Clinical impact of Doppler reference charts on management of small-for-gestational-age fetuses: need for standardization.

OBJECTIVE: To assess clinical variability in the management of small-for-gestational-age (SGA) fetuses according to different published Doppler reference charts for umbilical artery (UA) and fetal middle cerebral artery (MCA) Doppler indices and cerebroplacental ratio (CPR). METHODS: We performed a systematic search of MEDLINE, EMBASE, CINAHL and the Web of Science databases from 1954 to 2018 for studies with the sole aim of creating fetal Doppler reference values for UA, MCA and CPR. The top cited articles for each Doppler parameter were included. Variability in Doppler values at the following clinically relevant cut-offs was assessed: UA-pulsatility index (PI) > 95th percentile; MCA-PI < 5th percentile; and CPR < 5th percentile. Variability was calculated for each week of gestation and expressed as the percentage difference between the highest and lowest Doppler value at the clinically relevant cut-offs. Simulation analysis was performed in a cohort of SGA fetuses (n = 617) to evaluate the impact of this variability on clinical management. RESULTS: From a total of 40 studies that met the inclusion criteria, 19 were analyzed (13 for UA-PI, 10 for MCA-PI and five for CPR). Wide discrepancies in reported Doppler reference values at clinically relevant cut-offs were found. MCA-PI showed the greatest variability, with differences of up to 51% in the 5th percentile value at term. Variability in the 95th percentile of UA-PI and the 5th percentile of CPR at each gestational week ranged from 21% to 41% and 15% to 33%, respectively. As expected, on simulation analysis, these differences in Doppler cut-off values were associated with significant variation in the clinical management of SGA fetuses, despite using the same protocol. CONCLUSIONS: The choice of Doppler reference chart can result in significant variation in the clinical management of SGA fetuses, which may lead to suboptimal outcomes and inaccurate research conclusions. Therefore, an attempt to standardize fetal Doppler reference ranges is needed. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Reference ranges for Doppler indices of umbilical and fetal middle cerebral arteries and cerebroplacental ratio: systematic review.

OBJECTIVE: To assess studies reporting reference ranges for umbilical artery (UA) and fetal middle cerebral artery (MCA) Doppler indices and cerebroplacental ratio (CPR), using a set of predefined methodological quality criteria for study design, statistical analysis and reporting methods. METHODS: This was a systematic review of observational studies in which the primary aim was to create reference ranges for UA and MCA Doppler indices and CPR in fetuses of singleton gestations. A search for relevant articles was performed in MEDLINE, EMBASE, CINAHL, Web of Science (from inception to 31 December 2016) and references of the retrieved articles. Two authors independently selected studies, assessed the risk of bias and extracted the data. Studies were scored against a predefined set of independently agreed methodological criteria and an overall quality score was assigned to each study. Linear multiple regression analysis assessing the association between quality scores and study characteristics was performed. RESULTS: Thirty-eight studies met the inclusion criteria. The highest potential for bias was noted in the following fields: 'ultrasound quality control measures', in which only two studies demonstrated a comprehensive quality-control strategy; 'number of measurements taken for each Doppler variable', which was apparent in only three studies; 'sonographer experience', in which no study on CPR reported clearly the experience or training of the sonographers, while only three studies on UA Doppler and four on MCA Doppler did; and 'blinding of measurements', in which only one study, on UA Doppler, reported that sonographers were blinded to the measurement recorded during the examination. Sample size estimations were present in only seven studies. No predictors of quality were found on multiple regression analysis. Reference ranges varied significantly with important clinical implications for what is considered normal or abnormal, even when restricting the analysis to the highest scoring studies. CONCLUSIONS: There is considerable methodological heterogeneity in studies reporting reference ranges for UA and MCA Doppler indices and CPR, and the resulting references have important implications for clinical practice. There is a need for the standardization of methodologies for Doppler velocimetry and for the development of reference standards, which can be correctly interpreted and applied in clinical practice. We propose a set of recommendations for this purpose. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Intervalos de referencia para los índices Doppler de la arterias umbilical y cerebral media del feto y la relación cerebroplacentaria: una revisión sistemática OBJETIVO: Evaluar los estudios que informan sobre intervalos de referencia para los índices Doppler y la relación cerebroplacentaria (RCP) de la arteria umbilical (AU) y la arteria cerebral media (ACM) del feto, mediante un conjunto de criterios de calidad metodológica predefinidos para el diseño del estudio, el análisis estadístico y los métodos de notificación. MÉTODOS: Esta fue una revisión sistemática de estudios observacionales en los que el objetivo principal fue crear intervalos de referencia para los índices Doppler de la AU y la ACM y la RCP de fetos de gestaciones con feto único. Se realizó una búsqueda de artículos relevantes en MEDLINE, EMBASE, CINAHL, Web of Science (desde el inicio hasta el 31 de diciembre de 2016) y en las referencias de los artículos recuperados. Dos autores, de forma independiente, seleccionaron los estudios, evaluaron el riesgo de sesgo y extrajeron los datos. Los estudios se calificaron según un conjunto predefinido de criterios metodológicos acordados de forma independiente y se asignó una puntuación de calidad global a cada estudio. Se realizó un análisis de regresión múltiple lineal para evaluar la asociación entre las puntuaciones de calidad y las características del estudio. RESULTADOS: Un total de 38 estudios cumplieron los criterios de inclusión. El mayor potencial de sesgo se observó en los siguientes casos: 'medidas de control de calidad del ultrasonido', donde sólo dos estudios demostraron una estrategia integral de control de calidad; 'número de mediciones tomadas para cada variable Doppler', que solo fue aparente en tres estudios; 'experiencia del ecografista', puesto que ningún estudio sobre la RCP informó claramente sobre la experiencia o la formación de los ecografistas, y tan solo lo hicieron tres estudios sobre el Doppler de la AU y cuatro sobre el Doppler de la ACM; y 'mediciones a ciegas', donde tan sólo un estudio sobre el Doppler de la AU comunicó que los ecografistas no tuvieron acceso a la medición registrada durante el estudio. Las estimaciones del tamaño de la muestra sólo se comunicaron en siete estudios. No se encontraron predictores de calidad en el análisis de regresión múltiple. Los intervalos de referencia variaron significativamente con implicaciones clínicas importantes para lo que se considera normal o anómalo, incluso cuando se restringió el análisis a los estudios con mayor puntuación. CONCLUSIONES: Existe una heterogeneidad metodológica considerable en los estudios que informan sobre los intervalos de referencia para los índices Doppler de la AU y la ACM y la RCP, y las referencias resultantes tienen implicaciones importantes para la práctica clínica. Es necesario estandarizar las metodologías de la velocimetría Doppler y desarrollar estándares de referencia que puedan ser interpretados y aplicados correctamente en la práctica clínica. Se propone una serie de recomendaciones para este fin.

Socio-epidemiological characterisation of blood donors with asymptomatic Leishmania infantum infection from three Brazilian endemic regions and analysis of the transfusional transmission risk of visceral leishmaniasis.

OBJECTIVES: This study assessed the prevalence of visceral leishmaniasis in blood donors from three endemic regions in Brazil and evaluated the risk of transmission by transfusion. BACKGROUND: Despite strong evidence of the transmission of visceral leishmaniasis through blood transfusion, the real risk, an essential condition for taking effective measures to control this serious disease, has not been determined. METHODS: A multicentre study was performed in highly endemic areas. Candidates eligible for their first blood donation underwent a socio-epidemiological interview, and blood samples were collected for enzyme-linked immunosorbent assay (ELISA) analysis, Western blot and polymerase chain reaction (PCR). Patients transfused with red blood cells or random platelet concentrates collected from these donors were also studied. The results were analysed using descriptive statistics and prevalence estimates, with significance defined as p-values <0·05. RESULTS: Of the 608 eligible donors, 37 (6·1%) were positive for visceral leishmaniasis as per ELISA. The socio-epidemiological analysis showed a significantly higher prevalence in non-Caucasians (p = 0·008). Among 296 patients who received blood components from these donors, the pre-transfusion seropositivity was 7·7%, and 13 patients received blood positive for Leishmania infantum. Six patients were followed up for 90 days, of which two (33·3%) had serological conversion at 60 days. CONCLUSIONS: The results confirm the high prevalence of L. infantum seropositivity among donors in the three regions; the seroconversion in a short period of time in two of six patients suggests the possibility of transmission of the infection by transfusion.

[Synaptic plasticity as a substrate of resilience]. / Plasticidad sinaptica como sustrato de la resiliencia.

INTRODUCTION: Adverse life experiences promote the development of mental illness such as depression, anxiety or schizophrenia. However, some individuals are capable to overcome adversity, achieving a physical and psychological normal development; this process is known as resilience. AIM: To discuss the neuronal substrates of resilience. DEVELOPMENT: We propose that resilience at neuronal level needs systems for representing and evaluating the context (adverse situation) in order to display an adequate behavioural output, and for reorganizing memory associated to the adverse situation in order to tell a new story using the same elements of experience; this is, a system that allows to reorganize neuronal ensembles associated to the adverse memory. In this sense, it is not coincidence that neuronal substrates involving in resilience include the reward-guided behavior system (nucleus accumbens-ventral tegmental area), the emotional system (amygdala-hippocampus), the stress system (hypothalamus-pituitary-adrenal) and the system for context evaluation, representation and discrimination (prefrontal cortex-hippocampus). We emphasize that each adverse experience shapes both the activity of the resilience neuronal system and the behavioral output. CONCLUSIONS: We propose that synaptic plasticity in structures for representing and evaluating context is the neuronal substrate of resilience. Specifically, cortico-hippocampal interactions would allow to re-build adverse experiences through the reorganization of neuronal ensembles.

TITLE: Plasticidad sinaptica como sustrato de la resiliencia.Introduccion. Las experiencias adversas facilitan el desarrollo de enfermedades mentales como la depresion, la ansiedad o la esquizofrenia. Sin embargo, algunos individuos muestran capacidades para superar la adversidad logrando un desarrollo fisico y psicologico adecuado; este proceso se conoce como resiliencia. Objetivo. Discutir cual es el sustrato neuronal de la resiliencia. Desarrollo. Se plantea que la resiliencia, neuronalmente, necesita sistemas que representen y evaluen el contexto (la situacion adversa) para dar una salida conductual adecuada, y que reorganicen la memoria de la situacion adversa para poder contar otro relato a partir de los mismos elementos de la experiencia, es decir, un sistema que permita reorganizar los ensambles neuronales de dicha memoria. En este sentido, no es casualidad que los sustratos neuronales involucrados en la resiliencia incluyan al sistema de la motivacion-accion-recompensa (nucleo accumbens-area tegmental ventral), de las emociones (amigdala-hipocampo), del estres (eje hipotalamo-hipofiso-adrenal) y de la representacion, evaluacion y discriminacion del contexto (corteza prefrontal-hipocampo). Se hace enfasis en mostrar como las experiencias adversas especificas modulan tanto la actividad del sistema neuronal de la resiliencia como la salida conductual de cada individuo. Conclusiones. Se propone que la plasticidad sinaptica en estructuras que representan y evaluan el contexto son el sustrato neuronal de la resiliencia. Especificamente, las interacciones corticohipocampicas permitirian la reestructuracion de las experiencias adversas a traves de la reorganizacion de los ensambles neuronales.

[From neuronal recovery to the reorganisation of neuronal circuits: a review of the functions of sleep]. / De la restauración neuronal a la reorganización de los circuitos neuronales: una aproximación a las funciones del sueño.

AIM: To analyse the data and concepts that have been produced in relation to one of the functions that have been suggested for sleep, namely, neuronal recovery. DEVELOPMENT: Sleep is a state of consciousness that is different to that of arousal. Mammals devote an important part of their lives to sleeping; for example, as humans, we sleep for a third of our lives, but why do we spend so much time in a state where we lose contact with our surroundings? What would happen if we didn't sleep? Total sleep deprivation alters cognitive processes such as memory or attention, and if this deprivation is prolonged, the individual deteriorates and dies. It has been suggested that sleep provides the organism with time to recover from the wear and tear that occurs during the waking state and, given that the first effects of the absence of sleep are seen to affect processes that are directly dependent on the brain, it has been claimed that its main purpose is to allow neuronal recovery. In this work we analyse some of the studies on the effects of total sleep deprivation in humans and rats, as well as the relationship between sleep and the neurotrophin system, which promotes neuronal survival and recovery. Finally, the latest theories about the function of sleep are discussed. CONCLUSIONS: Neuron recovery is not the ultimate purpose of sleep; rather it is to allow for maintenance and reorganisation of neuronal circuits, including new synapse formation, which enables existing neuronal networks to be modified by the effect of experience, and all this makes it possible for the brain to work properly and to adapt itself to the environment.

De la restauración neuronal a la reorganización de los circuitos neuronales: una aproximación a las funciones del sueño / From neuronal recovery to the reorganisation of neuronal circuits: a review of the functions of sleep

Objetivo. Analizar datos y conceptos que se han generadoen torno a una de las funciones propuestas para el sueño: la restauraciónneuronal. Desarrollo. El sueño es un estado de concienciadiferente de la vigilia. Los mamíferos invierten una buena partede su vida en dormir; por ejemplo, los humanos dormimos una terceraparte de nuestra vida, pero ¿para qué invertir tanto tiempo enun estado donde perdemos contacto con el entorno?, ¿qué pasaríasi no durmiéramos? La privación de sueño total altera procesoscognitivos, como la memoria o la atención; si esta privación seprolonga, el sujeto se deteriora y muere. Se ha propuesto que elsueño sirve para restaurar a los organismos del desgaste ocurridodurante la vigilia y, dado que los primeros efectos de la ausenciade sueño se observan en procesos que dependen directamente delcerebro, se ha sugerido que la restauración neuronal es su principalobjetivo. En este trabajo se analizan algunos estudios sobre losefectos de la privación de sueño total en humanos y ratas, así comola relación entre el sueño y el sistema de las neurotrofinas, el cualpromueve la supervivencia y la restauración neuronal. Finalmente,se discuten teorías recientes sobre la función del sueño. Conclusiones.La restauración de las neuronas no es el fin último del sueño,sino mantener y reorganizar los circuitos neuronales, incluyendo laneoformación de sinapsis, que permiten modificar redes neuronalesexistentes, por efecto de la experiencia, y todo esto para el adecuadofuncionamiento del cerebro y su adaptación al ambiente

Aim. To analyse the data and concepts that have been produced in relation to one of the functions that have beensuggested for sleep, namely, neuronal recovery. Development. Sleep is a state of consciousness that is different to that ofarousal. Mammals devote an important part of their lives to sleeping; for example, as humans, we sleep for a third of our lives,but why do we spend so much time in a state where we lose contact with our surroundings? What would happen if we didn’tsleep? Total sleep deprivation alters cognitive processes such as memory or attention, and if this deprivation is prolonged, theindividual deteriorates and dies. It has been suggested that sleep provides the organism with time to recover from the wear andtear that occurs during the waking state and, given that the first effects of the absence of sleep are seen to affect processes thatare directly dependent on the brain, it has been claimed that its main purpose is to allow neuronal recovery. In this work weanalyse some of the studies on the effects of total sleep deprivation in humans and rats, as well as the relationship betweensleep and the neurotrophin system, which promotes neuronal survival and recovery. Finally, the latest theories about thefunction of sleep are discussed. Conclusions. Neuron recovery is not the ultimate purpose of sleep; rather it is to allow formaintenance and reorganisation of neuronal circuits, including new synapse formation, which enables existing neuronalnetworks to be modified by the effect of experience, and all this makes it possible for the brain to work properly and to adaptitself to the environment