Novel methods for in vitro modeling of pancreatic cancer reveal important aspects for successful primary cell culture.

BACKGROUND: Pancreatic cancer remains a fatal disease. Experimental systems are needed for personalized treatment strategies, drug testing and to further understand tumor biology. Cell cultures can serve as an excellent preclinical platform, but their generation remains challenging. METHODS: Tumor cells from surgically removed pancreatic ductal adenocarcinoma (PDAC) specimens were cultured under novel protocols. Cellular growth and composition were analyzed and culture conditions were continuously optimized. Characterization of cell cultures and primary tumors was performed via hematoxylin and eosin (HE) and immunofluorescence (IF) staining. RESULTS: Protocols for two- and three-dimensional PDAC primary cell cultures could successfully be established. Primary cell culture depended on dissociation techniques, growth factor supplementation and extracellular matrix components containing Matrigel being crucial for the transformation to three-dimensional PDAC organoids. The generated cultures showed to be highly resemblant to established PDAC primary cell cultures. HE and IF staining for cell culture and corresponding primary tumor characterization could successfully be performed. CONCLUSIONS: The work presented herein shows novel and effective methods to successfully establish primary PDAC cell cultures in a distinct time frame. Factors contributing to cell growth and differentiation could be identified with important implications for further primary cell culture protocols. The established protocols might serve as novel tools in personalized tumor therapy.

Testing of the WHO Infection Prevention and Control Assessment Framework at acute healthcare facility level.

BACKGROUND: Monitoring and evaluation are an essential part of infection prevention and control (IPC) implementation. The authors developed an IPC assessment framework (IPCAF) to support implementation of the World Health Organization (WHO) guidelines on core components of IPC programmes in acute healthcare facilities. AIM: To evaluate the usability and reliability of the IPCAF tool for global use. METHODS: The IPCAF is a questionnaire with a scoring system to measure the level of IPC implementation according to the eight WHO core components. The tool was pre-tested qualitatively, revised and translated selectively. A convenience sample of hospitals was invited to participate in the final testing. At least two IPC professionals from each hospital independently completed the IPCAF and a usability questionnaire online. The tool's internal consistency and interobserver reliability or intraclass correlation coefficient (ICC) were assessed, and usability questions were summarized descriptively. FINDINGS: In total, 46 countries, 181 hospitals and 324 individuals participated; 52 (16%) and 55 (17%) individual respondents came from low- and lower-middle income countries, respectively. Fifty-two percent of respondents took less than 1 h to complete the IPCAF. Overall, there was adequate internal consistency and a high ICC (0.92, 95% confidence interval 0.89-0.94). Ten individual questions had poor reliability (ICC <0.4); these were considered for revision according to usability feedback and expert opinion. CONCLUSIONS: The WHO IPCAF was tested using a robust global study and revised as necessary. It is now an effective tool for IPC improvement in healthcare facilities.

Correction to: Antimicrobial-coated sutures to decrease surgical site infections: a systematic review and meta-analysis.

In the original version of this article, reference citations found in Tables 2, 3, and 4 contain errors in linking. The correct tables are reproduced below.

Antimicrobial-coated sutures to decrease surgical site infections: a systematic review and meta-analysis.

To investigate the effectiveness of antimicrobial-coated sutures compared with non-coated sutures in reducing surgical site infection (SSI) and develop recommendations for World Health Organization (WHO) SSI prevention guidelines. We searched Medline, Embase, Cinahl, Cochrane Central Register of Controlled Trials, and WHO Global Health from 1990-16/02/2015 with language restricted to English, Spanish, and French. Meta-analysis was performed with a random-effects model. Meta-regression analysis assessed whether the effect of antimicrobial coating changed according to the type of suture and surgery. Subgroup analyses were based on types of sutures. Quality of the retrieved evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation. Thirteen randomized controlled trials (RCTs) and five observational studies (OBSs) met the inclusion criteria. Antimicrobial sutures significantly reduced SSI risk (for RCTs: OR 0.72, 95 % CI 0.59-0.88, p = 0.001, I2 = 14 %; for OBSs: OR 0.58, 95 % CI 0.40-0.83, p = 0.003, I2 = 22 %). Only Vicryl Plus vs Vicryl revealed consistent results in favor of antimicrobial sutures (for seven RCTs: OR 0.62, 95 % CI 0.44-0.88, p = 0.007, I2 = 3 %; for four OBSs: OR 0.58, 95 % CI 0.37-0.92, p = 0.02, I2 = 41 %). The effect of antimicrobial coating was similar between different suture, wound, and procedure types. Quality of RCT evidence was moderate, and OBS evidence was very low quality. Triclosan-coated sutures may reduce SSI risk. However, the available evidence is of moderate/low quality, and many studies had conflicts of interest.

At-wavelength metrology facility for soft X-ray reflection optics.

A new Optics Beamline coupled to a versatile UHV reflectometer is successfully operating at BESSY-II. It is used to carry out at-wavelength characterization and calibration of in-house produced gratings and novel nano-optical devices as well as mirrors and multilayer systems in the UV and XUV spectral region. This paper presents most recent commissioning data of the beamline and shows their correlation with initial beamline design calculations. Special attention is paid to beamline key parameters which determine the quality of the measurements such as high-order suppression and stray light behavior. The facility is open to user operation.

The at-wavelength metrology facility for UV- and XUV-reflection and diffraction optics at BESSY-II.

A technology center for the production of high-precision reflection gratings has been established. Within this project a new optics beamline and a versatile reflectometer for at-wavelength characterization of UV- and XUV-reflection gratings and other (nano-) optical elements has been set up at BESSY-II. The Plane Grating Monochromator beamline operated in collimated light (c-PGM) is equipped with an SX700 monochromator, of which the blazed gratings (600 and 1200 lines mm(-1)) have been recently exchanged for new ones of improved performance produced in-house. Over the operating range from 10 to 2000 eV this beamline has very high spectral purity achieved by (i) a four-mirror arrangement of different coatings which can be inserted into the beam at different angles and (ii) by absorber filters for high-order suppression. Stray light and scattered radiation is removed efficiently by double sets of in situ exchangeable apertures and slits. By use of in- and off-plane bending-magnet radiation the beamline can be adjusted to either linear or elliptical polarization. One of the main features of a novel 11-axes reflectometer is the possibility to incorporate real life-sized gratings. The samples are adjustable within six degrees of freedom by a newly developed UHV-tripod system carrying a load up to 4 kg, and the reflectivity can be measured between 0 and 90° incidence angle for both s- and p-polarization geometry. This novel powerful metrology facility has gone into operation recently and is now open for external users. First results on optical performance and measurements on multilayer gratings will be presented here.

[Undesired awareness phenomena during general anesthesia: Evidence-based state of knowledge, current discussions and strategies for prevention and management]. / Unerwünschte Wachphänomene ("Awareness") während Allgemeinanästhesie: Evidenzbasierter Kenntnisstand, aktuelle Diskussionen und Strategien zu Prävention und Management.

Patient awareness during general anesthesia and the later recall of what happened during surgery can be experienced by patients as horrifying events that leave lasting mental trauma in the form of posttraumatic stress syndrome (PTSS). Awareness is related to a temporary insufficient depth of anesthesia. This phenomenon has been discussed for more than 20 years. According to randomized controlled studies, in the absence of risk factors awareness phenomena occur in 1-2 per 1000 operations involving general anesthesia (0.1-0.2%) and are classified as occasionally occurring critical events. An astonishing twist occurred elicited by the recent data from the 5th National Audit Project from Great Britain (NAP5) published in the British Journal of Anaesthesia and in Anaesthesia. The NAP5 evaluated patient reports of accidental awareness during general anesthesia (AAGA) in a multicenter manner in more than 2.7 million cases and indicated incidences of awareness of only 1:19,600, a frequency 20 times less than previously reported. These results gave rise to some controversy. It seems likely that, due to the absence of structured interviews, the NAP5 data only demonstrated the tip of the iceberg and may have vastly underestimated the real incidence of intraoperative awareness. The present overview summarizes the current knowledge about awareness. Furthermore, it addresses the question whether the awareness problem has been overestimated by evidence-based criteria or underestimated by the results of the NAP5. The responsibility for sufficient anesthesia in the clinical routine requires knowledge of awareness risks and potential sequelae. A formal recommendation from the German Society of Anesthesia and Intensive Care Medicine (DGAI) concerning awareness is not yet available; however, the recognition of evidence-based strategies in the management of anesthesia may minimize the occurrence of awareness and its sequelae.

[Hygiene measures in the intensive care station]. / Hygienemaßnahmen auf der Intensivstation.

Medical personnel in intensive care units (ICU) deal with critically ill patients and a high work load. Patients face a higher risk of acquiring a nosocomial infection during their ICU stay. Especially, invasively ventilated patients are threatened. A catheter-related bloodstream infection might even lead to more severe complications. The number of multiresistant pathogens continues to rise; thus, comprehensive infection control measures are crucial to avoid pathogen transmission and infection. The most important measure is hand disinfection. With a proper personnel-patient ratio, educational programs, and infection control bundles, it is possible to reduce infection rates and enhance compliance among health care workers.

[The thickened left ventricle: etiology, differential diagnosis and implications for cardiovascular radiology]. / Der dicke linke Ventrikel: Ursachen und Differenzialdiagnose der linksventrikulären Hypertrophie und Implikationen für die kardiovaskuläre Radiologie.

Hypertrophy of the left ventricular myocardium is a common finding and can be reliably detected by echocardiography, CT and MRI. Common causes include diseases associated with increased cardiac afterload as well as primary and secondary cardiomyopathy. With the opportunity to determine functional parameters and myocardial mass precisely as well as to detect structural changes of the cardiac muscle simultaneously, cardiac MRI is the most precise imaging method for quantifying left ventricular hypertrophy as well as determining the cause and the exact characterization of the myocardial changes. It is mandatory, however, to create a flexible, individually adapted examination protocol. This review presents useful diagnostic algorithms in relation to different underlying pathologies in patients with left ventricular hypertrophy.

AgGaSe2 thin films grown by chemical close-spaced vapor transport for photovoltaic applications: structural, compositional and optical properties.

Thin films of chalcopyrite AgGaSe(2) have been successfully grown on glass and glass/molybdenum substrates using the technique of chemical close-spaced vapor transport. The high crystallinity of the samples is confirmed by grazing-incidence x-ray diffraction, scanning and transmission electron microscopy, and optical transmission/reflection spectroscopy. Here, two of the three expected direct optical bandgaps are found at 1.77(2) and 1.88(6) eV at 300 K. The lowest bandgap energy at 4 K is estimated to be 1.82(3) eV. Photoluminescence spectroscopy has further revealed the nature of the point defects within the AgGaSe(2), showing evidence for the existence of very shallow acceptor levels of 5(1) and 10(1) meV, and thus suggesting the AgGaSe(2) phase itself to exhibit a p-type conductivity. At the same time, electrical characterization by Hall, Seebeck and four-point-probe measurements indicate properties of a compensated semiconductor. The electrical properties of the investigated thin films are mainly influenced by the presence of Ag(2)Se and Ga(2)O(3) nanometer-scaled surface layers, as well as by Ag(2)Se inclusions in the bulk and Ag clusters at the layers' rear side.

Large-area 2D periodic crystalline silicon nanodome arrays on nanoimprinted glass exhibiting photonic band structure effects.

Two-dimensional silicon nanodome arrays are prepared on large areas up to 50 cm² exhibiting photonic band structure effects in the near-infrared and visible wavelength region by downscaling a recently developed fabrication method based on nanoimprint-patterned glass, high-rate electron-beam evaporation of silicon, self-organized solid phase crystallization and wet-chemical etching. The silicon nanodomes, arranged in square lattice geometry with 300 nm lattice constant, are optically characterized by angular resolved reflection measurements, allowing the partial determination of the photonic band structure. This experimentally determined band structure agrees well with the outcome of three-dimensional optical finite-element simulations. A 16% photonic bandgap is predicted for an optimized geometry of the silicon nanodome arrays. By variation of the duration of the selective etching step, the geometry as well as the optical properties of the periodic silicon nanodome arrays can be controlled systematically.

EPR analysis of the effects of accelerated carbon ion and fast neutron irradiations on table sugar.

Table sugar samples were irradiated with accelerated carbon ions and fast neutrons. Electron paramagnetic resonance (EPR) analysis performed after the irradiation revealed a complex spectrum similar to that observed after gamma-ray irradiations. The total concentration of the paramagnetic centers induced by accelerated carbon ions and neutrons was proportional to the absorbed dose. Good stability of the produced free radicals was observed for a typical period of sugar storage. Sugar was more sensitive to accelerated carbon ions than to neutrons. The results show that table sugar can be a useful material for dosimetry in the case of a radiation accident.

[Uveitis-quiz 2007]. / Uveitis-Quiz 2007.

Six cases with pathognomonic uveitis pathologies are presented and discussed using multiple-choice questions.

[Measurement of the depth of anaesthesia]. / Messung der Narkosetiefe.

One of the most important mandates of the anaesthesiologist is to control the depth of anaesthesia. An unsolved problem is that a straight definition of the depth of anaesthesia does not exist. Concerning this it is rational to separate hypnosis from analgesia, from muscle relaxation and from block of cardiovascular reactions. Clinical surrogate parameters such as blood pressure and heart rate are not well-suited for a valid statement about the depth of hypnosis. To answer this question the brain has become the focus of interest as the target of anaesthesia. It is possible to visualize the brain's electrical activity from anelectroencephalogram (EEG). The validity of the spontaneous EEG as an anesthetic depth monitor is limited by the multiphasic activity, especially when anaesthesia is induced (excitation) and in deep anaesthesia (burst suppression). Recently, various commercial monitoring systems have been introduced to solve this problem. These monitoring systems use different interpretations of the EEG or auditory-evoked potentials (AEP). These derived and calculated variables have no pure physiological basis. For that reason a profound knowledge of the algorithms and a validation of the monitoring systems is an indispensable prerequisite prior to their routine clinical use. For the currently available monitoring systems various studies have been reported. At this time it is important to know that the actual available monitors can only value the sedation and not the other components of anaesthesia. For example, they cannot predict if a patient will react to a painful stimulus or not. In the future it would be desirable to develop parameters which allow an estimate of the other components of anaesthesia in addition to the presently available monitoring systems to estimate sedation and muscle relaxation. These could be sensoric-evoked potentials to estimate analgesia and AEPs for the detection of awareness.

Anesthetics drug pharmacodynamics.

Anesthesia cannot be defined in an unambiguous manner. The essential components of general anesthesia are absence of consciousness and pain. This translates into two particular qualities: (1) sedation and hypnosis, i.e., mental blockade and (2) analgesia/antinociception, i.e., sensory blockade. Anesthetic actions on these two subcomponents are difficult to separate. On the one hand, very few anesthetics act exclusively on one of these components. On the other hand, these components are closely related to each other. Unconsciousness prevents (conscious) perception of pain, and nociception may serve as an arousal stimulus and change the level of sedation and hypnosis. The art of anesthesia lies in adequate dosing of drugs to reach both mental and sensory blockade. Drug administration can be based on pharmacokinetic considerations. Pharmacokinetic models allow an estimation of what happens to the administered drug in the body. Models with an effect site compartment may facilitate a tailored administration of anesthetic drugs. Finally, the quantification of pharmacodynamic effects allows a precise titration of drugs. Clinical assessment of mental blockade is often dichotomous, and therefore not very helpful to guide drug administration. Several scoring systems exist, but once consciousness is lost they become less reliable, in particular because reaction to stimuli is assessed, which mixes assessment of mental blockade with assessment of sensory blockade. Clinical assessment of analgesia requires a conscious patient, so antinociception is difficult to measure. Several methods of objective quantification on the basis of electrical brain activity are discussed including EEG and evoked potentials. Despite numerous indexes of the hypnotic component of anesthesia, there is no parameter that unambiguously quantifies the level of mental or sensory blockade.

[The new regulations for the licence to practice medicine. Implementation for the faculty of anesthesiology at the University Clinic Hamburg-Eppendorf]. / Die neue Approbationsordnung für Arzte. Umsetzung für das Fach Anästhesiologie am Universitätsklinikum Hamburg-Eppendorf.

After the amendments to the regulations for the licence to practice medicine, the rating of the faculty of anesthesiology has clearly increased. In the following article a concept will be described whereby these standards were implemented at the University of Hamburg. The basic principle, especially the training in the practical proficiencies, is to achieve a continuous learning process from students through to specialists for anesthesiology.

Monitoring methods: SNAP.

The SNAP electroencephalogram (EEG) monitor, described as an interesting, innovative EEG tool that samples raw EEG signals and uses its own unique algorithm, analyses both high- (80-420 Hz) and low- (0-20 Hz) frequency components of the signal. This is termed the SNAP index, and it ranges from 100 (arbitrarily representing the fully awake state) to 0 to provide functional data points for patient management. The SNAP is the first commercial EEG-monitoring tool to use Personal Digital Assistant computer technology. The first version of SNAP index was introduced in 2002, and so far there has been little experience with the SNAP device reported in the literature. Compared with other EEG devices, there is no evidence that SNAP is superior to others in generating more specific information about 'depth of sedation'. Moreover, the influence of high-frequency electromyographic activity on the SNAP needs to be clarified.

Ruthenium (II)-derived organometallic compounds induce cytostatic and cytotoxic effects on mammalian cancer cell lines through p53-dependent and p53-independent mechanisms.

The metallic compound cisplatin has been used for many years to treat various human cancers. Here, we describe the cytostatic and cytotoxic properties of a new class of organometallic compounds that contain a ruthenium (II) atom covalently linked to carbon and nitrogen atoms. We found that several ruthenium-derived compounds (RDCs) led to G1 arrest and induced apoptosis in tumor cell lines derived from glioblastomas, neuroblastomas, and lymphoid tumors at least as efficiently as cisplatin. We further analyzed the signaling pathways underlying these effects, and we showed that both RDCs and cisplatin induced p53 and p73 protein levels but with different intensities and kinetics. This accumulation of p53 and p73 proteins correlated with an increase in p21 and Bax expression, two p53 target genes linked to cell growth arrest and apoptosis. However, in contrast to cisplatin-induced apoptosis, overexpression of DeltaNp73, a p53 and p73 dominant-negative isoform, only partly reduced RDC-induced apoptosis, suggesting p53-dependent and p53-independent modes of action. This observation was further confirmed by the ability of RDC to induce apoptosis in p53-/- cells. Altogether, this study highlights key cellular and molecular features of RDCs and suggests that further development of this new class of compounds may contribute to improve future chemotherapeutic protocols.