Refine
Has Fulltext
- yes (16) (remove)
Is part of the Bibliography
- yes (16)
Year of publication
Document Type
- Journal article (15)
- Review (1)
Keywords
- Anorganische Chemie (2)
- ARIA (1)
- Brain μ-opioid receptors (1)
- CARAT (1)
- MASK (1)
- Merkel cell carcinoma (1)
- Molecular imaging (1)
- PET (1)
- PET imaging (1)
- PET/CT (1)
Institute
- Physikalisches Institut (5)
- Institut für Anorganische Chemie (2)
- Institut für diagnostische und interventionelle Radiologie (Institut für Röntgendiagnostik) (2)
- Klinik und Poliklinik für Allgemein-, Viszeral-, Gefäß- und Kinderchirurgie (Chirurgische Klinik I) (2)
- Klinik und Poliklinik für Nuklearmedizin (2)
- Institut für Klinische Epidemiologie und Biometrie (1)
- Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie (1)
- Klinik und Poliklinik für Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie (1)
- Neurologische Klinik und Poliklinik (1)
- Rudolf-Virchow-Zentrum (1)
EU-Project number / Contract (GA) number
- 018696 (1)
The ability to perform mathematical tasks is required in everyday life. Although heritability estimates suggest a genetic contribution, no previous study has conclusively identified a genetic risk variant for mathematical performance. Research has shown that the prevalence of mathematical disabilities is increased in children with dyslexia. We therefore correlated genome-wide data of 200 German children with spelling disability, with available quantitative data on mathematic ability. Replication of the top findings in additional dyslexia samples revealed that rs133885 was a genome-wide significant marker for mathematical abilities\((P_{comb}=7.71 x 10^{-10}, n=699)\), with an effect size of 4.87%. This association was also found in a sample from the general population (P=0.048, n=1080), albeit with a lower effect size. The identified variant encodes an amino-acid substitution in MYO18B, a protein with as yet unknown functions in the brain. As areas of the parietal cortex, in particular the intraparietal sulcus (IPS), are involved in numerical processing in humans, we investigated whether rs133885 was associated with IPS morphology using structural magnetic resonance imaging data from 79 neuropsychiatrically healthy adults. Carriers of the MYO18B risk-genotype displayed a significantly lower depth of the right IPS. This validates the identified association between rs133885 and mathematical disability at the level of a specific intermediate phenotype.
Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
BACKGROUND: In the face of growing resistance in malaria parasites to drugs, pharmacological combination therapies are important. There is accumulating evidence that methylene blue (MB) is an effective drug against malaria. Here we explore the biological effects of both MB alone and in combination therapy using modeling and experimental data.
RESULTS: We built a model of the central metabolic pathways in P. falciparum. Metabolic flux modes and their changes under MB were calculated by integrating experimental data (RT-PCR data on mRNAs for redox enzymes) as constraints and results from the YANA software package for metabolic pathway calculations. Several different lines of MB attack on Plasmodium redox defense were identified by analysis of the network effects. Next, chloroquine resistance based on pfmdr/and pfcrt transporters, as well as pyrimethamine/sulfadoxine resistance (by mutations in DHF/DHPS), were modeled in silico. Further modeling shows that MB has a favorable synergism on antimalarial network effects with these commonly used antimalarial drugs.
CONCLUSIONS: Theoretical and experimental results support that methylene blue should, because of its resistance-breaking potential, be further tested as a key component in drug combination therapy efforts in holoendemic areas.
A semiempirical model is presented that correlates the broadening of the absorption edge with both transitions below the energy gap and with transitions by the Kane band model. This model correctly fits both the absorption and luminescence spectra of narrow-gap (Hg,Cd)Te samples that have been grown by the traveling heater method as well as by molecular-beam epitaxy. The accuracy of the band-gap determination is enhanced by this model.
Background
Salvage radiotherapy (SRT) is clinically established in prostate cancer (PC) patients with PSA persistence or biochemical relapse (BCR) after prior radical surgery. PET/CT imaging prior to SRT may be performed to localize disease recurrence. The recently introduced \(^{68}\)Ga-PSMA outperforms other PET tracers for detection of recurrence and is therefore expected also to impact radiation planning.
Forty-five patients with PSA persistence (16 pts) or BCR (29 pts) after prior prostatectomy, scheduled to undergo SRT of the prostate bed, underwent \(^{68}\)Ga-PSMA PET/CT. The median PSA level was 0.67 ng/ml. The impact of \(^{68}\)Ga-PSMA PET/CT on the treatment decision was assessed. Patients with oligometastatic (≤5 lesions) PC underwent radiotherapy (RT), with the extent of the RT area and dose escalation being based on PET positivity.
Results
Suspicious lesions were detected in 24/45 (53.3 %) patients. In 62.5 % of patients, lesions were only detected by 68Ga-PSMA PET. Treatment was changed in 19/45 (42.2 %) patients, e.g., extending SRT to metastases (9/19), administering dose escalation in patients with morphological local recurrence (6/19), or replacing SRT by systemic therapy (2/19). 38/45 (84.4 %) followed the treatment recommendation, with data on clinical follow-up being available in 21 patients treated with SRT. All but one showed biochemical response (mean PSA decline 78 ± 19 %) within a mean follow-up of 8.12 ± 5.23 months.
Conclusions
\(^{68}\)Ga-PSMA PET/CT impacts treatment planning in more than 40 % of patients scheduled to undergo SRT. Future prospective studies are needed to confirm this significant therapeutic impact on patients prior to SRT.
Ischemic stroke is the second leading cause of death worldwide. Only one moderately effective therapy exists, albeit with contraindications that exclude 90% of the patients. This medical need contrasts with a high failure rate of more than 1,000 pre-clinical drug candidates for stroke therapies. Thus, there is a need for translatable mechanisms of neuroprotection and more rigid thresholds of relevance in pre-clinical stroke models. One such candidate mechanism is oxidative stress. However, antioxidant approaches have failed in clinical trials, and the significant sources of oxidative stress in stroke are unknown. We here identify NADPH oxidase type 4 (NOX4) as a major source of oxidative stress and an effective therapeutic target in acute stroke. Upon ischemia, NOX4 was induced in human and mouse brain. Mice deficient in NOX4 (Nox42/2) of either sex, but not those deficient for NOX1 or NOX2, were largely protected from oxidative stress, blood-brain-barrier leakage, and neuronal apoptosis, after both transient and permanent cerebral ischemia. This effect was independent of age, as elderly mice were equally protected. Restoration of oxidative stress reversed the stroke-protective phenotype in Nox42/2 mice. Application of the only validated low-molecular-weight pharmacological NADPH oxidase inhibitor, VAS2870, several hours after ischemia was as protective as deleting NOX4. The extent of neuroprotection was exceptional, resulting in significantly improved long-term neurological functions and reduced mortality. NOX4 therefore represents a major source of oxidative stress and novel class of drug target for stroke therapy.
Twenty silanes of the type R\(^1\)R\(^2\)Si(H)CH\(_2\)OR\(^3\) (A) were syn- and entropy of activation) of these reactions were studied by thesized {R\(^1\), R\(^2\) = Me, Ph, 1-naphthyl, PhCH\(_2\), Me\(_3\)SiCH\(_2\); OR\(^3\) means of düferential scanning calorimetry (DSC). In addition, = OC(O)Me, OC(O)Ph, OC(O)CF\(_3\) , OS(0)\(_2\)CF\(_3\), OP(O)Ph\(_2\), the kinetics of all reactions were investigated by 1H-NMR OC(O)Cl, and studied for their thermal behaviour. The silanes spectroscopy. The transition state of the rearrangement was A undergo a thermally induced rearrangement to give the investigated by an ab initio study based on the model comcorresponding silanes R\(^1\)R\(^2\)Si(OR\(^3\))Me (B). For compounds with pound H\(_3\)SiCH\(_2\)OC(O)H (-> MeH\(_2\)SiOC(O)H]. The theoretical OR3 = OC(O)Cl, an additional decarboxylation takes place to data and the experimentally obtained energetic and kinetic yield the chlorosilanes R1R2Si(Cl)Me. Except for the deriva- data are discussed in terms of mechanistic aspects of the retives with OR\(^3\) = OC(O)Cl, the energetic (reaction enthalpy) arrangement reaction A -> B. and kinetic data (reaction order, frequency factor, enthalpy ...
The surface sublimation of Cd and Te atoms from the zinc blende (111)A CdTe surface has been investigated in detail by reflection high energy electron diffraction and x-ray photoelectron spectroscopy. These experiments verify that Te is much easier to evaporate than Cd. The experimental value for the Te activation energy from a Te stabilized (111)A CdTe surface is 1.41 ±0.1O eV, which is apparently inconsistent with recent theoretical results.
The selected area epitaxial overgrowth of narrow gap HgTe as well as wide gap CdTe and ZnTe on CdTe/GaAs substrates, which had been structured by dry etching techniques, has been investigated. A plasma etching process using a barrel reactor with CH\(_4\)-CH\(_2\) gases has been employed to prepare stripes with a width of about 1 μm with anisotropic as well as isotropic etching profiles. It has been found, that the selected area HgTe overgrowth takes place with a high local selectivity to the low index planes of the patterned surface. In contrast, the selected area overgrowth of the wide gap CdTe and ZnTe is controlled by anisotropic growth kinetics provided that the substrate temperature is not lower than 220°C and the starting surface consists of well developed low index crystallographic planes.