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- D-1221-2009 (1)
(1) Background: Evidence has accumulated that patients with anorexia nervosa (AN) are at higher risk for vitamin D deficiency than healthy controls. In epidemiologic studies, low 25(OH) vitamin D (25(OH)D) levels were associated with depression. This study analyzed the relationship between 25(OH)D serum levels in adolescent patients and AN and depressive symptoms over the course of treatment. (2) Methods: 25(OH)D levels and depressive symptoms were analyzed in 93 adolescent (in-)patients with AN from the Anorexia Nervosa Day patient versus Inpatient (ANDI) multicenter trial at clinic admission, discharge, and 1 year follow up. Mixed regression models were used to analyze the relationship between 25(OH)D levels and depressive symptoms assessed by the Beck Depression Inventory (BDI-II). (3) Results: Although mean 25(OH)D levels constantly remained in recommended ranges (≥50 nmol/L) during AN treatment, levels decreased from (in)patient admission to 1 year follow up. Levels of 25(OH)D were neither cross-sectionally, prospectively, nor longitudinally associated with the BDI-II score. (4) Conclusions: This study did not confirm that 25(OH)D levels are associated with depressive symptoms in patients with AN. However, increasing risks of vitamin D deficiency over the course of AN treatment indicate that clinicians should monitor 25(OH)D levels.
Background: Different parameters have been determined for prediction of treatment outcome in hepatitis c virus genotype 1 infected patients undergoing pegylated interferon, ribavirin combination therapy. Results on the importance of vitamin D levels are conflicting. In the present study, a comprehensive analysis of vitamin D levels before and during therapy together with single nucleotide polymorphisms involved in vitamin D metabolism in the context of other known treatment predictors has been performed.
Methods: In a well characterized prospective cohort of 398 genotype 1 infected patients treated with pegylated interferon-alpha and ribavirin for 24-72 weeks (INDIV-2 study) 25-OH-vitamin D levels and different single nucleotide polymorphisms were analyzed together with known biochemical parameters for a correlation with virologic treatment outcome.
Results: Fluctuations of more than 5 (10) ng/ml in 25-OH-vitamin D-levels have been observed in 66 (39) % of patients during the course of antiviral therapy and neither pretreatment nor under treatment 25-OH-vitamin D-levels were associated with treatment outcome. The DHCR7-TT-polymorphism within the 7-dehydrocholesterol-reductase showed a significant association (P = 0.031) to sustained viral response in univariate analysis. Among numerous further parameters analyzed we found that age (OR = 1.028, CI = 1.002-1.056, P = 0.035), cholesterol (OR = 0.983, CI = 0.975-0.991, P<0.001), ferritin (OR = 1.002, CI = 1.000-1.004, P = 0.033), gGT (OR = 1.467, CI = 1.073-2.006, P = 0.016) and IL28B-genotype (OR = 2.442, CI = 1.271-4.695, P = 0.007) constituted the strongest predictors of treatment response.
Conclusions: While 25-OH-vitamin D-levels levels show considerable variations during the long-lasting course of antiviral therapy they do not show any significant association to treatment outcome in genotype 1 infected patients.
The biology of vitamin D3 is well defined, as are the effects of its active metabolites on various cells, including mesenchymal stromal/stem cells (MSCs). However, the biological potential of its precursor, cholecalciferol (VD3), has not been sufficiently investigated, although its significance in regenerative medicine — mainly in combination with various biomaterial matrices — has been recognized. Given that VD3 preconditioning might also contribute to the improvement of cellular regenerative potential, the aim of this study was to investigate its effects on bone marrow (BM) MSC functions and the signaling pathways involved. For that purpose, the influence of VD3 on BM-MSCs obtained from young human donors was determined via MTT test, flow cytometric analysis, immunocytochemistry, and qRT-PCR. Our results revealed that VD3, following a 5-day treatment, stimulated proliferation, expression of pluripotency markers (NANOG, SOX2, and Oct4), and osteogenic differentiation potential in BM-MSCs, while it reduced their senescence. Moreover, increased sirtuin 1 (SIRT1) expression was detected upon treatment with VD3, which mediated VD3-promoted osteogenesis and, partially, the stemness features through NANOG and SOX2 upregulation. In contrast, the effects of VD3 on proliferation, Oct4 expression, and senescence were SIRT1-independent. Altogether, these data indicate that VD3 has strong potential to modulate BM-MSCs' features, partially through SIRT1 signaling, although the precise mechanisms merit further investigation.
Myeloid-derived suppressor cells (MDSCs) represent a major population controlling T cell immune responses. However, little is known about their molecular requirements for homing and T cell interaction to mediate suppression. Here, we investigated the functional role of the homing and collagen IV receptor VLA-1 (α1β1-integrin) on in vitro GM-CSF generated murine MDSCs from wild-type (WT) and CD49a/α1-integrin (Itga1\(^{−/−}\)) gene-deficient mice. Here, we found that effector (Teff) but not naive (Tn) CD4\(^+\) T cells express VLA-1 and monocytes further up-regulated their expression after culture in GM-CSF when they differentiated into the monocytic subset of resting MDSCs (R-MDSCs). Subsequent activation of R-MDSCs by LPS+IFN-γ (A-MDSCs) showed increased in vitro suppressor potential, which was independent of VLA-1. Surprisingly, VLA-1 deficiency did not influence A-MDSC motility or migration on collagen IV in vitro. However, interaction times of Itga1\(^{−/−}\) A-MDSCs with Teff were shorter than with WT A-MDSCs on collagen IV but not on fibronectin substrate in vitro. After injection, A-MDSCs homed to the splenic red pulp where they co-localized with Teff and showed immediate suppression already after 6 h as shown by inhibition of T cell proliferation and induction of apoptosis. Injection of A-MDSCs from Itga1\(^{−/−}\) mice showed equivalent homing into the spleen but a reduced suppressive effect. Interaction studies of A-MDSCs with Teff in the subcapsular red pulp with intravital two-photon microscopy revealed also here that MDSC motility and migration parameters were not altered by VLA-1 deficiency, but the interaction times with Teff were reduced. Together, our data point to a new role of VLA-1 adhesion to collagen IV as a prerequisite for extended contact times with Teff required for suppression.
No abstract available
Vogelzwerge des Waldes
(1964)
No abstract available
In this study, we examined the conditional indirect and direct relations of pain-related cognitions to depression. Subjective helplessness was included as presumably mediating the relations of catastrophizing and thought suppression to depression due to motivational deficits. In addition, moderating effects of dispositional action versus state orientation were analyzed, whereby state orientation indicates volitional deficits in coping with distress. The study was based on self-report data from 536 patients with chronic non-specific low back pain at the beginning of inpatient rehabilitation. Moderated mediation analyses were performed. The indirect catastrophizing- and thought suppression-depression relations were (partially) mediated by subjective helplessness; and moderated by failure-related action versus state orientation. Moreover, action versus state orientation moderated the direct relation of thought suppression to depression. Results suggest that catastrophizing, thought suppression, and subjective helplessness do not lead to depression unless associated with self-regulatory inability (i.e., state orientation). In contrast, action-oriented patients more effectively self-regulate pain-related emotions, disengage from rumination, and distract from pain and thus better avoid the debilitating effects of negative pain-related cognitions on depression. Future research and treatment may more strongly focus on the role of motivational and volitional deficits underlying learned helplessness and depression in chronic pain.
In contrast to the plasma membrane, the vacuole membrane has not yet been associated with electrical excitation of plants. Here, we show that mesophyll vacuoles from Arabidopsis sense and control the membrane potential essentially via the K\(^+\)-permeable TPC1 and TPK channels. Electrical stimuli elicit transient depolarization of the vacuole membrane that can last for seconds. Electrical excitability is suppressed by increased vacuolar Ca\(^{2+}\) levels. In comparison to wild type, vacuoles from the fou2 mutant, harboring TPC1 channels insensitive to luminal Ca\(^{2+}\), can be excited fully by even weak electrical stimuli. The TPC1-loss-of-function mutant tpc1-2 does not respond to electrical stimulation at all, and the loss of TPK1/TPK3-mediated K\(^{+}\) transport affects the duration of TPC1-dependent membrane depolarization. In combination with mathematical modeling, these results show that the vacuolar K\(^+\)-conducting TPC1 and TPK1/TPK3 channels act in concert to provide for Ca\(^{2+}\)- and voltage-induced electrical excitability to the central organelle of plant cells.
The present study was performed to qua ntify the distribution of a peptide neurotransmitter after microinjection into the medial preoptic area (POM), using a technique suitable for conscious animal preparations. The results indicate that only 50-ni volumes of injected tracer were sufficiently localized with 77 ± 9% recovery in the POM. Injections of higher volumes resulted in an increasing spread of tracer into distant anatomical regions and structures, including the needle tract and cerebral ventricles. The amount of tracer localized in the POM decreased to 38±4% (200 nl) (P < 0.05) and 41 ±8% (500 nl) (P <0.05), respectively. The data suggest that the volume of injection is critical for intraparenchymal injections into structures of a diameter of I mm or less, such as the POM and should not exceed 50 nl in conscious animal preparations.
Purpose: The metabolically most active lesion in 2-deoxy-2-(\(^{18}\)F)fluoro-D-glucose (\(^{18}\)F-FDG) PET/CT can predict progression-free survival (PFS) in patients with medullary thyroid carcinoma (MTC) starting treatment with the tyrosine kinase inhibitor (TKI) vandetanib. However, this metric failed in overall survival (OS) prediction. In the present proof of concept study, we aimed to explore the prognostic value of intratumoral textural features (TF) as well as volumetric parameters (total lesion glycolysis, TLG) derived by pre-therapeutic \(^{18}\)F-FDG PET.
Methods: Eighteen patients with progressive MTC underwent baseline \(^{18}\)F-FDG PET/CT prior to and 3 months after vandetanib initiation. By manual segmentation of the tumor burden at baseline and follow-up PET, intratumoral TF and TLG were computed. The ability of TLG, imaging-based TF, and clinical parameters (including age, tumor marker doubling times, prior therapies and RET (rearranged during transfection) mutational status) for prediction of both PFS and OS were evaluated.
Results: The TF Complexity and the volumetric parameter TLG obtained at baseline prior to TKI initiation successfully differentiated between low- and high-risk patients. Complexity allocated 10/18 patients to the high-risk group with an OS of 3.3y (vs. low-risk group, OS=5.3y, 8/18, AUC=0.78, P=0.03). Baseline TLG designated 11/18 patients to the high-risk group (OS=3.5y vs. low-risk group, OS=5y, 7/18, AUC=0.83, P=0.005). The Hazard Ratio for cancer-related death was 6.1 for Complexity (TLG, 9.5). Among investigated clinical parameters, the age at initiation of TKI treatment reached significance for PFS prediction (P=0.02, OS, n.s.).
Conclusions: The TF Complexity and the volumetric parameter TLG are both independent parameters for OS prediction.
While French Enlightenment seems philosophically dominated by a pejorative idea of the medieval past as the ‘Dark Ages’, this is only one conception among others. This article focuses on a different, a positive, representation of the Middle Ages in eighteenth-century literature, analyzing the chivalric novella Bliombéris (1784) by Jean-Pierre Claris de Florian. On the one hand, the eponymous hero is considered a ‘noble savage’ who develops into an ideal knight by education and successful learning – two central ideas of the Enlightenment period. On the other hand, the study shows how the medieval topic of the Matière de Bretagne, exclusively required by English literature for a long time, is finally regained by the French and is reintegrated into their national memory.
It is shown that the rate of convergence in the von Mises conditions of extreme value theory determines the distance of the underlying distribution function F from a generalized Pareto distribution. The distance is measured in terms of the pertaining densities with the limit being ultimately attained if and only if F is ultimately a generalized Pareto distribution. Consequently, the rate of convergence of the extremes in an lid sample, whether in terms of the distribution of the largest order statistics or of corresponding empirical truncated point processes, is determined by the rate of convergence in the von Mises condition. We prove that the converse is also true.
Background and Purpose
In animal models, von Willebrand factor (VWF) is involved in thrombus formation and propagation of ischemic stroke. However, the pathophysiological relevance of this molecule in humans, and its potential use as a biomarker for the risk and severity of ischemic stroke remains unclear. This study had two aims: to identify predictors of altered VWF levels and to examine whether VWF levels differ between acute cerebrovascular events and chronic cerebrovascular disease (CCD).
Methods
A case–control study was undertaken between 2010 and 2013 at our University clinic. In total, 116 patients with acute ischemic stroke (AIS) or transitory ischemic attack (TIA), 117 patients with CCD, and 104 healthy volunteers (HV) were included. Blood was taken at days 0, 1, and 3 in patients with AIS or TIA, and once in CCD patients and HV. VWF serum levels were measured and correlated with demographic and clinical parameters by multivariate linear regression and ANOVA.
Results
Patients with CCD (158±46%) had significantly higher VWF levels than HV (113±36%, P<0.001), but lower levels than AIS/TIA patients (200±95%, P<0.001). Age, sex, and stroke severity influenced VWF levels (P<0.05).
Conclusions
VWF levels differed across disease subtypes and patient characteristics. Our study confirms increased VWF levels as a risk factor for cerebrovascular disease and, moreover, suggests that it may represent a potential biomarker for stroke severity, warranting further investigation.
Der Atlantische Wildkohl (Brassica oleracea L. subsp. oleracea) wächst auf den Küstenfelsen des Atlantiks und der Nordsee zwischen Nord-Spanien, Schottland und der Nordseeinsel Helgoland. 2001 wurde auch ein Vorkommen des Wildkohls an den Kreidefelsen der Ostseeinsel Rügen nachgewiesen, das aus ungefähr 50 Individuen besteht. Die Pflanzen unterscheiden sich phänotypisch nicht von Wildpflanzen der Atlantikküsten. Da alle verbreiteten Kultursorten des Gemüsekohls genetisch sehr eng mit dem Atlantischen Kohl verwandt sind, vom dem sie höchstwahrscheinlich abstammen, wird die Frage erörtert, ob eine spontane Rückverwandlung (Rückkreuzung) von in die Natur entwichenen Kultursorten in den Wildkohl-Phänotyp möglich ist. Dieses wird als wenig wahrscheinlich angesehen. Dagegen ist Introgression zwischen Kultursorten und Wildsorten gut belegt. Die Frage nach einer möglichen Hybridisierung von Grünkohl mit Pflanzen vom Wildkohlphänotyp oder mit anderen Kultursorten an der Kreideküste der dänischen Ostseeinsel Seeland wird anhand eigener Beobachtungen erörtert. Die dortige Population besteht offensichtlich aus verwilderten Kulturkohlhybriden, die sich deutlich von den Wildpflanzen Rügens unterscheiden. Das neue Vorkommen des Atlantischen Wildkohls in der westlichen Ostsee kann im Zusammenhang mit der Ostausbreitung anderer atlantischer Sippen im Rahmen des Klimawandels gesehen werden.
Vorkommen und Manipulation von MHC Klasse II Antigenen auf Zellen isolierter Langerhans-Inseln
(1986)
No abstract available
The article starts with the etymology of the words Vorlesung („lecture“) and Hörsaal (“lecture hall”). On the one hand, it turns out that the two expressions are deeply anchored in the history of the old Latin scientific language. They transmit Latin structures and perspectives in German neologisms. On the other hand, the two words arose exactly at the time when the sciences were moving from Latin to German, thus distancing themselves from the traditional forms of Latin scholarship. In this light, they exemplify an epochal change in the history of the German language, but at the same time they represent a great European continuity. Against this background, the two words can be interpreted as symptomatic words associated with the Enlightenment’s confident outlook on the future relationship between science and society. Further corpus linguistic surveys also show how productively the two words appear in word formation processes. In particular, these surveys show by way of example that and how German standard language has benefited from the emergence of German academic language.
Vorwort (Das Kind (1988) 4)
(1988)
No abstract available
Vorwort (Das Kind (1989) 5)
(1989)
No abstract available
Vorwort (Das Kind (1989) 6)
(1989)
No abstract available