Free thyroxine measurement in clinical practice: how to optimize indications, analytical procedures, and interpretation criteria while waiting for global standardization

Thyroid dysfunctions are among the most common endocrine disorders and accurate biochemical testing is needed to confirm or rule out a diagnosis. Notably, true hyperthyroidism and hypothyroidism in the setting of a normal thyroid-stimulating hormone level are highly unlikely, making the assessment of free thyroxine (FT4) inappropriate in most new cases. However, FT4 measurement is integral in both the diagnosis and management of relevant central dysfunctions (central hypothyroidism and central hyperthyroidism) as well as for monitoring therapy in hyperthyroid patients treated with anti-thyroid drugs or radioiodine. In such settings, accurate FT4 quantification is required. Global standardization will improve the comparability of the results across laboratories and allow the development of common clinical decision limits in evidence-based guidelines. The International Federation of Clinical Chemistry and Laboratory Medicine Committee for Standardization of Thyroid Function Tests has undertaken FT4 immunoassay method comparison and recalibration studies and developed a reference measurement procedure that is currently being validated. However, technical and implementation challenges, including the establishment of different clinical decision limits for distinct patient groups, still remain. Accordingly, different assays and reference values cannot be interchanged. Two-way communication between the laboratory and clinical specialists is pivotal to properly select a reliable FT4 assay, establish reference intervals, investigate discordant results, and monitor the analytical and clinical performance of the method over time

Differences in zinc status and the leptin axis in anorexic and recovered adolescents and young adults: a pilot study

Evidence from animal studies suggests that leptin metabolism is associated with zinc (Zn) status. However, research investigating this relationship in adolescents and young adults with anorexia nervosa (AN) is scarce; the present study aims to fill that gap.Serum concentrations of leptin, the soluble leptin receptor (sOB-R) and the free leptin index (FLI) were obtained in healthy control subjects (n=19), acutely ill individuals (n=14) and recovered patients with AN (n=15). Serum Zn concentrations noted in previous research data were also incorporated for all groups.Leptin, FLI and Zn concentrations were higher in recovered subjects with AN when compared with acutely ill AN patients. Remitted patients showed higher sOB-R concentrations but no difference in FLI compared with the control group. Leptin and FLI were lower in the acutely ill patients compared with the control subjects, who showed no differences in Zn concentrations. Zn concentrations were not correlated with leptin, sOB-R or FLI concentrations in any of the three investigated subgroups.The present investigation does not entirely support an association between Zn, Leptin and FLI concentrations in subjects with AN, possibly due to limited statistical power. Further research and replication of the present findings related to the interaction between leptin and Zn is warranted. However, with respect to serum leptin levels the data of the present investigation indicate that acutely ill and remitted patients with AN differ as regards serum leptin concentrations and FLI, which is in line with previous research

Hydrodynamic modeling of mineral wool fiber suspensions in a two-dimensional flow

A consequence of a loss of coolant accident is that the local insulation material is damaged and maybe transported to the containment sump where it can penetrate and/or block the sump strainers. An experimental and theoretical study, which examines the transport of mineral wool fibers via single and multi-effect experiments is being performed. This paper focuses on the experiments and simulations performed for validation of numerical models of sedimentation and resuspension of mineral wool fiber agglomerates in a racetrack type channel. Three velocity conditions are used to test the response of two dispersed phase fiber agglomerates to two drag correlations and to two turbulent dispersion coefficients. The Eulerian multiphase flow model is applied with either one or two dispersed phases

Verification and validation of numerical models of the transport of insulation debris

Damage to insulation materials located near to a primary circuit coolant leak may compromise the operation of the emergency core cooling system (ECCS). Insulation material in the form of mineral wool fiber agglomerates (MWFA) maybe transported to the containment sump strainers, where they may block or penetrate the strainers. Though the impact of MWFA on the pressure drop across the strainers is minimal, corrosion products formed over time may also accumulate in the fiber cakes on the strainers, which can lead to a significant increase in the strainer pressure drop and result in cavitation in the ECCS. An experimental and theoretical study performed by the Helmholtz-Zentrum Dresden-Rossendorf and the Hochschule Zittau/Görlitz is investigating the phenomena that maybe observed in the containment vessel during a primary circuit coolant leak. The study entails the generation of fiber agglomerates, the determination of their transport properties in single and multi-effect experiments and the long-term effect that corrosion and erosion of the containment internals by the coolant has on the strainer pressure drop. The focus of this paper is on the verification and validation of numerical models that can predict the transport of MWFA. A number of pseudo-continuous dispersed phases of spherical wetted agglomerates represent the MWFA. The size, density, the relative viscosity of the fluid-fiber agglomerate mixture and the turbulent dispersion all affect how the fiber agglomerates are transported. In the cases described here, the size is kept constant while the density is modified. This definition affects both the terminal velocity and volume fraction of the dispersed phases. Note that the relative viscosity is only significant at high concentrations. Three single effect experiments were used to provide validation data on the transport of the fiber agglomerates under conditions of sedimentation in quiescent fluid, sedimentation in a horizontal flow and suspension in a horizontal flow. The experiments were performed in a rectangular column for the quiescent fluid and a racetrack type channel that provided a near uniform horizontal flow. The numerical models of sedimentation in the column and the racetrack channel found that the sedimentation characteristics are consistent with the experiments. For channel suspension, the heavier fibers tend to accumulate at the channel base even at high velocities, while lighter phases are more likely to be transported around the channel

Fibre agglomerate transport in a horizontal flow

An experimental and theoretical study of the transport of mineral wool fibre agglomerates in nuclear power plant containment sumps is being performed. A racetrack channel was devised to provide data for the validation of numerical models, which are intended to model the transport of fibre agglomerates. The racetrack channel provides near uniform and steady conditions that lead to either the sedimentation or suspension of the agglomerates. Various experimental techniques were used to determine the velocity conditions and the distribution of the fibre agglomerates in the channel. The fibre agglomerates are modelled as fluid particles in the Eulerian reference frame. Simulations of pure sedimentation of a known mass and volume of agglomerations show that the transport of the fibre agglomerates can be replicated. The suspension of the fibres is also replicated in the simulations; however, the definition of the fibre agglomerate phase is strongly dependent on the selected density and diameter. Detailed information on the morphology of the fibre agglomerates is lacking for the suspension conditions, as the fibre agglomerates may undergo breakage and erosion. Therefore, ongoing work, which is described here, is being pursued to improve the experimental characterisation of the suspended transport of the fibre agglomerates

Increased serum NSE and S100B indicate neuronal and glial alterations in subjects under 71 years with mild neurocognitive disorder/mild cognitive impairment

Background: Mild cognitive impairment (MCI) is considered a pre-stage of different dementia syndromes. Despite diagnostic criteria refined by DSM-5 and a new term for MCI - "mild neurocognitive disorder" (mild NCD) - this diagnosis is still based on clinical criteria.Methods: To link mild NCD to the underlying pathophysiology we assessed the degree of white matter hyperintensities (WMH) in the brain and peripheral biomarkers for neuronal integrity (neuron-specific enolase, NSE), plasticity (brain-derived neurotrophic factor, BDNF), and glial function (S100B) in 158 community-dwelling subjects with mild NCD and 82 healthy controls. All participants (63-79 years old) were selected from the Leipzig-population-based study of adults (LIFE).Results: Serum S100B levels were increased in mild NCD in comparison to controls (p = 0.007). Serum NSE levels were also increased but remained non-significant after Bonferroni-Holm correction (p = 0.04). Furthermore, age by group interaction was significant for S100B. In an age-stratified sub-analysis, NSE and S100B were higher in younger subjects with mild NCD below 71 years of age. Some effects were inconsistent after controlling for potentially confounding factors. The discriminatory power of the two biomarkers NSE and S100B was insufficient to establish a pathologic threshold for mild NCD. In subjects with mild NCD, WMH load correlated with serum NSE levels (r = 0.20, p = 0.01), independently of age.Conclusion: Our findings might indicate the presence of neuronal (NSE) and glial (S100B) injury in mild NCD. Future studies need to investigate whether younger subjects with mild NCD with increased biomarker levels are at risk of developing major NCD

Hydrodynamic modeling of mineral wool fiber suspensions in a two-dimensional channel flow

A consequence of a loss of coolant accident is the damage of adjacent insulation materials (IM). IM may then be transported to the containment sump strainers where water is drawn into the ECCS (emergency core cooling system). Blockage of the strainers by IM lead to an increased pressure drop acting on the operating ECCS pumps. IM can also penetrate the strainers, enter the reactor coolant system and then accumulate in the reactor pressure vessel. An experimental and theoretical study that concentrates on mineral wool fiber transport in the containment sump and the ECCS is being performed. The study entails fiber generation and the assessment of fiber transport in single and multi-effect experiments. The experiments include measurement of the terminal settling velocity, the strainer pressure drop, fiber sedimentation and resuspension in a channel flow and jet flow in a rectangular tank. An integrated test facility is also operated to assess the compounded effects. Each experimental facility is used to provide data for the validation of equivalent computational fluid dynamic models. The channel flow facility allows the determination of the steady state distribution of the fibers at different flow velocities. The fibers are modeled in the Eulerian-Eulerian reference frame as spherical wetted agglomerates. The fiber agglomerate size, density, the relative viscosity of the fluid-fiber mixture and the turbulent dispersion of the fibers all affect the steady state accumulation of fibers at the channel base. In the current simulations, two fiber phases are separately considered. The particle size is kept constant while the density is modified, which affects both the terminal velocity and volume fraction. The relative viscosity is only significant at higher concentrations. The numerical model finds that the fibers accumulate at the channel base even at high velocities; therefore, modifications to the drag and turbulent dispersion forces can be made to reduce fiber accumulation

Association of estradiol and visceral fat with structural brain networks and memory performance in adults

Importance Changes in estradiol during aging are associated with increased dementia risk. It remains unclear how estradiol supports cognitive health and whether risk factors, such as midlife obesity, are exacerbated by estrogen loss. Objectives To assess whether visceral adipose tissue (VAT) moderates the association between age and brain network structure and to investigate whether estradiol moderates the association between VAT and brain network structure. Design, Setting, and Participants Cross-sectional study of data from 974 cognitively healthy adults in Germany who participated in the Health Study of the Leipzig Research Centre for Civilization Diseases, a previously described population-based cohort study. Two moderation analyses were performed, including VAT as the moderator variable between age and brain network structure and estradiol as the moderator variable between VAT and brain network structure. The study was conducted from August 1, 2011, to November 23, 2014. Analyses were conducted from August 2017 to September 201

A metabolic obesity profile is associated with decreased gray matter volume in cognitively healthy older adults

Obesity is a risk factor for cognitive decline and gray matter volume loss in aging. Studies have shown that different metabolic factors, e.g., dysregulated glucose metabolism and systemic inflammation, might mediate this association. Yet, even though these risk factors tend to co-occur, they have mostly been investigated separately, making it difficult to establish their joint contribution to gray matter volume structure in aging. Here, we therefore aimed to determine a metabolic profile of obesity that takes into account different anthropometric and metabolic measures to explain differences in gray matter volume in aging. We included 748 elderly, cognitively healthy participants (age range: 60 – 79 years, BMI range: 17 – 42 kg/m2) of the LIFE-Adult Study. All participants had complete information on body mass index, waist-to-hip ratio, glycated hemoglobin, total blood cholesterol, high-density lipoprotein, interleukin-6, C-reactive protein, adiponectin and leptin. Voxelwise gray matter volume was extracted from T1-weighted images acquired on a 3T Siemens MRI scanner. We used partial least squares correlation to extract latent variables with maximal covariance between anthropometric, metabolic and gray matter volume and applied permutation/bootstrapping and cross-validation to test significance and reliability of the result. We further explored the association of the latent variables with cognitive performance. Permutation tests and cross-validation indicated that the first pair of latent variables was significant and reliable. The metabolic profile was driven by negative contributions from body mass index, waist-to-hip ratio, glycated hemoglobin, C-reactive protein and leptin and a positive contribution from adiponectin. It positively covaried with gray matter volume in temporal, frontal and occipital lobe as well as subcortical regions and cerebellum. This result shows that a metabolic profile characterized by high body fat, visceral adiposity and systemic inflammation is associated with reduced gray matter volume and potentially reduced executive function in older adults. We observed the highest contributions for body weight and fat mass, which indicates that factors underlying sustained energy imbalance, like sedentary lifestyle or intake of energy-dense food, might be important determinants of gray matter structure in aging