Psychological and cognitive effects of laser printer emissions: A controlled exposure study.

The possible impact of ultrafine particles from laser printers on human health is controversially discussed although there are persons reporting substantial symptoms in relation to these emissions. A randomized, single-blinded, cross-over experimental design with two exposure conditions (high-level and low-level exposure) was conducted with 23 healthy subjects, 14 subjects with mild asthma, and 15 persons reporting symptoms associated with laser printer emissions. To separate physiological and psychological effects, a secondary physiologically based categorization of susceptibility to particle effects was used. In line with results from physiological and biochemical assessments, we found no coherent, differential, or clinically relevant effects of different exposure conditions on subjective complaints and cognitive performance in terms of attention, short-term memory, and psychomotor performance. However, results regarding the psychological characteristics of participants and their situational perception confirm differences between the participants groups: Subjects reporting symptoms associated with laser printer emissions showed a higher psychological susceptibility for adverse reactions in line with previous results on persons with multiple chemical sensitivity or idiopathic environmental intolerance. In conclusion, acute psychological and cognitive effects of laser printer emissions were small and could be attributed only to different participant groups but not to differences in exposure conditions in terms of particle number concentrations.

Health effects of laser printer emissions: a controlled exposure study.

Ultrafine particles emitted from laser printers are suspected to elicit adverse health effects. We performed 75-minute exposures to emissions of laser printing devices (LPDs) in a standardized, randomized, cross-over manner in 23 healthy subjects, 14 mild, stable asthmatics, and 15 persons reporting symptoms associated with LPD emissions. Low-level exposures (LLE) ranged at the particle background (3000 cm-3 ) and high-level exposures (HLE) at 100 000 cm-3 . Examinations before and after exposures included spirometry, body plethysmography, transfer factors for CO and NO (TLCO, TLNO), bronchial and alveolar NO, cytokines in serum and nasal secretions (IL-1ß, IL-5, IL-6, IL-8, GM-CSF, IFNγ, TNFα), serum ECP, and IgE. Across all participants, no statistically significant changes occurred for lung mechanics and NO. There was a decrease in volume-related TLNO that was more pronounced in HLE, but the difference to LLE was not significant. ECP and IgE increased in the same way after exposures. Nasal IL-6 showed a higher increase after LLE. There was no coherent pattern regarding the responses in the participant subgroups or single sets of variables. In conclusion, the experimental acute responses to short but very high-level LPD exposures were small and did not indicate clinically relevant effects compared to low particle number concentrations.

[The Meaning of Neurological and Psychiatric Disease and Addiction for Pregnancy Outcome: A Case-control Study of the Birth Cohort 2010-2012]. / Die Bedeutung neurologischer, psychiatrischer und Suchterkrankungen für den Schwangerschaftsausgang: Fall-Kontroll-Studie der Geburtsjahrgänge 2010-2012.

BACKGROUND AND AIMS: The worldwide prevalence of neurological and psychiatric illnesses is steadily increasing. Consequently women of childbearing age are concerned as well. This survey examines the question of what kind of effects these illnesses have prenatally on mother and child. METHODS: In a case-control study, differences in pregnancy, birth process, and birth outcome were associated with a neurological or psychiatric illness of the expectant mother. 325 pregnant women with 331 born children were identified as cases, which were compared to 5 103 non diseased pregnant women with 5 195 born children. RESULTS: The age of the mother for admission was significantly lower in the case group than in the control group. The number of previous gestations and the number of previous induced abortion were significantly higher in the case group. Also the BMI before pregnancy and the length of stationary stay showed significantly higher values in the case group. Children belonging to the case group were born significantly earlier, had a lower birth weight, height, and head circumference. Furthermore Apgar scores were significantly lower in the case group. The frequency of postpartum stationary stay in a children's clinic as well as the length of stationary stay were also significantly higher when the mother suffered from a neurological or a psychiatric illness. CONCLUSION: The present results point out the correlation between most of the tested parameters and a neuropsychiatric illness of the newborn's mother. The interdisciplinary collaboration between gynecologists and pediatricians, as well as neurologists and psychiatrists should be strengthened to guarantee the best possible medical care.

Development of a digital zebrafish phantom and its application to dedicated small-fish PET.

Objective. We are developing a small-fish positron emission tomography (PET) scanner dedicated to small aquatic animals relevant for biomedical and biological research, e.g. zebrafish. We plan to use Monte Carlo simulations to optimize its configuration and the required water-filled imaging chambers. Our objectives were: (1) to create a digital 3D zebrafish phantom using conventional micro-CT, (2) include the phantom into a simulated PET environment based on the framework GATE, and (3) investigate the effects of the water environment on the reconstructed images.Approach. To create the phantom, we performedex vivomeasurements of zebrafish specimen using a tabletop micro-CT and compared three methods to fixate the specimen. From segmented micro-CT images we created digital emission and transmission phantoms which were incorporated in GATE via tessellated volumes. Two chamber sizes were considered. For reference, a simulation with the zebrafish in air was implemented. The simulated data were reconstructed using CASToR. For attenuation correction, we used the exact attenuation information or a uniform distribution (only water). Several realizations of each scenario were performed; the reconstructed images were quantitatively evaluated.Main results. Fixation in formalin led to the best soft-tissue contrast at the cost of some specimen deformation. After attenuation correction, no significant differences were found between the reconstructed images. The PET images reflected well the higher uptake simulated in the brain and heart, despite their small size and surrounding background activity; the swim bladder (no activity) was clearly identified. The simplified attenuation map, consisting only of water, slightly worsened the images.Significance. A conventional micro-CT can provide sufficient image quality to generate numerical phantoms of small fish without contrast media. Such phantoms are useful to evaluate in-silico small aquatic animal imaging concepts and develop imaging protocols. Our results support the feasibility of zebrafish PET with an aqueous environment.

Diurnal variations of short-term variation and the impact of multiple recordings on measurement accuracy.

OBJECTIVE: Short-term variation (STV) from computerized cardiotocogram heart rate analysis is a parameter that complements decision making, regarding the delivery of fetuses in several high-risk situations. Although studies on the effects of gestational age and fetal pathology are convincing, there is a lack of data exploring diurnal variation and the adequacy of a single measurement. STUDY DESIGN: In this prospective observational study, fetal STV was monitored with the AN24 fetal ECG monitor (Monica Healthcare) each hour for at least 10 h in total, beginning at different times. This resulted in data covering all 24 h of the day. Seventy fetuses, low risk with respect to conditions accessible to heart rate monitoring (median 37th week of gestation) were monitored for an average of 12 h. Results of STV per hour were categorized as 'compromised' (STV<4 ms) or 'healthy', (STV⩾4 ms) to calculate the model of predictability. RESULTS: The model proposed (STV of 'healthy' fetuses: 9.6±2.6 ms, 'compromised' fetuses 3.0±0.5 ms, prevalence 1%) leads to a positive predictive value of 39%, which increased to 68 or 80% given two or three pathological (STV<4 ms) measurements, respectively. Diurnal variation was not observed. CONCLUSIONS: Single pathological STV values should be corroborated by further measurements in a 24-h interval in otherwise low-risk fetuses before inducing delivery. This may help to avoid unnecessary early births and give the fetus valuable days for intrauterine maturity.

Fluorimetric multiparameter cell assay at the single cell level fabricated by optical tweezers.

A fluorimetric multi-parameter cell sensor at the single cell level is presented which makes it possible to observe the physiological behavior of different cell lines, different physiological parameters, and statistical data at the same time. Different cell types were immobilized at predefined positions with high accuracy using optical tweezers and adhesion promoting surface layers. The process is applicable to both adherent and non-adherent cells. Coating of the immobilization area with mussel adhesive protein was shown to be essential for the process. Intracellular proton and calcium concentrations in different cell classes were simultaneously imaged and the specific activation of T lymphocytes was demonstrated. This method should be especially useful for drug screening due to the small sample volume and high information density.

Forbidden light detection from single molecules

We present a new concept for ultrasensitive detection of surface-generated fluorescence which is made possible by a new optical module. The detection method leads to an enhancement in fluorescence collection efficiency to more than 65% of the total of emitted light, whereas high-aperture microscope objectives are able to collect 44% at best. Moreover, by employing this new optical module, the detection volume can be restricted to approximately 10(-17) L. This allows for an exceptional discrimination of bulk-generated against surface-generated fluorescence, which may be of great value when surface-binding processes are monitored. We demonstrate the performance of the new detection system by detecting single fluorescent molecules and by determining antigen concentrations down to 5 fmol.

Estimation of volumes of distribution and intratumoral ethanol concentrations by computed tomography scanning after percutaneous ethanol injection.

RATIONALE AND OBJECTIVES: We developed a technique for estimating the volumes of distribution and intratumoral ethanol concentrations using computed tomography (CT) scanning in patients undergoing percutaneous ethanol injection (PEI) treatment of malignant hepatic tumors. METHODS: A phantom containing anhydrous ethanol diluted with deionized distilled water to concentrations of 0-100% ethanol was scanned by CT. Thirty-seven treatment sessions were performed on eight patients with malignant hepatic tumors undergoing PEI under CT guidance. The patients were scanned pre- and post-PEI, and a region of interest containing the treated hepatic tissue was selected for pixels between -250 and 15 Hounsfield units (H). The mean density of the pixels in this range was computed and the concentration of ethanol estimated. Volumes of distribution of ethanol and intratumoral concentration were then correlated with volume of ethanol injected during PEI. The ratios of volumes of distribution of ethanol to ethanol injected (adjusted in-range [IR]/volume injected) were compared for responders (n = 4) and nonresponders (n = 4). RESULTS: CT numbers in the phantom scaled linearly with ethanol concentration; 100% ethanol measured -234 H. On CT scans after PEI, the volume of distribution of ethanol correlated positively with the volume injected. Calculated intratumoral ethanol concentrations ranged from 4% to 31%. The adjusted IR/volume injected was significantly higher for responders than nonresponders (p < .5). CONCLUSION: CT density data can be used to estimate volume of ethanol distribution in tissue; a larger relative intratumoral distribution of alcohol appears to correlate with a favorable response to PEI. However, CT measurement of intratumoral ethanol concentrations may require more complex computational techniques.

The laser microbeam trap as an optical tool for living cells.

Pulsed ultraviolet lasers coupled into a microscope can be used for micromanipulation of cells and subcellular structures. In addition, continuous infrared lasers can be used as ultrafine optical tweezers (or synonymously: optical trap). The pulsed UV lasers (for example excimer lasers or nitrogen lasers) can be used as optical scalpels for the preparation of protoplasts from plant root hairs. The precise microdissection of chromosomes with the laser microbeam provides access to chromosome segments where a specific gene is supported to be localized. From such segments, specific DNA libraries can be prepared for the search after such genes or markers in their environment. With the optical trap contact between effector cells of the immune system and their target cells can be established in a very simple and gentle way. The kinetics of the attack of a natural killer on an erythroleukemia cell can be studied from the first seconds after contact. Isolated plant cells as well as cells in a plant embryo tissue can be perforated and DNA or fluorescent molecules can be injected. From the temperature dependence of laser induced membrane lesions one can obtain predictions on laser induced cell fusion, which can be performed at slightly modified irradiation conditions under total microscopic control. Since focusing into the depth of a cell with an accuracy of better than a micrometer is possible, one can work on subcellular structures in the interior of a cell without opening it. For example, in rapeseed protoplasts subcellular structures such as mitochondria or chloroplasts can be perforated or moved out of their original position. Interestingly, such structures find their way back into the original position after the laser is switched off. From their speed one can obtain estimates on intracellular viscoelasticity.

AgGaSe2 thin films grown by chemical close-spaced vapor transport for photovoltaic applications: structural, compositional and optical properties.

Thin films of chalcopyrite AgGaSe(2) have been successfully grown on glass and glass/molybdenum substrates using the technique of chemical close-spaced vapor transport. The high crystallinity of the samples is confirmed by grazing-incidence x-ray diffraction, scanning and transmission electron microscopy, and optical transmission/reflection spectroscopy. Here, two of the three expected direct optical bandgaps are found at 1.77(2) and 1.88(6) eV at 300 K. The lowest bandgap energy at 4 K is estimated to be 1.82(3) eV. Photoluminescence spectroscopy has further revealed the nature of the point defects within the AgGaSe(2), showing evidence for the existence of very shallow acceptor levels of 5(1) and 10(1) meV, and thus suggesting the AgGaSe(2) phase itself to exhibit a p-type conductivity. At the same time, electrical characterization by Hall, Seebeck and four-point-probe measurements indicate properties of a compensated semiconductor. The electrical properties of the investigated thin films are mainly influenced by the presence of Ag(2)Se and Ga(2)O(3) nanometer-scaled surface layers, as well as by Ag(2)Se inclusions in the bulk and Ag clusters at the layers' rear side.

Optical tweezers in pharmacology.

Current applications of optical tweezers in pharmacology are presented. The manufacture of cellular biosensor arrays employing optical tweezers is reviewed. Using this technique, a new approach to cellular drug screening, based on single cells patterned with the laser tweezers was introduced. Specific stimulation of different immobilized, viable cells could be shown simultaneously. Furthermore, the usefulness of optical tweezers for analyzing the interactions of ligands with cellular membrane receptors is demonstrated. The laser tweezers could successfully be used to compare neuron interactions with glycoproteins of the extracellular matrix by applying the optical tweezers as picotensometer. The forces of interactions between polystyrene beads coated with different proteins of the extracellular matrix and the cell membrane receptors of cerebellar neurons from postnatal day 6 (P6) mice were measured. When antibodies to the extracellular matrix proteins were added, forces were significantly reduced for the corresponding antigens but not for the other glycoproteins. This proved the specificity of the measured interactions. Information regarding the receptor anchorage of tenascin-C could be deduced.

Optical determination of pH on surfaces using immobilized Fluorescent dyes.

The attachment of pH-sensitive Fluorescent dyes on to hydroxylapatite for measuring the pH of small volumes is described. Fluorescein and acridine were used, both activated with reactive functions, such as isothiocyanate or succinimidyl ester groups, to enhance the possibility of a covalent linkage to the surface. First investigations were carried out on synthetic hydroxylapatite as the surface material. After the preparation of a particular surface with the fluorescent dye, steady-state and time-resolved fluorescence spectroscopies were employed for estimating the pH value of a solution applied to the surface. In this paper we present the results of our investigations done with both methods. Fluorescein shows significant variation in excitation spectra with pH, whereas in the case of acridine, the fluorescence lifetimes are very sensitive to pH.

Highly efficient optical detection of surface-generated fluorescence.

We present a theoretical study of a new highly efficient system for optical light collection, designed for ultrasensitive fluorescence detection of surface-bound molecules. The main core of the system is a paraboloid glass segment acting as a mirror for collecting the fluorescence. A special feature of the system is its ability to sample not only fluorescence that is emitted below the angle of total internal reflection (the critical angle) but also particularly the light above the critical angle. As shown, this is especially advantageous for collecting the fluorescence of surface-bound molecules. A comparison is made with conventional high-aperture microscope objectives. Furthermore, it is shown that the system allows not only for highly efficient light collection but also for confocal imaging of the detection region, which is of great importance for rejecting scattered light in potential applications such as the detection of only a few molecules.

Metabolites from the biodegradation of pharmaceutical residues of ibuprofen in biofilm reactors and batch experiments.

The three metabolites hydroxyibuprofen (OH-Ibu), carboxyibuprofen (CA-Ibu), and carboxyhydratropic acid (CA-HA), also known from human metabolism of ibuprofen, could be identified in biodegradation experiments. Identification was based on EI mass spectra and comparison with literature data. Detection was performed by selective MS-MS measurements by GC-ion-trap MS and online methylation. Ibuprofen (Ibu), OH-Ibu, and CA-Ibu could be detected with a signal-to-noise ratio of 10:1 at a concentration of 2 nmol L(-1), CA-HA at 0.5 nmol L(-1). Degradation experiments in both biofilm reactors (BFR) and batch experiments with activated sludge (BAS) reveal OH-Ibu as the major metabolite under oxic conditions, and CA-HA under anoxic conditions. CA-Ibu was found under oxic and anoxic conditions almost only in the BAS. The metabolites together do not account for more than 10% of the initial concentration of Ibu.

[Effect of intraaortic-ballon-counterpulsation on the changes of myocardial blood flow following coronary artery stenosis and occlusion (author's transl)]. / Einfluss der intraaortalen Ballonpulsation auf die Umverteilung der Myokarddurchblutung bei Koronararterienstenose und Verschluss

To prove the effectiveness of the IABP in case of impending myocardial infarction in one series of experiments myocardial blood flow changes due to IABP in dogs with stenosis of the left circumflex coronary artery (LC) were investigated using tracer microspheres. In a control series the left anterior descending artery (LAD) was occluded. In acute LAD occlusion the IABP caused an increase of blood flow in the epicardial layer. In case of LC stenosis there was a far greater increase in blood flow by the IABP most prominent in the endocardial layer. Our experiments indicate that the IABP seems to be effective in impending myocardial infarction.

Counting of single protein molecules at interfaces and application of this technique in early-stage diagnosis.

The fluorescence-based detection and counting of single protein molecules after specific binding to antibodies at interfaces is presented. A diode laser was used as the excitation source. The unspecific binding at the interface has been reduced to a level of only 0.1% of the maximum signal level. At present, the detection limit of this molecule-counting process is in the range of 10(-17) mol/L, and the dynamic range of the signal corresponds to 7 orders of magnitude of antigen concentration, but these values are not limiting. As a preliminary application in early-stage diagnosis, we have investigated the detection of a single cardiac actin molecule in human plasma, which is of interest in myocardial infarction diagnosis.

Application of laser optical tweezers in immunology and molecular genetics.

Optical tweezers, based on a compact diode pumped Nd:YAG laser providing 350 mW at 1,064 nm coupled into a Zeiss IM 35 microscope, were used to sort CD4+ T cells into a capillary for further mechanical handling and to establish contact between single human natural killer (NK) cells and human erythroleukemia cells (K562) as targets. After contact and a lag phase of a few tens of seconds, the target cell starts to change its morphology and membrane blebbing occurs. The kinetics of the attack of the NK cell on K562 cells is not straightforward but governed by temporal oscillations in the shape of the target cell (zeosis). In a second application, the optical tweezers are combined with a UV laser microbeam based on a pulsed UV laser and with flow cytometry and sorting. With the pulsed laser, segments of sorted chromosome 1 of the chinese hamster karyotype (CHV 79) can be easily micro-dissected and subsequently collected using the optical tweezers. This allows preparation of a few hundred chromosome segments per day without mechanical contact and in an absolutely sterile way and thus may provide an interesting basic technique in any type of genome sequencing project.

Simultaneous antigen detection using multiplex dyes.

To detect several antigens simultaneously, antibodies directed against different antigens were immobilized on a quartz surface. The antigens were tagged with multiplex, dyes, which show different fluorescence lifetimes but similar excitation and emission spectra. The antigens were detected by recognizing the characteristic fluorescence lifetime. Furthermore, the effect of labeling of the dye on the antigen molecules was examined.