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The molecular composition of presynaptic and postsynaptic neuronal terminals is dynamic, and yet long-term stabilizations in postsynaptic responses are necessary for synaptic development and long-term plasticity. The need to reconcile these concepts is further complicated by learning- and memory-related plastic changes in the molecular make-up of synapses. Advances in single-particle tracking mean that we can now quantify the number and diffusive properties of specific synaptic molecules, while statistical thermodynamics provides a framework to analyse these molecular fluctuations. In this Review, we discuss the use of these approaches to gain quantitative descriptions of the processes underlying the turnover, long-term stability and plasticity of postsynaptic receptors and show how these can help us to understand the balance between local molecular turnover and synaptic structural identity and integrity.

Angesichts der zunehmenden antimikrobiellen Resistenzentwicklung ist Antibiotic Stewardship (ABS) eine wichtige Masnahme gegen die Ausbreitung resistenter Erreger und die Entstehung von Multiresistenz. Fur Deutschland und Osterreich steht eine 2018 aktualisierte umfangreiche S3-Leitlinie zur Verfugung. Die Steuerung des Antibiotika‑/Antiinfektivaeinsatzes im Krankenhausbereich sollen ABS-Teams begleiten. ABS beinhaltet auf Krankenhausebene die fortlaufende Analyse lokaler Antibiotikaverbrauchs- und Resistenzdaten. Daraus sollen Empfehlungen fur lokal angepasste Therapieschemata abgeleitet werden. In regelmasigen Visiten diskutieren Mitglieder des ABS-Teams am Krankenbett Indikation, Dosierung, Applikationsweg und Dauer einer antimikrobiellen Therapie. Herausfordernd ist der „sparsame“ Umgang mit Antibiotika, ohne den Patienten zu gefahrden. Digitalisierung und kunstliche Intelligenz bieten neue Moglichkeiten fur ABS. Wichtig ist auch die Adaptierung stationarer Konzepte an die ambulante Versorgung.

Antibiotic stewardship (ABS) is an important measure to counteract the spread of resistant pathogens and multidrug resistance. The most important ABS tools include the implementation of local guidelines, the development of a house-related list of anti-infective agents, regular ABS visits and practice-oriented internal training events. Effective strategies for therapy optimization include indication testing and therapy evaluation, dose optimization as well as determining an appropriate duration of therapy. Oralization of anti-infectives (sequence therapy) should be supported by consistent clinical criteria in in-house guidelines. The incidence of Clostridioides difficile infections (CDI) can be more than halved by restricting the so-called "4C antibiotics". Point-of-care tests help to minimize the use of antibiotics in the outpatient setting. Vaccination reduces the need for antibiotic therapy.

Due to a processing error, the shared first authorship between Sebastian Schober and Uwe Thiel nor the shared last authorship between Stefan Burdach and Peter Lang was not taken. The original article has been corrected. Korrektur zu: 10.1038/s41409-020-01200-x

Mutual Health Organizations (MHOs) can be a potential means to reduce barriers to health care in low-income countries with poor access to health care and high health care costs for the population. One important challenge is the relationship between MHOs and health care professionals (HCPs). Our study evaluates HCPs experiences of, and attitudes towards MHOs. A total of 210 HCPs from three private and two public clinics in Kumbo and Bamenda (Cameroon) were interviewed with a structured questionnaire, where answers are quantified by a five-point ordinal scale. We identified regional and institutional differences. HCPs in Kumbo and in private clinics tend to have a more positive attitude towards MHOs than in Bamenda and in public clinics (mean 1.66 vs. 2.02, respectively 1.72 vs. 2.05,). HCPs in Bamenda and in public clinics report more negative experiences with MHO members (mean 2.86 vs. 3.67, respectively 2.72 vs. 3.56) and rank quality of health care lower. Our findings underline the important role of HCPs in the context of MHOs; therefore, programs should aim to involve HCPs in respect of regional and institutional differences.

Korrektur zu 10.1038/s41375-020-0826-9

Vor der Anlage eines arteriovenosen (AV) Gefaszugangs zur Hamodialyse wird zusatzlich zur klinischen Untersuchung die Durchfuhrung bildgebender Verfahren empfohlen. Dieser Artikel diskutiert die relative Bedeutung der unterschiedlichen Methoden und legt hierbei seinen Schwerpunkt auf die Duplexsonographie, die als einzige Methode nichtinvasiv Arterien und Venen gemeinsam untersuchen kann. Die Wertigkeit verschiedener sonographischer Befunde fur die Planung der Shuntanlage wird aufgezeigt und Vorschlage fur eine rationelle Diagnostik werden unterbreitet.

EINLEITUNG: Bei Patienten mit chronischer Herzinsuffizienz ist eine erhohte Inzidenz schlafbezogener Atmungsstorungen (SBAS) bekannt. In dieser Studie wurde untersucht, ob Patienten mit der Kombination aus chronischer Herzinsuffizienz und SBAS nachts haufiger ventrikulare Tachyarrhythmien (Couplets, nichtanhaltende ventrikulare Tachykardien) aufweisen als Patienten mit chronischer Herzinsuffizienz ohne SBAS. METHODE: Bei 63 Patienten, 49 Manner und 14 Frauen, mit chronischer Herzinsuffizienz (Ejektionsfraktion

Human hantavirus (serotype Puumala) infections are prevalent throughout Europe. The bank vole is the main reservoir of the Puumala virus (PUUV). Between 2001 and 2006, the annual incidences in Germany ranged from 0.1 to 0.5 per 100,000 inhabitants. About half of the cases were reported from the state of Baden-Württemberg (BW) in southwest Germany. In 2007, 1,089 PUUV infections were reported from BW. This reflects an incidence of 10.1:100,000, which is more than 11 times higher than the mean incidence of the previous 6 years. Spatial analysis highlights incidences up to 90:100,000 in the most affected district. The winter season 2006/2007 showed an all time high in reported mean temperature. The previous summer and autumn led to a beech mast year, resulting in favourable feed conditions for bank voles in the winter season 2006/2007. The causes of the observed increase in PUUV infections in 2007 cannot be restricted to known cycles in the bank vole population. Favourable feed conditions, a mild winter and an early onset of spring may have influenced bank vole population size as well as human exposure to infectious rodent excretions. Further epidemiologic studies are necessary to better understand the interaction between environmental factors, occurrence of Puumala virus in bank voles and the risk for human disease.

The aim of this prospective study was to investigate how often and at which dose levels gustatory disturbances appear during radiotherapy of the tongue and to which extent permanent gustatory deficiencies occur. The study included 44 patients treated by definitive irradiation for malignant head-and-neck tumors. In 22 patients the posterior two thirds of the tongue (group 1), and in the other 22 patients the entire tongue (group 2) were exposed to radiation. The control group comprised 30 patients with non-small cell lung cancer receiving definitive radiation therapy (group 3). The dose distribution in the tongue area was calculated using CT-based three-dimensional planning. Before, during and after irradiation the gustatory function was determined by means of gustometry and correlated with the corresponding results of enoral inspection and the patients' subjective statements on gustatory function. The gustatory ability of the control group was not affected, whereas patients in the locally irradiated groups in parallel with enoral mucositis suffered from loss of gustatory function after a total dose of 20 Gy with a maximum between 40 and 60 Gy. Supportive measures had little influence on acute side effects. The gustatory disturbances regressed within 8 weeks after radiotherapy in patients with partial-tongue irradiation and almost completely after 6 months in patients with entire-tongue irradiation. The severity of gustatory disturbances and the longer recovery time in patients with entire-tongue irradiation suggest an influence of the volume exposed. Therefore, reduction of the highly exposed tongue volume by intensity-modulated radiotherapy opens up possibilities for a reduction of this undesirable side effect.

Der elektive Beginn der Dialysetherapie uber einen gut geplanten gereiften Dialysezugang erfordert die fruhzeitige Vorstellung beim Nephrologen. Als Zugang sind native Fisteln mit ihren zahlreichen Modifikationen den Prothesenshunts deutlich uberlegen, sowohl hinsichtlich des Uberlebens der Patienten als auch hinsichtlich der Infektions- und Verschlussraten. Dialyseshunts sollten mindestens 3 Monate vor Dialysebeginn angelegt werden, Prothesenshunts 4 Wochen zuvor. Sollten AV-Fisteln oder Prothesenshunts nicht moglich sein oder sonstige Kontraindikationen wie z. B. eine schwere Herzinsuffizienz vorliegen, ware die Dialyse uber einen getunnelten Dialysekatheter zu beginnen. In Deutschland wird aktuell die Dialyse bei einer durchschnittlichen GFR von 7,8 ml/min begonnen. Ein Dialysebeginn bei einer GFR 15 ml/min.

Only few clinical factors predict the prognosis of patients with Ewing tumors. Unfavorable outcome is associated with primary metastatic disease, age > 15 years, tumor volume above 200 ml, and the histological response to chemotherapy. The aim of this study was to elucidate the prevalence and clinical impact of microsatellite instability (MSI) together with the relation between MSI and mismatch repair protein expression in Ewing tumors. DNA from 61 primary Ewing tumors and 11 Ewing tumor cell lines was extracted and microsatellite analysis for the detection of instability or loss of heterozygosity was performed for the five markers of the Bethesda panel BAT25, BAT26, D5S346, D2S123, and D17S250, which represents the established marker panel for the analysis of hereditary non-polyposis colorectal carcinoma (HNPCC) patients. In addition, single nucleotide repeat regions of the two tumor genes BAX and transforming growth factor receptor II (TGFBR2) were also included. All of the 61 samples were suitable for LOH analysis and 55 for the determination of MSI-status. LOH of these microsatellite markers was detected in 9 of the 61 patients (14.8%). Over all, genetic instability, i.e. MSI and/or LOH, was detected in 17 tumors (27.9%). One out of the 11 tumor cell lines (STA ET1) was characterized by instability of all the five Bethesda markers, while from primary tumor samples, only one showed MSI in more than one microsatellite marker (D5S346 and D17S250, MSI-high). Eight of the fifty-five patients (14.5%) showed instability of one microsatellite locus (MSI-low). No instability was detected in BAT26, D2S123, BAX and TGFBR2. There was no significant correlation between MSI and loss of expression of mismatch repair proteins MLH1, MSH2, or MSH6. The impairment of the p53 signaling pathway (expression of TP53 and/or MDM2 by immunohistochemistry) was significantly associated with reduced overall survival (15 of 49 patients (30.6%), P = 0.0410, log-rank test). We conclude that MSI is not prevalent in Ewing tumor and that the nature of instability differs from the form observed in colorectal carcinoma, the model tumor of MSI. This is documented by the different pattern of MSI (no BAT26 instability) in Ewing tumors and the lack of a strict correlation between MSI-high and loss of expression of MSH2, MSH6 and MLH1.

The aim of the study was to investigate the association between exposure to environmental tobacco smoke of 6-year-old children and parental educational level in Germany under the changing socioeconomic conditions after reunification. Logistic regression was used to examine the relationship between tobacco smoke exposure of children (current environmental tobacco smoke, maternal smoking during pregnancy, environmental tobacco smoke during the first 3 years of the child’s life) and the determinants parental educational level, time and region. In Germany, the risk of environmental tobacco smoke exposure among 6-year-old children was strongly associated with parental educational level (odds ratio: ≥2 ‘low’/‘middle’ versus ‘high’ parental educational level). In West Germany, environmental tobacco smoke exposure generally exhibited a decreasing trend of about 20%. In contrast, in East Germany the environmental tobacco smoke exposure was only decreasing for children of parents with higher education. The gap between low and high parental educational level with respect to current children’s tobacco smoke exposure has increased from 1991 to 2000 in East Germany. A considerable fresh increase of maternal smoking during pregnancy could be observed around 1991 in both parts of Germany. In East Germany, the transition from a socialist economic system to a market economy after reunification might in part explain the increased gap of tobacco smoke exposure between children of parents with lower and higher educational levels.

Objectives: Hormone-replacement therapy (HRT) is an established risk factor for breast cancer. HRT users are different from non-users with respect to socio-economic and other characteristics. There may be women where the HRT-related risk could be modulated by other factors. Methods: We conducted a population-based case–control study with 688 breast cancer cases and 724 controls to characterize HRT users and to estimate odds ratios (OR) and 95% confidence intervals (CI) for HRT use and potentially risk modifying factors. Results: In women aged 50 years and older, 58% of controls and 61% of cases ever used HRT. Among women in natural menopause, HRT use for 10 years and more years was associated with an increased breast cancer risk (OR 1.79, 95% CI, 1.12–2.87), but not among women in surgical menopause (OR 0.61, 95% CI, 0.09–4.17). In the subgroup of women with a positive family history of breast cancer, each year of HRT use increased the risk by 1.22 (95% CI, 1.02–1.47). Another subgroup comprised women with at least 10 diagnostic mammograms (OR 4.04, 95% CI, 1.10–14.81 for using HRT 10 or more years). Conclusions: Long-term HRT use was associated with a breast cancer risk in women with natural menopause. Our findings suggest that this risk may be increased in women with a positive family history of breast cancer and in women who received frequent diagnostic mammographic screens.

The associations between As levels in fingernails with both As concentrations in urine and environmental samples are reported. The participants (aged 20-80 years, mean 66 years) lived in the vicinity of a coal-burning power plant with high As emissions in the Prievidza District, Slovakia. Samples were taken in 1999 and 2000. The As levels in fingernails (n = 524) were measured after washing and digestion with microwave heating by hydride generation atomic absorption spectrometry. The spot urine samples (n = 436) were speciated for inorganic As (As(inorg)), monomethylarsonic (MMA) and dimethylarsinic acid (DMA) by hydride-cryogenic trap-atomic absorption spectrometry. The geometric mean As level in fingernails was 0.10 mug/g (range,0.01-2.94 microg/g). There was a clear association between As in fingernails and the distance of the home to the power plant (P0.001). Geometric mean As levels were: 0.17 microg/g distanceor = 5 km, 0.10 microg/g 6-10 km and 0.08 microg/g10 km. The association between the distance to the power plant and total urinary As (As(sum)) (n = 436, no fish consumption during the last 3 days before sample collection) was less pronounced (P = 0.018). The As levels in fingernails were positively correlated to As in soil (n = 207, r = 0.23, P0.001) and to As in house dust (n = 209, r = 0.30, P0.001). The associations between urinary As(sum) and As concentrations in soil (n = 159, r = 0.13, P0.105) and in house dust (n = 162, r = 0.14, P0.081) were quite similar. As levels in fingernails were associated with urinary As(sum) and with the different As species in urine. It is concluded that As levels in fingernails are a reliable marker of environmental As exposure, and that As concentrations in fingernails reflect the As exposure in a similar manner compared with urinary As(sum) and As species.

Objectives: We examined which occupations and industries are currently at high risk for bladder cancer in men. Methods: We combined data from 11 case–control studies conducted between 1976–1996 in six European countries. The study comprised 3346 incident cases and 6840 controls, aged 30–79 years. Lifetime occupational and smoking histories were examined using common coding. Results: Odds ratios for eight a priori defined high-risk occupations were low, and with the exception of metal workers and machinists (OR = 1.16, 95% CI = 1.02–1.32), were not statistically significant. Higher risks were observed for specific categories of painters, metal, textile and electrical workers, for miners, transport operators, excavating-machine operators, and also for non-industrial workers such as concierges and janitors. Industries entailing a high risk included salt mining, manufacture of carpets, paints, plastics and industrial chemicals. An increased risk was found for exposure to PAHs (OR for highest exposure tertile = 1.23, 95% CI = 1.07–1.4). The risk attributable to occupation ranged from 4.2 to 7.4%, with an estimated 4.3% for exposure to PAHs. Conclusions: Metal workers, machinists, transport equipment operators and miners are among the major occupations contributing to occupational bladder cancer in men in Western Europe. In this population one in 10 to one in 20 cancers of the bladder can be attributed to occupation.

Mercury levels measured in urine, hair, and saliva of 245 German children (8-10 years old) are reported. Mercury concentrations in urine ranged between

Im innovativen Dachkonzept des neuen Porsche 911 Targa wurde ein groser Glasschiebedeckel mit einer erstmals in der Baureihe 911 eingesetzten glasernen Heckklappe kombiniert. Dadurch verbindet dieses Fahrzeug in einzigartiger Weise die Vorteile des zugarmen Offenfahrens mit den Komfort- und Sicherheitsmerkmalen von Coupes mit Heckklappe.

The innovative roof concept of the new Porsche 911 Targa combines a big sliding glass roof with a tiltable rear glass window which serves the purpose of a rear lid — a novelty in 911 series vehicles. With this configuration, the new 911 Targa uniquely couples the advantages of draught-free open-top driving with the comfort and safety offered by a coupe with a rear lid.

Objectives: We examined the importance of occupational exposures for bladder cancer in women. Methods: We combined data from 11 case-control studies conducted between 1976 and 1996 in six European countries. The pooled data comprised 700 incident female cases and 2425 population or hospital controls, aged 3079 years. Lifetime occupational and smoking history were examined using common coding. Results: Excess risks were found in only a few of the occupations previously identified at high risk for bladder cancer. Statistically significant excess risks were observed for metal workers, particularly blacksmiths, toolmakers and machine tool operators (OR: 2.0, 95% CI: 1.1-3.6), tobacco workers (OR: 3.1, 95% CI: 1.1-9.3), field crop and vegetable farm workers (OR: 1.8, 95% CI: 1.0-3.1), tailors and dress makers (OR: 1.4, 95% CI: 1.0-2.1), saleswomen (OR: 2.6, 95% CI: 1.0-6.9), and mail sorting clerks (OR: 4.4, 95% CI: 1.0-19.5). About 8% (95% CI: 3.1-19.9) of all bladder cancers in women could be attributed to occupation after adjusting for smoking. The attributable risk was higher in women aged less than 65 years (12%), compared to older women (4%). Conclusions: The calculation of the attributable risk on the basis of results from this analysis may have caused some overestimation of the proportion of occupational bladder cancer in women. A significant proportion, however, of bladder cancer cases among European women less than 65 years is likely to be attributed to occupation. This link between bladder cancer in women and occupational factors has received little recognition, probably because studies addressing these issues have predominantly been done in men.

The cross sections for the production of hadrons in quasi-real photon-photon collisions in proton-proton and heavy ion interactions are compared with the corresponding cross sections for central diffraction and for photon-pomeron collisions. The signatures, heavy ions or protons with only slightly changed momenta together with two large rapidity gaps and a cluster of produced hadrons in the central region, are nearly identical in all three processes. Therefore, it will be rather difficult to distinguish the reactions experimentally. It is found, that central diffraction is the dominant process in collisions of protons, light and medium-heavy ions. The photon-pomeron and photon-photon processes have quite similar cross sections in collisions of heavy ions like lead.

A formation zone intranuclear cascade model is applied to peripheral nucleus-nucleus collisions. We calculate the excitation energies of prefragments, treat their further nuclear disintegration and introduce a model for nuclear deexcitation by photon emission. Results are compared to data on target associated particle production in nucleus-nucleus collisions. We discuss implications of these models to the description of particle production in the fragmentation regions. Special emphasis is put on applications for air showers induced by cosmic ray nuclei and for residual nucleus production at heavy ion colliders., 19 pages, Latex, 15 uuencoded figures

A sensitive and reliable method is described for the determination of aromatic and chlorinated hydrocarbons (benzene, toluene, o-, m-, p-xylene, trichloromethane, trichloroethane, trichloroethene and tetrachloroethene) in indoor and outdoor air at environmental concentration levels. The procedure can be easily extended to other VOCs. Using passive samplers the VOCs have been adsorbed onto charcoal during a four-week sampling period and subsequently desorbed with carbon disulfide. After injection with a cold split-splitless multi-injector the VOCs have been separated by capillary gas chromatography. Quantification has been achieved using an electron capture detector (ECD) and a flame ionization detector (FID) switched in series. A limit of about 1 μg/m3 for aromatic hydrocarbons and of about 0.01 μg/m3 for chlorinated hydrocarbons has been obtained. The procedure has been successfully applied in the framework of a field study to measure indoor and outdoor air concentrations in Essen and Borken, two differently polluted areas of Northrhine-Westphalia.

Single diffractive hadron-nucleus interactions are studied within the framework of the dual parton model. Introducing a diffractive component into the Monte-Carlo event generator DTUNUC we investigate particle production and the dependence of the diffractive cross section on the atomic number of the target nucleus. A comparison of the numerical results with recent experimental data is presented. We furthermore introduce hadronic cross section fluctuations and discuss their influence on diffractive proton-nucleus cross sections.