A fully ingrowing implant for cranial reconstruction: Results in critical size defects in sheep using 3D-printed titanium scaffold.

Current alloplastic materials such as PMMA, titanium or PEEK don't show relevant bone ingrowth into the implant when used for cranioplasty, ceramic implants have the drawback being brittle. New materials and implant designs are urgently needed being biocompatible, stable enough for cranioplasty and stimulating bone formation. In an in vivo critical size sheep model circular cranial defects (>2.4 cm) were covered with three different types of a 3D-printed porous titanium scaffolds with multidirectional, stochastically distributed architecture (uncoated scaffold, hydroxyapatite-coated scaffold, uncoated scaffold filled with a calcium phosphate bone cement paste containing ß-TCP granules). An empty titanium mesh served as control. Among the different investigated setups the hydroxyapatite-coated scaffolds showed a surprisingly favourable performance. Push-out tests revealed a 2.9 fold higher force needed in the hydroxyapatite-coated scaffolds compared to the mesh group. Mean CT density at five different points inside the scaffold was 2385HU in the hydroxyapatite-coated group compared to 1978HU in the uncoated scaffold at nine months. Average lateral bone ingrowth after four months in the hydroxyapatite-coated scaffold group was up to the implant center, 12.1 mm on average, compared to 2.8 mm in the control group covered with mesh only. These properties make the investigated scaffold with multidirectional, stochastically distributed structure superior to all products currently on the market. The study gives a good idea of what future materials for cranioplasty might look like.

Accurate detection of Zika virus IgG using a novel immune complex binding ELISA.

OBJECTIVES: Accurate serological assays are urgently needed to support public health responses to Zika virus (ZIKV) infection with its potential to cause foetal damage during pregnancy. Current flavivirus serology for ZIKV infections lacks specificity due to cross-reacting antibodies from closely related other flaviviruses. In this study, we evaluated novel serological tests for accurate ZIKV IgG detection. METHODS: Our ELISAs are based on immune complex binding. The high specificity is achieved by the simultaneous incubation of labelled ZIKV antigen and unlabelled flavivirus homolog protein competitors. Two assays were validated with a panel of 406 human samples from PCR-confirmed ZIKV patients collected in Brazil (n = 154), healthy blood donors and other infections from Brazil, Europe, Canada and Colombia (n = 252). RESULTS: The highest specificity (100% [252/252, 95% confidence interval (CI) 98.5-100.0]) was shown by the ZIKV ED3 ICB ELISA using the ED3 antigen of the ZIKV envelope. A similar test using the NS1 antigen (ZIKV NS1 ICB ELISA) was slightly less specific (92.1% [232/252, 95% CI 88.0-95.1]). The commercial Euroimmun ZIKV ELISA had a specificity of only 82.1% (207/252, 95% CI 76.8-86.7). Sensitivity was high (93-100%) from day 12 after onset of symptoms in all three tests. Seroprevalence of ZIKV IgG was analysed in 87 samples from Laos (Asia) confirming that the ED3 ELISA showed specific reactions in other populations. CONCLUSIONS: The novel ED3 ICB ELISA will be useful for ZIKV-specific IgG detection for seroepidemiological studies and serological diagnosis for case management in travellers and in countries where other flavivirus infections are co-circulating.

Pearl Index study with levonorgestrel-releasing intravaginal rings: using pharmacokinetic results to investigate treatment compliance as a potential contributor for contraceptive failure.

STUDY QUESTION: What is the reason for insufficient contraceptive efficacy of levonorgestrel (LNG) delivered by intravaginal ring (IVR) releasing comparable amounts of LNG as approved progestogen-only pills (POPs)? SUMMARY ANSWER: The pharmacokinetic (PK) evaluation in a subpopulation indicated that the steady-state concentration of plasma LNG was markedly lower in the participants in the USA compared to those in Japan suggesting non-compliance in the US participants which may explain a clearly higher Pearl Index (PI) in USA (8.2, unadjusted PI) compared to Japan (1.4, unadjusted PI). WHAT IS KNOWN ALREADY: Contraceptive efficacy of LNG in POPs has been demonstrated following different routes of administration (e.g. orally, implants, intrauterine systems), and the PK is well-characterized including a target exposure needed for contraception. Exposure above this target concentration was reached in Phase 1 studies using IVR delivering 40 µg LNG per day. STUDY DESIGN, SIZE, DURATION: The primary objective of this multicenter, open-label, single-arm study conducted in the USA and in Japan was to assess the contraceptive efficacy of an LNG-containing IVR during a planned treatment period of 1 year in healthy women 18-35 years of age. The study was planned to be conducted in 1600 participants (1300 in the USA, 300 in Japan). The study was prematurely terminated after approximately one-third of the planned exposure was reached due to a high number of pregnancies (28) in the US study population. PARTICIPANTS/MATERIALS, SETTING, METHODS: In total, 1471 participants were treated (1166 participants in the USA and 305 participants in Japan). The PI as a measure of contraceptive efficacy was calculated from the frequency of unintended pregnancies during treatment. LNG exposure in the systemic circulation was assessed during treatment in 136 participants (PK subgroups: 106 in the USA and 30 in Japan). MAIN RESULTS AND THE ROLE OF CHANCE: The PK evaluation in the PK subgroups indicated that the steady-state concentration of plasma LNG after 6 months was markedly lower in the participants in the USA (geometric mean 91.2 ng/l) compared to those in Japan (263.8 ng/l). This PK finding cannot be explained by the regional differences in body weight observed between the PK subgroups, thus suggesting non-compliance in the US participants. In 15.7% of the samples collected in the USA and 3.5% samples in Japan, the LNG concentration at steady state was below the lower limit of quantification (10 ng/l), which is not expected with the required continuous use of the IVR documented in most of the eDiaries. LIMITATIONS, REASONS FOR CAUTION: The planned duration of treatment was 12 months, but due to the premature termination of the study none of the participants completed the 12-month treatment. All data collected until the study termination were considered, but it is to be noted that the amount of missing data limits the conclusions that can be drawn from the data. WIDER IMPLICATIONS OF THE FINDINGS: The results of this study triggered the termination of the project, because the objective to show sufficient contraceptive efficacy of the LNG IVR was not met. The choice of a user-dependent contraceptive method with an LNG dose that is not inhibiting ovulation is not advisable for women who may have compliance issues. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by Bayer AG and all authors are employees of Bayer AG. TRIAL REGISTRATION NUMBER: NCT02403401.

Neurophysiological Evaluation of a Customizable µECoG-based Wireless Brain Implant.

The number of implantable bidirectional neural interfaces available for neuroscientific research applications is still limited, despite the rapidly increasing number of customized components. We previously reported on how to translate available components into "ready-to-use" wireless implantable systems utilizing components off-the-shelf (COTS). The aim of the present study was to verify the viability of a micro-electrocorticographic ($\mu $ECoG) device built by this approach. Functionality for both neural recording and stimulation was evaluated in an ovine animal model using acoustic stimuli and cortical electrical stimulation, respectively. We show that auditory evoked responses were reliably recorded in both time and frequency domain and present data that demonstrates the cortical electrical stimulation functionality. The successful recording of neuronal activity suggests that the device can compete with existing implantable systems as a neurotechnological research tool.

Pharmacokinetics, pharmacodynamics, safety and tolerability of an intravaginal ring releasing anastrozole and levonorgestrel in healthy premenopausal women: a Phase 1 randomized controlled trial.

STUDY QUESTION: What are suitable doses of the aromatase inhibitor anastrozole (ATZ) and the progestin levonorgestrel (LNG), when delivered to the systemic circulation by an intravaginal ring (IVR), for further clinical development as a potential new therapy for the treatment of endometriosis? SUMMARY ANSWER: Anticipated targets for pharmacokinetics, pharmacodynamics and safety/tolerability were achieved for both drug components of the IVR at the doses investigated, supporting selection of the doses to be investigated in Phase 2 studies. WHAT IS KNOWN ALREADY: Aromatase is a key enzyme in the biosynthesis of estrogens and is known to increase local levels of estradiol (E2) at extragonadal sites. Up-regulation of aromatase expression has been demonstrated in endometriotic lesions and the use of oral aromatase inhibitors has been shown to reduce endometriosis-associated pelvic pain in small-scale clinical trials. STUDY DESIGN, SIZE, DURATION: This Phase 1, randomized, multicentre, parallel-group, three-arm, open-label study assessed the pharmacokinetics, pharmacodynamics, safety and tolerability of various IVRs intended for systemic drug delivery. After screening, healthy, ovulating women aged 18-35 years were randomized to use IVRs releasing one of the three ATZ/LNG dose combinations (in vitro nominal daily drug release rates on Day 29: ATZ/LNG 500 µg/20 µg [low dose], ATZ/LNG 1000 µg/30 µg [mid dose] or ATZ/LNG 1500 µg/40 µg [high dose]) for two consecutive 28-day wearing periods without a treatment break. PARTICIPANTS/MATERIALS, SETTING, METHODS: Sixty women were included in the per protocol set. The primary variables were plasma concentrations of ATZ and LNG at the end of each treatment period and the mean size of largest follicle-like structures (FLSs) over 56 days. Serum concentrations of several hormones were also evaluated, with emphasis on E2 levels. MAIN RESULTS AND THE ROLE OF CHANCE: At the end of the first treatment period, geometric mean plasma concentrations of LNG and ATZ, respectively, were 0.228 and 12.5 µg/l for the low dose, 0.269 and 19.8 µg/l for the mid dose and 0.384 and 37.3 µg/l for the high dose; results were similar at the end of the second treatment period. Over the entire treatment period, mean FLS sizes were higher in all three treatment groups than during the pretreatment cycle; more women in the mid- and high-dose groups had FLSs of at least 30 mm (32-45%) than those in the low-dose group (14-24%). Changes in the mean size of FLSs were similar to those reported for low-dose progestin-only oral contraceptives and generally resolved during the 2-month treatment period. Serum E2 levels were decreased, but only one woman in each of the mid- and high-dose groups, and no woman in the low-dose group, had a serum E2 level below 20 pg/ml in both cycles. All ATZ and LNG combinations showed good tolerability. LIMITATIONS, REASONS FOR CAUTION: This was an exploratory study; no formal power calculation was performed. WIDER IMPLICATIONS OF THE FINDINGS: The results of this first-in-human study of the ATZ/LNG IVR facilitated the selection of ATZ and LNG doses to be investigated in the Phase 2 studies of patients with endometriosis. STUDY FUNDING/COMPETING INTEREST: The study was funded by Bayer Pharma AG. T.R. is an employee of DINOX GmbH, which received funding from Bayer Pharma AG to perform this study. M.-H.S.-M., K.W., R.N., S.K., J.K., H.S. and B.R. are or have been employees of Bayer Pharma AG. H.S. is a named inventor on EP 2 552 404 B1, a patent application relating to this work. TRIAL REGISTRATION NUMBER: EudraCT number: 2011-005620-18. TRIAL REGISTRATION DATE: 16 November 2011. DATE OF FIRST PATIENT'S ENROLMENT: 14 March 2012.

Environmental determinants on the assemblage structure of Drosophilidae flies in a temperate-subtropical region.

The species composition and the relative abundance of species in an insect community can vary in time and space for many reasons, including climatic variables and habitat preferences. Drosophilids were collected each quarter from April 2011 to April 2012 (five collections in all) in a natural area of the Pampa biome, considering three environments: open field, forest edge and the interior of forest patches. Kruskal-Wallis and chi-square tests were used to examine the effects of temporal and spatial components on the drosophilid assemblage. Four diversity measures: S obs , S rar , H' and E var were used to evaluate the community structure. A total of 7164 drosophilids belonging to 51 species were collected. The interaction of species in each environment varied among sampling periods. The abundance of both Neotropical and exotic species was affected by temporal and spatial components. The species of the D. repleta group were predominantly more abundant in the open field, but they migrated to the forest patches during periods of thermal stress. Generally, diversity was greatest in the interior of forest patches. Nevertheless, temporal components appear to be the predominant environmental determinant of the characteristics of the drosophilid community of the Pampas. Furthermore, the forest patches appear to act as a center of recolonization, reinforcing their importance in the maintenance of biodiversity in the Pampas; this function will be even more important in the future, when the temperatures will, most likely, be higher.

Population dynamics of drosophilids in the pampa biome in response to temperature.

Environmental variables such as temperature and rainfall can directly affect the community structure of dipterans. Seasonal oscillations in the abundance of species of Drosophilidae reflect differences in how tolerant populations are to climatic conditions. Over a period of 14 months, we collected samples in two habitats in the Pampa biome in the municipality of São Luiz Gonzaga, state of Rio Grande do Sul, Brazil (28°24'28″S, 54°57'39″W). The influence of environmental variables on populations of Drosophilidae was evaluated for both collecting sites by using correlation analysis. The results suggested a negative correlation between the abundances of Drosophila cardinoides Dobzhansky & Pavan, Drosophila maculifrons Duda, Drosophila melanogaster Meigen, Drosophila nigricruria Patterson & Mainland, and Zygothrica vittimaculosa Burla with temperature, which is reflected in the distribution of these species within Brazil. Our findings are important for characterizing and preserving biodiversity in this almost-unknown biome in southern Brazil given the current climate change scenario.

Drosophilid assemblages at different urbanization levels in the city of Porto Alegre, state of Rio Grande do Sul, southern Brazil.

The present study analyzed the drosophilid assemblages in different levels of urbanization in the city of Porto Alegre, Rio Grande do Sul, Brazil. Collections were carried out in 2008 in three different environments: a highly urbanized area-"Jardim Botânico," a forested area with intermediary urbanization-"Parque Gabriel Knijnik," and in a relatively well-preserved forested area, although threatened by the urban growth-"Morro Santana." In Jardim Botânico, 36 species belonging to four genera were found, with high abundance of exotic species as Drosophila simulans Sturtevant and Zaprionus indianus (Gupta). In Parque Gabriel Knijnik, 33 species that belonged to four genera were found, with higher abundances of native species belonging to the Drosophila tripunctata species group and Drosophila willistoni species subgroup, and lower abundance of exotic species. As for Morro Santana, 32 species and three genera were found, with higher abundances of native groups, low representativeness of exotic species, and absence of Zaprionus indianus. The analysis of the Jaccard index showed higher similarity in the species composition between samples collected in summer and autumn, and between samples collected in winter and spring. On the other hand, the Morisita index differentiated Jardim Botânico from the other two studied sites. Our results show that Morro Santana is an important area of native biodiversity, reinforcing, therefore, the inclusion of this area in the project for the creation of an ecological corridor as proposed by the Ministry of the Environment of Brazil.

[One-stage revision of knee endoprosthesis due to periprosthetic infection and Klippel-Trenaunay syndrome]. / Einzeitiger Knieendoprothesenwechsel bei periprothetischer Infektion und Klippel-Trenaunay-Syndrom.

We present the case of a patient with Klippel-Trenaunay syndrome (KTS) who underwent a one-stage revision of an infected total knee arthroplasty. A detailed orthopedic description of KT is presented as well as a discussion on the implementation of one-stage or multi-stage revision following infections of total knee arthroplasty. Due to vascular anomalies with severe coagulation problems, soft tissue swelling and increased risk of infection, surgical treatment of such patients presents a special challenge.

Quantum walk of a trapped ion in phase space.

We implement the proof of principle for the quantum walk of one ion in a linear ion trap. With a single-step fidelity exceeding 0.99, we perform three steps of an asymmetric walk on the line. We clearly reveal the differences to its classical counterpart if we allow the walker or ion to take all classical paths simultaneously. Quantum interferences enforce asymmetric, nonclassical distributions in the highly entangled degrees of freedom (of coin and position states). We theoretically study and experimentally observe the limitation in the number of steps of our approach that is imposed by motional squeezing. We propose an altered protocol based on methods of impulsive steps to overcome these restrictions, allowing to scale the quantum walk to many, in principal to several hundreds of steps.

Mathematical modelling of epidemics under specific regard of adenoviral keratoconjunctivitis.

At first ADV is presented as a typical pandemic. The contagiosity of adenovirus is high because of the viability of the virus on inorganic surfaces in medical offices up to 35 days. Outbreaks and epidemics occur 3-30 days after infection, which is mainly contracted from medical facilities. EKC is considered a notifiable condition in most countries, and outbreaks, suspects and infections must be reported. Symptoms like "pink eye", foreign body sensations, photophobia, pain, signs such as follicles, hemorrhages and corneal infiltrates, and vision decrease associated with malaise are frequently observed first in one eye, later involving the fellow eye. Unilateral disease has a high rate of misdiagnosis. Currently no vaccine or virustatic is available, which is effective, cost-efficient and tolerable. Treatment is symptomatic and antiinflammatory. Late scarring may be amenable to phototherapeutic keratectomy. Infection control measures focus on the disinfection of equipment and hands of staff, the handling of infected patients with gloves, spatial separation of infected individuals resp. cohorting of infected patients, use of unit-dose eye solutions, and the chlorination of pools by approved and registered disinfectants and germicides. In connection with this it is shown how to handle the dynamics of infections by mathematical models like cellular automation, systems of differential equations and to visualize periodic effects by Fourier Analysis and to calculate costs by mathematical programming. Using mathematical analysis the percentage of a population needing vaccination to prevent spreading of pandemic can be calculated. It is shown here that especially the method of cellular automation is a simple way to simulate complex epidemiological situations without completely knowing the mathematical details.

Reverse ELISA for the detection of anti West Nile virus IgG antibodies in humans.

We have developed a specific reverse ELISA to investigate the potential of the domain III of the West Nile virus envelope protein to detect virus-specific antibodies. For this purpose, the domain III antigen was expressed in Escherichia coli, refolded and directly labelled with peroxidase. By mixing serum samples with the enzyme-labelled antigen, immune complexes will form that are simultaneously recognized by rheumatoid factor coated microtiter plates. Specific antibodies to the domain III were found in 160 out of 206 sera of patients with neutralising antibodies to West Nile virus (77.6% sensitivity). The antigen differentiated reliably between sera of West Nile virus- and dengue virus-infected patients. In combination with indirect immunofluorescence, to exclude four false-positive samples, the specificity was 100% (280 samples). Assuming a prevalence rate of anti-West-Nile virus antibodies of 5%, the positive and negative predictive values were 93.3% and 98.8% respectively. These results indicate that the reverse ELISA using a specific portion of the envelope antigen of West Nile virus is especially suitable for studies on the prevalence of West Nile infections in affected countries.

Quality assurance for the diagnostics of viral diseases to enhance the emergency preparedness in Europe.

The threat posed by emerging and re-emerging communicable diseases and, more recently, by the intentional release of infectious agents in a susceptible population, has been receiving considerable attention at the national and international levels. Public health efforts to strengthen disease detection, surveillance and control have been intensified. However, clinicians and clinical microbiology laboratories play an important role in the early detection of disease, the identification of the putative agent, and notification of the appropriate authorities. To be effective in this role, laboratories must be specially prepared to handle viral agents safely, and need, among other things, the appropriate rapid and sensitive diagnostic tests. In 1998 the European Network for Diagnostics of 'Imported' Viral Diseases (ENIVD) was established. ENIVD presently comprises, as permanent members, 44 expert laboratories in 21 European Union (EU) member states and 4 non-EU countries and is one of the networks on infectious diseases funded by the European Commission. ENIVD fulfils many of the important tasks required for the surveillance and control of imported, rare and emerging viral infections such as the exchange of expertise and the organisation of external quality assurance (EQA) programmes, both of which are needed to improve diagnostics. Here, we summarise the data generated by recent EQA activities focussed on the diagnostics of infections with hantavirus, dengue virus, filovirus, Lassa virus, orthopox virus and the SARS-coronavirus (SARS-CoV). These were carried out between 1999 and 2004 and involved 93 laboratories from 41 countries, including laboratories from additional countries outside of Europe. Particularly the EU-candidate countries and Eastern neighbouring countries will be invited to join the network in the near future. A public website is available at http://www.enivd.de.

Evaluation of the efficacy and tolerability of acarbose in patients with diabetes mellitus : a postmarketing surveillance study.

OBJECTIVE: The efficacy and tolerability of acarbose were examined in a postmarketing surveillance study of 27 803 patients with diabetes mellitus (26 044 were diagnosed as having type 2 diabetes) over a 12-week treatment period. PATIENTS AND M ethods: Overall efficacy data were reported for type 1 and type 2 diabetes, and a detailed data analysis was conducted for patients with type 2 diabetes. Tolerability was described for the total group. Of the type 2 diabetes patients, 37.6% were treated with diet only; 44.2% were additionally treated with sulphonylureas; 6.3% with metformin or metformin plus sulphonylurea; and 11.6% with insulin alone or in combination with oral treatment. The frequency of two or more concomitant diseases was 45.8% for all type 2 diabetes patients, and 62.4% in elderly patients (age >/=70 years). RESULTS: In patients with type 2 diabetes, acarbose administration in addition to the existing treatment resulted in reductions in mean blood glucose levels (fasting 50 mg/dL, 1h post-prandial [pp] 60 mg/dL, 2h pp 56 mg/dL), glycosylated haemoglobin (HbA(1c) 1.3%; HbA(1) 1.6%) and bodyweight (1.5 kg). Results for type 1 diabetes patients were similar. No clinically relevant influence of age, body mass index or number of concomitant diseases on the results could be observed. Tolerability was good: 83% of patients had no adverse events, 13.7% reported flatulence, and 2.2% had at least one occurrence of diarrhoea. Hypoglycaemia was found in 0.07% of patients, mainly in combination with metformin or insulin. Tolerability was independent of patients' age. Laboratory investigations gave no indication of other adverse events. CONCLUSION: This postmarketing surveillance study documents the therapeutic benefit and good tolerability and compliance of acarbose as mono- and combination therapy, even in elderly and multimorbid patients.

Quality assurance for the diagnostics of viral diseases to enhance the emergency preparedness in Europe.

The threat posed by emerging and re-emerging communicable diseases and, more recently, by the intentional release of infectious agents in a susceptible population, has been receiving considerable attention at the national and international levels. Public health efforts to strengthen disease detection, surveillance and control have been intensified. However, clinicians and clinical microbiology laboratories play an important role in the early detection of disease, the identification of the putative agent, and notification of the appropriate authorities. To be effective in this role, laboratories must be specially prepared to handle viral agents safely, and need, among other things, the appropriate rapid and sensitive diagnostic tests. In 1998 the European Network for Diagnostics of "Imported" Viral Diseases (ENIVD) was established. ENIVD presently comprises, as permanent members, 44 expert laboratories in 21 European Union (EU) member states and 4 non-EU countries and is one of the networks on infectious diseases funded by the European Commission. ENIVD fulfils many of the important tasks required for the surveillance and control of imported, rare and emerging viral infections such as the exchange of expertise and the organisation of external quality assurance (EQA) programmes, both of which are needed to improve diagnostics. Here, we summarise the data generated by recent EQA activities focussed on the diagnostics of infections with hantavirus, dengue virus, filovirus, Lassa virus, orthopox virus and the SARS-coronavirus (SARS-CoV). These were carried out between 1999 and 2004 and involved 93 laboratories from 41 countries, including laboratories from additional countries outside of Europe. Particularly the EU-candidate countries and Eastern neighbouring countries will be invited to join the network in the near future. A public website is available at http://www.enivd.de.

Toxicity of green tea extracts and their constituents in rat hepatocytes in primary culture.

Recent reports on sporadic cases of liver disorders (acute hepatitis, icterus, hepatocellular necrosis) after ingestion of dietary supplements based on hydro-alcoholic extracts from green tea leaves led to restrictions of the marketing of such products in certain countries of the EU. Since green tea is considered to exert a number of beneficial health effects, and, therefore, green tea products are widely used as dietary supplements, we were interested in the possible mechanism of hepatotoxicity of green tea extracts and in the components involved in such effects. Seven hours after seeding on collagen, rat hepatocytes in primary culture were treated with various hydro-alcoholic green tea extracts (two different native 80% ethanolic dry extracts and an 80% ethanolic dry extract cleared from lipophilic compounds). Cells were washed, and reduction of resazurin, used as a viability parameter monitoring intact mitochondrial function, was determined. It was found that all seven green tea extracts examined enhanced resazurin reduction significantly at a concentration range of 100-500 microg/ml medium, while a significant decrease was observed at 1-3mg/ml medium. Decreased levels were concomitant with abundant necrosis as observed by microscopic inspection of the cultures and with increased leakage of lactate dehydrogenase activity from the cells. In a separate series of experiments, the green tea constituents (-)-epicatechin, (-)-epigallocatechin-3-gallate, caffeine and theanine were tested at concentrations reflecting their levels in a typical green tea extract. Synthetic (+)-epigallocatechin (200 microM) was used for comparison. Cytotoxicity was found with (-)-epigallocatechin-3-gallate only. The concomitant addition of 0.25 mM ascorbate/0.05 mM alpha-tocopherol had no influence on cytotoxicity. In conclusion, our results suggest that high concentrations of green tea extract can exert acute toxicity in rat liver cells. (-)-Epigallocatechin-3-gallate seems to be a key constituent responsible for this effect. The relatively low bioavailability of catechins reported after oral exposure to green tea argues, however, against a causal role of these constituents in the reported liver disorders.

[Performance and costs of outpatient clinics of university hospitals for medical care, teaching, research activities]. / Leistungen und Kosten der Hochschulambulanzen in Forschung, Lehre und Versorgung -- Ergebnisse der Hochschulambulanzenstudie.

BACKGROUND: Outpatient clinics of university hospitals (Hochschulambulanzen) play a significant role in the German health care system. Universities have in contrast to other hospitals the right to implement an outpatient clinic, but the health care services they can render are restricted to clinical research and teaching activities. The university outpatient clinic study evaluates the intensity of medical care, teaching, research activities, and the related costs. METHOD AND DATABASE: 6 university hospitals with 51 outpatient departments in Germany were included. The prospective documentation of consultations was restricted to 800 visits per department. A total of 26,312 consultations with approximately 40,000 diagnoses and 150,000 services were documented. Furthermore, data concerning costs, teaching activities and research facilities were documented. RESULTS: Clinical treatment without any correlation to research or teaching activities amounted to about 81 % of the working time in the outpatient department (research 11 %; teaching 8 %). The primary task of the university outpatient clinics takes up less than 20 % of the working time. The physicians documented that the disease of every fourth visit was in accordance with their main field of research. 6.9 % of the visits were asked to take part in clinical trials, of these 1.25 % were included for the first time, 3.7 % were already included. 6.5 % of the visits were addressed to participate in specific teaching activities. The average total costs per case added up to 149 Euro. No outpatient clinic could cover the total per case costs with the lump sum payments. On the average 31 % of these costs were covered by lump sum payments (without cases concerning research and teaching). CONCLUSION: Treatment in outpatient departments of university clinics is far beyond research and teaching activities required by law. However, the ability of outpatient departments of universities to provide excellent outpatient services should have a more dominant role in the health care system. Therefore access to care should be deregulated for the patients and reimbursement schemes should be adjusted to adjust for the present losses.

Nature as a model for technical sensors.

Nature has developed a stunning diversity of sensory systems. Humans and many animals mainly rely on visual information. In addition, they may use acoustic, olfactory, and tactile cues for object detection and spatial orientation. Beyond these sensory systems a large variety of highly specialized sensors have evolved. For instance, some buprestid beetles use infrared organs for the detection of forest fires. The infrared sensors of boid and crotalid snakes are used for prey detection at night. For object detection and spatial orientation many species of nocturnal fish employ active electrolocation. This review describes certain aspects of the detection and processing of infrared and electrosensory information. We show that the study of natural exotic sensory systems can lead to discoveries that are useful for the construction of technical sensors and artificial control systems. Comparative studies of animal sensory systems have the power to uncover at least a small fraction of the gigantic untapped reservoir of natural solutions for perceptive problems.

[Relevance of coronaviruses. The SARS example]. / Die Bedeutung von Coronaviren. Das Beispiel SARS.

The emergence of the new SARS coronavirus has shown dramatically the high relevance of human coronavirus infections. This overview presents data of both epidemiological and clinical studies of this new virus infection. Moreover, details of research on the pathogenesis, diagnostics, and therapy are given. The recent infections in December 2003 clearly document that SARS will be a major topic also in 2004.

Qualitative effect of fenofibrate and quantitative effect of atorvastatin on LDL profile in combined hyperlipidemia with dense LDL.

INTRODUCTION: The association of elevated plasma triglyceride concentrations, decreased HDL-cholesterol, and dense LDL (dLDL) is referred to as the atherogenic lipoprotein phenotype. dLDL particularly plays a role in the metabolic syndrome and type 2 diabetes and may be one of the factors responsible for the increased risk for coronary artery disease in these patients. The effect of fenofibrate and atorvastatin on the LDL subfraction profile in patients with combined hyperlipidemia and a preponderance of dLDL was studied in a sequential design. METHODS: Six male patients with combined hyperlipidemia and dLDL received 160 mg/die supra-bioavailable fenofibrate. After a washout phase of 8 weeks all patients received 10 mg/die atorvastatin for another 8 weeks. At baseline, after fenofibrate, and after atorvastatin treatment LDL subfractions were analyzed by equilibrium density gradient ultracentrifugation. RESULTS: Treatment with atorvastatin and fenofibrate reduced serum cholesterol by 30 % and 21 % (p = 0.046) (p-values for differences between treatment groups), triglycerides by 32 % and 45 %, LDL cholesterol by 28 % and 16 %, and increased HDL cholesterol by 3 % and 6 %, respectively. Atorvastatin and fenofibrate treatment resulted in the following changes of apoB and LDL subfractions: LDL-1 (1.019 - 1.031 kg/L) - 31 % and + 15 % (p = 0.028); LDL-2 (1.031 - 1.034 kg/L) - 14 % and + 57 % (p = 0.028); LDL-3 (1.034 - 1.037 kg/L) - 20 % and + 30 % (p = 0.028); LDL-4 (1.037 - 1.040 kg/L) - 25 % and - 6 %; LDL-5 (1.040 - 1.044 kg/L) - 29 % and - 38 %; and LDL-6 (1.044 - 1.063 kg/L) - 39 % and - 55 % (p = 0.028). As a consequence, fenofibrate reduced LDL density significantly (p = 0.028 versus atorvastatin). CONCLUSIONS: Atorvastatin decreased all LDL-subfractions to a similar extent (quantitative effect) whereas fenofibrate reduced predominantly dLDL and changed the LDL profile towards medium dense LDL-particles (qualitative effect). Since medium dense LDL have a higher affinity to the LDL-receptor fenofibrate may have a higher antiatherogenic potential than assessed by the reduction of total LDL-cholesterol and triglycerides alone.