Energie- und Nährstoffaufnahme von Osteoarthrosepatienten

Ziel vorliegender Diplomarbeit war die Beschreibung der Energie- und Nährstoffzufuhr und der körperlichen Aktivität in verschiedenen Lebensabschnitten von Patienten über 50 Jahren mit Gelenksarthrose im Vergleich zu Personen ohne Gelenksarthrose. Dazu wurden im Rahmen der „Osteoarthrose und Lebensstil Studie“ an der Universitätsklinik Innsbruck in Zusammenarbeit mit dem Institut für Ernährungswissenschaften insgesamt 102 Personen mittels Fragebogen, Aktivitätsprofil und 24-h Stunden Ernährungsprotokoll befragt. Die körperliche Aktivität wurde in drei ausgewählten Lebensabschnitten, in der Jugend, im mittleren Alter und im letzten Jahr vor Teilnahme an der Studie, mittels Fragebogen erhoben. Der Body Mass Index von Personen mit einer Gelenksarthrose zeigte mit 28,28 kg/m2 einen signifikant höheren Wert als bei Personen ohne Arthrose mit 26,18 kg/m2. Die Gesamtenergieaufnahme zeigte keinen signifikanten Unterschied. Die Osteoarthrosegruppe nahm mit durchschnittlich 1589 kcal um 160 kcal weniger auf als die Referenzgruppe mit 1749 kcal. Die Aufnahme der knochenspezifischen Nährstoffe zeigte einen signifikanten Unterschied. Die Osteoarthrosegruppe nahm durchschnittlich 0,89 µg Vitamin D auf. Die Referenzgruppe hatte eine Vitamin D Zufuhr von 1,47 µg. Die Calciumaufnahme lag in der Osteoarthrosegruppe bei 599 mg, in der Referenzgruppe bei 808 mg. Die Phosphor Zufuhr lag in der Osteoarthrosegruppe bei 887 mg durchschnittlich, die Referenzgruppe nahm durchschnittlich 1130 mg Phosphor auf. Auch in der Aktivität konnte ein deutlicher Unterschied festgestellt werden. Es zeigte sich, dass die Intensität der Bewegung in der Osteoarthrosegruppe von der Jugend bis hin zum letzten Jahr stetig abnahm. Das Bewegungsverhalten der Referenzgruppe war hingegen genau gegensätzlich. Während die Osteo-arthrosegruppe mit 839 Stunden Bewegung jährlich in der Jugend am aktivsten war, hatte die Referenzgruppe mit nur 663 Stunden jährlich am wenigsten Aktivität. Über das mittlere Alter bis hin zum letzten Jahr sank die Aktivität in der Osteoarthrosegruppe auf 535 Stunden pro Jahr, wobei die Bewegung der Referenzgruppe auf 893 Stunden stieg und somit im letzten Jahr die meiste Bewegung verzeichnen konnte. Zusammenfassend kann gesagt werden, dass auch in der Osteoarthroseprävention eine ausgewogene und vielfältige Ernährung in Kombination mit moderater Bewegung ein wichtiges Element ist.The aim of the present thesis was to describe the energy and nutrient intake of patients with osteoarthritis age 50 years and older and the physical activity in different phases of their lives. As part of the "Osteoarthritis and Lifestyle Study" conducted at the University Hospital of Innsbruck in cooperation with the Department of Nutritional Sciences, University of Vienna, questionnaires, 24h dietary recalls and activity profiles of 102 patients were analysed. The patients' physical activity was analysed for three selected periods of their lives: their youth, their middle age, and the last year before they participated in the study. Patients with osteoarthritis were found to have a significantly higher body mass index (28,28 kg/m2) than patients without arthritis (26,18 kg/m2). No significant difference in the overall energy intake was found between the two groups. The osteoarthritisgroup had an overall energy intake of 1589 kcal, whereas the referencegroup had an energy intake of 1749 kcal per day. The intake of nutrients relevant to bone metabolism was significantly higher in patients without arthritis. Their vitamin D intake was 1,47 µg per day, whereas the intake of the patients with osteoarthritis was only 0,89 µg. The calcium intake was 599 mg per day in the osteoarthritis group and 808 mg daily in the reference group. Patients with arthritis had a phosphorus intake of 887 mg per day, patients without had an intake of 1140 mg daily. Also, the activity profile showed a significant difference between the two groups. Whereas patients suffering from arthritis had their highest level of activity in their Youth, patients without arthritis were most active in the last year before participating in the study. In their Youth, patients with arthritis had an activity level of 839 hours per year which decreased throughout their life to 535 hours. The activity of patients without arthritis was exactly converse. They had their lowest activity level in their Youth with just 663 hours per year which increased to 893 hours in the last year. In summary, we may say that a well balanced and versatile diet combined with moderate physical activity is an important element in the prevention of osteoarthritis

Effects of BPA in snails : Oehlmann et al. respond

We welcome critical appraisals that help to provide balance; however, Dietrich et al. gave an unjustified reproach. We feel that Dietrich’s position is severely compromised because he serves as an expert for the bisphenol A (BPA) Industry Group (Brussels, Belgium). We would like to respond to the issues raised by Dietrich et al., as well as to their oversights and inappropriate interpretations of our findings..

Bisphenol A induces superfeminization in the Ramshorn snail Marisa cornuarietis (Gastropoda: Prosobranchia) at environmentally relevant concentrations

Previous investigations have shown that bisphenol A (BPA) induces a superfeminization syndrome in the freshwater snail Marisa cornuarietis at concentrations as low as 1 μg/L. Superfemales are characterized by the formation of additional female organs, enlarged accessory sex glands, gross malformations of the pallial oviduct, and a stimulation of egg and clutch production, resulting in increased female mortality. However, these studies were challenged on the basis of incomplete experimentation. Therefore, the objective of the current approach was to bridge several gaps in knowledge by conducting additional experiments. In an initial series of experiments, study results from the reproductive phase of the snails were evaluated in the sub-micrograms per liter range. Before and after the spawning season, superfemale responses were observed [NOEC (no observed effect concentration) 7.9 ng/L, EC10 (effective concentration at 10%) 13.9 ng/L], which were absent during the spawning season. A further experiment investigated the temperature dependence of BPA responses by exposing snails at two temperatures in parallel. The adverse effect of BPA was at least partially masked at 27°C (EC10 998 ng/L) when compared with 20°C (EC10 14.8 ng/L). In M. cornuarietis, BPA acts as an estrogen receptor (ER) agonist, because effects were completely antagonized by a co-exposure to tamoxifen and Faslodex. Antiandrogenic effects of BPA, such as a significant decrease in penis length at 20°C, were also observed. Competitive receptor displacement experiments indicate the presence of androgen- and estrogen-specific binding sites. The affinity for BPA of the estrogen binding sites in M. cornuarietis is higher than that of the ER in aquatic vertebrates. The results emphasize that prosobranchs are affected by BPA at lower concentrations than are other wildlife groups, and the findings also highlight the importance of exposure conditions

Bisphenol A Induces Superfeminization in the Ramshorn Snail (Gastropoda: Prosobranchia) at Environmentally Relevant Concentrations

Previous investigations have shown that bisphenol A (BPA) induces a superfeminization syndrome in the freshwater snail Marisa cornuarietis at concentrations as low as 1 μg/L. Superfemales are characterized by the formation of additional female organs, enlarged accessory sex glands, gross malformations of the pallial oviduct, and a stimulation of egg and clutch production, resulting in increased female mortality. However, these studies were challenged on the basis of incomplete experimentation. Therefore, the objective of the current approach was to bridge several gaps in knowledge by conducting additional experiments. In an initial series of experiments, study results from the reproductive phase of the snails were evaluated in the sub-micrograms per liter range. Before and after the spawning season, superfemale responses were observed [NOEC (no observed effect concentration) 7.9 ng/L, EC10 (effective concentration at 10%) 13.9 ng/L], which were absent during the spawning season. A further experiment investigated the temperature dependence of BPA responses by exposing snails at two temperatures in parallel. The adverse effect of BPA was at least partially masked at 27°C (EC10 998 ng/L) when compared with 20°C (EC10 14.8 ng/L). In M. cornuarietis, BPA acts as an estrogen receptor (ER) agonist, because effects were completely antagonized by a co-exposure to tamoxifen and Faslodex. Antiandrogenic effects of BPA, such as a significant decrease in penis length at 20°C, were also observed. Competitive receptor displacement experiments indicate the presence of androgen- and estrogen-specific binding sites. The affinity for BPA of the estrogen binding sites in M. cornuarietis is higher than that of the ER in aquatic vertebrates. The results emphasize that prosobranchs are affected by BPA at lower concentrations than are other wildlife groups, and the findings also highlight the importance of exposure conditions

Strukturierte Versorgung von Patient*innen mit atraumatischen Bauchschmerzen in der Notaufnahme

Background: Patients with atraumatic abdominal pain are common in the emergency department and have a relatively high hospital mortality, with a very wide spectrum of different causes. Rapid, goal-directed diagnosis is essential in this context. Methods: In a Delphi process with representatives of different disciplines, a diagnostic treatment pathway was designed, which is called the Abdominal Pain Unit (APU). Results: The treatment pathway was designed as an extended event process chain. Crucial decision points were specified using standard operating procedures. Discussion: The APU treatment pathway establishes a consistent treatment structure for patients with atraumatic abdominal pain. It has the potential to improve the quality of care and reduce intrahospital mortality over the long term

Superfeminization as an effect of bisphenol A in \u3ci\u3eMarisa cornuarietis\u3c/i\u3e & Response from Forbes et al. to Oehlmann et al.

[Oehlmann et al.]: Recently, we had the opportunity to read two articles in volume 66 of Ecotoxicology and Environmental Safety. Forbes et al. (2007a, , 2007b) declare “to explore the reproducibility of prior work” showing that bisphenol A (BPA) induces superfeminization in the freshwater snail Marisa cornuarietis (Oehlmann et al., 2000, 2006; Schulte- Oehlmann et al., 2001). Based on the outcome of a toxicity test with the same species, the authors conclude that their results “do not support previous claims of enhanced reproduction in M. cornuarietis in response to exposure to BPA.” We take issue with the declaration of exploring the reproducibility of our challenged work and the validity of the conclusions made by Forbes et al. (2007a, 2007b). Furthermore, we feel the toxicity test is flawed because its experimental design and the selected exposure conditions result in an irresponsiveness of test animals to the tested compound. ... [Forbes et al.]:We thank the editor for giving us the opportunity to respond to Oehlmann et al.’s comments (Oehlmann et al., 2008) on our papers (Forbes et al., 2007a,b). In response to the criticisms of our studies we would first like to emphasize that it was not our aim to exactly repeat the experiments of Oehlmann and colleagues, but rather to produce robust and reproducible results that were statistically valid and that therefore could be used in the risk assessment of bisphenol A (BPA). We are disturbed by the highly speculative suggestion by Oehlmann et al. that we may have studied a different ‘cryptic’ species of Marisa cornuarietis, as there is no evidence to support such suggestion. Furthermore, the snails used in our studies were collected from a documented pristine field site and identified to species by Dr. Sharon File-Emperador from University of Puerto Rico, a recognized snail expert. They were reared for a known number of generations under tightly controlled and documented conditions. In contrast, the snails used in Oehlmann et al.’s studies (e.g., Oehlmann et al., 2006) came from the Dusseldorf Zoo (original site of field collection not indicated) and were periodically supplemented with snails from Florida (location not indicated). There is likewise very little information in the published studies about the culture and husbandry conditions of Oehlmann et al.’s snails, whereas a major portion of our research aimed to identify appropriate husbandry and culture conditions for M. cornuarietis. It is on the basis of such detailed study that our toxicity tests with BPA were conducted

The underestimated burden of monogenic kidney disease in adults waitlisted for kidney transplantation

Purpose: Chronic kidney disease (CKD) is a major health-care burden. Increasing evidence suggests that a considerable proportion of patients are affected by a monogenic kidney disorder. Methods: In this study, the kidney transplantation waiting list at the Charité was screened for patients with undetermined cause of CKD. By next-generation sequencing (NGS) we targeted all 600 genes described and associated with kidney disease or allied disorders. Results: In total, 635 patients were investigated. Of these, 245 individuals had a known cause of CKD (38.5%) of which 119 had a proven genetic disease (e.g., ADPKD, Alport). The other 340 patients (53.5%) were classified as undetermined diagnosis, of whom 87 had kidney failure (KF) onset <40 years. To this latter group genetic testing was offered as well as to those patients (n = 29) with focal segmental glomerulosclerosis (FSGS) and all individuals (n = 21) suspicious for thrombotic microangiopathy (TMA) in kidney biopsy. We detected diagnostic variants in 26 of 126 patients (20.6%) of which 14 of 126 (11.1%) were pathogenic or likely pathogenic. In another 12 of 126 (9.5%) patients, variants of unknown significance (VUS) were detected. Conclusion: Our study demonstrates the diagnostic value of comprehensive genetic testing among patients with undetermined CKD

Regulatory feedback cycle of the insulin-degrading enzyme and the amyloid precursor protein intracellular domain: Implications for Alzheimer's disease

One of the major pathological hallmarks of Alzheimer´s disease (AD) is an accumulation of amyloid-β (Aβ) in brain tissue leading to formation of toxic oligomers and senile plaques. Under physiological conditions, a tightly balanced equilibrium between Aβ-production and -degradation is necessary to prevent pathological Aβ-accumulation. Here, we investigate the molecular mechanism how insulin-degrading enzyme (IDE), one of the major Aβ-degrading enzymes, is regulated and how amyloid precursor protein (APP) processing and Aβ-degradation is linked in a regulatory cycle to achieve this balance. In absence of Aβ-production caused by APP or Presenilin deficiency, IDE-mediated Aβ-degradation was decreased, accompanied by a decreased IDE activity, protein level, and expression. Similar results were obtained in cells only expressing a truncated APP, lacking the APP intracellular domain (AICD) suggesting that AICD promotes IDE expression. In return, APP overexpression mediated an increased IDE expression, comparable results were obtained with cells overexpressing C50, a truncated APP representing AICD. Beside these genetic approaches, also AICD peptide incubation and pharmacological inhibition of the γ-secretase preventing AICD production regulated IDE expression and promoter activity. By utilizing CRISPR/Cas9 APP and Presenilin knockout SH-SY5Y cells results were confirmed in a second cell line in addition to mouse embryonic fibroblasts. In vivo, IDE expression was decreased in mouse brains devoid of APP or AICD, which was in line with a significant correlation of APP expression level and IDE expression in human postmortem AD brains. Our results show a tight link between Aβ-production and Aβ-degradation forming a regulatory cycle in which AICD promotes Aβ-degradation via IDE and IDE itself limits its own production by degrading AICD

COMPRENDO: Focus and approach

Tens of thousands of man-made chemicals are in regular use and discharged into the environment. Many of them are known to interfere with the hormonal systems in humans and wildlife. Given the complexity of endocrine systems, there are many ways in which endocrine-disrupting chemicals (EDCs) can affect the body’s signaling system, and this makes unraveling the mechanisms of action of these chemicals difficult. A major concern is that some of these EDCs appear to be biologically active at extremely low concentrations. There is growing evidence to indicate that the guiding principle of traditional toxicology that “the dose makes the poison” may not always be the case because some EDCs do not induce the classical dose–response relationships. The European Union project COMPRENDO (Comparative Research on Endocrine Disrupters—Phylogenetic Approach and Common Principles focussing on Androgenic/Antiandrogenic Compounds) therefore aims to develop an understanding of potential health problems posed by androgenic and antiandrogenic compounds (AACs) to wildlife and humans by focusing on the commonalities and differences in responses to AACs across the animal kingdom (from invertebrates to vertebrates)