Effects of Multidimensional Vs. Functional Health Literacy Educational Interventions on Standardized Patient-Nurse Interactions: A Feasibility Study

Background. Patients with limited health literacy (HL) are use fewer preventive services, access more emergent care and report poorer health outcomes than those with adequate literacy. Nurse have little consistent preparation to use HL competencies in practice, thus exacerbating risks for miscommunication and harm with patients of diverse literacy levels. Purpose. The purpose was crafting educational interventions to compare effects of two contrasting theoretical approaches on HL practice uptake including initial assessments of a HL competencies tool. Problem/Aims. For nine nurses and nursing faculty, did use of multidimensional versus functional HL educational strategies lead to changes in HL knowledge and HL- related behaviors in recorded standardized patient- nurse interactions? The four aims were to develop the Health Literacy Patient-Nurse Interaction Competencies Evaluation or HLP-NICE tool, craft two contrasting HL curricula and teaching approaches, evaluate intervention effects on HL knowledge and HL-related behaviors of participants, and then identify future research directions. Design/Theoretical Basis. A sequential mixed methods feasibility study design compared effects of the contrasting implementations on HL knowledge and HL-related behavior changes of the nine randomly assigned participants. Zarcadoolas, Pleasant & Greer’s multidimensional HL theoretical framework was integrated through HLP-NICE items and multidimensional teaching activities Procedures. Preliminary qualitative case study methodology shaped standardized patient, teacher and HLP-NICE development through individual cognitive, focus group and expert panel interviews. A quantitative two group between subjects design assessed study feasibility. HL experiences and changes in HL knowledge were based on the Health Literacy Knowledge and Experiences Survey or HLK-ES scores. Kalamazoo Essential Elements Communication Competencies-Adapted or KEECC-A and HLP-NICE ratings evaluated communication and HL-related behavior changes. Findings. HL knowledge did not increase overall for participants, nor was prior HL educational experience associated with HL knowledge gains. Increases in communication and HL-related behaviors were noted for both groups, although functional group gains were greater for KEECC-A communication ratings. Study implementation was feasible for enhancing short-term HL– related behavior changes although challenges existed in recruitment. Conclusions. Improving acceptability for participation, creating additional standardized HL training resources, enhancing educational strategies and strengthening HLP-NICE psychometric support is warranted to advance HL integration in nursing educational and clinical practice

Central mode and soft mode behavior in PbMg1/Nb2/3O3 relaxor ferroelectric

The relaxor ferroelectric PbMg1/Nb2/3O3 was investigated by means of broad-band dielectric and Fourier Transform Infrared (FTIR) transmission spectroscopy in the frequency range from 1 MHz to 15 THz at temperatures between 20 and 900 K using PMN films on infrared transparent sapphire substrates. While thin film relaxors display reduced dielectric permittivity at low frequencies, their high frequency intrinsic or lattice response is shown to be the same as single crystal/ceramic specemins. It was observed that in contrast to the results of inelastic neutron scattering, the optic soft mode was underdamped at all temperatures. On heating, the TO1 soft phonon followed the Cochran law with an extrapolated critical temperature equal to the Burns temperature of 670 K and softened down to 50 cm-1. Above 450 K the soft mode frequency leveled off and slightly increased above the Burns temperature. A central mode, describing the dynamics of polar nanoclusters appeared below the Burns temperature at frequencies near the optic soft mode and dramatically slowed down below 1 MHz on cooling below room temperature. It broadened on cooling, giving rise to frequency independent losses in microwave and lower frequency range below the freezing temperature of 200 K. In addition, a new heavily damped mode appeared in the FTIR spectra below the soft mode frequency at room temperature and below. The origin of this mode as well as the discrepancy between the soft mode damping in neutron and infrared spectra is discussed.Comment: 7 pages with 7 figures, submitted to Phys. Rev.

Maui-VIA: a user-friendly software for visual identification, alignment, correction, and quantification of gas chromatography-mass spectrometry data

A current bottleneck in GC-MS metabolomics is the processing of raw machine data into a final datamatrix that contains the quantities of identified metabolites in each sample. While there are many bioinformatics tools available to aid the initial steps of the process, their use requires both significant technical expertise and a subsequent manual validation of identifications and alignments if high data quality is desired. The manual validation is tedious and time consuming, becoming prohibitively so as sample numbers increase. We have, therefore, developed Maui-VIA, a solution based on a visual interface that allows experts and non-experts to simultaneously and quickly process, inspect, and correct large numbers of GC-MS samples. It allows for the visual inspection of identifications and alignments, facilitating a unique and, due to its visualization and keyboard shortcuts, very fast interaction with the data. Therefore, Maui-Via fills an important niche by (1) providing functionality that optimizes the component of data processing that is currently most labor intensive to save time and (2) lowering the threshold of expertise required to process GC-MS data. Maui-VIA projects are initiated with baseline-corrected raw data, peaklists, and a database of metabolite spectra and retention indices used for identification. It provides functionality for retention index calculation, a targeted library search, the visual annotation, alignment, correction interface, and metabolite quantification, as well as the export of the final datamatrix. The high quality of data produced by Maui-VIA is illustrated by its comparison to data attained manually by an expert using vendor software on a previously published dataset concerning the response of Chlamydomonas reinhardtii to salt stress. In conclusion, Maui-VIA provides the opportunity for fast, confident, and high-quality data processing validation of large numbers of GC-MS samples by non-experts

Analysing central metabolism in ultra-high resolution: at the crossroads of carbon and nitrogen

BACKGROUND: Cancer cell metabolism can be characterised by adaptive metabolic alterations, which support abnormal proliferative cell growth with high energetic demand. De novo nucleotide biosynthesis is essential for providing nucleotides for RNA and DNA synthesis, and drugs targeting this biosynthetic pathway have proven to be effective anticancer therapeutics. Nevertheless, cancers are often able to circumvent chemotherapeutic interventions and become therapy resistant. Our understanding of the changing metabolic profile of the cancer cell and the mode of action of therapeutics is dependent on technological advances in biochemical analysis. SCOPE OF REVIEW: This review begins with information about carbon- and nitrogen-donating pathways to build purine and pyrimidine moieties in the course of nucleotide biosynthesis. We discuss the application of stable isotope resolved metabolomics to investigate the dynamics of cancer cell metabolism and outline the benefits of high-resolution accurate mass spectrometry, which enables multiple tracer studies. CONCLUSION: With the technological advances in mass spectrometry that allow for the analysis of the metabolome in high resolution, the application of stable isotope resolved metabolomics has become an important technique in the investigation of biological processes. The literature in the area of isotope labelling is dominated by (13)C tracer studies. Metabolic pathways have to be considered as complex interconnected networks and should be investigated as such. Moving forward to simultaneous tracing of different stable isotopes will help elucidate the interplay between carbon and nitrogen flow and the dynamics of de novo nucleotide biosynthesis within the cell

Decoding the dynamics of cellular metabolism and the action of 3-bromopyruvate and 2-deoxyglucose using pulsed stable isotope-resolved metabolomics

BACKGROUND: Cellular metabolism is highly dynamic and continuously adjusts to the physiological program of the cell. The regulation of metabolism appears at all biological levels: (post-) transcriptional, (post-) translational, and allosteric. This regulatory information is expressed in the metabolome, but in a complex manner. To decode such complex information, new methods are needed in order to facilitate dynamic metabolic characterization at high resolution. RESULTS: Here, we describe pulsed stable isotope-resolved metabolomics (pSIRM) as a tool for the dynamic metabolic characterization of cellular metabolism. We have adapted gas chromatography-coupled mass spectrometric methods for metabolomic profiling and stable isotope-resolved metabolomics. In addition, we have improved robustness and reproducibility and implemented a strategy for the absolute quantification of metabolites. CONCLUSIONS: By way of examples, we have applied this methodology to characterize central carbon metabolism of a panel of cancer cell lines and to determine the mode of metabolic inhibition of glycolytic inhibitors in times ranging from minutes to hours. Using pSIRM, we observed that 2-deoxyglucose is a metabolic inhibitor, but does not directly act on the glycolytic cascade

Selective transport of neurotransmitters and modulators by distinct volume-regulated LRRC8 anion channels

In response to swelling, mammalian cells release chloride and organic osmolytes through VRAC volume-regulated anion channels. VRACs are heteromers of LRRC8A and other LRRC8 isoforms (B-E) which are co-expressed in HEK293 and most other cells. The spectrum of VRAC substrates and its dependence on particular LRRC8 isoforms remains largely unknown. We show that besides the osmolytes taurine and myo-inositol, LRRC8 channels transport the neurotransmitters glutamate, aspartate and GABA and the co-activator D-serine. HEK293 cells engineered to express defined subsets of LRRC8 isoforms were used to elucidate the subunit-dependence of transport. Whereas LRRC8D was crucial for the translocation of overall neutral compounds like myo-inositol, taurine and GABA and sustained the transport of positively charged lysine, flux of negatively charged aspartate was equally well supported by LRRC8E. Disruption of LRRC8B or LRRC8C failed to decrease transport rates of all investigated substrates, but their inclusion into LRRC8 heteromers influenced VRAC's substrate preference. This suggested that individual VRACs can contain three or more different LRRC8 subunits, a conclusion confirmed by sequential co-immunoprecipitations. Our work suggests a composition-dependent role of VRACs in extracellular signal transduction

Magnetothermal Conductivity of Highly Oriented Pyrolytic Graphite in the Quantum Limit

We report on the magnetic field (0T$\le B \le 9$T) dependence of the longitudinal thermal conductivity $\kappa(T,B)$ of highly oriented pyrolytic graphite in the temperature range 5 K $\le T\le$ 20 K for fields parallel to the $c-$axis. We show that $\kappa(T,B)$ shows large oscillations in the high-field region (B > 2 T) where clear signs of the Quantum-Hall effect are observed in the Hall resistance. With the measured longitudinal electrical resistivity we show that the Wiedemann-Franz law is violated in the high-field regime.Comment: 4 Figures, to be published in Physical Review B (2003

Proteome dynamics and early salt stress response of the photosynthetic organism Chlamydomonas reinhardtii

BACKGROUND: The cellular proteome and metabolome are underlying dynamic regulation allowing rapid adaptation to changes in the environment. System-wide analysis of these dynamics will provide novel insights into mechanisms of stress adaptation for higher photosynthetic organisms. We applied pulsed-SILAC labeling to a photosynthetic organism for the first time and we established a method to study proteome dynamics in the green alga chlamydomonas reinhardtii, an emerging model system for plant biology. In addition, we combined the analysis of protein synthesis with metabolic profiling to study the dynamic changes of metabolism and proteome turnover under salt stress conditions. RESULTS: To study de novo protein synthesis an arginine auxotroph Chlamydomonas strain was cultivated in presence of stable isotope-labeled arginine for 24 hours. From the time course experiment in 3 salt concentrations we could identify more than 2500 proteins and their H/L ratio in at least one experimental condition; for 998 proteins at least 3 ratio counts were detected in the 24 h time point (0 mM NaCl). After fractionation we could identify 3115 proteins and for 1765 of them we determined their de novo synthesis rate. Consistently with previous findings we showed that RuBisCO is among the most prominent proteins in the cell; and similar abundance and turnover for the small and large RuBisCO subunit could be calculated. The D1 protein was identified among proteins with a high synthesis rates. A global median half-life of 45 h was calculated for Chlamydomonas proteins under the chosen conditions. CONCLUSION: To investigate the temporal co-regulation of the proteome and metabolome, we applied salt stress to chlamydomonas and studied the time dependent regulation of protein expression and changes in the metabolome. The main metabolic response to salt stress was observed within the amino acid metabolism. In particular, proline was up-regulated manifold and according to that an increased carbon flow within the proline biosynthetic pathway could be measured. In parallel the analysis of abundance and de novo synthesis of the corresponding enzymes revealed that metabolic rearrangements precede adjustments of protein abundance