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"Schrader, J"
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True grit : American prints from 1900 to 1950
\"An examination of thirty-eight prints by American artists from the first half of the twentieth century\"--Provided by publisher.
Book
Repeated elevated plus maze trials as a measure for tracking within-subjects behavioral performance in rats (Rattus norvegicus)
The elevated plus maze (EPM) is routinely used in neuroscience research to evaluate emotional behavior in rodents by measuring general exploratory performance and avoidance of the aversive open arms of the maze. According to standard practice, behavior on the EPM is evaluated during a single trial to avoid the possibility of habituation to the apparatus that would result in lost sensitivity of key outcome measures. However, this possibility has not been systematically evaluated across repeated trials or across different environmental conditions. In the current study, we assessed within-subject behavior on the EPM in adult male rats over thirteen trials (tested twice weekly) repeated under identical conditions. We also assessed within-subject behavior on the EPM in adult male rats under dim (1 lux in the closed arm) and lit (246 lux in the closed arm) environmental conditions. We found that measures of general performance (basic movements and total distanced travelled throughout the maze) were stable across repeated trials and environmental conditions. We found that measures of open arm avoidance (distance travelled in, time spent in and entries in to the open arm) varied across trials and environmental conditions and were sensitive to the lighting conditions of the initial test. Though measures of open arm avoidance did show a linear trend indicative of habituation across repeated trials, this effect was variable across trials. Notably, preference for the open arm over the closed arm (measured as % of time spent in the open arm) assessed among individual animals occurred rarely and was never observed on the group level across the thirteen repeated trials. Together, these data demonstrate that measures of general performance such as basic movements and total distance traveled are robust to repeated testing and changing environmental lighting conditions. In contrast, measures of open arm avoidance show habituation with repeated testing and are sensitive to changing environmental lighting conditions. Based on these results, we suggest that within-subjects repeated testing on the EPM is valid in well-controlled studies that include an untreated control group to account for inter-trial variability and habituation.
Journal Article
Rembrandt and the inspiration of India
\"Accompanying an exhibition at the J. Paul Getty Museum in Los Angeles, this volume brings together Rembrandt's drawings after Mughal paintings and demonstrates how Rembrandt's contact with Mughal art inspired him to draw in an entirely new, refined style.\"--Provided by publisher.
BOOK
Validation of CRP as prognostic marker for renal cell carcinoma in a large series of patients
Background
To evaluate the prognostic significance of the pre-operative C-reactive protein (CRP) serum level in patients with renal cell cancer (RCC).
Methods
We evaluated 1,161 RCC patients with complete patient and tumour specific characteristics as well as information about their pre-operative CRP-level, who had undergone either radical nephrectomy or nephron-sparing surgery at two German high-volume centres (University Hospitals of Hannover and Ulm). The mean follow-up was 54 months.
Results
The CRP-level, stratified to three subgroups (CRP ≤ 4, 4–10, and >10 mg/l), correlated significantly with tumour stage (p < 0.001), the risk of presenting nodal disease (2.1, 3.1, and 16.4%) and distant metastasis (2.9, 8.6, and 30.0%; p < 0.001). The Kaplan-Meier 5-year cancer specific survival (CSS) rates were 89.4, 77.9, and 49.5%, respectively (p < 0.001). Multivariate analysis identified CRP as an independent prognosticator for CSS as well as overall survival (p < 0.001). Patients with a CRP of 4–10 and >10 mg/l had a 1.67 and 2.48 fold higher risk of dying due to their RCC compared to those with a pre-operative CRP ≤4 mg/l, respectively.
Conclusions
A high preoperative serum CRP level is an independent predictor of poor survival in patients with RCC. Its routine use could allow better risk stratification and risk-adjusted follow-up of RCC patients.
Journal Article
Beyond the light : identity and place in nineteenth-century Danish art
\"Denmark in the nineteenth century experienced the disastrous fallout of the Napoleonic Wars, the devastating bombardment of Copenhagen, bankruptcy, and mounting antagonism with Germany. Yet, this sociopolitical and economic tumult also gave rise to a vibrant cultural and philosophical environment for nineteenth-century Danish artists. Beyond the Light places the drawings, oil sketches, and paintings created by these artists firmly in this period, one that witnessed the transformation of a once-powerful Denmark into a small, somewhat marginalized country at the edge of Europe. Danish artists forged a close-knit community during this time, and the artworks they created explore notions of place, identity and belonging, and what it means to travel and return home. The exhibition features approximately 100 works from The Met collection, SMK - The National Gallery of Denmark, and several American collections, and highlights such artists as Christoffer Wilhelm Eckersberg, Christen Købke, Constantin Hansen, Martinus Rørbye, and Vilhelm Hammershøi as well as lesser-known figures like Anton Melbye, Johan Thomas Lundbye, Peter Christian Skovgaard, and Heinrich Gustav Ferdinand Holm, among others. Five thematic essays by leading scholars in Denmark and the United States explore the way Danish artists manifested the pride, traditions, and anxieties of their nation; the sea's ever-changing role as a marker of Danish identity; the evolving nature of portraiture; nostalgia for the Danish landscape and folk traditions; and the influence on Danish artists of their travels throughout Europe.\" -- Metropolitan Museum of Art website (viewed November 30, 2022) https://www.metmuseum.org/exhibitions/listings/2023/beyond-the-light
Book
Comparison of circulating tumor cells and AR-V7 as clinical biomarker in metastatic castration-resistant prostate cancer patients
Biomarker in metastatic castration resistant prostate cancer (mCRPC) treatment are rare. We aimed to compare the clinical value of circulating tumor cells (CTCs) and androgen receptor splice variant 7 (AR-V7) as biomarker in mCRPC patients undergoing androgen receptor-targeted agent (ARTA) treatment. Overall cohort (65 patients) was stratified regarding either CTC or AR-V7 status followed by further sub-stratification of the respective other marker. Subsequently, prostate specific antigen (PSA) response, progression free survival (PFS) and overall survival (OS)) of subgroups was compared. CTCs and AR-V7 were detected in 54 (83%) and 33 (61%) patients, respectively. All AR-V7 + were CTC +. We detected PSA response in all subgroups. For PFS and OS, biomarker stratification revealed differences between all subgroups. Interestingly, no significant differences of AR-V7 transcript copy numbers were detected between responding and non-responding patients. Additionally, multivariable analysis revealed no independent prognostic value of AR-V7 positivity. Both biomarkers show clinical value in prognosticating clinical outcome. Nonetheless, AR-V7 stratification underestimates the heterogenous subgroup of CTC − and CTC + patient, the latter requiring more intense clinical surveillance. Additionally, AR-V7 level does not correlate with clinical response. Thus, the value of AR-V7 as a clinical biomarker must be considered skeptically.
Journal Article
Antihypertensive therapy in the elderly
Arterial hypertension is the most common modifiable risk factor for cerebrovascular and cardiovascular morbidity and mortality in old age. The prevention of cognitive brain disorders is also a therapeutic goal of long-term treatment of hypertension. Older patients also have a higher risk of developing cardiovascular diseases and therefore benefit from a relatively moderate reduction in blood pressure. With respect to the high prevalence of hypertension in old age and the increasing incidence with time, the therapy of hypertension is becoming increasingly more important to achieve an improved prognosis for patients along with a reduction of costs. The accurate blood pressure measurement for elderly patients includes repeated measurements while standing and sitting. Additionally, the measurements should also be conducted by the patient or by a family member. The most accurate method for assessing the daily blood pressure level, e.g. practice hypertension, non-dipping and intermittent hypertension, is the 24-h blood pressure measurement by ambulatory blood pressure monitoring (ABPM). General measures and lifestyle interventions are effective for reducing blood pressure of elderly patients with hypertension and a low salt diet is scientifically proven to be superior. The same drugs used for young people are also recommended for older patients and most give preference to diuretics, renin-angiotensin-aldosterone system (RAAS) inhibitors and calcium antagonists. The target blood pressure in elderly patients is repeatedly the focus of scientific discussions. The current recommendations are presented in the text and the characteristics which must be particularly considered in the therapy of elderly patients are presented in detail.
Journal Article
Regional analysis of inflammation and contractile function in reperfused acute myocardial infarction by in vivo 19F cardiovascular magnetic resonance in pigs
Inflammatory cell infiltration is central to healing after acute myocardial infarction (AMI). The relation of regional inflammation to edema, infarct size (IS), microvascular obstruction (MVO), intramyocardial hemorrhage (IMH), and regional and global LV function is not clear. Here we noninvasively characterized regional inflammation and contractile function in reperfused AMI in pigs using fluorine (19F) cardiovascular magnetic resonance (CMR). Adult anesthetized pigs underwent left anterior descending coronary artery instrumentation with either 90 min occlusion (n = 17) or without occlusion (sham, n = 5). After 3 days, in surviving animals a perfluorooctyl bromide nanoemulsion was infused intravenously to label monocytes/macrophages. At day 6, in vivo 1H-CMR was performed with cine, T2 and T2* weighted imaging, T2 and T1 mapping, perfusion and late gadolinium enhancement followed by 19F-CMR. Pigs were sacrificed for subsequent ex vivo scans and histology. Edema extent was 35 ± 8% and IS was 22 ± 6% of LV mass. Six of ten surviving AMI animals displayed both MVO and IMH (3.3 ± 1.6% and 1.9 ± 0.8% of LV mass). The 19F signal, reflecting the presence and density of monocytes/macrophages, was consistently smaller than edema volume or IS and not apparent in remote areas. The 19F signal-to-noise ratio (SNR) > 8 in the infarct border zone was associated with impaired remote systolic wall thickening. A whole heart value of 19F integral (19F SNR × milliliter) > 200 was related to initial LV remodeling independently of edema, IS, MVO, and IMH. Thus, 19F-CMR quantitatively characterizes regional inflammation after AMI and its relation to edema, IS, MVO, IMH and regional and global LV function and remodeling.
Journal Article
Biotechnological production of 2-phenylethanol
2-Phenylethanol (2-PE) is an important flavour and fragrance compound with a rose-like odour. Most of the world's annual production of several thousand tons is synthesised by chemical means but, due to increasing demand for natural flavours, alternative production methods are being sought. Harnessing the Ehrlich pathway of yeasts by bioconversion of L-phenylalanine to 2-PE could be an option, but in situ product removal is necessary due to product inhibition. This review describes the microbial production of 2-PE, and also summarizes the chemical syntheses and the market situation.
Journal Article
Stilbene Induced Inhibition of Androgen Receptor Dimerization: Implications for AR and ARΔLBD-Signalling in Human Prostate Cancer Cells
Advanced castration resistant prostate cancer (CRPC) is often characterized by an increase of C-terminally truncated, constitutively active androgen receptor (AR) variants. Due to the absence of a ligand binding domain located in the AR-C-terminus, these receptor variants (also termed ARΔLBD) are unable to respond to all classical forms of endocrine treatments like surgical/chemical castration and/or application of anti-androgens.
In this study we tested the effects of the naturally occurring stilbene resveratrol (RSV) and (E)-4-(2, 6-Difluorostyryl)-N, N-dimethylaniline, a fluorinated dialkylaminostilbene (FIDAS) on AR- and ARΔLBD in prostate cancer cells. The ability of the compounds to modulate transcriptional activity of AR and the ARΔLBD-variant Q640X was shown by reporter gene assays. Expression of endogenous AR and ARΔLBD mRNA and protein levels were determined by qRT-PCR and Western Blot. Nuclear translocation of AR-molecules was analyzed by fluorescence microscopy. AR and ARΔLBD/Q640X homo-/heterodimer formation was assessed by mammalian two hybrid assays. Biological activity of both compounds in vivo was demonstrated using a chick chorioallantoic membrane xenograft assay.
The stilbenes RSV and FIDAS were able to significantly diminish AR and Q640X-signalling. Successful inhibition of the Q640X suggests that RSV and FIDAS are not interfering with the AR-ligand binding domain like all currently available anti-hormonal drugs. Repression of AR and Q640X-signalling by RSV and FIDAS in prostate cancer cells was caused by an inhibition of the AR and/or Q640X-dimerization. Although systemic bioavailability of both stilbenes is very low, both compounds were also able to downregulate tumor growth and AR-signalling in vivo.
RSV and FIDAS are able to inhibit the dimerization of AR and ARΔLBD molecules suggesting that stilbenes might serve as lead compounds for a novel generation of AR-inhibitors.
Journal Article