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Serum selenium concentration of a healthy northwest Spanish population.

Selenium (Se) is an essential element, cofactor for glutathione peroxidase (GSHPx) activity, whose deficiency may induce modifications in the cellular antioxidative status and induce the appearance of different diseases. Current views suggest that a serum Se concentration inferior to 45 micrograms/L may correlate with an increased risk of coronary hearth diseases, coronary atherosclerosis and cancer. Since the Se concentration in human blood varies between geographical areas, we initiated a study to evaluate the Se status in the general healthy population of Barcelona. Serum Se concentration was investigated in a random sample of 150 subjects (age range 18-70 yr) by graphite furnace atomic spectrometry (FLAAS). L'vov platform, Zeeman background correction, and other specifications of stabilized temperature platform furnace (STPF) concept were followed. The results show that in the general population of Barcelona, Se serum concentration ranges between 60 and 106 micrograms/L (X = 80.7 +/- 10 micrograms/L). These values can be considered within the safe limits, since no subject was found with a concentration lower than the threshold of 45 micrograms/L.

Adolescent↗

Simple but reliable solutions for spiral MRI gradient design.

The efficiency of gradient design in MRI is limited by the simple fact that the gradient coil current and slew rate cannot exceed hardware threshold values. In spiral MRI, which requires gradients to be very rapidly switched between positive and negative values, minimization of the acquisition time is achieved by maintaining the current and slew rate as high as possible during the entire measurement. Since the current and slew rate compete against each other, an efficient gradient design consists of two parts in which current and slew rate are pushed alternatively to their limits. Values for these types of gradients can be obtained by solving numerically the equation of motion for the spiral trajectory. This paper shows that simple but reasonable mathematical approximations deliver reliable analytical solutions. Images obtained using these analytical solutions do not show evident distortions when compared with images obtained with numerical solutions.

Algorithms↗

Deactivation kinetics of different components of calcium inward current in the membrane of mice sensory neurones.

1. Deactivation kinetics of different components of calcium inward current were analysed by measuring 'tail currents' in intracellularly perfused sensory neurones isolated from dorsal root ganglia of newborn mice. 2. Deactivation of a low-threshold inactivating component had a mono-exponential time course with time constants that decreased as the potential was made more negative, and reached a limiting value of 1.0-1.2 ms at extreme hyperpolarizations. Replacement of Ca2+ by Ba2+ as a charge carrier decreased this value almost twofold. 3. Deactivation of the high-threshold component of calcium current contained two exponential components with time constants of similar potential dependence. The fast time constant became practically constant (0.1-1.2 ms) during repolarizations beyond -50 mV, and the slow time constant became constant (0.80-0.85 ms) at repolarization beyond -70 mV. 4. Replacement of intracellular aspartate with phosphate, or a depolarized holding potential of -40 mV, abolished reversibly the slow component of the tail current; in parallel, the peak current-voltage relation of the current became shifted by 15-20 mV in the depolarizing direction. 5. Extracellular application of the calcium channel agonist Bay K 8644 (2.5-5 mumol/l) did not change deactivation kinetics of the low-threshold current; however, it increased considerably the slow exponential component of high-threshold current deactivation or induced such a component in conditions when the latter was absent before application (Vh = -40 mV; cell perfusion with Tris phosphate). 6. The data obtained are analysed on the basis of the presence of three types of calcium channels in the neuronal membrane which possess similar kinetic mechanisms of activation and deactivation but differ in the activation thresholds and the time constants of transitions between open and closed states. The three calcium channels differ also in interaction with different permeant ions and calcium channel agonists.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Assessment of exercise tolerance in chronic congestive heart failure.

In patients with chronic heart failure, exercise capacity is poorly related to cardiac hemodynamics, and peripheral circulation is an important determinant of exercise tolerance. The ability of the muscle vasculature to dilate is markedly impaired, in part, because of exaggerated neurohumoral activity increasing vascular wall stiffness. For this reason, increasing cardiac output is not sufficient to increase exercise capacity if not accompanied by improving vascular reactivity. The poor reliability and reproducibility of exercise tolerance assessed by maximal exercise duration or maximal attained work load (particularly on a treadmill) has led to widespread measurement of respiratory gas during exercise. Peak oxygen consumption (peak VO2), even if it is symptom-limited, has been shown to be a very reproducible criterion of exercise tolerance; moreover, because VO2 is the product of cardiac output and arteriovenous oxygen difference, it also has a qualitative hemodynamic significance. Ventilatory threshold can be determined before maximal exercise; however, problems of determination limit the practical value of this criterion. Unfortunately, peak VO2 lacks sensitivity to detect minor improvement or impairment of symptoms during daily life, although these are significant to the patient. Submaximal exercises have been proposed for this purpose and are currently being evaluated.

Exercise Test↗

Diagnosing broken ergodicity using an energy fluctuation metric.

The Mountain and Thirumalai energy fluctuation metric, Omega(t), has been used to study the effective ergodicity of 60- and 256-atom binary Lennard-Jones mixtures in order to determine the reliability of the calculated diffusion constants at different energies. A plot of Omega(t) against 1time allows the identification of two distinct regimes: ergodic supercooled liquids, where Omega(t) approaches zero, and nonergodic glassy states, where Omega(t) asymptotically approaches a nonzero value on the molecular dynamics time scale. This approach seems to be more appropriate than attempting to define a threshold value for Omega(t)/Omega(0). The behavior of systems between these two limits, which are nonergodic on the time scale considered but may be approaching ergodicity, was examined for a range of simulation times. The calculated diffusion constants change as effective ergodicity is approached, moving closer to the Vogel-Tammann-Fulcher fit defined by higher-energy systems that are already considered to be effectively ergodic. Using the form of the decay of the metric as a measure of ergodicity, we have been able to reproduce the trend in fragility obtained by Sastry for a 256-atom system [Nature (London) 409, 164 (2001)], correcting some of our earlier results [J. Chem. Phys. 120, 8314 (2004)].

Journal Article↗

A correlation of the rate of N-hydroxylation of aminoazo dyes with their carcinogenic activity in the rat.

The rate of formation of N-hydroxy-N-methyl-4-aminoazobenzene (N-OH-MAB) derivatives from N,N-dimethyl-4-aminoazobenzene (DAB) derivatives and from N-methyl-4-aminoazobenzene (MAB) derivatives was measured by the e.s.r. spectroscopy, and the rate of N-demethylation of DAB derivatives was measured by h.p.l.c. The rate of formation of N-OH-MAB derivatives from DAB derivatives showed a strong correlation with their carcinogenic activity. This reaction occurs in two-steps, i.e. N-demethylation followed by N-hydroxylation. The rate of N-demethylation of DAB derivatives was not correlated with their carcinogenic activity. On the other hand, the rate of N-hydroxylation of MAB derivatives was well correlated with the carcinogenic activity of corresponding DAB derivatives. These results suggest that the carcinogenic activity of DAB derivatives in the rat was dependent upon the enzyme concerned with N-hydroxylation. The positive carcinogenicity is limited to those derivatives with a rate of N-hydroxylation above the threshold value.

Animals↗

Plasma lipid concentrations: the concept of "normality" and its implications for detection of high cardiovascular risk.

The relation between serum cholesterol concentrations and the incidence of coronary heart disease is continuous and curvilinear; there is neither epidemiological nor biological evidence to support the existence of a threshold value. There is a clinical need, however, for an acceptable definition of action limits and desirable ranges, based on the evidence that raised cholesterol concentrations are causally related to atherosclerotic heart disease. The European Atherosclerosis Society has proposed a set of cut off points, which, together with age and the presence of other risk factors, direct the clinician to an appropriate level of treatment. Because the changes of serum cholesterol during adult life appear unphysiological, these action limits do not require adjustment for age. The distribution of serum cholesterol in the United Kingdom population is such that a case finding strategy is required to identify the many persons at very high risk of coronary disease. Measurements of triglyceride, high density lipoprotein, apolipoproteins, and the investigation of hyperlipoproteinemia are informative but less mandatory.

Adult↗

Actinides in deer tissues at the rocky flats environmental technology site.

Limited hunting of deer at the future Rocky Flats National Wildlife Refuge has been proposed in U.S. Fish and Wildlife planning documents as a compatible wildlife-dependent public use. Historically, Rocky Flats site activities resulted in the contamination of surface environmental media with actinides, including isotopes of americium, plutonium, and uranium. In this study, measurements of actinides [Americium-241 (241Am); Plutonium-238 (238Pu); Plutonium-239,240 (239,240Pu); uranium-233,244 (233,234U); uranium-235,236 (235,236U); and uranium-238 (238U)] were completed on select liver, muscle, lung, bone, and kidney tissue samples harvested from resident Rocky Flats deer (N = 26) and control deer (N = 1). In total, only 17 of the more than 450 individual isotopic analyses conducted on Rocky Flats deer tissue samples measured actinide concentrations above method detection limits. Of these 17 detects, only 2 analyses, with analytical uncertainty values added, exceeded threshold values calculated around a 1 x 10(-6) risk level (isotopic americium, 0.01 pCi/g; isotopic plutonium, 0.02 pCi/g; isotopic uranium, 0.2 pCi/g). Subsequent, conservative risk calculations suggest minimal human risk associated with ingestion of these edible deer tissues. The maximum calculated risk level in this study (4.73 x 10(-6)) is at the low end of the U.S. Environmental Protection Agency's acceptable risk range.

Animals↗

The Topcon SP 1000 and Image-NET systems. A comparison of four methods for evaluating corneal endothelial cell density.

The objective of this study was to compare four methods of counting corneal endothelial cell density using the Topcon SP 1000 microscope and Image-NET digital graphic software. Two independent observers quantified cell density from 63 endothelial photomicrographs using the various standardized techniques. The first method was that suggested for use with Topcon SP 1000, employing five different reference grids to compare subjectively with the endothelial cell density of the unknown sample. The other three methods involved the automated, semiautomated, and manual procedures developed for use with the Image-NET system software. The manual Image-NET system is presently considered to yield accurate cell morphology data. Confidence limits and standard errors of mean differences between values obtained by different methods were used to evaluate agreement and reproducibility of computerized methods. Sensitivity and specificity were calculated for two different threshold limits of endothelial cell density. Results showed that the automated Image-NET system is not reliable for clinical use because of its poor agreement with other methods and its lack of sensitivity and specificity at the selected threshold limits of endothelial cell density. The comparative Topcon method of using reference grids, although inexpensive and accurate for 500 cell/mm2 increments, was considered too imprecise for most clinical situations. The semiautomated Image-NET system, in half the analysis time required by the manual method, provided endothelial cell count estimates that were not clinically different from those obtained with manual counting.

Cell Count↗

Hydrodynamic fluctuations in the Kolmogorov flow: linear regime.

The Landau-Lifshitz fluctuating hydrodynamics is used to study the statistical properties of the linearized Kolmogorov flow. The relative simplicity of this flow allows a detailed analysis of the fluctuation spectrum from near equilibrium regime up to the vicinity of the first convective instability threshold. It is shown that in the long time limit the flow behaves as an incompressible fluid, regardless of the value of the Reynolds number. This is not the case for the short time behavior where the incompressibility assumption leads in general to a wrong form of the static correlation functions, except near the instability threshold. The theoretical predictions are confirmed by numerical simulations of the full nonlinear fluctuating hydrodynamic equations.

Journal Article↗

A survey on noise exposure level in an aluminum can production plant.

The present investigation was designed to quantify noise exposure of laborers at various sections of an aluminum can production plant. The acoustic environment in each area was described by sound pressure level (SPL). Decibel (dB) readings were taken for a range of individual frequencies and weighting scales (A and C). Speech interference level (SIL) values for laborers in different production sections were also determined. Moreover, by means of a personal noise dosimetry technique, the equivalent continuous noise exposure level (dB(A)) during an 8-h shift (Leq, 8) was computed. The results obtained were as follows. Spectral analysis of the noise indicated that high SPL associated with high frequency noise exceeded the permissible limit against hearing damage, and it generally amounted to levels higher than 90 dB(A), whereas those inside the control rooms were in the range of 54-60.5 dB(A). Assessment of the results obtained from personal noise dosimeters also revealed that the Leq,8 values were higher than the prescribed limit (85 dB(A)). By preliminary audiometric examinations on the right ears of workers, hearing threshold shifts (HTS) were noticed in the range of 7-11 dB at 1 kHz and 12-16 dB at 4 kHz. With regards to the SIL values (93.2-96.5 dB(A)) which were more than the maximum vocal effort, communication between workers and/or with supervisor were appraised to be very difficult (shouting) or impossible. It was concluded that (a) the dB readings observed in this survey indicate a potentially serious possibility of hearing disability, even though high level of HTS could not be noticed in the preliminary audiometric test, and (b) the risk of accidents should also be taken into account regarding the nonauditory effects of such a high level of noise. We suggest that (1) minimizing the transmission of noise through acoustical countermeasures need to be considered, and (2) introducing a schedule comprising on-time and off-time could be beneficial in a workers' health conservation program.

Aluminum↗

Frequency sensitivity and directional hearing in the gleaning bat, Plecotus auritus (Linnaeus 1758).

1. The neural audiogram of the common long-eared bat, Plecotus auritus was recorded from the inferior colliculus (IC). The most sensitive best frequency (BF) thresholds for single neurones are below 0 dB SPL between 7-20 kHz, reaching a best value of -20 dB SPL between 12-20 kHz. The lower and upper limits of hearing occur at 3 kHz and 63 kHz, respectively, based on BF thresholds at 80 dB SPL. BF threshold sensitivities are about 10 dB SPL between 25-50 kHz, corresponding to the energy band of the sonar pulse (26-78 kHz). The tonotopic organization of the central nucleus of the IC (ICC) reveals that neurones with BFs below 20 kHz are disproportionately represented, occupying about 30% of ICC volume, occurring in the more rostral and lateral regions of the nucleus. 2. The acoustical gain of the external ear reaches a peak of about 20 dB between 8-20 kHz. The gain of the pinna increases rapidly above 4 kHz, to a peak of about 15 dB at 7-12 kHz. The pinna gain curve is similar to that of a simple, finite length acoustic horn; expected horn gain is calculated from the average dimensions of the pinna. 3. The directional properties of the external ear are based on sound diffraction by the pinna mouth, which, to a first approximation, is equivalent to an elliptical opening due to the elongated shape of the pinna. The spatial receptive field properties for IC neurones are related to the directional properties of the pinna. The position of the acoustic axis of the pinna and the best position (BP) of spatial receptive fields are both about 25 degrees from the midline between 8-30 kHz but approach the midline to 8 degrees at 45 kHz. In elevation, the acoustic axis and the BP of receptive fields move upwards by 20 degrees between 9-25 kHz, remaining stationary for frequencies up to 60 kHz. 4. The extremely high auditory sensitivity shown by the audiogram and the directionality of hearing are discussed in terms of the adaptation of the auditory system to low frequencies and the role of a large pinna in P. auritus. The functional significance of low frequency hearing in P. auritus is discussed in relation to hunting for prey by listening and is compared to other gleaning species.

Acoustic Stimulation↗

The limitations due to exposure detection limits for regression models.

Biomarker use in exposure assessment is increasingly common, and consideration of related issues is of growing importance. Exposure quantification may be compromised when measurement is subject to a lower threshold. Statistical modeling of such data requires a decision regarding the handling of such readings. Various authors have considered this problem. In the context of linear regression analysis, Richardson and Ciampi (Am J Epidemiol 2003;157:355-63) proposed replacement of data below a threshold by a constant equal to the expectation for such data to yield unbiased estimates. Use of such an imputation has some limitations; distributional assumptions are required, and bias reduction in estimation of regression parameters is asymptotic, thereby presenting concerns about small studies. In this paper, the authors propose distribution-free methods for managing values below detection limits and evaluate the biases that may result when exposure measurement is constrained by a lower threshold. The authors utilize an analytical approach and a simulation study to assess the effects of the proposed replacement method on estimates. These results may inform decisions regarding analytical plans for future studies and provide a possible explanation for some amount of the discordance seen in extant literature.

Bias↗

Bulbocavernosus reflex in normal men and in patients with neurogenic bladder and/or impotence.

The bulbocavernosus reflex was investigated electrophysiologically in 14 normal adult male subjects and in 80 patients with neurogenic bladders and/or impotence due to various neurological causes as well as in patients with functional impotence. The glans penis was stimulated superficially by single electrical shocks and the reflex responses were recorded from the bulbocavernosus (BC) and the striated anal sphincter muscles by means of concentric needle EMG electrodes. In all normal subjects, the BC reflex was recorded from the BC muscle as a stable and constant response having a mean latency of 36.1 msec. A response from the external anal sphincter was obtained in only 21% of the subjects investigated. In 13 patients with cauda equina lesions, the BC reflex was either absent or was present with a prolonged latency. Twenty-two patients with polyneuropathy of various causes were also investigated; in these patients the latency of the BC reflex was significantly greater than in the normal controls, but the most abnormal results were obtained in cases of alcoholic polyneuropathy. In the 19 cases of spinal cord disease with spasticity the BC reflex response was very intense, often with after discharges but latency values were within normal limits. In the 16 cases with functional impotence, the BC reflexes were basically normal; but in 3 cases, the threshold of the reflex was significantly raised, and in 1 case a prolonged latency was observed. The value and the practical application of the BC reflex in the BC reflex in the differential diagnosis of bladder dysfunction and of impotence was stressed.

Adolescent↗

[Generation of action potentials by cortical neurons in turtles. Dendritic and somatic spikes].

Action potentials in single neurons were studied intracellularly in the general cortex of the turtle. It is shown that neurons generate full spikes and, besides them, partial spikes of different amplitude. The partial spikes can be combined into a full spike. The threshold of generation and the amplitude of each partial spike are not constant values, they fluctuate within certain limits spontaneously and gradually without any change in the resting potential of the neuron. Somatic spike and dendritic spikes can be distinguished. Zones of the dendritic spikes initiation are located at different distances from the soma. Under orthodromic activation of cortical neurons the dendritic spikes are generated in succession and conducted to the soma electrotonically with a decrement. The dendritic spikes can reach the threshold for initiation of a somatic spike.

Action Potentials↗

Quantile estimation to derive optimized test thresholds for random field statistics.

We present a numerical method to estimate the true threshold values in random fields needed to determine the significance of apparent signals observed in noisy images. To accomplish this, a quantile estimation algorithm is applied to derive the threshold with a predefined confidence interval from a large number of simulated random fields. Also, a computationally efficient method for generating a random field simulation is presented using resampling techniques. Applying these techniques, thresholds have been determined for a large variety of parameter settings (smoothness, voxel size, brain shape, type of statistics). By means of interpolation techniques, thresholds for additional arbitrary settings can be quickly derived without the need to run individual simulations. Compared to the parametric approach of Worsley et al. (1996) (Worsley, K.J., Marrett, S., Neelin P., Vandal, A.C., Friston, K.J., Evans, A.C., 1996. A unified statistical approach for determining significant signals in images of cerebral activation. Hum. Brain Mapp. 4, 58-73) and Friston et al. (1991) (Friston, K.J., Frith, C.D., Liddle, P.F., Frackowiak, R.S. 1991. Comparing functional (PET) images: the assessment of significant change. J. Cereb. Blood Flow Metab. 11(4), 690-699), and to the Bonferroni approach, these optimized thresholds lead to higher levels of significance (i.e., lower p values) with a specific amount of activation especially with fields of moderate smoothness (i.e., with a relative full width half maximum between 2 and 6). Alternatively, the threshold for a specified level of significance can be lowered. This improved statistical sensitivity is illustrated by the analysis of an actual event related functional magnetic resonance data set, and its limitations are tested by determining the false positive rate with experimental MR noise data. The grid of estimated threshold values as well as the interpolation algorithm to derive thresholds for arbitrary parameter settings are made available over the internet (http://neuro2.med.uni-magdeburg.de/quantile_estimation).

Algorithms↗

Deficits in the coordination of agonist and antagonist muscles in stroke patients: implications for normal motor control.

Movement impairments about a single joint in stroke patients may be related to deficits in the central regulation of stretch reflex (SR) thresholds of agonist and antagonist muscles. One boundary of the SR threshold range for elbow flexor and extensor muscles was measured in hemiparetic subjects by analysing electromyographic activity during stretching of relaxed muscles at seven different velocities. For each velocity, dynamic SR thresholds were measured as angles at which electromyographic activity appeared. These data were used to determine the sensitivity of the threshold to velocity and the static SR thresholds for flexors and extensors. In contrast to relaxed muscles in healthy subjects, static flexor and extensor thresholds lay within the physiological range in 11/12 and 4/12 subjects, respectively. This implies that, in the range between the static SR threshold and one of the physiological joint limits, relaxation of the muscle was impossible. Subjects then made slow movements against different loads to determine their ranges of active movement. Maximal flexor and extensor torques were lower in hemiparetic subjects throughout the angular range. In some subjects, ranges were found in which no active torque could be produced in either extensor or both muscle groups. These ranges were related to the boundary values of SR thresholds found during passive muscle stretch. The range in which reciprocally organized agonist and antagonist muscle activity could be generated was limited in all but one subject. When attempting to produce torque from positions outside their measured range of movement, excessive muscle coactivation occurred, typically producing no or paradoxical motion in the opposite direction. Results suggest a relationship between spasticity measured at rest and the movement deficit in stroke by demonstrating a link between motor deficits and control deficits in the central regulation of individual SR thresholds.

Adult↗

Retinal damage threshold of ophthalmic Q-switched Nd-YAG laser in monkey eyes.

Q-Switched Nd-YAG laser was irradiated to the ocular fundus of 24 eyes of 12 monkeys (Macaca fascicularis) using MICRORUPTOR II (LASAG AG, Thun, Switzerland) through the Goldmann type three-mirror contact lens. Multimode irradiation conditions were used; the pulse duration of 12 nanoseconds, spot size of 80 micrometers, convergence angle of 16 degrees and with various energy levels from 0.05 to 2.8 mJ. After irradiation, the fundus changes were observed by ophthalmoscopy and color fundus photography at 24 hours, 48 hours, 1, 2 and 5 weeks, and by fluorescein angiography at 24 hours, 1 and 5 weeks. Immediately after the irradiation and at 2 and 5 weeks, eyeballs were enucleated and histological observations were carried out. The fundus changes were more evident at 24 hours than at the immediate period after irradiation. At 24 hours, findings by fundus photography and fluorescein angiography were compared: both findings were in agreement. Consequently the retinal damage threshold was determined from the 24-hour findings; the threshold in ED50 was 296.3 microJ with 95% confidence limits from 249.8 to 351.1 microJ. These values corresponded to the retinal energy density of 3.5 J cm-2. Histological observations revealed that the site of damage was mainly in the retinal pigment epithelium when the irradiation was below 1.4 mJ. When the energy was increased to 1.9 mJ, the tissue damage extended to the middle layer of the neuroretina and also disruption of the Bruch's membrane occurred, leading to subretinal hemorrhage. With the energy of 2.8 mJ, destruction extended over wide areas including whole layers of the choroid and retina, leading to vitreous hemorrhage. Over the period of 5 weeks, proliferation of the retinal pigment epithelial cells took place and replaced the damaged retinal tissues.

Animals↗