Reference measurement procedure for total bilirubin in serum re-evaluated and measurement uncertainty determined.

BACKGROUND: For the determination of total bilirubin in serum the candidate reference method developed by Doumas et al. has international recognition. The primary standard SRM 916a (NIST) was recommended for use as the primary reference material for calibration. Nowadays, no primary standard is anymore commercially available. Further, a description of uncertainty components was missing. METHODS: Two reference laboratories have re-investigated the candidate reference measurement procedure. Beside minor modifications, mainly the use of a molar absorption coefficient instead of calibration by use of bilirubin standard solutions has facilitated the operating, and improved the analytical performance. All relevant sources of measurement uncertainty were investigated. RESULTS: A measurement range of 5-525 µmol/L and a CV of 0.5% to 1.4% (long term imprecision) were determined. Excellent agreement was obtained comparing to Doumas procedure (r = 0.9999) and during a two laboratory comparison participating at IFCC RELA ring trials (mean deviation: 0.6%). The combined expanded measurement uncertainty (probability 95%) for bilirubin concentrations >30 µmol/L was estimated as 2.2%. CONCLUSION: A reference system for total bilirubin based on the described reference procedure shall enable metrological traceability and optimized standardization of the values obtained in clinical routine laboratories.

Effects of progesterone on hyperoxia-induced damage in mouse C8-D1A astrocytes.

INTRODUCTION: The birth of most mammals features a dramatic increase in oxygen while placenta-derived hormones such as ß-estradiol and progesterone plummet. In experimental newborn animals, transiently elevated oxygen concentrations cause death of neurons, astrocytes, and oligodendrocyte precursors. High oxygen has been associated with cerebral palsy in human preterm infants while progesterone is being used to prevent preterm delivery and investigated as a neuroprotective agent. METHODS: In this study, we investigated the effects of hyperoxia (80% O2 for 24, 48, and 72 h) on cultured C8-D1A astrocytes in the presence or absence of progesterone at concentrations ranging from 10(-9) to 10(-5) mol/L. RESULTS: Hyperoxia measured by methytetrazolium assay (MTT) reduced cell viability, increased release of lactate dehydrogenase (LDH), reduced carboxyfluorescein diacetate succinimidyl ester (CFSE)-assessed cell proliferation, and downregulated Cylin D2 expression. Progesterone did not affect any of these hyperoxia-mediated indicators of cell death or malfunctioning. Real-time PCR analysis showed that hyperoxia caused downregulation of the progesterone receptors PR-AB und PR-B. CONCLUSIONS: Our experiments showed that there was no protective effect of progesterone on hyperoxia-inducted cell damage on mouse C8-D1A astrocytes. Down regulation of the progesterone receptors might be linked to the lack of protective effects.

Thinking about thinking: Neural mechanisms and effects on memory.

It is a well-established finding that memory encoding is impaired if an external secondary task (e.g. tone discrimination) is performed simultaneously. Yet, while studying we are also often engaged in internal secondary tasks such as planning, ruminating, or daydreaming. It remains unclear whether such a secondary internal task has similar effects on memory and what the neural mechanisms underlying such an influence are. We therefore measured participants' blood oxygenation level dependent responses while they learned word-pairs and simultaneously performed different types of secondary tasks (i.e., internal, external, and control). Memory performance decreased in both internal and external secondary tasks compared to the easy control condition. However, while the external task reduced activity in memory-encoding related regions (hippocampus), the internal task increased neural activity in brain regions associated with self-reflection (anterior medial prefrontal cortex), as well as in regions associated with performance monitoring and the perception of salience (anterior insula, dorsal anterior cingulate cortex). Resting-state functional connectivity analyses confirmed that anterior medial prefrontal cortex and anterior insula/dorsal anterior cingulate cortex are part of the default mode network and salience network, respectively. In sum, a secondary internal task impairs memory performance just as a secondary external task, but operates through different neural mechanisms.

Does "thinking about thinking" interfere with memory? An experimental memory study in obsessive-compulsive disorder.

Neuropsychological assessments of participants with obsessive-compulsive disorder (OCD) indicate impaired verbal memory if to be remembered material has to be organized. People with OCD also tend to focus their attention on their thoughts (heightened cognitive self-consciousness). We tested the hypothesis that cognitive self-consciousness causes verbal memory deficits by provoking a division of attention between study task and thoughts. Thirty-six participants with OCD, 36 matched healthy controls and 36 participants with major depressive disorder (MDD) learned under proactive interference in three study conditions: single-task condition, condition with heightened cognitive self-consciousness and condition with an external secondary task. Memory was impaired in the cognitive self-consciousness condition compared to both other conditions. Independent of condition, participants with OCD showed a reduced memory performance compared to healthy controls, but did not differ from participants with MDD. Our results are in line with the hypothesis that cognitive self-consciousness causes memory impairment.

The effect of sleep-specific brain activity versus reduced stimulus interference on declarative memory consolidation.

Studies suggest that the consolidation of newly acquired memories and underlying long-term synaptic plasticity might represent a major function of sleep. In a combined repeated-measures and parallel-group sleep laboratory study (active waking versus sleep, passive waking versus sleep), we provide evidence that brief periods of daytime sleep (42.1 ± 8.9 min of non-rapid eye movement sleep) in healthy adolescents (16 years old, all female), compared with equal periods of waking, promote the consolidation of declarative memory (word-pairs) in participants with high power in the electroencephalographic sleep spindle (sigma) frequency range. This observation supports the notion that sleep-specific brain activity when reaching a critical dose, beyond a mere reduction of interference, promotes synaptic plasticity in a hippocampal-neocortical network that underlies the consolidation of declarative memory.

Interlaboratory comparison of the Doumas bilirubin reference method.

OBJECTIVES: To assess the performance of the Doumas bilirubin reference method. DESIGN AND METHODS: Ring trails using pooled patient specimens, a calibrator and human sera enriched with unconjugated bilirubin were analyzed in five laboratories using the Doumas bilirubin reference method. RESULTS: The coefficient of variation for the linear measurement range between laboratories ranged from 1-3%. CONCLUSIONS: The Doumas bilirubin reference method is robust and reproducible. Bilirubin results using this method may be used in the development of more accurate and reliable calibrators.