Fluorescent annulated imidazo[4,5-c]isoquinolines via a GBB-3CR/imidoylation sequence - DNA-interactions in pUC-19 gel electrophoresis mobility shift assay.

Herein we report the development of a sequential synthesis route towards annulated imidazo[4,5-c]isoquinolines comprising a GBB-3CR, followed by an intramolecular imidoylative cyclisation. X-Ray crystallography revealed a flat 3D structure of the obtained polyheterocycles. Thus, we evaluated their interactions with double-stranded DNA by establishing a pUC-19 plasmid-based gel electrophoresis mobility shift assay, revealing a stabilising effect on ds-DNA against strand-break inducing conditions.

Guideline-compliant prescription of biologicals and possible barriers in dermatological practices in Bavaria.

INTRODUCTION: Psoriasis and urticaria are chronic inflammatory skin diseases, which account for a substantial socioeconomic burden and severely affect patients' quality of life. According to the respective German guidelines, biologicals can be used for the treatment of severe forms of these diseases. However, only a minority of patients receive this advised treatment. OBJECTIVE: To analyse the prescription of biologicals according to the German national guidelines for psoriasis and chronic spontaneous urticaria and to assess possible barriers to prescription. MATERIALS AND METHODS: Cross-sectional, questionnaire-based study including all Bavarian dermatologists based in private practices. Linear and logistic regression models were used to identify significant influencing factors on the perception of possible barriers. RESULTS: Between January 2017 and February 2017, a total of 137 (of 499) dermatologists participated. Of all patients with moderate to severe psoriasis and chronic spontaneous urticaria, participating dermatologists indicated treating 14.2% and 6.9% with biologicals, respectively. The most prevalent barriers to prescription were the high cost of the therapy, the low reimbursement and the fear of recourse. Analysis showed that age, years spent working in a dermatological hospital and the number of patients treated with moderate to severe psoriasis affect the perception of many barriers. Furthermore, age and barriers related to physician factors and external factors were identified as modifiers to the prescription scheme of dermatologists. CONCLUSIONS: The role of clinical education and the importance of external and economic barriers in comparison with medical barriers have to be emphasised. Guideline-compliant use of biologicals has to be optimised. Further research is needed to ascertain not only a barrier pattern for Bavaria but also for wider settings. Actions based on this for psoriasis are needed to achieve the goal of the WHO Global Psoriasis Report to strengthen the role of patient-centred care and improve the quality of life of affected patients. Analogue, this applies also for urticaria.

Do outdoor workers know their risk of NMSC? Perceptions, beliefs and preventive behaviour among farmers, roofers and gardeners.

BACKGROUND: Non-melanoma skin cancer (NMSC) was officially recognized in 2015 as an occupational disease for outdoor workers in Germany. Together with the enormous socioeconomic impact of NMSC, this has led to the continuous demand of evidence-based prevention. However, studies assessing the perceptions and beliefs along with risk behaviour of outdoor workers as an essential prerequisite for prevention are rare. OBJECTIVE: To assess perceptions, beliefs, barriers, risk and preventive behaviours towards non-melanoma skin cancer among different outdoor groups as a basis for the development of sustainable prevention programmes. PATIENTS AND METHODS: Cross-sectional study among outdoor workers of three different occupational groups (farmer, gardener, roofer) using a 20-question online survey on NMSC awareness, risk and preventive behaviours. RESULTS: Between March and April 2016, 353 outdoor workers participated in the study. Of these, 153 (43.4%) reported never to use sunscreen during work. Wearing headgear and long pants were the most common sun protection measures. Poor use of sunscreen was more likely in males and farmers. A low perceived skin cancer risk was significantly associated with poor use of sunscreen, long-sleeved shirts, sunglasses and headgear. CONCLUSIONS: Despite great evidence on NMSC risk in outdoor professions throughout the literature, high-risk groups in fact are not yet aware of the topic. Sustainable target group-oriented awareness prevention programmes are needed to lower the immense burden of NMSC.

Simplifying the WHO 'how to hand rub' technique: three steps are as effective as six-results from an experimental randomized crossover trial.

OBJECTIVES: The World Health Organization (WHO) issued guidelines on hand hygiene recommending a six-step 'how to hand rub' technique for applying alcohol-based hand rub. However, adherence to all six steps is poor. We assessed a simplified three-step technique and compared it to the conventional WHO six-step technique in terms of bacterial count reduction on healthcare workers' hands. METHODS: Thirty-two participants were randomly assigned to clean their hands following the six-step 'how to hand rub' technique (WHO reference group) or a simplified three-step technique (intervention group). Assignments were reversed after 1 day. The degree of bacterial killing was assessed following the European norm for testing hand hygiene products. Hands were contaminated with Escherichia coli, and the mean logarithmic reduction in bacterial counts was compared between both techniques. RESULTS: Bacterial density before hand hygiene performance did not differ between the WHO reference group (median 6.37 log10 CFU, interquartile range (IQR) 6.19-6.54) and the intervention group (median 6.34 log10 CFU, IQR 6.17-6.60, p 0.513). After hand hygiene, the logarithmic reduction factor was higher in the intervention group (median 4.45, IQR 4.04-5.15) compared to the WHO reference group (median 3.91, IQR 3.69-4.62, p 0.021). CONCLUSIONS: The WHO six-step 'how to hand rub' technique can be simplified to a 3-step procedure based on the reduction of bacterial counts on healthcare workers' hands achieved under experimental conditions. The proposed technique is easier to perform and could improve adherence to the execution of hand hygiene action.

[The diagnostic and therapeutic challenges of bilateral renal oncocytosis : Illustrative case presentations and a review of the literature]. / Die bilaterale renale Onkozytose als diagnostische und therapeutische Herausforderung : Falldarstellung und Literaturreview.

Bilateral oncocytosis along with multiple tumours in both kidneys represents a very rare pathology that is accompanied by diagnostic and therapeutic challenges. We report the case of a 60-year old male patient who underwent computer tomography with incidental detection of multiple bilateral and contrast enhancing renal tumours of different size. Subsequently the patient underwent nephron-sparing tumor resection, first on the right side and 4 weeks later on the left side. The histology of all removed tumors showed evidence of pure oncocytoma. There were no postoperative complications and renal function reached a stable state within 6 months follow-up. The major challenge regarding diagnostic process and therapy of this pathology is to distinguish benign oncocytoma from chromophobe renal cell carcinoma and hybrid tumours, which can all be associated with renal oncocytosis. Because of limitations concerning imaging processes and biopsy, all patients should undergo nephron-sparing surgery as far as possible. On the other hand alternative therapies should - regarding to therapy-associated morbidity and the basically benign prognosis of oncocytoma - be well discussed to obtain informed consent. In this case report different therapy options and the international literature concerning renal oncocytosis will be discussed.

Hour-glass magnetic excitations induced by nanoscopic phase separation in cobalt oxides.

The magnetic excitations in the cuprate superconductors might be essential for an understanding of high-temperature superconductivity. In these cuprate superconductors the magnetic excitation spectrum resembles an hour-glass and certain resonant magnetic excitations within are believed to be connected to the pairing mechanism, which is corroborated by the observation of a universal linear scaling of superconducting gap and magnetic resonance energy. So far, charge stripes are widely believed to be involved in the physics of hour-glass spectra. Here we study an isostructural cobaltate that also exhibits an hour-glass magnetic spectrum. Instead of the expected charge stripe order we observe nano phase separation and unravel a microscopically split origin of hour-glass spectra on the nano scale pointing to a connection between the magnetic resonance peak and the spin gap originating in islands of the antiferromagnetic parent insulator. Our findings open new ways to theories of magnetic excitations and superconductivity in cuprate superconductors.

Mechanism of spin crossover in LaCoO3 resolved by shape magnetostriction in pulsed magnetic fields.

In the scientific description of unconventional transport properties of oxides (spin-dependent transport, superconductivity etc.), the spin-state degree of freedom plays a fundamental role. Because of this, temperature- or magnetic field-induced spin-state transitions are in the focus of solid-state physics. Cobaltites, e.g. LaCoO3, are prominent examples showing these spin transitions. However, the microscopic nature of the spontaneous spin crossover in LaCoO3 is still controversial. Here we report magnetostriction measurements on LaCoO3 in magnetic fields up to 70 T to study the sharp, field-induced transition at Hc ≈ 60 T. Measurements of both longitudinal and transversal magnetostriction allow us to separate magnetovolume and magnetodistortive changes. We find a large increase in volume, but only a very small increase in tetragonal distortion at Hc. The results, supported by electronic energy calculations by the configuration interaction cluster method, provide compelling evidence that above Hc LaCoO3 adopts a correlated low spin/high spin state.

[The link between food intolerance and weight: a new perspective in the treatment of obesity].

In the article is presented the correlation between body weight and food intolerance to certain products, often associated with the development of food intolerances.

Glycerol significantly decreases the three hour efficacy of alcohol-based surgical hand rubs.

BACKGROUND: Glycerol in alcohol-based hand rubs has positive effects on skin condition and user acceptability, but, to the authors' knowledge, its effect on the bactericidal effect of alcohol-based pre-operative hand rubs has not been reported. AIM: To investigate the impact of glycerol on the reduction of resident hand flora by ethanol 80% (w/w), isopropanol 75% (w/w) and n-propanol 60% (V/V). METHODS: In three series of in-vivo laboratory tests on volunteers hands, the efficacy of each of three alcohol-based formulations was tested concurrently with and without added glycerol 1.45% (V/V) according to European Norm EN 12791 for testing pre-operative hand rubs. Formulations were allotted at random to 24 volunteers to rub on to their hands for 3 min. Viable counts from fingertip samples were compared with the respective pretreatment counts immediately after treatment and 3 h later. FINDINGS: The 3-h bactericidal effects of the three pure alcoholic formulations were significantly greater than those of formulations containing glycerol (P < 0.01). With ethanol, this was also true for the immediate effect. CONCLUSION: Glycerol 1.45% (V/V) inhibits the bactericidal efficacy of alcohol-based surgical hand rubs, especially sustained efficacy.

Testing the performance of a cryogenic visualization system on thermal counterflow by using hydrogen and deuterium solid tracers.

An experimental apparatus has been designed to analyze by visualization cryogenic flows of liquid (4)He and consequently address unresolved problems of quantum turbulence. The newly implemented flow visualization setup is described and its specific features discussed. Thermal counterflow experiments have been performed and the motion of solid hydrogen and deuterium tracers studied by using the particle tracking velocimetry technique in order to probe the system capabilities. It is shown that the obtained results are consistent with the two-fluid model describing the behavior of superfluid (4)He. A number of technical and fundamental issues, such as particles' aggregation, role of rotating particles in counterflow and evidence of non-Gaussian distribution of tracers' velocities, are also discussed. The apparatus appears to be well-suited to the task of analyzing cryogenic flows and potentially capable of obtaining new results stimulating further understanding of the underlying physics.

Dispersive crystal field excitations and quadrupolar interactions in UPd3.

We report inelastic neutron scattering measurements and random phase approximation calculations of the dispersive crystal field excitations of UPd(3). The measured spectra at lower energies agree with those calculated using quadrupolar interaction parameters deduced from bulk and x-ray scattering measurements. The more intense excitations arising from the hexagonal sites were used to obtain exchange parameters which proved to be anisotropic.

Oxidative stress is associated with liver damage, inflammatory status, and corticosteroid therapy in patients with systemic lupus erythematosus.

Oxidative stress exerts an important role on the pathophysiological mechanisms of systemic lupus erythematosus (SLE). This study investigated oxidative stress in patients with SLE and its correlation with disease activity, corticosteroid therapy, and liver function biomarkers. The study included 58 patients with SLE and 105 healthy volunteers. Patients showed oxidative stress increase evaluated by tert-butyl hydroperoxide-initiated chemiluminescence (CL-LOOH), advanced oxidation protein products (AOPP), and nitric oxide metabolites. C-reactive protein (CRP) was associated with CL-LOOH and with AOPP. Aspartate aminotransferase correlated significantly with CL-LOOH and with AOPP. Patients with disease activity showed an inverse significant correlation of daily prednisone doses and CL-LOOH and a direct correlation with total antioxidant capacity. In conclusion, patients with SLE have persistent lipoperoxidation and protein oxidation even with inactive disease or mild disease activity. The significant correlation between oxidative stress and CRP suggests that, despite clinical remission, the persistence of an inflammatory condition favors oxidative stress. Oxidative stress was associated with liver enzymes, and this relationship seems to support the hypothesis of drug-induced oxidative stress with consequent liver injury. In relation to non-active disease, patients with active SLE did not present oxidative stress and antioxidant capacity changes, due to the antioxidant drugs used in SLE treatment, especially prednisone.

Testing of the World Health Organization-recommended formulations for surgical hand preparation and proposals for increased efficacy.

The 2009 World Health Organization (WHO) Guidelines on hand hygiene in health care recommend alcohol-based hand rubs for both hygienic and pre-surgical hand treatment. Two formulations based on ethanol 80% v/v and 2-propanol 75% v/v are proposed for local preparation in healthcare settings where commercial products are not available or too expensive. Both formulations and our suggested modifications (using mass rather than volume percent concentrations) were evaluated for their conformity with the efficacy requirements of the forthcoming amendment of the European Norm (EN) 12791, i.e. non-inferiority of a product when compared with a reference procedure (1-propanol 60% v/v for 3 min) immediately and 3 h after antisepsis. In this study, the WHO-recommended formulations were tested for 3 min and 5 min. Neither formulation met the efficacy requirements of EN 12791 with 3 min application. Increasing the respective concentrations to 80 w/w (85% v/v) and 75 w/w (80% v/v), together with a prolonged application of 5 min, rendered the immediate effect of both formulations non-inferior to the reference antisepsis procedure. This was not the case with the 3h effect, which remained significantly inferior to the reference. Although the original formulations do not meet the efficacy requirements of EN 12791, the clinical significance of this finding deserves further clinical trials. To comply with the requirement of EN 12791, an amendment to the formulations is possible by increasing the alcohol concentrations through changing volume into mass percent and prolonging the duration of application from 3 min to 5 min.

Ethanol in pre-surgical hand rubs: concentration and duration of application for achieving European Norm EN 12791.

In Europe, ethanol is a common active agent in hand rub formulations and nowadays it is also recommended in guidelines for hand hygiene published by the Centers for Disease Control and Prevention and by the World Health Organization. However, data on the range of concentrations and durations of application providing a basis for passing the efficacy test of the European norm EN 12791 are still lacking. Therefore, the bactericidal efficacy of rubbing clean hands with pure ethanol in volume concentrations of 95%, 85% or 75% during 3 min was compared with that of the reference procedure of EN 12791 employing n-propanol 60% v/v for 3 min, immediately and 3h after disinfection. Ethanol 85% was also tested at a 5 min application. A Latin-square design was used with 20 randomly allotted volunteers. Whereas the mean immediate bacterial reductions caused by ethanol at concentrations of 75% (log RF 1.68) and 95% (log RF 2.70) were significantly less efficacious compared to that of the reference (log RF 3.27), at 85% they were not significantly less active with both applications, 3 and 5 min (log RFs 2.90 and 3.12, respectively). Three hours after antisepsis, the bacterial reduction on the gloved hand was only significantly less efficacious than that of the reference when 75% ethanol was used. It is concluded that ethanol-based hand rubs have a good chance of meeting the EN 12791 requirements if their ethanol concentration is >75% v/v but <95% v/v and if they are applied for at least 3 min.

[Abscess-forming retroperitoneal actinomycosis after urogynaecological surgery]. / Retroperitoneal abszedierende Aktinomykose nach urogynäkologischer Voroperation.

Human actinomycosis is an infrequent chronic infection caused by gram-positive anaerobic bacteria with predominantly cervicofacial and intestinal manifestation. Retroperitoneal abscess formation displays a very rare localisation and is mostly incidentally diagnosed by histological examination. We report on a 44-year-old woman with left-sided flank pain and retroperitoneal abscess formation diagnosed by CT scan. Case history revealed preceding nephroureterectomy of the left kidney due to loss of kidney function and recurrent ureteral-vaginal fistulas. After CT scan-guided puncture and negative bacterial culture, actinomycosis could only be diagnosed by histopathological examination. Subsequently, besides abscess drainage calculated antibiotic therapeutic regimen was initiated. During the follow-up of 9 months there was no local or systemic recurrence. In the present case report, aetiology, clinical symptoms as well as diagnostic and therapeutic consequences are discussed.

Surgical hand preparation: state-of-the-art.

Surgical hand preparation has been recommended since the nineteenth century as a measure to reduce infection resulting from surgery. We review the evidence and major objectives of surgical hand preparation, as well as the criteria for the choice of products currently in use. Test and validation procedures for selecting products for surgical hand preparation in North America and Europe are compared. Surgical hand antisepsis using medicated soap and alcohol-based hand-rub formulations is discussed, including the technical aspects, time required for the procedure, drying time, potential for side-effects, and the parameters for the selection of the most appropriate formulations. Brushes are not recommended for surgical hand preparation. Rapid antimicrobial action, wider spectrum of activity, lower side-effects, and the absence of the risk of hand contamination by the rinsing water, clearly favour the use of alcohol-based hand rubs for surgical hand preparation, even in countries with limited resources where the provision of water is scarce or of doubtful quality.

Methods to evaluate the microbicidal activities of hand-rub and hand-wash agents.

In vitro carrier tests, suspension tests, time-kill curves, and determinations of minimum inhibitory concentrations to evaluate the microbicidal activities of hand antiseptics provide only a preliminary indication of the antimicrobial spectrum and speed of action of a given formulation. Ex vivo testing with human or animal skin at human skin temperature and at contact times reflecting field conditions may give a better indication of a formulation's ability to tackle hand-transmitted pathogens. Field testing of hands for levels of skin microbiota before and after antisepsis may be easier to perform, but it is subject to many uncontrollable factors. Whereas randomised clinical trials may be the ultimate approach to assess the effectiveness of hand hygiene protocols and products in preventing microbial cross-transmission and, ultimately, infections, they can be prohibitively expensive, time-consuming, difficult to design, and therefore impractical. Hence, the primary emphasis should be on in vivo testing on human hands, using a well-designed protocol that closely simulates the recommended field use of the formulation, and possibly followed by clinical studies. The use of these method is the most likely to yield useful data on the potential of a formulation to interrupt the spread of pathogens transmitted by hands in healthcare settings. This review provides a critical assessment of the methods currently used to meet regulatory requirements for hand antiseptics in Europe and North America.

Surgical hand disinfection using alcohol: the effects of alcohol type, mode and duration of application.

Due to their strong antimicrobial activity, rapid action, good dermal tolerance and ease of application, alcohol-based hand rubs are recommended for pre-operative preparation of the surgical team's hands. Using the EN 12791 protocol, three commercial products containing either mixtures of propan-1-ol and propan-2-ol or ethanol at total alcohol concentrations (w/w) between 73% (propanols) and 78.2% (ethanol), as the main active agents, were tested with a shortened application of 1.5 min rather than the usual 3 min. Preparation A containing 30% propan-1-ol and 45% propan-2-ol not only passed the test at this short application but even exceeded, though not significantly, the efficacy of the reference disinfection procedure in EN 12791 when applied for 3 min. Preparation B containing 45% propan-1-ol and 28% propan-2-ol fulfilled the required standard whereas the ethanol (78.2%)-based product C did not (P<0.1). This demonstrates that some, but not all, alcohol-based hand rubs pass the test even within 1.5 min, emphasising the importance of validation before a product is introduced into clinical practice. In another series with both preparation A and 60% v/v propan-1-ol, it was demonstrated that the additional inclusion of the forearms into the disinfection procedure, not required by EN 12791 but normal practice in surgical hand disinfection, does not significantly interfere with the antimicrobial efficacy of either hand rub. Therefore, the mode of test procedure in EN 12791 does not need specific adaptation for hand disinfection by surgical teams.