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The olfactory bulbectomized (OBX) rat is extensively used as an animal model to detect putative antidepressant drugs. The model has some unusual characteristics, as it detects antidepressant activity of drugs only after medium to long-term administration, thereby reflecting the human situation, as antidepressants do not work acutely but only after long-term administration. The slow onset of action of antidepressants is a major drawback of current antidepressants and the availability of an animal depression model that potentially reveals rapid onset of antidepressant activity might be a great asset. Although an animal model of depression ideally should reflect correlates of human depression, several ‘surrogate’ parameters, like ‘hyperactivity’, reflect astonishingly well the ‘antidepressant’ profile of antidepressants in human depression. Using a new environment (open field) and a home cage to measure activity, imipramine, a classic tricyclic antidepressant, reduced hyperactivity in OBX rats, both in home cage and open field. Telemetrically measured, OBX-induced hyperactivity was already found after a couple of days and indicated that the OBX model is able to detect early (days) effects of (classic) antidepressants. Although imipramine treatment for 3, 7 and 14 days reduced OBX-induced hyperactivity, daily treatment with imipramine for 14 days, but not for 3 or 7 days, reduced hyperactivity (both in home cage and open field) of OBX rats up to 6 weeks after cessation of treatment, indicating neuroplastic changes in the brain. The attractiveness of the OBX model for detection of antidepressants lies in the resemblance to the human situation (onset of action). Moreover, the model suggests that long-term antidepressant treatment (in rats at least 14 days) leads to long-term behavioral changes that far outlast the presence of the antidepressant in the body. Whether this aspect contributes to efficient antidepressant effects needs further investigation.

Objective Robotic distal pancreatectomy (DP) is emerging as the preferred treatment for body and tail tumors of the pancreas. To enable conclusive comparisons with the standard open or laparoscopic approaches and robotic surgery among centers, novel benchmark outcome values are urgently needed. Therefore, the aim of this study was to identify benchmark values from expert centers beyond the learning curve. Methods This multicenter study analyzed outcomes from consecutive patients undergoing robotic DP for resectable malignant or benign lesions from 14 international expert centers. After the learning curve, defined as the first 10 cases of robotic DP, all consecutive patients were included from the start of the program up to June 2020 with a minimum follow-up of 1 year. Benchmark patients were those without significant comorbidities including obesity (BMI >35 kg/m2) cardiac disease, chronic pulmonary disease. Benchmark cutoff values were derived from the 75th or the 25th percentile of the median values of all benchmark centers. Results After reaching the learning curve, 289 (47%) of a total of 614 consecutive patients qualified as benchmark cases. The proportion of benchmark patients varied between 24%-64% per center. Benchmark cut-offs showed a low 6 month- postoperative mortality ( 19 with an R0 resection rate of > 85%, and an overall survival of >86% and >52% after 1- and 5-years, respectively. Centers with a low cohort of benchmark patients (more difficult cases) had less clinically relevant pancreatic fistula (9% vs. 23%) and less overall complications (32% vs. 48%). Conclusion This benchmark analysis sets novel reference values for robotic DP, indicating favorable outcomes as compared to laparoscopic and open DP. These references values may serve for quality control of surgery in centers embarking in robotic DP, and include the procedure in the standard of care.

Berichtet wird uber einen atypischen lipomatosen Tumor (ALT) der Submentalloge bei einer 59-jahrigen Patientin, der uber mehrere Jahre in unmittelbarer Nahe zum Unterkiefer entstanden ist. Aufgrund der knochernen Verbindung der Lasion zur lingualen Kompakta der Mandibula liese sich der Tumor als parostealer ALT bezeichnen. Ein ALT im Kopf-Hals-Bereich ist sehr selten, die Diagnosestellung war durch Nachweis einer Amplifikation des MDM2-Gens mittels Fluoreszenz-in-situ-Hybridisierung moglich.

In baseline surveys that were conducted in Florida, North Carolina, and South Carolina, extension personnel were asked whether, how, and which farmers would use climate forecasts to manage production and other aspects of their agribusinesses. In making such assessments extensionists use their expertise to account for, the authors assume, net benefits to farmers of the forecasts, given any help that they also expect to provide their clients. Models of conditional probabilities are estimated to show how the assessments depend on the expertise and other characteristics of the extensionist and her clientele. For example, if a person has worked at least 7 years in extension, she is more likely to agree or strongly agree that farmers are interested in using climate forecasts. An extensionist who works with field crop producers is more likely than one who does not to think that a farmer can use climate forecasts to improve planting schedules, harvest planning, crop selection, nutrient management, and land allocation. An extensionist is more likely to assess that farmers who produce particular crops can use climate forecasts to be more successful if she works with them. An extensionist whose clientele’s average farm size exceeds 200 acres is more likely to indicate that a farmer can use climate forecasts to improve irrigation management, harvest planning, and crop selection. In addition to serving as references for future work, these conditional assessments almost always provide more nuanced and useful information than unconditional ones about potential farmer interest in and uses of climate forecasts for the three-state region.

Script stakeholder workshop 1 and 2. Description of half-day workshops, including timing. (PDF 28 kb)

Item does not contain fulltext To allow the rational design of effective treatment strategies for human mitochondrial disorders, a proper understanding of their biochemical and pathophysiological aspects is required. The development and evaluation of these strategies require suitable model systems. In humans, inherited complex I (CI) deficiency is one of the most common deficiencies of the mitochondrial oxidative phosphorylation system. During the last decade, various cellular and animal models of CI deficiency have been presented involving mutations and/or deletion of the Ndufs4 gene, which encodes the NDUFS4 subunit of CI. In this review, we discuss these models and their validity for studying human CI deficiency. (c) 2013 IUBMB Life, 65(3):202-208, 2013.

Contains fulltext : 108693.pdf (Publisher’s version ) (Open Access) The biologist Lewis Thomas once wrote: "my mitochondria comprise a very large proportion of me. I cannot do the calculation, but I suppose there is almost as much of them in sheer dry bulk as there is the rest of me". As humans, or indeed as any mammal, bird, or insect, we contain a specific molecular makeup that is driven by vast numbers of these miniscule powerhouses residing in most of our cells (mature red blood cells notwithstanding), quietly replicating, living independent lives and containing their own DNA. Everything we do, from running a marathon to breathing, is driven by these small batteries, and yet there is evidence that these molecular energy sources were originally bacteria, possibly parasitic, incorporated into our cells through symbiosis. Dysfunctions in these organelles can lead to debilitating, and sometimes fatal, diseases of almost all the bodies' major organs. Mitochondrial dysfunction has been implicated in a wide variety of human disorders either as a primary cause or as a secondary consequence. To better understand the role of mitochondrial dysfunction in human disease, a multitude of pharmacologically induced and genetically manipulated animal models have been developed showing to a greater or lesser extent the clinical symptoms observed in patients with known and unknown causes of the disease. This review will focus on diseases of the brain and spinal cord in which mitochondrial dysfunction has been proven or is suspected and on animal models that are currently used to study the etiology, pathogenesis and treatment of these diseases. 01 maart 2012

Current antidepressants have a delayed onset of action and disturbing side effects, including inhibition of sexual behavior. It is hypothesized that novel drugs, hitting multiple disease-relevant targets, may yield a new generation of superior antidepressants. One such approach is simultaneous inhibition of serotonin, norepinephrine and dopamine transporters. We tested the triple uptake inhibitor (TUI), DOV 216,303 (5, 10 and 20 mg/kg) after 1, 7 and 14 days administration in the olfactory bulbectomized (OBX) rat depression model, and in a model of rat sexual behavior to detect putative sexual side effects. Chronic, but not acute treatment of DOV 216,303 (20 mg/kg) normalized OBX-induced hyperactivity in the open field, similar to the effect of imipramine (20 mg/kg). None of the doses of DOV 216,303 had any effect on sexual behavior at any time point. The results indicate that DOV 216,303 displays antidepressant efficacy and is devoid of sexual side effects.

ITIH5 ist ein kurzlich von uns neu charakterisiertes Extrazellularmatrix-Protein, dessen Expression in einer Vielzahl von humanen Tumorentitaten, wie z. B. dem Mammakarzinom, deutlich herabreguliert wird. Ziel der vorliegenden Studie war es, die molekulare Ursache des ITIH5-Expressionsverlusts beim Brustkrebs zu entschlusseln und mehr uber die Rolle dieses Molekuls bei Tumorerkrankungen zu lernen. Wir zeigen, dass das ITIH5-Protein bei 42% aller invasiven Mammakarzinome herabreguliert wird und dieses signifikant mit einem verkurzten Uberleben der Patientinnen assoziiert ist. Sowohl in Brust-Zelllinien als auch in primaren Mammakarzinomen (40%) konnten wir eine frequente Methylierung des ITIH5-Promotors detektieren, welche funktionell mit einem ITIH5-mRNA-Verlust assoziiert war. Daneben zeigte auch die ITIH5-Promotormethylierung ein signifikant verkurztes Uberleben der Patientinnen an und war zusatzlich assoziiert mit Eigenschaften der Lymphknoten- und Fernmetastasierung. Unsere Ergebnisse sprechen dafur, dass ITIH5 einen neuen Metastasierungsrepressor des Mammakarzinoms darstellt, dessen Proteinverlust und Promotormethylierung zukunftig als prognostische Biomarker genutzt werden konnten.

Olfactory bulbectomy (OBX) in rats causes several behavioral and neurochemical CNS changes, reminiscent of symptoms of human depression. Such depression-like behavior after OBX can be reversed with antidepressants. Recently, a connection between the vasopressin 1b (V1b) receptor and the development of depression has been suggested; therefore, a vasopressin V1b receptor antagonist (SSR149415) was investigated in the OBX model. Male rats received olfactory bulbectomy or sham surgery. After recovery, animals received 14 consecutive daily doses of SSR149415 (10 or 30 mg/kg), imipramine (20 mg/kg), or vehicle (5% hydroxy-propyl methylcellulose). Animals were tested in an open field after acute treatment, on days 7 and 14 of treatment and 1 week after cessation of treatment. Similar to imipramine, repeated, but not acute, administration of SSR149415 completely reversed OBX-induced hyperactivity, leaving activity in shams unaffected. This reversal of OBX-induced hyperactivity in the SSR149415 treated rats was still present 7 days after cessation of treatment. Although the behavioral effects of treatment with SSR149415 were specific for the OBX animals, adrenal gland weights were reduced in both sham and OBX animals treated with 30 mg/kg SSR149415. Chronic but not acute administration of SSR149415 normalizes OBX-induced hyperactivity up to 1 week after cessation of treatment, suggesting that a V1b receptor antagonist may have long-lasting antidepressant activity.

Overproduction of corticotrophin-releasing factor (CRF), the major mediator of the stress response, has been linked to anxiety, depression and addiction. CRF excess results in increased arousal, anxiety and altered cognition in rodents. The ability to adapt to a potentially threatening stimulus is crucial for survival, and impaired adaptation may underlie stress-related psychiatric disorders. Therefore, we examined the effects of chronic transgenic neural CRF overproduction on behavioural adaptation to repeated exposure to a non-home cage environment. We report that CRF transgenic mice show impaired adaptation in locomotor response to the novel open field. In contrast to wild-type (WT) mice, anxiety-related behaviour of CRF transgenic mice does not change during repeated exposure to the same environment over the period of 7 days or at retest 1 week later. We found that locomotor response to novelty correlates significantly with total locomotor activity and activity in the centre at the last day of testing and at retest in WT but not in CRF transgenic mice. Mice were divided into low responders and high responders on the basis of their initial locomotor response to novelty. We found that differences in habituation and re-exposure response are related to individual differences in locomotor response to novelty. In summary, these results show that CRF transgenic mice are fundamentally different from WT in their ability to adapt to an environmental stressor. This may be related to individual differences in stress reactivity. These findings have implications for our understanding of the role of CRF overproduction in behavioural maladaptation and stress-related psychiatric disorders.

Inter-alpha-trypsin inhibitors (ITIs) are protease inhibitors stabilizing the extracellular matrix. ITIs consist of one light (bikunin) and two heavy chains (ITIHs). We have recently characterized ITIH5, a novel member of the ITIH gene family, and showed that its messenger RNA is lost in a high proportion of breast tumours. In the present study, an ITIH5-specific polyclonal antibody was generated, validated with western blot and used for immunohistochemical analysis on a tissue microarray; ITIH5 was strongly expressed in epithelial cells of normal breast (n=11/15), while it was lost or strongly reduced in 42% (92/217) of invasive breast cancers. ITIH5 expression in invasive carcinomas was associated with positive expression of oestrogen receptor (P=0.008) and histological grade (P=0.024). Correlation of ITIH5 expression with clinical outcome revealed that patients with primary tumours retaining abundant ITIH5 expression had longer recurrence-free survival (RFS; P=0.037) and overall survival (OS; P=0.044), compared to those with reduced expression (mean RFS: 102 vs 78 months; mean OS: 120 vs 105 months). Methylation-specific PCR analysis frequently showed strong methylation of the ITIH5 promoter in primary breast tumours (41%, n=109) and breast cancer cell lines (n=6). Methylation was significantly associated with mRNA loss (P

Background Olfactory bulbectomy (OBX) in rats causes several behavioral and neurochemical central nervous system changes, reminiscent of symptoms of human depression. Moreover, depression-like behavior after OBX can be reversed with antidepressant drugs. However, the lasting effects of these antidepressant drugs on behavior after cessation of treatment have never been studied. Methods Male rats received OBX or sham surgery. After recovery, animals received 14 consecutive daily doses of imipramine (20 mg/kg), escitalopram (5 and 10 mg/kg), or vehicle. Animals were tested in an open field after acute, sub-chronic, and chronic injections, as well as 1, 2, 6, and 10 weeks after cessation of treatment. Results The OBX-induced hyperactivity was normalized after sub-chronic administration of imipramine and escitalopram. Two weeks after treatment, activity of OBX animals was comparable to sham-treated animals, but after 6 weeks, OBX animals treated with both doses of escitalopram had returned to pre-treatment hyperactivity levels. The OBX animals treated with the high imipramine dose (20 mg/kg) retained activity levels comparable to sham-treated animals until 10 weeks after cessation of treatment. Conclusions Chronic but not acute administration of imipramine and escitalopram normalizes OBX-induced hyperactivity. This effect continues for up to 10 weeks after cessation of treatment in a dose dependant manner.

Background Bilateral removal of the olfactory bulbs (OBX) in rats results in a complex constellation of behavioral, neurochemical, neuroendocrine, and neuroimmune alterations, many of which are also reported in patients with major depressive disorder (MDD). Drawing on clinical findings, there has been considerable interest in the role of serotonin in the mechanism of action of OBX. However, to date, there has been no report of direct measurement of serotonergic functioning of bulbectomized animals using microdialysis. The present study describes the effects of olfactory bulbectomy on functioning of the serotonergic system. Methods In vivo microdialysis was performed in conscious rats that underwent OBX or sham surgery. Alterations in the functioning of the serotonergic system were assessed by administration of fluvoxamine, fenfluramine, and 3-hydroxybenzylhydrazine (NSD-1015). Animals were also repeatedly tested in an open field. Results Bilateral removal of the olfactory bulbs decreased basal extracellular levels by decreasing the releasable pool of serotonin (5-HT) in the basolateral amygdala 2 weeks after surgery and in the dorsal hippocampus 2 weeks and 5 months after surgery. Olfactory bulbectomized animals showed a lower rate of 5-HT synthesis under basal conditions. However, the capacity of the system to synthesize 5-HT was not affected. Olfactory bulbectomized rats were hyperactive in the open field. This hyperactivity remained after successive testing, indicating permanent behavioral changes. Conclusions This microdialysis study shows that OBX has profound and long-lasting effects on serotonergic functioning and on activity levels and is therefore considered an intriguing and promising animal model for affective processes in the brain.

In this study we tested the validity of the National Organic Program (NOP) requirement for a ≥120-day interval between application of noncomposted manure and harvesting of vegetables grown in manure-fertilized soil. Noncomposted bovine manure was applied to 9.3-m 2 plots at three Wisconsin sites (loamy sand, silt loam, and silty clay loam) prior to spring and summer planting of carrots, radishes, and lettuce. Soil and washed (30 s under running tap water) vegetables were analyzed for indigenous Escherichia coli . Within 90 days, the level of E. coli in manure-fertilized soil generally decreased by about 3 log CFU/g from initial levels of 4.2 to 4.4 log CFU/g. Low levels of E. coli generally persisted in manure-fertilized soil for more than 100 days and were detected in enriched soil from all three sites 132 to 168 days after manure application. For carrots and lettuce, at least one enrichment-negative sample was obtained ≤100 days after manure application for 63 and 88% of the treatments, respectively. The current ≥120-day limit provided an even greater likelihood of not detecting E. coli on carrots (≥1 enrichment-negative result for 100% of the treatments). The rapid maturation of radishes prevented conclusive evaluation of a 100- or 120-day application-to-harvest interval. The absolute absence of E. coli from vegetables harvested from manure-fertilized Wisconsin soils may not be ensured solely by adherence to the NOP ≥120-day limit. Unless pathogens are far better at colonizing vegetables than indigenous E. coli strains are, it appears that the risk of contamination for vegetables grown in Wisconsin soils would be elevated only slightly by reducing the NOP requirement to ≥100 days.

Sediment and water can potentially be altered, chemically, physically and biologically as they are sampled at the seafloor, brought to the surface, processed and analysed. As a result, in situ observations of relatively undisturbed systems have become the goal of a growing body of scientists. Our understanding of sediment biogeochemistry and exchange fluxes was revolutionized by the introduction of benthic chambers and in situ micro-electrode profilers that allow for the direct measurement of chemical fluxes between sediment and water at the sea floor and for porewater composition. Since then, rapid progress in the technology of in situ sensors and benthic chambers (such as the introduction of gel probes, voltammetric electrodes or one- and two-dimensional optodes) have yielded major breakthroughs in the scientific understanding of benthic biogeochemistry. This paper is a synthesis of discussions held during the workshop on sediment biogeochemistry at the "Benthic Dynamics: in situ surveillance of the sediment-water interface" international conference (Aberdeen, UK--March 25-29, 2002). We present a review of existing in situ technologies for the study of benthic biogeochemistry dynamics and related scientific applications. Limitations and possible improvement (e.g., technology coupling) of these technologies and future development of new sensors are discussed. There are countless important scientific and technical issues that lend themselves to investigation using in situ benthic biogeochemical assessment. While the increasing availability of these tools will lead research in yet unanticipated directions, a few emerging issues include greater insight into the controls on organic matter (OM) mineralization, better models for the understanding of benthic fluxes to reconcile microelectrode and larger-scale chamber measurements, insight into the impacts of redox changes on trace metal behavior, new insights into geochemical reaction pathways in surface sediments, and a better understanding of contaminant fate in nearshore sediments.

Syngas, from biomass gasification, needs to be purified of condensible tars before being used as a fuel for spark ignition engines. A novel tar tolerant system is being developed, wherein a (Homogeneous Charge Compression Ignition) HCCI engine is fueled by impure syngas at intake temperatures above the tar dew point, thus avoiding the condensation of tars and its consequent problems. This paper introduces the novel concept and studies the sensitivities of HCCI combustion to key context relevant issues such as the variations in the combustible composition (H2:CO ratio from 30:70 to 55:45%), moisture (upto 12% by volume) and tars (from 3 to 17 g/Nm3) at the intake temperatures of around 250 °C. The effects of intake temperatures (230–270 °C) and pressures (1.0–1.2 bar) are also studied. The experiments are carried out with artificial syngas on a 435 cc mono-cylinder HCCI engine with a compression ratio of 12 and operated at 1500 RPM. Indicated efficiencies about 34% and Indicated Mean Effective Pressures about 2.5 bar were achieved at equivalence ratios between 0.3 and 0.34. In the tested ranges, moisture delayed the combustion while the effect of tars were insignificant.

Ziel der vorliegenden Arbeit ist, die Brustkrebsinzidenz der Aachener Region 1996/1997 mit 16 Regionen aus 14 europaischen Landern zu vergleichen. Dies geschieht vor dem Hintergrund, dass einige europaische Regionen staatliche „Mammographie-Screening-Programme” eingefuhrt haben, andere, wie in Aachen bzw. in Deutschland, jedoch nicht. Die Feldstudie Mammakarzinom verwendete die Dateien des Tumorzentrums Aachen. Die Brustkrebsinzidenzraten wurden als rohe Inzidenz berechnet oder an die Europaische Standardpopulation (ESR) bzw. an die Weltstandardpopulation (WSR) adaptiert. Die Inzidenzraten sind einschlieslich oder ausschlieslich der Zweittumoren und der Carcinomata in situ angegeben. Die aktuellen Daten zur Brustkrebsinzidenz der verschiedenen europaischen Lander wurden durch Kontaktaufnahme mit den jeweiligen Krebsregistern erhoben. Dabei fanden die unterschiedlichen Kriterien zur Berechnung der Krebsinzidenz besondere Berucksichtigung. Die Brustkrebsinzidenzraten gemas ESR liegen in Aachen 1996 bei 94 und 1997 bei 90 invasiven Ersttumoren auf 100 000 Frauen und sind damit gut vergleichbar mit den Werten der europaischen Gebiete ohne ein landesweites Mammographie-Screening. Die Gruppe der Regionen mit einem Mammographie-Screening wiesen eine signifikant hohere Inzidenz auf. Der Anstieg der Brustkrebsinzidenz lag in den Landern ohne ein landesweites Mammographie-Screening in 10 Jahren durchschnittlich im Gesamtuberblick bei etwa 17 %. Die Brustkrebsinzidenz in den Regionen mit Mammographie-Screening stieg insbesondere unmittelbar nach Einfuhrung des Screenings stark an. Die vorliegende Studie belegt erstmals, dass die Haufigkeit des Mammakarzimons in Aachen gut vergleichbar ist mit der anderer zentraleuropaischer Regionen ohne ein landesweites Mammographie-Screening. Die hohe und wohl weiter steigende Inzidenz des weiblichen Brustkrebses gibt Anlass zu der Vermutung, dass die Bedeutung dieser Erkrankung fur das Gesundheitssystem noch weiter zunehmen wird. Eine Moglichkeit diesem Problem zu begegnen kann ein nationales Mammographie-Screening-Programm sein, wobei zukunftige Untersuchungen zu belegen haben, inwieweit ein Mammographie-Screening nicht nur die Inzidenz beeinflussen, sondern auch das Patientenuberleben verbessert. Aim of the present study is to compare the incidence of breast cancer in the region of Aachen in 1996 and 1997 with 16 regions from 14 European countries. Moreover, the fact that some countries started nationwide mammographic screening programs was also taken into consideration. Specifically in Aachen and in Germany in general, there is no national mammographic screening program. The field study of breast cancer used data files of the Tumor Registry in Aachen. Incidence rates were calculated as crude value, adapted to the European Standard Population (ESR) or to the World Standard Population (WSR) and presented in- or excluding second tumors and carcinomata in situ, respectively. Recent data on the incidence of breast cancer of distinct regions in Europe were inquired by contacting the European cancer registries. Of note, the specific criteria of the cancer registries for the calculation of the incidence were considered. The incidence of breast cancer in Aachen according to the ESR was in 1996 94 and in 1997 90 invasive primary tumors per 100,000 women. These incidences are in line with the incidence of other European regions without a nationwide mammographic screening program. Those regions with a nationwide mammographic screening program revealed a significant higher rate of breast cancer. The mean increase of the breast cancer incidence was about 17 % in the regions without a nation-wide mammographic screening in a period of 10 years. In countries with a national mammographic screening program the incidence increased strongly in particular immediately after onset of the screening. For the first time, the present study demonstrates that the incidence of breast cancer in Aachen is in a comparable range with other regions in central Europe without a mammographic screening. The high and probably further increasing incidence of breast cancer suggests that this disease will become even more relevant for the health care system. One option to encounter this problem could be a mammographic screening. However, future studies have to demonstrate that mammographic screening programs do not only influence the incidence, but improve also the survival of the patients.

Studies from six regions of Germany (Aachen (W1), Dresden (E1), Jena (E2), Marburg (W2), Munich (W3), and Stuttgart (C1)) have been compared to verify and assess the quality of healthcare using breast cancer as an example. All of the data collection was carried out in comprehensive cancer centres and is population-based, with the exception of C1. Classic prognostic factors and the initial treatment of 8661 women with breast cancer, diagnosed between 1996 and 1998, were examined. Primary therapy, breast conserving therapy (BCT), and the use of subsequent local radiation and/or systemic therapy (chemotherapy or hormonal therapy) were analysed. BCT was performed on 39.3–57.7% of patients. By pT-category, the proportion of BCT in the six regions were as follows: for pTis between 37.8 and 64.3%, for pT1 between 51.7 and 71.5%, for pT2 between 25.9 and 51.1%, for pT3 between 0 and 13.1% and for pT4 between 0 and 15.2%. Multivariate analyses, adjusted for age and biological factors, showed a significant influence of the treating hospital on the mastectomy rate. The use of radiotherapy after BCT (80%) was quite homogeneous in the six regions. The application of radiotherapy after mastectomy, however, varied between 10.4 and 32.2%. In all regions, for premenopausal patients, the use of adjuvant systemic therapy almost reflected the St. Gallen-Consensus recommendations. In contrast, post-menopausal women with positive lymph nodes were not always treated according to these standards. In all regions, age had an influence on the administration of treatment: elderly breast cancer patients received less BCT, less radiotherapy and less adjuvant therapy than recommended in the St. Gallen-Consensus. Feedback of the results was made available to each hospital, providing a comparative summary of patient care that could be used by the participating hospitals for self-assessment and quality-control.

Anabolic androgenic steroids (AAS) have been linked to indiscriminant and unprovoked aggression and violence. We employed a brief tail pinch to examine the effects of different AAS on intermale aggression in gonadally intact male rats in response to a mild physical provocation. Animals received 5 mg/kg testosterone propionate (TP), nandrolone (ND), or stanozolol (ST) 5 days/week. Controls received vehicle injections. After 12 weeks, rats were tested for aggression while treatments continued. Animals were paired with either gonadally intact or castrated opponents and were tested in the subject rat's home cage, the opponents's home cage, and a neutral cage. Aggression was tested during tail pinch of the subject rat and during tail pinch of the opponent rat. In TP-treated males, tail pinch significantly enhanced aggression in all social and environmental conditions compared to intact controls. TP treatment also significantly enhanced aggression when the opponents were tail pinched. Tail pinch did not increase aggression in ND-treated males, and aggression was significantly lower than controls in ST-treated males. As expected, cell nuclear androgen receptor binding was significantly elevated by the high dose of TP. Our results show that while AAS alone does not induce the indiscriminate and unprovoked aggression characteristic of 'roid rage, TP heightens the animals sensitivity to external stimuli and lowers the threshold for aggression and dominance in response to provocation.

This study examined the effects of anabolic androgenic steroids (AAS) on aggression under different social and environmental conditions. Three AAS were tested in gonadally intact male rats: testosterone propionate (TP), nandrolone (ND), and stanozolol (ST). Doses of 5 mg/kg were given 5 times/week, with gonadally intact controls receiving vehicle only (propylene glycol). Animals received six weekly tests under each condition in a counterbalanced order. Results show that the three AAS differed in their ability to elicit aggression. Males receiving TP were more aggressive than controls, ND males were similar to controls, and ST males were less aggressive than controls. In the social and environmental provocation tests TP-treated males were more aggressive than other groups, but were able to discriminate between intact and castrated opponents and between their home cage and a neutral cage. In the environmental provocation test, TP males were also more aggressive against opponents when tested in the opponent's home cage. It is suggested that chronic exposure to high levels of TP does not eliminate the ability to discriminate between social or environmental cues, as might be expected if it induces a “ ‘roid rage.” However, TP does increase the likelihood that the animal will respond with aggression/dominance in a provoking situation. All three AAS variably affected serum testosterone and LH levels, as well as testes, seminal vesicle, and prostate weights. No effect on body weight was observed.

HISTORY AND CLINICAL FINDINGS A 81-year-old patient free of pain was referred to the university hospital for further evaluation and therapy of tumour masses in the right thorax. Clinical examination revealed dullness to percussion and reduced breathing in the right lower lung. INVESTIGATIONS Computed tomography showed an enlarged solid tumour mass attached to the thoracic cavity and pleural effusion on the right side. Quantification of pulmonary perfusion presented significant defects in the right upper and middle lobe. DIAGNOSIS, TREATMENT AND COURSE The pulmonary masses were biopsied under CT-guidance. Biopsy and immunohistochemical findings proved a malignant solitary fibrous tumour of the chest wall, a mesenchymal tumour of its own entity. Because of pain in the right arm and because of missing other reliable therapeutic options a palliative irradiation was performed. The tumour did increase in size due to radiotherapy and a severe right ventricular heart failure occurred. The patient died 5 months after diagnosis has been made. Autopsy revealed a transition of tumour cells to sarcomatic growth. CONCLUSION In our case we conclude an accelerated progression of the solitary fibrous chest wall tumour in the course of irradiation. Whether the development of sarcomatic growth occurred as a result of radiotherapy remains speculative.

Item does not contain fulltext The development of neurologic disease is a complex and multi-faceted process. Several factors, such as physiology, environment and genetics may play key roles in the manifestation of the associated illnesses. During the past decades, it has become clear that, at the cellular level, mitochondria function as more than "just" an energy source for our cells and plays a significant role in such aspects as neuronal development, maintenance and degeneration. Malfunctions in mitochondrial respiration and ATP production may prove disastrous for our cells and neurons, ultimately resulting in apoptosis, neurodegeneration and consequently, neurodegenerative diseases.

Item does not contain fulltext Depression, especially in the elderly, is associated with poor cognitive functioning. Exercise has received much attention in the treatment for depression and also dementia. Here we studied the effect of an enriched environment combined with voluntary exercise (EE/VE) on the olfactory bulbectomized (OBX) rat. The OBX rat is hyperactive in an open field, which is normalized by chronic antidepressant treatment, and suffers from learning and memory impairments. Neurotrophic factors are thought to be involved in the antidepressant action of EE/VE. Hyperactivity and cognitive functioning (both hippocampal dependent and independent tasks) were investigated before and after EE/VE. We quantified hippocampal mRNA levels of the neurotrophic factors BDNF, VGF and VEGF. VEGF receptor (FLK-1) inhibition was achieved by i.c.v administration of the antagonist SU5416 during the period of EE/VE. OBX almost completely blocked fear memory acquired either 48 h or 28 days before surgery. EE/EV normalized OBX-induced hyperactivity in open field, while having no effect on the decrease in hippocampal dependent learning and memory. VEGF mRNA levels in hippocampus were significantly increased both in OBX and control rats following EE/VE. OBX reduced BDNF mRNA levels, but EE did not reverse this. Inhibition of the FLK-1 receptor did not suppress EE/VE induced normalization of the hyperactivity of the OBX rat. The lack of effect of EE/VE on cognitive parameters, while normalizing hyperactivity, suggests different neuronal mechanisms underlying OBX-induced behavioral changes. Since EE/VE still normalizes the OBX-induced hyperactivity while the FLK-1 receptor was blocked, we assume that VEGF is not obligatory for the antidepressant effect of EE/VE. This article is part of a Special Issue entitled 'Anxiety and Depression'.

BACKGROUND: Olfactory bulbectomy (OBX) in rats causes several behavioral and neurochemical changes. However, the extent and onset of physiological and behavioral changes induced after bulbectomy have been little examined.METHODS: Male Sprague-Dawley rats received telemetric implants. Before and immediately after OBX surgery, basal and stress-induced heart rate, body temperature, and locomotor activity were measured in the home cage in sham (n=9) and OBX animals (n=11). Stress was induced using novel cage stress or witness stress.RESULTS: Bulbectomized animals differed physiologically and behaviorally from shams. Nocturnally, OBX animals were significantly more active compared with shams, had a higher core body temperature and displayed a decreased heart rate variability. During the light period, OBX animals had a significantly lower basal heart rate and a reduced heart rate variability. These effects became apparent 2-3 days after OBX surgery, and were stable over time. After witness stress, OBX animals showed smaller autonomic (body temperature and heart rate) responses compared with shams, but showed no difference in locomotor responses. In contrast, novel cage stress led to increased locomotor responses in OBX rats compared with sham rats, while no differences were found in autonomic responses.CONCLUSION: Removal of the olfactory bulbs results in rapid, stable and persistent changes in basal locomotor activity, body temperature, heart rate and heart rate variability. Although the sleep-wake cycle of these parameters is not altered, increases in circadian amplitude are apparent within 3 days after surgery. This indicates that physiological changes in the OBX rat are the immediate result of olfactory bulb removal. Further, stress responsivity in OBX rats depends on stressor intensity. Bulbectomized rats display smaller temperature and heart rate responses to less intense witness stress compared with sham rats. Increased locomotor responses to more intense novel cage stress are present in the home cage as well as the open field. The present study shows that olfactory bulbectomy has rapid and persistent influence on basal and stress-induced physiological parameters.

Background Y-box binding protein-1 (YB-1) is the prototypic member of the cold shock protein family that fulfills numerous cellular functions. In the nucleus YB-1 protein orchestrates transcription of proliferation-related genes, whereas in the cytoplasm it associates with mRNA and directs translation. In human tumor entities, such as breast, lung and prostate cancer, cellular YB-1 expression indicates poor clinical outcome, suggesting that YB-1 is an attractive marker to predict patients' prognosis and, potentially, is suitable to individualize treatment protocols. Given these predictive qualities of YB-1 detection we sought to establish a highly specific monoclonal antibody (Mab) for diagnostic testing and its characterization towards outcome prediction (relapse-free and overall survival). Methods Hybridoma cell generation was carried out with recombinant YB-1 protein as immunogen and Mab characterization was performed using immunoblotting and ELISA with recombinant and tagged YB-1 proteins, as well as immunohistochemistry of healthy and breast cancer specimens. Breast tumor tissue array staining results were analyzed for correlations with receptor expression and outcome parameters. Results YB-1-specific Mab F-E2G5 associates with conformational binding epitopes mapping to two domains within the N-terminal half of the protein and detects nuclear YB-1 protein by immunohistochemistry in paraffin-embedded breast cancer tissues. Prognostic evaluation of Mab F-E2G5 was performed by immunohistochemistry of a human breast cancer tissue microarray comprising 179 invasive breast cancers, 8 ductal carcinoma in situ and 37 normal breast tissue samples. Nuclear YB-1 detection in human breast cancer cells was associated with poor overall survival (p = 0.0046). We observed a close correlation between nuclear YB-1 detection and absence of progesterone receptor expression (p = 0.002), indicating that nuclear YB-1 detection marks a specific subgroup of breast cancer. Likely due to limitation of sample size Cox regression models failed to demonstrate significance for nuclear YB-1 detection as independent prognostic marker. Conclusion Monoclonal YB-1 antibody F-E2G5 should be of great value for prospective studies to validate YB-1 as a novel biomarker suitable to optimize breast cancer treatment., BMC Cancer, 9 (1), ISSN:1471-2407

We have recently characterized ITIH5 as a new extracellular matrix protein that exhibits clear expression loss in a variety of human tumour entities, including breast cancer. The aim of the present study was to decipher the molecular cause of ITIH5 expression loss in breast cancer and to learn more about the possible role of this molecule in cancer diseases. ITIH5 protein expression was found to be strongly reduced in 42% of invasive breast carcinomas-interestingly, with significant association with poor patient outcome. ITIH5 promoter methylation was frequently detected in breast cell lines and in primary carcinomas (40%), and it was functionally correlated with loss of ITIH5 mRNA expression. Moreover, ITIH5 promoter methylation was also significantly associated with poor clinical patient outcome and also with the occurrence of lymph node and distant metastases. In conclusion, we propose that ITIH5 may represent a novel metastasis repressor in human breast cancer. Both ITIH5 protein expression and ITIH5 promoter methylation may serve as prognostic biomarkers, thereby helping improve clinical patient outcome.

Treatment with pramipexole, a dopamine D3/D2 receptor agonist, reduces depressive symptoms in patients suffering from Parkinson's disease. To test the putative antidepressant quality of pramipexole, its effects were assessed in one of the most attractive animal models of depression, the olfactory bulbectomized (OBX) rat. Two experiments studied the effects of pramipexole on bulbectomy-induced hyperactivity. In experiment I, pramipexole was tested at 0.3 and 1.0 mg/kg together with the reference dopamine D3 receptor agonist 7-OH-DPAT (0.1 mg/kg) and the tri-cyclic antidepressant imipramine (10 mg/kg). In experiment II, pramipexole was tested at lower doses: 0.03 and 0.1 mg/kg, with the same reference compounds. All animals were tested in the open field on days one (acute), seven (sub-chronic) and fourteen (chronic) of administration, as well as one week after cessation of treatment. Pramipexole, in a U-shaped dose response, reduced bulbectomy-induced hyperactivity after (sub) chronic but not acute administration (like imipramine and 7-OH-DPAT). The highest dose of pramipexole (1.0 mg/kg) did not reduce OBX hyperactivity during treatment. However, one week after cessation of treatment, all pramipexole (including the 1.0 mg/kg dose), 7-OH-DPAT and imipramine groups showed a reduction in OBX-induced hyperactivity. Pramipexole and 7-OH-DPAT exert an antidepressant profile in the OBX-rat model in normalizing bulbectomy-induced hyperactivity during (sub) chronic treatment. Moreover, treatment with both these compounds induced long-lasting changes in the bulbectomized brain similar to established antidepressants, strongly predicting antidepressant activity in major depression.

With 47 samples of commercially available oil paints, the applicability of Optical coherence tomography to noninvasive tomography of paint layers was examined. Two different instruments, utilizing near-infrared light with central wavelength of 823 nm and, for the first time, 1.55μm, were used to obtain cross-sectional images. Example tomograms are given; a ray tracing correction of images is also discussed. The tests revealed that applicability of OCT is limited to certain pigments and the longer wavelength is better suited for this application.

Marine coastal ecosystems are among the most productive and diverse communities on Earth and are of importance to global climate, nutrient budgets, and primary productivity. Shelf sea sediments and their associated biota represent a reservoir for biodiversity, hosting benthic communities as well as resting and reproductive stages of planktonic organisms. Yet, these ecosystems, and in particular sedentary benthic (bottom-living) invertebrate communities at their base, are compromised by human-induced stresses, such as over-fishing, habitat destruction and pollution. This in turn compromises biodiversity, ecosystem stability and biogeochemical processes. However, due to the remoteness and spatio-temporal variability of the benthic environment, the relationships between tightly coupled biological and geochemical processes are poorly understood. The overall objective of COBO was to integrate emerging and innovative technologies from different disciplines (physics, chemistry, biology, imagery) to provide in situ monitoring of sediment habitats, in order to understand complex interactions between the biota (function and diversity) and their chemical environment. Existing standard technologies have limited spatial and temporal sampling resolutions and as such hamper progress in determining key parameters, explaining biogeochemical patterns/processes and in modelling ecosystem dynamics. Improved in situ technologies were required to provide rigorous scientific information on processes regulating this unique and fragile habitat and for assessing, controlling and minimising human impact on European coastal waters. COBO scientists have developed powerful tools to significantly advance our understanding of organism-sediment interactions under dynamic coastal conditions; enhancing predictive capability and contributing to ecosystem management and policy development.

Fresh bovine manure was mechanically incorporated into loamy sand and silty clay loam Wisconsin soils in April 2004. At varying fertilization-to-planting intervals, radish, lettuce, and carrot seeds were planted; crops were harvested 90, 100, 110 or 111, and 120 days after manure application. As an indicator of potential contamination with fecal pathogens, levels of Escherichia coli in the manure-fertilized soil and presence of E. coli on harvested vegetables were monitored. From initial levels of 4.0 to 4.2 log CFU/g, E. coli levels in both manure-fertilized soils decreased by 2.4 to 2.5 log CFU/g during the first 7 weeks. However, E. coli was consistently detected from enriched soil samples through week 17, perhaps as a result of contamination by birds and other wildlife. In the higher clay silty clay loam soil, the fertilization-to-planting interval affected the prevalence of E. coli on lettuce but not on radishes and carrots. Root crop contamination was consistent across different fertilization-to-harvest intervals in silty clay loam, including the National Organic Program minimum fertilization-to-harvest interval of 120 days. However, lettuce contamination in silty clay loam was significantly (P < 0.10) affected by fertilization-to-harvest interval. Increasing the fertilization-to-planting interval in the lower clay loamy sand soil decreased the prevalence of E. coli on root crops. The fertilization-to-harvest interval had no clear effect on vegetable contamination in loamy sand. Overall, these results do not provide grounds for reducing the National Organic Program minimum fertilization-to-harvest interval from the current 120-day standard.

Es gibt wenige angelsachsische Begriffe in der Unternehmenspraxis, die von Anfang an so selbstverstandlich auch im deutschsprachigen Alltagsgebrauch Anwendung fanden wie Investor Relations. Gelegentliche Versuche der Ubersetzung wie zum Beispiel „Aktionarsbetreuung“ oder „Investorenpflege“ wurden schnell wieder eingestellt.

A 81-year-old patient free of pain was referred to the university hospital for further evaluation and therapy of tumour masses in the right thorax. Clinical examination revealed dullness to percussion and reduced breathing in the right lower lung.Computed tomography showed an enlarged solid tumour mass attached to the thoracic cavity and pleural effusion on the right side. Quantification of pulmonary perfusion presented significant defects in the right upper and middle lobe.The pulmonary masses were biopsied under CT-guidance. Biopsy and immunohistochemical findings proved a malignant solitary fibrous tumour of the chest wall, a mesenchymal tumour of its own entity. Because of pain in the right arm and because of missing other reliable therapeutic options a palliative irradiation was performed. The tumour did increase in size due to radiotherapy and a severe right ventricular heart failure occurred. The patient died 5 months after diagnosis has been made. Autopsy revealed a transition of tumour cells to sarcomatic growth.In our case we conclude an accelerated progression of the solitary fibrous chest wall tumour in the course of irradiation. Whether the development of sarcomatic growth occurred as a result of radiotherapy remains speculative.

Foretelling the future is always a highly speculative task and one that involves many pitfalls. For example there is often a tendency to underestimate the achievements of past generations and to overestimate technological progress, although in today’s banking industry the opposite seems to be the case. Another pitfall is to extrapolate existing trends into the future without paying attention to the conditions and circumstances for business. Indeed many forecasts tell us more about the present and the recent past than about the future.

Lasst man die Entwicklung der internationalen Finanzmarkte in den letzten Jahren Revue passieren, so lassen sich die folgenden funf Entwicklungen als die dominanten Trends identifizieren: Starkes Wachstum der internationalen Kapitalstrome: Das Volumen der internationalen Finanzstrome hat sich dramatisch ausgeweitet. Der Devisenumsatz ist von durchschnittlich 590 Mrd. USD pro Tag im Jahr 1989 auf fast 1.500 Mrd. USD pro Tag 1998 gestiegen. Das internationale syndizierte Kreditgeschaft ist volumenmasig stark angewachsen (von 400 Mrd. USD im Jahr 1992 auf uber 1,4 Bio. USD im Jahr 2000), allerdings ging die Expansion einher mit einem Verfall der Margen auf wenig mehr als 10 bis 20 Basispunkte. Grenzuberschreitende Umsatze in Anleihen und Aktienwerten, die noch Mitte der achtziger Jahre in den meisten Landern unterhalb der Grosenordnung des jeweiligen BIP lagen, ubersteigen diese mittlerweile um ein Vielfaches (vgl. Tabelle 1). Auslandische Direktinvestitionen (FDI), deren Volumen im Jahre 2000 bei uber 1,1 Bio. USD lag, haben sich gegenuber 1980 verzwanzigfacht, selbst gegenuber 1990 noch verfunffacht (vgl. Abbildung 1).