Effect of adding B-vitamins to vitamin D and calcium supplementation on CpG methylation of epigenetic aging markers.

BACKGROUND AND AIM: B-vitamins may influence DNA methylation. We studied the effects of vitamin D + Ca + B versus D + Ca on epigenetic age markers and biological age. METHODS AND RESULTS: Participants (mean ± SD of age = 68.4 ± 10.1 years) were randomized to receive 1200 IE vitamin D3 plus 800 mg Ca-carbonate alone (n = 31) or with 0.5 mg B9, 50 mg B6, and 0.5 mg B12 (n = 32). The CpG methylation of 3 genes (ASPA, ITGA2B, and PDE4C) and the changes in methylation were compared between the groups after 1 year. The changes of ASPA methylation from baseline were higher in the D + Ca + B than in the D + Ca group (1.40 ± 4.02 vs. -0.96 ± 5.12, respectively; p = 0.046, adjusted for age, sex, and baseline methylation). The changes in PDE4C from baseline were slightly higher in the D + Ca + B group (1.95 ± 3.57 vs. 0.22 ± 3.57; adjusted p = 0.062). Methylation of ITGA2B and its changes from baseline were not different between the intervention groups. Sex-adjusted odds ratio of accelerated aging (chronological age < biological age at 1 year) was 5.26 (95% confidence interval 1.51-18.28) in the D + Ca + B compared with the D + Ca group. Accelerated aging in both groups was associated with younger age. In the D + Ca + B group, it was additionally associated with lower baseline homocysteine. CONCLUSIONS: Vitamin D + Ca + B and D + Ca differentially affected epigenetic age markers, although the effect size appeared to be small after 1 year. B-vitamins effect in young subjects with low homocysteine requires further investigation. ClinicalTrials.gov ID: NCT02586181.

Human serum substitution by artificial sera of scalable allergen reactivity based on polyclonal antibodies and chimeras of human FcγRI and IgE domains.

Human sera are the first choice as controls for diagnostic applications such as immunoassays, but are limited regarding availability, varying quality, and high costs. In this study, we aimed to circumvent these limitations by the use of a chimeric adaptor molecule comprising the extracellular domains of the human FcγRI (CD64) fused with human IgE Fc domains (CD64-IgE Fc). Allergen-specific antibodies were produced in rabbits using eight different allergens, extracts, and allergen mixtures including mites, pollen, drugs, and food. Preincubation of polyclonal IgG with CD64-IgE Fc established allergen-specific artificial sera that showed comparable results for more than 20 allergens and allergen extracts in three diagnostic systems for the determination of specific IgE. The agreement for these artificial sera is within ±1 radioallergosorbent test (RAST) class. Hence, rabbit IgG complexed with the IgG-specific CD64-IgE Fc adaptor molecule could provide a substitute for human reference sera with specificity for virtually any protein of interest.

Investigating the roots of successful IT adoption processes - an empirical study exploring the shared awareness-knowledge of Directors of Nursing and Chief Information Officers.

BACKGROUND: The majority of health IT adoption research focuses on the later stages of the IT adoption process: namely on the implementation phase. The first stage, however, which is defined as the knowledge-stage, remains widely unobserved. Following Rogers' Diffusion of Innovation Theory (DOI) this paper presents a research framework to examine the possible lack of shared IT awareness-knowledge, i.e. an information gradient, of two crucial stakeholders, the Chief Information Officer (CIO) and the Director of Nursing (DoN). This study shall answer the following research questions: (1.) Does this gradient exist? (2.) Which direction does it have? (3.) Are certain health IT (HIT) attributes associated with a potential gradient? (4.) Which determinants of diffusion go along with this gradient? METHOD: Results of two surveys that focused on the topic "IT support of clinical workflows" from the viewpoint of CIOs and DoNs with corresponding datasets from 75 hospitals were used in a secondary data analysis. The gradient was operationalised by measuring the disagreement of CIOs and DoNs on the availability and implementation status of 29 IT functions. HIT attributes tested were relevance and market penetration of the IT functions, determinants of diffusion were inter-professional leadership and IT service density. RESULTS: The analysis revealed a significant disagreement on the availability of 9 out of 29 HIT functions. In 23 HIT functions, the CIOs reported a higher implementation status than the DoNs, which pointed to a trend for a unidirectional gradient. The disagreement was significantly lower when the relevance of the IT function was high. Both determinants of diffusion correlated significantly negative with the degree of disagreement. CONCLUSION: This is the first study to empirically examine shared awareness-knowledge of two IT-stakeholders that are crucial for triggering IT adoption on the frontline level in hospitals. It could be shown that a gradient and thus a lack of shared awareness-knowledge existed and was associated with certain factors. In conclusion, hospitals should implement improved cooperation between IT staff and clinicians and IT service density when establishing the prerequisites for successful IT adoption processes.

The effect of silver thickness on the enhancement of polymer based SERS substrates.

We investigated silver-covered polymer based nanogratings as substrates for surface-enhanced Raman spectroscopy (SERS), in particular with respect to the thickness of the plasmonically active silver film. In order to obtain accurate geometrical input data for the simulation process, we inspected cross sections of the gratings prepared by breaking at cryogenic temperature. We noticed a strong dependence of the simulation results on geometrical variations of the structures. Measurements revealed that an increasing silver film thickness on top of the nanogratings leads to a blue shift of the plasmonic resonance, as predicted by numerical simulations, as well as to an increased field enhancement for an excitation at 488 nm. We found a clear deviation of the experimental data compared to the simulated results for very thin silver films due to an island-like growth at a silver thickness below 20 nm. In order to investigate the SERS activity. we carried out measurements with crystal violet as a model analyte at an excitation wavelength of 488 nm. The SERS enhancement increases up to a silver thickness of about 30 nm, whereas it remains nearly constant for thicker silver films.

Dressed-state amplification by a single superconducting qubit.

We demonstrate amplification of a microwave signal by a strongly driven two-level system in a coplanar waveguide resonator. The effect, similar to the dressed-state lasing known from quantum optics, is observed with a single quantum system formed by a persistent current (flux) qubit. The transmission through the resonator is enhanced when the Rabi frequency of the driven qubit is tuned into resonance with one of the resonator modes. Amplification as well as linewidth narrowing of a weak probe signal has been observed. The stimulated emission in the resonator has been studied by measuring the emission spectrum. We analyzed our system and found an excellent agreement between the experimental results and the theoretical predictions obtained in the dressed-state model.

Tertiary treatment of Berlin WWTP effluents with ferrate (Fe(VI)).

New and higher standards in the EU water framework directive necessitate advanced treatment of secondary effluents for reduction of trace organic compounds (TrOCs) and nutrients before the discharge into receiving surface waters. Due to its dual function as oxidant and coagulant, ferrate is considered as a promising alternative for tertiary treatment. The oxidation of selected TrOCs and simultaneous flocculation of phosphates by ferrate was tested in batch experiments with secondary effluent from Berlin Ruhleben. The concentrations of carbamazepine (CBZ) and diclofenac were reduced by >90% with ferrate dosages of 6 mg/L as Fe. CBZ was transformed to 1-(2-benzaldehyde)-4-hydro-(1H,3H)-quinazoline-2-one, which is known as the major product from the reaction of CBZ with ozone. In contrast to ozonation, no further transformation of this product was observed. The concentration of ibuprofen was not reduced by ferrate treatment. For efficient removal of 60-100 µg/L phosphate-P to values <20 µg/L, ferrate dosages of 3-4 mg/L as Fe were sufficient.

An actinometric method to characterize performance of reflecting UVC reactors used for water treatment.

The applicability of chemical actinometry to characterize the fluence in UV reactors with reflections, non-parallel light, and variable water transmittance is limited due to the unknown effective path length or hydraulic shortcuts within the reactor. In this study, the effects of reflection and transmittance on actinometry were examined and a new, optimized and easy method for determining fluence was developed. KI/KIO3 and uridine actinometry experiments were carried out under controlled conditions using a collimated beam apparatus and a completely mixed batch reactor with or without diffuse reflection and compared to biodosimetry results. Whereas optically opaque actinometers such as KI/KIO3 are not directly capable of predicting the fluence of reflecting reactors, the results of uridine actinometry are influenced by reflection and transmission. To precisely predict the fluence rate in UV reactors with uridine, knowledge about the effective optical path length of the light is needed. Here, an existing method to mathematically calculate the optical path length was adopted and optimized for uridine actinometry. Results for average fluence were validated by biodosimetry using MS2 phages under different degrees of reflection and transmission. It could be shown that by modifying the bottom of the reactor with diffusely reflecting polytetrafluoroethylene foil, the fluence rate was increased by a factor of approximately 2.6 and the path length by factor of 2.4. When only half of the bottom was covered with reflective foil, fluence rate increased by a factor of 1.8 and path length by 1.8. Although this new approach cannot replace biodosimetry, to predict the fluence distribution received by microorganisms, it can provide means to characterize more complex reactor designs, validate results of advanced reactor modeling, and quantify fluence for non-parallel irradiation and reflective light, especially for the application of high fluence (e.g., advanced oxidation processes), where biodosimetry may be too sensitive. Further, comparing the fluence obtained with actinometry to the results of biodosimetry might qualitatively indicate hydraulic short cuts or unideal fluence distributions for flow-through reactors.

Optical properties of metamaterials based on asymmetric double-wire structures.

We performed theoretical and experimental investigations of the magnetic properties of metamaterials based on asymmetric double-wire structures. Using the multipole model for the description of metamaterials, we investigated the influence of the geometrical asymmetry of the structure on the macroscopic effective parameters. The results show that the larger wire in the system dominates the dynamics of the structure and defines the orientation and the strength of the microscopic currents. As a result the magnetization of the structure can be significantly enhanced for certain asymmetric configurations of the double-wire structure.

Single and multilayer metamaterials fabricated by nanoimprint lithography.

We demonstrate for the first time a fast and easy nanoimprint lithography (NIL) based stacking process of negative index structures like fishnet and Swiss-cross metamaterials. The process takes a few seconds, is cheap and produces three-dimensional (3D) negative index materials (NIMs) on a large area which is suitable for mass production. It can be performed on all common substrates even on flexible plastic foils. This work is therefore an important step toward novel and breakthrough applications of NIMs such as cloaking devices, perfect lenses and magnification of objects using NIM prisms. The optical properties of the fabricated samples were measured by means of transmission and reflection spectroscopy. From the measured data we retrieved the effective refractive index which is shown to be negative for a wavelength around 1.8 µm for the fishnet metamaterial while the Swiss-cross metamaterial samples show a distinct resonance at wavelength around 1.4 µm.

Doubly resonant optical nanoantenna arrays for polarization resolved measurements of surface-enhanced Raman scattering.

We report that rhomb-shaped metal nanoantenna arrays support multiple plasmonic resonances, making them favorable bio-sensing substrates. Besides the two localized plasmonic dipole modes associated with the two principle axes of the rhombi, the sample supports an additional grating-induced surface plasmon polariton resonance. The plasmonic properties of all modes are carefully studied by far-field measurements together with numerical and analytical calculations. The sample is then applied to surface-enhanced Raman scattering measurements. It is shown to be highly efficient since two plasmonic resonances of the structure were simultaneously tuned to coincide with the excitation and the emission wavelength in the SERS experiment. The analysis is completed by measuring the impact of the polarization angle on the SERS signal.

Antibiotic microbial resistance (AMR) removal efficiencies by conventional and advanced wastewater treatment processes: A review.

The World Health Organization (WHO) has identified the spread of antibiotic resistance as one of the major risks to global public health. An important transfer route into the aquatic environment is the urban water cycle. In this paper the occurrence and transport of antibiotic microbial resistance in the urban water cycle are critically reviewed. The presence of antibiotic resistance in low impacted surface water is being discussed to determine background antibiotic resistance levels, which might serve as a reference for treatment targets in the absence of health-based threshold levels. Different biological, physical and disinfection/oxidation processes employed in wastewater treatment and their efficacy regarding their removal of antibiotic resistant bacteria and antibiotic resistance geness (ARGs) were evaluated. A more efficient removal of antibiotic microbial resistance abundances from wastewater effluents can be achieved by advanced treatment processes, including membrane filtration, ozonation, UV-irradiation or chlorination, to levels typically observed in urban surface water or low impacted surface water.

Combining super-resolution microscopy with neuronal network recording using magnesium fluoride thin films as cover layer for multi-electrode array technology.

We present an approach for fabrication of reproducible, chemically and mechanically robust functionalized layers based on MgF2 thin films on thin glass substrates. These show great advantages for use in super-resolution microscopy as well as for multi-electrode-array fabrication and are especially suited for combination of these techniques. The transparency of the coated substrates with the low refractive index material is adjustable by the layer thickness and can be increased above 92%. Due to the hydrophobic and lipophilic properties of the thin crystalline MgF2 layers, the temporal stable adhesion needed for fixation of thin tissue, e.g. cryogenic brain slices is given. This has been tested using localization-based super-resolution microscopy with currently highest spatial resolution in light microscopy. We demonstrated that direct stochastic optical reconstruction microscopy revealed in reliable imaging of structures of central synapses by use of double immunostaining of post- (homer1 and GluA2) and presynaptic (bassoon) marker structure in a 10 µm brain slice without additional fixing of the slices. Due to the proven additional electrical insulating effect of MgF2 layers, surfaces of multi-electrode-arrays were coated with this material and tested by voltage-current-measurements. MgF2 coated multi-electrode-arrays can be used as a functionalized microscope cover slip for combination with live-cell super-resolution microscopy.

Elucidation of removal processes in sequential biofiltration (SBF) and soil aquifer treatment (SAT) by analysis of a broad range of trace organic chemicals (TOrCs) and their transformation products (TPs).

Many chemicals with different physico-chemical properties are present in municipal wastewater. In this study, the removal of a broad range of trace organic chemicals (TOrCs) was determined in two biological treatment processes differing in hydraulic retention time: sequential biofiltration (SBF) and soil-aquifer treatment (SAT), operated in Germany and Spain. Occurrence and the degree of removal of more than 150 TOrCs with different physico-chemical properties were analysed, including precursors as well as human metabolites and environmental transformation products (TPs). Ninety TOrCs were detected in the feed water of the SBF system, 40% of these showed removal efficiencies of higher than 30% during biological treatment. In SAT, 70 TOrCs were detected in the feed water, 60% of these could be reduced by more than 30% after approximately 3 days of subsurface treatment. For uncharged and negatively charged TOrCs biological degradation was mainly responsible for the removal, while positively charged TOrCs were most likely also removed by ionic interactions. The detections of TPs confirmed that biodegradation was a major removal process in both systems. The analysis of positively and negatively charged, neutral and zwitterionic TOrCs and the simultaneous analysis of precursors and their biologically formed TPs enabled a detailed understanding of underlying mechanisms of their removal in the two systems. On this basis, criteria for site-specific indicator selection were proposed.

Magnetically induced transparency of a quantum metamaterial composed of twin flux qubits.

Quantum theory is expected to govern the electromagnetic properties of a quantum metamaterial, an artificially fabricated medium composed of many quantum objects acting as artificial atoms. Propagation of electromagnetic waves through such a medium is accompanied by excitations of intrinsic quantum transitions within individual meta-atoms and modes corresponding to the interactions between them. Here we demonstrate an experiment in which an array of double-loop type superconducting flux qubits is embedded into a microwave transmission line. We observe that in a broad frequency range the transmission coefficient through the metamaterial periodically depends on externally applied magnetic field. Field-controlled switching of the ground state of the meta-atoms induces a large suppression of the transmission. Moreover, the excitation of meta-atoms in the array leads to a large resonant enhancement of the transmission. We anticipate possible applications of the observed frequency-tunable transparency in superconducting quantum networks.

Comparative in vitro study of the cell proliferation of ovine and human osteoblast-like cells on conventionally and rapid prototyping produced scaffolds tailored for application as potential bone replacement material.

Reconstruction of bone defects in the field of craniomaxillofacial surgery is a relevant problem. In regenerative medicine, autologous bone is not available sufficiently. The full replacement of autologous bone grafts is required. A promising research field is the bone engineering. Especially the application of rapid prototyping (RP) enables new perspectives concerning the scaffold design. The aim of the study was to compare scaffolds produced by RP-technology (native and plasma-coated PLGA-scaffolds) with conventionally produced scaffolds (agar plates with hydroxyapatite and hyaluronic acid coated agar plates with hydroxyapatite) relating to proliferation, adhesion, and morphology of osteoblasts to get knowledge about the application potential of such 3D-manufactured matrices for bone engineering. TissueFoil E served as reference. To compare the scaffolds, 12 ovine and 12 human osteoblast-like cell cultures of the skull were used. Results were obtained by EZ4U, scanning electron microscopy, and light microscopy. The highest cell proliferation rate of human osteoblast-like cells was measured on TissueFoil E followed by plasma-coated PLGA-scaffolds and uncoated PLGA-scaffolds, whereas of ovine osteoblast-like cells on plasma-coated PLGA-scaffolds followed by TissueFoil E and uncoated PLGA-scaffolds. Human and ovine osteoblast-like cells on coated and uncoated agar plates had significant lower proliferation rates compared with TissueFoil E and PLGA-scaffolds. These results showed the potential of RP in the field of bone engineering. Mechanical properties of such scaffolds and in vivo studies should be investigated to examine if the scaffolds hold up the pressure it will undergo long enough to allow regrowth of bone and to examine the revascularization.

Structure and in vitro cytocompatibility of the gastropod shell of Helix pomatia.

Distinguishing features of biological constructions are high stability and adaptation to their environment. Beside biocompatibility, nontoxicity and degradability these characteristics are demanded for new biomaterials in the field of tissue engineering. This study investigated the chemical composition, the organization and the in vitro osteoconductive potential of the terrestrial gastropod shell (Helix pomatia) on CAL72 and human osteoblast-like cells. Chemical composition of the biomaterial was examined by X-ray diffraction (XRD) and scanning electron microscopy (SEM) was performed to analyze the architecture of the snail shell and the morphology of the seeded cells. A double staining procedure (FDA/PI) and a proliferation test (EZ4U) assessed the viability of the cells. Microscopical images showed the multilayered architecture of the aragonite shell with hexagonal crystals on the inner side. The cells spread well on the biomaterial and the highest proliferation rate could be measured with CAL72 cells on the inner shell surface. The osteoconductive effects of this natural biomaterial could encourage further experiments in the field of tissue engineering.

Failure of orally administered dipyridamole to enhance the antineoplastic activity of fluorouracil in combination with leucovorin in patients with advanced colorectal cancer: a prospective randomized trial.

PURPOSE: A randomized trial was performed to investigate the ability of the nucleoside transport inhibitor dipyridamole (DP) to enhance the antitumor activity of fluorouracil (5-FU)/leucovorin (folinic acid [FA]). PATIENTS AND METHODS: One hundred eighty-one untreated patients with advanced colorectal cancer were randomized to receive 5-FU 600 mg/m2 plus FA 300 mg/m2 on days 2 to 4 with or without DP 75 mg orally three times daily on days 1 to 5. Cycles were repeated every 3 weeks. Only patients with documented tumor progression before therapy were eligible. 5-FU pharmacokinetics using high-performance liquid chromatography (HPLC) were assessed in 11 nonrandomized patients receiving paired cycles with or without DP. RESULTS: One hundred seventy-four patients were assessable for toxicity and response. There was no significant difference in toxicity, except DP-related headache in 24% of patients. An objective response rate of 15% (one complete response [CR] and 13 partial responses [PRs]) for 5-FU/FA and 13% (two CRs and nine PRs) for 5-FU/FA/DP was observed. The dose-intensity of 5-FU delivered was significantly higher (1.09- to 1.16-fold) for the DP-containing arm. Pharmacokinetic parameters of 5-FU did not differ significantly, except for a prolonged half-life (t1/2) induced by DP. The median time to progression (P = .8) and the median survival time (11.6 months for 5-FU/FA v 9.3 months for 5-FU/FA/DP; P = .14, log-rank test) were not different between treatment arms. CONCLUSION: Orally administered DP did not improve the antineoplastic activity of 5-FU/FA in patients with advanced colorectal cancer when used at this dose and schedule. The observed increase in 5-FU dose-intensity for FU/FA/DP was not clinically relevant.

Current and future use of ICT for patient care and management in German acute hospitals--a comparison of the nursing and the hospital managers' perspectives.

OBJECTIVES: This study aimed at gaining comprehensive information on the current status of patient care and management applications used in German acute hospitals. Since the degree of ICT coverage in hospitals depends on the attitude of the key decision makers we also wanted to capture their plans and priorities and herewith try to predict future use. METHODS: We therefore conducted a nation-wide survey including all acute hospitals in Germany in which two questionnaires were mailed to each hospital, one to the nursing managers, the other to the hospital managers. RESULTS: Six hundred hospitals participated in the survey which corresponds to an overall response rate of 27.6%. Accounting (84%) was found to be the most prevalent management module. Rostering was implemented in every second hospital. For clinical applications laboratory systems ranked first (69%). Ordering systems were used in nearly every second hospital. Nineteen percent of the hospitals reported employing an electronic patient record, 7% a nursing documentation system. Ranked by their priorities ordering systems hold the first position and care planning the last position. According to their plans, hospital managers, not nursing managers, intend to introduce nursing documentation. In contrast, nursing managers favor ordering and rostering for the near future. CONCLUSIONS: There is still a preponderance of management-oriented systems in German hospitals, yet clinical applications, in particular those supporting communications, will gain ground. The future of documentation systems is unclear, unless they not only provide statistical data for the management but support the clinical process properly.

What Are Complex eHealth Innovations and How Do You Measure Them? Position Paper.

OBJECTIVES: eHealth and innovation are often regarded as synonyms - not least because eHealth technologies and applications are new to their users. This position paper challenges this view and aims at exploring the nature of eHealth innovation against the background of common definitions of innovation and facts from the biomedical and health informatics literature. A good understanding of what constitutes innovative eHealth developments allows the degree of innovation to be measured and interpreted. METHODS: To this end, relevant biomedical and health informatics literature was searched mainly in Medline and ACM digital library. This paper presents seven facts about implementing and applying new eHealth developments hereby drawing on the experience published in the literature. RESULTS: The facts are: 1. eHealth innovation is relative. 2. Advanced clinical practice is the yardstick. 3. Only used and usable eHealth technology can give birth to eHealth innovatio. 4. One new single eHealth function does not make a complex eHealth innovation. 5. eHealth innovation is more evolution than revolution. 6. eHealth innovation is often triggered behind the scenes; and 7. There is no eHealth innovation without sociocultural change. CONCLUSIONS: The main conclusion of the seven facts is that eHealth innovations have many ingredients: newness, availability, advanced clinical practice with proven outcomes, use and usability, the supporting environment, other context factors and the stakeholder perspectives. Measuring eHealth innovation is thus a complex matter. To this end we propose the development of a composite score that expresses comprehensively the nature of eHealth innovation and that breaks down its complexity into the three dimensions: i) eHealth adoption, ii) partnership with advanced clinical practice, and iii) use and usability of eHealth. In order to better understand the momentum and mechanisms behind eHealth innovation the fourth dimension, iv) eHealth supporting services and means, needs to be studied. Conceptualising appropriate measurement instruments also requires eHealth innovation to be distinguished from eHealth sophistication, performance and quality, although innovation is intertwined with these concepts. The demanding effort for defining eHealth innovation and measuring it properly seem worthwhile and promise advances in creating better systems. This paper thus intends to stimulate the necessary discussion.

Cognitive Maps to Visualise Clinical Cases in Handovers. Design, Implementation, Usability, and Attractiveness Testing.

BACKGROUND: Clinical handovers at changes of shifts are typical scenarios of time restricted and information intensive communication, which are highly cognitively demanding. The currently available applications supporting handovers typically present complex information in a textual checklist-like manner. This presentation style has been criticised for not meeting the specific user requirements. OBJECTIVES: We, therefore, aimed at developing a concept for visualising the overview of a clinical case that serves as an alternative way to checklist-like presentations in clinical handovers. We also aimed at implementing this concept in a handoverEHR in order to support the pre-handover phase, the actual handover, and the post-handover phase as well as at evaluating its usability and attractiveness. RESULTS: We developed and implemented a concept that draws on Tolman's pioneering work on cognitive maps that we designed in accordance with Gestalt principles. These maps provide a pictorial overview of a clinical case. The application to build, manipulate, and store the cognitive maps was integrated into an openEHR based handover record that extends conventional records with handover specific information. Usability (n = 28) and attractiveness (n = 26) testing with experienced clinicians resulted in good ratings for suitability for the task as well as for attractiveness and pragmatism. CONCLUSION: We propose cognitive maps to represent and visualise the clinical case in situations where there is limited time to present complex information.