Probing nonadiabatic effects in strong-field tunnel ionization.

We investigate experimentally the validity of proposed theories extending the tunneling approximation towards the multiphoton regime in strong-field ionization of helium. We employ elliptically polarized laser pulses and demonstrate how the influence of the ion potential on the released electron encoded in the measured observable provides the desired sensitivity to detect nonadiabatic effects in tunnel ionization. Our results show that for a large intensity range the proposed nonadiabatic theories contradict the experimental trends of the data, while adiabatic assumptions are confirmed.

Spatial fingerprint of quantum path interferences in high order harmonic generation.

We have spatially and spectrally resolved the high order harmonic emission from an argon gas target. Under proper phase matching conditions we were able to observe for the first time the spatial fine structure originating from the interference of the two shortest quantum paths in the harmonic beam. The structure can be explained by the intensity-dependent harmonic phase of the contributions from the two paths. The spatially and spectrally resolved measurements are consistent with previous spatially integrated results. Our measurement method represents a new tool to clearly distinguish between different interference effects and to potentially observe higher order trajectories in the future with improved detection sensitivity. Here, we demonstrate additional experimental evidence that the observed interference pattern is only due to quantum-path interferences and cannot be explained by a phase modulation effect. Our experimental results are fully supported by simulations using the strong field approximation and including propagation.

Expression and activity profiling of the steroidogenic enzymes of glucocorticoid biosynthesis and the fdx1 co-factors in zebrafish.

The spatial and temporal expression of steroidogenic genes in zebrafish has not been fully characterised. Because zebrafish are increasingly employed in endocrine and stress research, a better characterisation of steroidogenic pathways is required to target specific steps in the biosynthetic pathways. In the present study, we have systematically defined the temporal and spatial expression of steroidogenic enzymes involved in glucocorticoid biosynthesis (cyp21a2, cyp11c1, cyp11a1, cyp11a2, cyp17a1, cyp17a2, hsd3b1, hsd3b2), as well as the mitochondrial electron-providing ferredoxin co-factors (fdx1, fdx1b), during zebrafish development. Our studies showed an early expression of all these genes during embryogenesis. In larvae, expression of cyp11a2, cyp11c1, cyp17a2, cyp21a2, hsd3b1 and fdx1b can be detected in the interrenal gland, which is the zebrafish counterpart of the mammalian adrenal gland, whereas the fdx1 transcript is mainly found in the digestive system. Gene expression studies using quantitative reverse transcriptase-PCR and whole-mount in situ hybridisation in the adult zebrafish brain revealed a wide expression of these genes throughout the encephalon, including neurogenic regions. Using ultra-high-performance liquid chromatography tandem mass spectrometry, we were able to demonstrate the presence of the glucocorticoid cortisol in the adult zebrafish brain. Moreover, we demonstrate de novo biosynthesis of cortisol and the neurosteroid tetrahydrodeoxycorticosterone in the adult zebrafish brain from radiolabelled pregnenolone. Taken together, the present study comprises a comprehensive characterisation of the steroidogenic genes and the fdx co-factors facilitating glucocorticoid biosynthesis in zebrafish. Furthermore, we provide additional evidence of de novo neurosteroid biosynthesising in the brain of adult zebrafish facilitated by enzymes involved in glucocorticoid biosynthesis. Our study provides a valuable source for establishing the zebrafish as a translational model with respect to understanding the roles of the genes for glucocorticoid biosynthesis and fdx co-factors during embryonic development and stress, as well as in brain homeostasis and function.

[Gaze-evoked amaurosis fugax]. / Blickinduzierte Amaurosis fugax.

Gaze-evoked amaurosis is a quite unique symptom. We present a 37-year-old patient with unilateral gaze-evoked amaurosis caused by an orbital tumor. Possible mechanisms include transient ischemia of the optic nerve and the retina or inhibition of the axonal impulses. While not common as a cause of amaurosis fugax, an orbital mass should be considered in the differential diagnosis of gaze-evoked atypical monocular amaurosis fugax.

Role of factor XIII Val34Leu polymorphism in retinal artery occlusion.

BACKGROUND AND PURPOSE: Factor XIII (FXIII) Val34Leu, a common polymorphism in the gene for factor XIII, has been associated with a lower risk of stroke, myocardial infarction, and deep vein thrombosis. Ineffective fibrin cross-linking has been suggested to be causative. The aim of the present case-control study was to investigate the role of FXIII Val34Leu polymorphism in patients with retinal artery occlusion. METHODS: A total of 108 patients with retinal artery occlusion and 313 age- and sex-matched controls were genotyped for the FXIII Val34Leu polymorphism. Factor XIII Val34Leu genotypes were determined by use of allele-specific polymerase chain reaction. RESULTS: Homozygous Leu genotype was found significantly more often in control subjects than in patients with retinal artery occlusion (P=0.018), with an odds ratio of 0.22 (95% confidence interval 0.07 to 0.74). Distribution of the Val/Val and Val/Leu genotypes did not differ significantly between groups. CONCLUSIONS: Because prevalence of homozygous Leu genotype was significantly higher in controls, we conclude that the Leu/Leu genotype is associated with a protective effect against retinal artery occlusion.

Androgens induce divergent proliferative responses in human breast cancer cell lines.

Although the majority of primary human breast cancers express the androgen receptor (AR), the role of androgens in breast cancer growth and progression is poorly understood. We have investigated the effects of the naturally occurring androgen, dihydrotestosterone (DHT), and a synthetic non-metabolizable androgen, mibolerone, on the proliferation of six human breast cancer cell lines. The anti-proliferative and proliferative effects of androgens were only observed in cell lines that expressed the AR. Two of the AR-positive cell lines, T47-D and ZR-75-1 were growth inhibited in the presence of either DHT or mibolerone, while the proliferation of MCF-7 and MDA-MB-453 cells was increased by both androgens. Co-incubation of cultures with 1 nM DHT and a 100-fold excess of the androgen receptor antagonist, hydroxyflutamide, resulted in reversal of both inhibitory and stimulatory effects of DHT on T47-D, MCF-7 and MDA-MB-453 cell proliferation, indicating that DHT action is mediated by the AR in these lines. Hydroxyflutamide only partially reversed the DHT-induced growth inhibition of ZR-75-1 cultures, which suggests that growth inhibition of these cells may be mediated by non-AR pathways of DHT (or DHT metabolite) action. Mibolerone action on breast cancer cell growth was similar to that of DHT, with the exception that growth stimulation of MCF-7 and MDA-MB-453 cells was only partially reversed in the presence of a 100-fold excess of hydroxyflutamide. Anandron, another androgen receptor antagonist, was able to reverse all inhibitory and stimulatory actions of the androgens. AR antisense oligonucleotides reduced the level of immunoreactive AR expression in MDA-MB-453 and ZR-75-1 cells by more than 60%, but only reversed the growth inhibitory action of mibolerone in ZR-75-1 cultures. The results suggest that androgen action in breast cancer cell lines may not be solely mediated by binding of androgen to the AR. For example, metabolites of DHT with oestrogenic activity, or androgen binding to receptors other than the AR, may explain the divergent responses to androgens observed in different breast cancer cell lines.

Hyperhomocyst(e)inaemia, but not MTHFR C677T mutation, as a risk factor for non-arteritic ischaemic optic neuropathy.

BACKGROUND/AIMS: Hyperhomocyst(e)inaemia has been identified as a strong risk factor for stroke, myocardial infarction, and deep vein thrombosis. A point mutation of methylene tetrahydrofolate reductase (MTHFR C677T) has been associated with increased plasma homocyst(e)ine levels. To investigate whether hyperhomocyst(e)inaemia and/or MTHFR C677T mutation are associated with non-arteritic ischaemic optic neuropathy (NAION), a case-control study including 59 consecutive patients with NAION and 59 controls matched for age and sex was performed. METHODS: Fasting plasma homocyst(e)ine levels, MTHFR C677T genotypes, and plasma levels of folate and vitamin B-12 were determined. RESULTS: Mean plasma homocyst(e)ine levels were significantly higher in patients than in controls (11.8 (SD 5.7) micromol/l v 9.8 (2.5) micromol/l, p = 0.02). The odds ratio for patients with homocyst(e)ine levels exceeding the 95th percentile of control homocyst(e)ine levels was 5.8 (95% CI 1.5-21.4). Mean plasma folate levels were significantly lower in patients than in controls (4.3 (1.7) ng/ml v 5.5 (1.9) ng/ml, p = 0.001), whereas plasma vitamin B-12 levels did not differ significantly. Prevalence of the MTHFR C677T mutation was not significantly increased in patients with NAION compared with controls. CONCLUSION: These results suggest that hyperhomocyst(e)inaemia, but not MTHFR C677T mutation is associated with NAION. Determination of plasma homocyst(e)ine levels might be of diagnostic value in patients with NAION.

The impact of diets with different magnesium contents on magnesium and calcium in serum and tissues of the rat.

The impact of three different magnesium diets (70, 1,000 and 9,000 ppm) on total, ionized and bound magnesium as well as ionized calcium in serum and total calcium and magnesium in femoral bone, skeletal muscle, heart and liver of male Sprague-Dawley rats was investigated. The percentage of ionized serum magnesium was unproportionally high in rats fed a low magnesium (70 ppm) diet. Femoral magnesium was correlated with ionized and total serum magnesium. In contrast, there was generally no correlation between total serum magnesium and the magnesium fractions in skeletal muscle, heart and liver. In rats fed the magnesium deficient diet, total cardiac concentration of magnesium was even significantly increased along with total calcium content, while there were no effects on total muscle and liver magnesium. Within the single groups, ionized serum calcium was never proportional to dietary magnesium, but in all three magnesium diet groups together, it was inversely correlated with dietary magnesium. Moreover, ionized serum calcium was inversely correlated with both ionized and total serum magnesium. In all 3 groups together, the concentrations of total calcium and magnesium in heart and skeletal muscle were correlated, within the single groups correlation existed only in the 1000 ppm group. Magnesium influx via calcium channels during low magnesium intake has been seen in non cardiac tissues [35,36], but nothing similar is known about non selective channels for divalent cations in the heart [33]. Thus, magnesium uptake by cardiac cells along with calcium seems to be possible, especially at low intracellular magnesium concentrations, but is still poorly investigated. We suggest that the calcium-antagonistic effect of magnesium is related to the turnover rate of magnesium rather than to its tissue concentrations.

Basic care I: the effect of dementia-specific training on certified nursing assistants and other staff.

This study evaluates the effectiveness of Basic Care I, a dementia-specific training course offered by the St. Louis Alzheimer's Association. Using three standardized measures, the effects of the course on knowledge gain, stress level, and sense of work-related self-esteem are examined Findings suggest that participation in Basic Care I increases retained learning, as 76.4 percent of the sample showed improvement on dementia knowledge scores. The outcomes of stress and self-esteem measures are inconclusive but indicate areas for future study. Implications for program planning are discussed.

Comparing the well-being of post-caregivers and noncaregivers.

Researchers who study family caregiving have begun to recognize the need to broaden the realm of inquiry to include the exploration of the positive aspects of caregiving as well as conceptualizing caregiving on a continuum from the pre-caregiving phase through the post-caregiving phase. Additionally, researchers are urged to use control groups in research. This study complements the current trends by examining the positive aspects of caregiving among former caregivers. Specifically, the well-being of post-caregivers is compared to that of noncaregivers. Bivariate analyses examine the factors that are significantly different between former caregivers and noncaregivers. Results show that former caregivers have higher well-being than noncaregivers. In the multivariate model, only one subscale of well-being (basic needs) is different between the two groups. Implications of this research are discussed.

[Transpupillary thermotherapy in exudative, age-related macular degeneration]. / Transpupilläre Thermotherapie bei exsudativer altersabhängiger Makuladegeneration.

OBJECTIVE: To assess the effectiveness of a single transpupillary thermotherapy (TTT) in patients with exudative, age-related macular degeneration (AMD). METHODS: In a prospective pilot study, 14 patients with a mean age of 78 years (range: 70-92 years) with subfoveal choroidal neovascularisation (CNV) due to exudative, age-related macular degeneration were treated with a single TTT using a diode laser (810 nm). Seven patients had a classic and seven an occult CNV. Laser beam size was 4.5 mm,the power setting was 800 mW and the exposure lasted 60 s. RESULTS: Twelve out of 14 patients could be followed for a period of 18 months. Stabilisation of the visual acuity was achieved in two patients, ten patients lost three or more Snellen lines. In none of the patients a regression of the CNV could be observed immediately after TTT. Inactive fibrotic scars developed in six patients at the end of the study. CONCLUSION: Our results suggest that TTT, according to our protocol, has no beneficial effect on the spontaneous course of the CNV in patients with AMD.

Long-term pharmacokinetics of doxorubicin HCl stealth liposomes in patients after polychemotherapy with vinorelbine, cyclophosphamide and prednisone (CCVP).

The concentration-time profiles of Doxorubicin (DOXO) from day 0 to day 21 after i.v. infusion of 25 or 30 mg/m2 doxorubicin HCI stealth liposomes (Caelyx) were investigated in 9 patients receiving combination polychemotherapy with cyclophosphamide, vinorelbine and prednisone. Peak serum concentrations occurred from 0.04 to 4.0 days after infusion (mean tmax = 1.79 +/- 1.55 d) with a mean cmax of 4,595 +/- 2,849 ng/ml. A total amount of 12.84 +/- 2.47 mg liposomal DOXO in the plasma volume (Vp = 2,794 + 537 ml) could be estimated at tmax (= 27 % of the mean dose of 47.6 mg). Stealth liposomes were eliminated slowly from the blood with a mean t 1/2el of 1.9 + 0.5 days (MRT was 4.6 + 2.5 days). AUClast values ranged from 8,070 to 33,446 ng/ml*d (mean 10,987 +/- 9,339 ng/ml*d). The low plasma clearance (Cltot = 4,681 +/- 2,835 ml/day) and the small volume of distribution (Vz = 11.7 +/- 6.31) suggested that stealth-liposomes were stable in the blood at least for 14 days. Polychemotherapy with Hyper-CCVP schedule did not alter the stability of stealth liposomes, but peak levels of DOXO seemed to be somewhat lower compared to regression analysis of literature data (cmax versus dosage range from 20 to 60 mg/m2). Due to clast occurring between day 12 to 18, no indices for an accumulation of the drug in the blood could be found, when liposomes were given every four weeks.

Versatile attosecond beamline in a two-foci configuration for simultaneous time-resolved measurements.

We present our attoline which is a versatile attosecond beamline at the Ultrafast Laser Physics Group at ETH Zurich for attosecond spectroscopy in a variety of targets. High-harmonic generation (HHG) in noble gases with an infrared (IR) driving field is employed to generate pulses in the extreme ultraviolet (XUV) spectral regime for XUV-IR cross-correlation measurements. The IR pulse driving the HHG and the pulse involved in the measurements are used in a non-collinear set-up that gives independent access to the different beams. Single attosecond pulses are generated with the polarization gating technique and temporally characterized with attosecond streaking. This attoline contains two target chambers that can be operated simultaneously. A toroidal mirror relay-images the focus from the first chamber into the second one. In the first interaction region a dedicated double-target allows for a simple change between photoelectron/photoion measurements with a time-of-flight spectrometer and transient absorption experiments. Any end station can occupy the second interaction chamber. A surface analysis chamber containing a hemispherical electron analyzer was employed to demonstrate successful operation. Simultaneous RABBITT measurements in two argon jets were recorded for this purpose.