Linear Versus Non-Linear Dose-Response Relationship Between Prenatal Alcohol Exposure and Meconium Concentration of Nine Different Fatty Acid Ethyl Esters

Presence of individual fatty acid ethyl esters (FAEEs) in meconium is considered to be a reliable biomarker of prenatal alcohol exposure, and their concentration has been found to be linearly associated with poor postnatal development, supporting the widely extended idea that ethanol is a non-threshold teratogen. However, a growing number of epidemiological studies have consistently found a lack of adverse short- and long-term fetal outcomes at low exposure levels. We therefore aimed to investigate the relationship between the concentration of individual FAEEs and prenatal alcohol exposure in meconium samples collected within the first 6 to 12?h after birth from 182 babies born to abstainer mothers and from 54 babies born to women who self-reported either light or moderate alcohol ingestion in the second or third trimester of pregnancy. In most cases, the individual FAEE concentrations were negligible and not significantly different (P >0.05) between exposed and control babies. The concentrations appeared to increase linearly with the dose only in the few babies born to mothers who reported >3 drinks/week. These results provide evidence that the correlation between prenatal alcohol exposure and individual FAEE concentrations in meconium is non-linear shape, with a threshold probably at 3 drinks/week.     

Measurement of chemosensory function

Although hundreds of thousands of patients seek medical help annually for disorders of taste and smell, relatively few medical practitioners quantitatively test their patients' chemosensory function, taking their complaints at face value. This is clearly not the approach paid to patients complaining of visual, hearing, or balance problems. Accurate chemosensory testing is essential to establish the nature, degree, and veracity of a patient's complaint, as well as to aid in counseling and in monitoring the effectiveness of treatment strategies and decisions. In many cases, patients perseverate on chemosensory loss that objective assessment demonstrates has resolved. In other cases, patients are malingering. Olfactory testing is critical for not only establishing the validity and degree of the chemosensory dysfunction, but for helping patients place their dysfunction into perspective relative to the function of their peer group. It is well established, for example, that olfactory dysfunction is the rule, rather than the exception, in members of the older population. Moreover, it is now apparent that such dysfunction can be an early sign of neurodegenerative diseases such as Alzheimer's and Parkinson's. Importantly, older anosmics are three times more likely to die over the course of an ensuring five-year period than their normosmic peers, a situation that may be averted in some cases by appropriate nutritional and safety counseling. This review provides the clinician, as well as the academic and industrial researcher, with an overview of the available means for accurately assessing smell and taste function, including up-to-date information and normative data for advances in this field.     

Growth and recovery of temporary threshold shift at 4 kHz due to a steady state noise and impulse noises

Summary 7 audiometrically normal, male students were exposed to a steady state noise S of 98 dBA and 2 steady state-impulse combined noises A and B (steady state component of 97 dBA, hammer noise 102 dBA and air exhaustion noise of 118 or 110 dBA) for 40–60 min. The regression line of temporary threshold shift (TTS) growth due to noise A on exposure duration was significantly steeper than that due to noise B. Both the lines were steeper than that due to noise S. The reason of the relatively larger effects of the noises A and B as compared with noise S could be explained by the fact that the noise S did not contain impulse components, because the octave band level at center frequency of 3 kHz of the noise S was roughly equal to that of the steady state noise component of noise A or B. The relatively larger effect of the noise A than B might be attributed mainly to the air exhaustion noise. It was suggested that the effect of a steady state noise on hearing might be additive to that of an impulse noise. The trend relationship between TTS during recovery and recovery time was nearly the same with the 3 noises.     

One-hertz subthreshold rTMS increases the threshold for evoking inhibition in the human motor cortex

Despite indisputable evidence that repetitive transcranial magnetic stimulation (rTMS) modulates motor cortical excitability, the effects of subthreshold low-frequency rTMS on intracortical inhibition (ICI) are controversial. In this paper we investigated whether increasing the level of baseline ICI increases the sensitivity of ICI for disclosing the after-effects of rTMS on cortical excitability. In experiment 1, we studied changes in ICI, tested at two different baseline levels, after a train of 900 subthreshold rTMS pulses delivered at 1 Hz. In experiment 2, we studied whether the same conditioning rTMS train changed the ICI threshold, and in experiment 3 whether it changed the facilitatory I-wave interaction. Conditioning rTMS reduced ICI tested at a baseline level of 75% but left ICI tested at a baseline level of 50% unchanged. It also increased the ICI threshold but left the facilitatory I-wave interaction unchanged. These findings suggest that conditioning rTMS selectively reduced ICI tested at a baseline level of 75% by increasing the threshold for evoking inhibition in the motor cortex. The inhibitory system mediating ICI may therefore be more efficient than other motor cortical systems in reducing high cortical excitability after external intervention. Hence studies investigating the after-effects of rTMS should standardize ICI levels at baseline.     

Magneto- and electrophosphenes: A comparative study

The purpose of this study was to compare the threshold values for magnetophosphenes and electrophosphenes under identical experimental conditions. Such comparisons between the phosphene types would increase our knowledge of the mechanism of the interaction between magnetic fields and electric current, respectively, and excitable tissue. The phosphenes were generated in the frequency range 10–45 Hz at moderate magnetic flux densities [up to 40 mT (400 G)] and electric currents up to 0.3 mA, respectively. The first part of the study was devoted to the problem of how electrode location and consequent current directions influence the threshold values of electrophosphenes. In the second part a comparison was made of the threshold values for electrophosphenes and magnetophosphenes under identical experimental conditions apart from the stimulation method. With electric-current stimulation in different directions no great differences were obtained with regard to the mean value for the threshold values within the frequency range 10–30 Hz. However, from 30 Hz upwards a significant difference developed between the threshold values for some of the curves. When generating electrophosphenes and magnetophosphenes we found significant differences in the threshold values between approximately 25 and 45 Hz. Both types of phosphenes had a concurring sensitivity maximum at 20 Hz. The deviations between the curves may be due, among other factors, to the generation of different current paths in electrical and magnetic stimulation, respectively.     

Effects of some different pulse parameters on the perception of intravaginal and intra-anal electrical stimulation

Electrical stimulation was performed in male and female subjects by means of intra-anal and intravaginal electrode carriers. Rectangular constant voltage pulses of alternating polarity, pulse repetition rate 10 Hz, and pulse durations between 0·1 and 5 ms were tested. The perception of stimulation was used as a measure of stimulation efficiency and the voltage amplitudes at detection threshold and at maximum tolerance were recorded. The aim of the study was to determine the voltage requirements of a new, totally integrated stimulation device for intravaginal application. The voltage requirement of the 0·1 ms pulse was more than twice that of the 5·0 ms pulse for an equal effect, its power dissipation was considerably lower. The detection threshold was significantly higher with intravaginal than with intra-anal stimulation. There was also a larger variation in voltage amplitudes between female subjects, whereas the ratio between maximum tolerance and detection threshold amplitudes was quite small. In intra-anal stimulation the scatter in threshold voltage between male subjects was smaller, but an almost twofold increase of the threshold voltage amplitude was required to reach the maximum tolerance level. The study points to the necessity of having adjustable stimulation parameters in intravaginal stimulation devices. Stimulation efficacy may be changed equally well by varying pulse duration as pulse amplitude.     

Analysis of frequency components of cortical potentials evoked by progressive misalignment of Kanizsa squares

Cortical gamma oscillations (20–100 Hz) are thought to play an important role in encoding visual perception. If so they should emerge at about threshold. In the present investigation we examined the latter proposal. Visual responses were recorded in occipital, temporal and parietal areas (stimulus duration 512 ms). Oscillation strength and frequency were derived from FFT analysis and wavelet transforms. The specific goals of the present study are: 1: To examine the parallel between gamma oscillations and the psychometric threshold of perception of Kanizsa square (KS). The latter is gradually altered by a progressive misalignment of lower inducers (pacmen). Results show that the perception of the KS is altered by lateral displacements of the lower inducers as small as 0.1 to 0.2°. In parallel, high frequency components of cortical responses gain in strength with misalignments. 2: Gamma oscillations emerge at or about the psychometric threshold. In addition, our data analysis demonstrates that gamma oscillations appear in short bursts (approx. 50 ms) in the time window between 200 and 500 ms after stimulus onset. Furthermore, controls indicated that these oscillations are of the induced-gamma type. Thus, our experiments suggest that gamma oscillations are associated with image structures and may be induced by local properties of the target.     

Origin of the TTC values for compounds that are genotoxic and/or carcinogenic and an approach for their re-evaluation

The threshold of toxicological concern (TTC) approach is a resource-effective de minimis method for the safety assessment of chemicals, based on distributional analysis of the results of a large number of toxicological studies. It is being increasingly used to screen and prioritize substances with low exposure for which there is little or no toxicological information. The first step in the approach is the identification of substances that may be DNA-reactive mutagens, to which the lowest TTC value is applied. This TTC value was based on the analysis of the cancer potency database and involved a number of assumptions that no longer reflect the state-of-the-science and some of which were not as transparent as they could have been. Hence, review and updating of the database is proposed, using inclusion and exclusion criteria reflecting current knowledge. A strategy for the selection of appropriate substances for TTC determination, based on consideration of weight of evidence for genotoxicity and carcinogenicity is outlined. Identification of substances that are carcinogenic by a DNA-reactive mutagenic mode of action and those that clearly act by a non-genotoxic mode of action will enable the protectiveness to be determined of both the TTC for DNA-reactive mutagenicity and that applied by default to substances that may be carcinogenic but are unlikely to be DNA-reactive mutagens (i.e. for Cramer class I–III compounds). Critical to the application of the TTC approach to substances that are likely to be DNA-reactive mutagens is the reliability of the software tools used to identify such compounds. Current methods for this task are reviewed and recommendations made for their application.     

Background, approaches and recent trends for setting health-based occupational exposure limits: a minireview

The setting of occupational exposure limits (OELs) are founded in occupational medicine and the predictive toxicological testing, resulting in exposure-response relationships. For compounds where a No-Observed-Adverse-Effect-Level (NOAEL) can be established, health-based OELs are set by dividing the NOAEL of the critical effect by an overall uncertainty factor. Possibly, the approach may also be used for carcinogens if the mechanism is epigenetic or the genetic effect is secondary to effect from reactions with proteins such as topoisomerase inhibitors, and mitotic and meiotic spindle poisons. Additionally, the NOAEL approach may also be used for compounds with weak genotoxic effect, playing no or only a minor role in the development of tumours. No health-based OEL can be set for direct-acting genotoxic compounds where the life-time risks may be estimated from the low-dose linear non-threshold extrapolation, allowing a politically based exposure level to be set. OELs are set by several agencies in the US and Europe, but also in-house in major chemical and pharmaceutical companies. The benchmark dose approach may in the future be used where it has advantage over the NOAEL approach. Also, more attention should be devoted to sensitive groups, toxicological mechanisms and interactions as most workplace exposures are mixtures.     

Is proprioception diminished in patients with patellar tendinopathy?

PurposePatellar tendinopathy is a highly prevalent overuse injury, and most treatments are only effective to some extent. This persistence of complaints could be linked to changed proprioception. One study showed diminished proprioception in athletes with lateral epicondylitis. Aim of this study was to determine differences in proprioception, by measuring threshold to detect passive motion (TTDPM) between recreational athletes diagnosed with patellar tendinopathy and healthy controls.MethodThe TTDPM as measure of proprioception was determined in 22 recreational athletes with patellar tendinopathy and 22 healthy recreational athletes using a validated instrument. Amount of knee flexion and extension before the movement was noticed by the subject was determined. 80 measurements per athlete (left and right leg, towards extension and flexion and with two starting angles of 20° and 40° flexion) were performed. Mean TTDPM was compared between groups and among the injured recreational athletes between the affected and unaffected knee.ResultsNo significant difference in TTDPM was found between recreational athletes with patellar tendinopathy and healthy controls. We did find a significant difference between the injured and non-injured knee in recreational athletes with patellar tendinopathy; mean TTDPM was 0.02° higher in the injured knee (p = 0.044).ConclusionNo difference was found in proprioception between recreational athletes with patellar tendinopathy and healthy recreational athletes. It is unclear whether such a small difference in TTDPM between affected and unaffected knee is important in clinical setting.