moiety can readily exchange with heme-bound ligands. Studying the dynamics of the heme domain of the Escherichia coli sensor protein YddV upon dissociation of NO from the ferric heme by ultrafast spectroscopy, we demonstrate that when the hydrophobic leucine residue in the distal heme pocket is mutated to glycine, in a substantial fraction of the protein water replaces NO as an internal ligand in as fast as ∼4 ps. This process, which is near-barrierless and occurs orders of magnitude faster than the corresponding process in myoglobin, corresponds to a ligand swap of NO with a water molecule present in the heme pocket, as corroborated by molecular dynamics simulations. Our findings provide important new insight into ligand exchange in heme proteins that functionally interact with different external ligands.