Spectrally resolved single-shot wavefront sensing of broadband high-harmonic sources.

Wavefront sensors are an important tool to characterize coherent beams of extreme ultraviolet radiation. However, conventional Hartmann-type sensors do not allow for independent wavefront characterization of different spectral components that may be present in a beam, which limits their applicability for intrinsically broadband high-harmonic generation (HHG) sources. Here we introduce a wavefront sensor that measures the wavefronts of all the harmonics in a HHG beam in a single camera exposure. By replacing the mask apertures with transmission gratings at different orientations, we simultaneously detect harmonic wavefronts and spectra, and obtain sensitivity to spatiotemporal structure such as pulse front tilt as well. We demonstrate the capabilities of the sensor through a parallel measurement of the wavefronts of 9 harmonics in a wavelength range between 25 and 49 nm, with up to λ/32 precision.

Comprehensive high-resolution genomic profiling and cytogenetics of human chondrocyte cultures by GTG-banding, locus-specific FISH, SKY and SNP array.

In the development of cell-based medicinal products, it is crucial to guarantee that the application of such an advanced therapy medicinal product (ATMP) is safe for the patients. The consensus of the European regulatory authorities is: "In conclusion, on the basis of the state of art, conventional karyotyping can be considered a valuable and useful technique to analyse chromosomal stability during preclinical studies". 408 chondrocyte samples (84 monolayers and 324 spheroids) from six patients were analysed using trypsin-Giemsa staining, spectral karyotyping and fluorescence in situ hybridisation, to evaluate the genetic stability of chondrocyte samples from non-clinical studies. Single nucleotide polymorphism (SNP) array analysis was performed on chondrocyte spheroids from five of the six donors. Applying this combination of techniques, the genetic analyses performed revealed no significant genetic instability until passage 3 in monolayer cells and interphase cells from spheroid cultures at different time points. Clonal occurrence of polyploid metaphases and endoreduplications were identified associated with prolonged cultivation time. Also, gonosomal losses were observed in chondrocyte spheroids, with increasing passage and duration of the differentiation phase. Interestingly, in one of the donors, chromosomal aberrations that are also described in extraskeletal myxoid chondrosarcoma were identified. The SNP array analysis exhibited chromosomal aberrations in two donors and copy neutral losses of heterozygosity regions in four donors. This study showed the necessity of combined genetic analyses at defined cultivation time points in quality studies within the field of cell therapy.

Ptychographic imaging with a compact gas-discharge plasma extreme ultraviolet light source.

We report the demonstration of a scanning probe coherent diffractive imaging method (also known as ptychographic CDI) using a compact and partially coherent gas-discharge plasma source of extreme ultraviolet (EUV) radiation at a 17.3 nm wavelength. Until now, CDI has been mainly carried out with coherent, high-brightness light sources, such as third generation synchrotrons, x-ray free-electron lasers, and high harmonic generation. Here we performed ptychographic lensless imaging of an extended sample using a compact, lab-scale source. The CDI reconstructions were achieved by applying constraint relaxation to the CDI algorithm. Experimental results indicate that our method can handle the low spatial coherence and broadband nature of the EUV illumination, as well as the residual background due to visible light emitted by the gas-discharge source. The ability to conduct ptychographic imaging with lab-scale and partially coherent EUV sources is expected to significantly expand the applications of this powerful CDI method.

A minimum set of stable blocks for rational design of polypeptide chains.

The aim of this work was to find a minimal set of structurally stable pentapeptides, which allows forming a polypeptide chain of a required 3D structure. To search for factors that ensure structural stability of the pentapeptide, we generated peptide sequences with no more than three functional groups, based on the alanine pentapeptide AAAAA. We analyzed 44,860 structures of peptides by the molecular dynamics method and found that 1,225 pentapeptides over 80% of the simulation time were in a stable conformation. Clustering of these conformations revealed 54 topological types of conformationally stable pentapeptides. These conformations relate to different combined elements of the protein secondary structure. So, we obtained a minimal set of amino acid structures of conformationally stable pentapeptides, creating a complete set of different topologies that ensure the formation of pre-folded conformation of protein structures.

Phenotypic transformation of CD52(pos) to CD52(neg) leukemic T cells as a mechanism for resistance to CAMPATH-1H.

Immunotherapy utilizing CAMPATH-1H for patients with chemotherapy-refractory chronic lymphocytic leukemia has yielded encouraging results with many reports of complete remission. Here we report the outcome of two patients with CD4-positive T cell prolymphocytic leukemia treated with CAMPATH-1H. Both patients responded rapidly to treatment and subsequently developed CD4 lymphopenia. One patient remained in complete remission after 14 weeks of treatment. Serial peripheral blood flow cytometry revealed that the CD52 antigen was present throughout treatment. The other patient who was initially CD52-positive, became CD52-negative after 6 weeks of treatment, and developed progressive symptoms of T cell prolymphocytic leukemia. Immunotherapy was stopped, chemotherapy proved futile, and the patient died. This change in phenotype from CD52-positive to -negative during CAMPATH-1H therapy points out a need to develop strategies for maintaining antigenic expression during monoclonal antibody therapy.

Mood-stabilisers reduce the risk of developing antidepressant-induced maniform states in acute treatment of bipolar I depressed patients.

BACKGROUND: The aim of this study was to give further support to the available evidence that mood stabilizers can reduce the risk of antidepressant-induced maniform switch phenomena in bipolar I depressed patients. METHODS: Medical records of 158 patients with bipolar I depression were analysed for the incidence of switch phenomena from depression to maniform states (mania and hypomania). The impact of mood stabilizers on reducing the risk of switching was analyzed using logistic regression analyses. RESULTS: Maniform switches during inpatient treatment were observed in 39 (25%) patients out of the total of 158 patients. Results indicate that especially patients receiving tricyclic antidepressants are at risk of switching to maniform states. This risk was shown to be significantly less when patients also received a mood stabilising medication (lithium, carbamazepine or valproic acid). LIMITATIONS: This was a retrospective study with patients receiving naturalistic treatment. A prospective, double-blind design would probably lead to more conclusive findings. CONCLUSIONS: Treatment with mood stabilizers may be a potent strategy to reduce the risk of antidepressant-induced maniform switches in bipolar I depressed patients.

Are bipolar I depressive patients less responsive to treatment with antidepressants than unipolar depressive patients? Results from a case control study.

The increasing evidence that bipolar and unipolar affective disorders have different biological etiologies and courses of illness has been associated with an intensifying interest in specific treatment regimens for both disorders during the last decade. In this context, the question arose whether antidepressants exert similar efficacy in the acute treatment of bipolar compared to unipolar depression. Although the clinical impression does not indicate substantial differences in the efficacy of antidepressants between these groups of patients, empirical databases concerning this topic are rare. The present study compared the efficacy of antidepressants in 50 unipolar and 50 bipolar depressed inpatients (ICD-9 criteria) under naturalistic treatment conditions. Both groups of patients were matched for age, gender and duration of illness. Clinical assessments of status at the time of admission and at discharge were used to rate response to antidepressant treatment. Analyses of the data revealed that both groups of patients needed the same time for treatment response and did not show any significant differences in outcome measures at discharge. These findings do not concur with the hypothesis formulated by some experts in the field of affective disorders that antidepressants are less effective in the acute treatment of bipolar depressed patients compared to unipolar depressed patients.

Effect of diltiazem-induced hypotension on normal and increased intracranial pressure of cats.

The commonly used vasodilators sodium nitroprusside and nitroglycerin increase intracranial pressure (ICP) and cause tachycardia. Since diltiazem is also a vasodilator, we designed this experiment in cats to study its effect on intracranial pressure and heart rate (HR). Twelve cats were assigned to two equal groups. One group had normal ICP (N-ICP), while in the other the ICP was raised artificially (AR-ICP) by placing a balloon into the intracranial extradural space. Both groups received an infusion of diltiazem to decrease the mean blood pressure (BP), which was maintained 30 per cent below the baseline value for 15 minutes. Diltiazem caused no significant change in ICP (5.7 +/- 1 to 6.7 +/- 1.5 mmHg, p less than 0.01) in cats with N-ICP while in cats with AR-ICP, the increase from 26.9 +/- 0.5 to 34.0 +/- 1.9 mmHg was significant (p less than 0.006). HR decreased significantly during the diltiazem infusion in both groups.

Are low basal serum levels of the thyroid stimulating hormone (b-TSH) a risk factor for switches into states of expansive syndromes (known in Germany as "maniform syndromes" in bipolar I depression?

Switching over from depression into states known an "maniform" in Germany ("expansive syndromes") been frequently, observed and appears to be partially related to the type of antidepressive medication. Apart from the medication, some evidence suggests that additional factors such as thyroid function may be relevant for the switchover. With this background, the aim of the present study was to evaluate the hypothesis that depressed bipolar patients with lower basal TSH serum levels (b-TSH) on admission at the hospital as inpatients are at a higher risk of switching from depression into "maniform" states than depressed bipolar patients with higher b-TSH. From a total of 158 bipolar depressed patients, 16 patients developed mania during their hospital stay. After dividing the sample of patients at the median b-TSH into one group with lower b-TSH (N = 78) and another group with higher b-TSH (N = 79), we found that the switchover rate to mania was significantly higher in the group of patients with lower b-TSH (15.4%) than in the group of patients with higher b-TSH (5.1 %). These findings suggest that lower b-TSH may be a risk factor for switching over from depression into "maniform" states in bipolar depressed patients.

Antidepressant-associated maniform states in acute treatment of patients with bipolar-I depression.

Medical records of 158 patients with bipolar depression were analysed for the incidence of a switch from depression to maniform states (mania and hypomania). Relation to psychopharmacological treatment was investigated. Thirty-nine (25%) patients of the total sample had switched to a maniform state during the treatment period in the hospital. Among that group the phenomenon occurred in 23 patients (15%) as a hypomania and in 16 patients (10%) as a mania. Patients with a switch were significantly more often treated with tricyclic antidepressants (TCA) than patients without switch (79.5% vs 51.3%). Mood stabilising medication might reduce the risk for switching, especially in patients treated with TCA; however, it seems not totally sufficient, since 59% of the switched patients received mood stabilisers. The switch phenomenon was not associated with sociodemographic or clinical data.

[Infections caused by Mycoplasma pneumoniae in children and adolescents]. / Uber Infektionen durch Mycoplasma pneumoniae bei Kindern und Jugendlichen.

The authors describe the signs and symptoms in 82 children and adolescents with infections due to Mycoplasma pneumoniae, diagnosed by the complement fixation reaction. They discuss the results in relation to other reports about mycoplasma infections.