Price-Performance Ratio Analysis Of Enteral Vitamin K Formulations.

BACKGROUND: Vitamin K compounded oral solution costs significantly less on a per-milligram basis compared with tablet formulations. Current literature has shown that international normalized ratio (INR) lowering in the reversal of vitamin K antagonists (VKAs) occurs to a similar degree when using vitamin K oral solution compared with tablet formulations. OBJECTIVE: To compare drug spending on vitamin K oral solution versus tablet using a price-performance ratio (PPR). METHODS: A retrospective chart review was conducted at a tertiary care academic medical center to compare INR reversal of VKA-induced coagulopathy on a price basis for vitamin K oral solution versus tablet. The price of the oral solution accounted for supplies and labor. A PPR was calculated based upon the following formula: vitamin K formulation cost divided by the hourly percent change in INR following vitamin K administration. RESULTS: The PPR for vitamin K tablets was 27.0 compared with 5.8 for the oral solution (P = 0.006). CONCLUSIONS: Utilization of vitamin K solution resulted in a significantly reduced cost per INR-lowering effect relative to commercially available tablets. Utilization of a compounded vitamin K solution represents an enticing means of cost-savings in the hospital setting.

Acute Hepatocellular Jaundice After Dofetilide Initiation: A Case Report.

Dofetilide's hepatotoxicity is not well described. In this case report, we describe acute hepatocellular jaundice related to dofetilide use in a 33-year-old male being treated for atrial fibrillation. Both viral and ischemic causes of hepatocellular damage were ruled out as unlikely in this case. This case report outlines a rare yet probable report of idiosyncratic dofetilide-induced liver injury.

Genome-wide RNAi screen identifies broadly-acting host factors that inhibit arbovirus infection.

Vector-borne viruses are an important class of emerging and re-emerging pathogens; thus, an improved understanding of the cellular factors that modulate infection in their respective vertebrate and insect hosts may aid control efforts. In particular, cell-intrinsic antiviral pathways restrict vector-borne viruses including the type I interferon response in vertebrates and the RNA interference (RNAi) pathway in insects. However, it is likely that additional cell-intrinsic mechanisms exist to limit these viruses. Since insects rely on innate immune mechanisms to inhibit virus infections, we used Drosophila as a model insect to identify cellular factors that restrict West Nile virus (WNV), a flavivirus with a broad and expanding geographical host range. Our genome-wide RNAi screen identified 50 genes that inhibited WNV infection. Further screening revealed that 17 of these genes were antiviral against additional flaviviruses, and seven of these were antiviral against other vector-borne viruses, expanding our knowledge of invertebrate cell-intrinsic immunity. Investigation of two newly identified factors that restrict diverse viruses, dXPO1 and dRUVBL1, in the Tip60 complex, demonstrated they contributed to antiviral defense at the organismal level in adult flies, in mosquito cells, and in mammalian cells. These data suggest the existence of broadly acting and functionally conserved antiviral genes and pathways that restrict virus infections in evolutionarily divergent hosts.

Quantitative multi-energy micro-CT: A simulation and phantom study for simultaneous imaging of four different contrast materials using an energy integrating detector.

Emerging from the development of single-energy Computed Tomography (CT) and Dual-Energy Computed Tomography, Multi-Energy Computed Tomography (MECT) is a promising tool allowing advanced material and tissue decomposition and thereby enabling the use of multiple contrast materials in preclinical research. The scope of this work was to evaluate whether a usual preclinical micro-CT system is applicable for the decomposition of different materials using MECT together with a matrix-inversion method and how different changes of the measurement-environment affect the results. A matrix-inversion based algorithm to differentiate up to five materials (iodine, iron, barium, gadolinium, residual material) by applying four different acceleration voltages/energy levels was established. We carried out simulations using different ratios and concentrations (given in fractions of volume units, VU) of the four different materials (plus residual material) at different noise-levels for 30 keV, 40 keV, 50 keV, 60 keV, 80 keV and 100 keV (monochromatic). Our simulation results were then confirmed by using region of interest-based measurements in a phantom-study at corresponding acceleration voltages. Therefore, different mixtures of contrast materials were scanned using a micro-CT. Voxel wise evaluation of the phantom imaging data was conducted to confirm its usability for future imaging applications and to estimate the influence of varying noise-levels, scattering, artifacts and concentrations. The analysis of our simulations showed the smallest deviation of 0.01 (0.003-0.15) VU between given and calculated concentrations of the different contrast materials when using an energy-combination of 30 keV, 40 keV, 50 keV and 100 keV for MECT. Subsequent MECT phantom measurements, however, revealed a combination of acceleration voltages of 30 kV, 40 kV, 60 kV and 100 kV as most effective for performing material decomposition with a deviation of 0.28 (0-1.07) mg/ml. The feasibility of our voxelwise analyses using the proposed algorithm was then confirmed by the generation of phantom parameter-maps that matched the known contrast material concentrations. The results were mostly influenced by the noise-level and the concentrations used in the phantoms. MECT using a standard micro-CT combined with a matrix inversion method is feasible at four different imaging energies and allows the differentiation of mixtures of up to four contrast materials plus an additional residual material.

Mapping precursor-binding site on TatC subunit of twin arginine-specific protein translocase by site-specific photo cross-linking.

A number of secreted precursor proteins of bacteria, archaea, and plant chloroplasts stand out by a conserved twin arginine-containing sequence motif in their signal peptides. Many of these precursor proteins are secreted in a completely folded conformation by specific twin arginine translocation (Tat) machineries. Tat machineries are high molecular mass complexes consisting of two types of membrane proteins, a hexahelical TatC protein, and usually one or two single-spanning membrane proteins, called TatA and TatB. TatC has previously been shown to be involved in the recognition of twin arginine signal peptides. We have performed an extensive site-specific cross-linking analysis of the Escherichia coli TatC protein under resting and translocating conditions. This strategy allowed us to map the recognition site for twin arginine signal peptides to the cytosolic N-terminal region and first cytosolic loop of TatC. In addition, discrete contact sites between TatC, TatB, and TatA were revealed. We discuss a tentative model of how a twin arginine signal sequence might be accommodated in the Tat translocase.

Analysis of transverse Anderson localization in refractive index structures with customized random potential.

We present a method to demonstrate Anderson localization in an optically induced randomized potential. By usage of computer controlled spatial light modulators, we are able to implement fully randomized nondiffracting beams of variable structural size in order to control the modulation length (photonic grain size) as well as the depth (disorder strength) of a random potential induced in a photorefractive crystal. In particular, we quantitatively analyze the localization length of light depending on these two parameters and find that they are crucial influencing factors on the propagation behavior leading to variably strong localization. Thus, we corroborate that transverse light localization in a random refractive index landscape strongly depends on the character of the potential, allowing for a flexible regulation of the localization strength by adapting the optical induction configuration.

Early contacts between substrate proteins and TatA translocase component in twin-arginine translocation.

Twin-arginine translocation (Tat) is a unique protein transport pathway in bacteria, archaea, and plastids. It mediates the transmembrane transport of fully folded proteins, which harbor a consensus twin-arginine motif in their signal sequences. In Gram-negative bacteria and plant chloroplasts, three membrane proteins, named TatA, TatB, and TatC, are required to enable Tat translocation. Available data suggest that TatA assembles into oligomeric pore-like structures that might function as the protein conduit across the lipid bilayer. Using site-specific photo-cross-linking, we have investigated the molecular environment of TatA under resting and translocating conditions. We find that monomeric TatA is an early interacting partner of functionally targeted Tat substrates. This interaction with TatA likely precedes translocation of Tat substrates and is influenced by the proton-motive force. It strictly depends on the presence of TatB and TatC, the latter of which is shown to make contacts with the transmembrane helix of TatA.

Multiplexing complex two-dimensional photonic superlattices.

We introduce a universal method to optically induce multiperiodic photonic complex superstructures bearing two-dimensional (2D) refractive index modulations over several centimeters of elongation. These superstructures result from the accomplished superposition of 2D fundamental periodic structures. To find the specific sets of fundamentals, we combine particular spatial frequencies of the respective Fourier series expansions, which enables us to use nondiffracting beams in the experiment showing periodic 2D intensity modulation in order to successively develop the desired multiperiodic structures. We present the generation of 2D photonic staircase, hexagonal wire mesh and ratchet structures, whose succeeded generation is confirmed by phase resolving methods using digital-holographic techniques to detect the induced refractive index pattern.

Photonic ratchet superlattices by optical multiplexing.

We present a method based on incremental holographic multiplexing to create a refractive index ratchet distribution into a photorefractive crystal as an example for the generation principle of such complex multiperiodic lattices. The implemented technique follows a finite optical series expansion of the desired index modulation. To analyze the induced lattice, we determine the phase retardation of a probe beam at the back face of the crystal by digital holography analysis. Our result depicts a first example to optically explore the fascinating phenomena of ratchet resembling systems.

Embedding defect sites into hexagonal nondiffracting wave fields.

We present a highly purposive technique to optically induce periodic photonic lattices enriched with a negative defect site by using a properly designed nondiffracting (ND) beam. As the interference of two or more ND beams with adequate mutual spatial frequency relations in turn reproduces an ND beam, we adeptly superpose a hexagonal and a Bessel beam to create the ND defect beam of demand. The presented wavelength-independent technique is of utmost universality in terms of structural scalability and does not make any specific requirements to the photosensitive medium. In addition, the technique is easily transferable to all pattern-forming holographic methods in general and its application is highly appropriate, e.g., in the fields of particle as well as atom trapping.

Measurement of arbitrary scan patterns for correction of imaging distortions in laser scanning microscopy.

Laser scanning microscopy requires beam steering through relay and focusing optics at sub-micron precision. In light-weight mobile systems, such as head mounted multiphoton microscopes, distortion and imaging plane curvature management is unpractical due to the complexity of required optic compensation. Thus, the resulting scan pattern limits anatomical fidelity and decreases analysis algorithm efficiency. Here, we present a technique that reconstructs the three-dimensional scan path only requiring translation of a simple fluorescent test probe. Our method is applicable to any type of scanning instrument with sectioning capabilities without prior assumptions regarding origin of imaging deviations. Further, we demonstrate that the obtained scan pattern allows analysis of these errors, and allows to restore anatomical accuracy relevant for complementary methods such as motion correction, further enhancing spatial registration and feature extraction.

Systematic approach to complex periodic vortex and helix lattices.

We present a general comprehensive framework for the description of symmetries of complex light fields, facilitating the construction of sophisticated periodic structures carrying phase dislocations. In particular, we demonstrate the derivation of all three fundamental two-dimensional vortex lattices based on vortices of triangular, quadratic, and hexagonal shape, respectively. We show that these patterns represent the foundation of complex three-dimensional lattices with outstanding helical intensity distributions which suggest valuable applications in holographic lithography. This systematic approach is substantiated by a comparative study of corresponding numerically calculated and experimentally realized complex intensity and phase distributions.

Reconstructing Attitudes towards Work from Home during COVID-19: A Survey of South Korean Managers.

This article explores how after almost two years of government-imposed work from home (WFH) for the purpose of curbing the spread of COVID-19, South Korean managers' general attitudes towards WFH may have been reconstructed and if this change influenced their expectations that WFH would persist for the long run. Before COVID-19, WFH was rare, and the country was well known for having one of the most hierarchical and rigid work cultures, with long hours at the office being the norm. The results of this study are based on survey responses from 229 South Korean managers and executives. Using means comparisons and hierarchical linear multiple regression models to answer three research questions, the present study evaluates theorized predictors of WFH take-up, general attitudes towards WFH, and the likelihood that WFH will continue post-COVID-19. The results indicate that forced WFH adoption during COVID-19 had statistically significant positive effects on the attitudes of South Korean managers and their intentions to continue working from home in the future. This study has practical implications for companies and governments that are interested in taking advantage of WFH and implementing it more permanently. It provides interesting findings on how managers from a country with minimal WFH prior to COVID-19 perceive the benefits of WFH and how they respond to its mandated adoption.

BioInspired, BioDriven, BioMADE: The U.S. Bioindustrial Manufacturing and Design Ecosystem as a driver of the 4th Industrial Revolution.

When we think about the potential that biology has to offer, the U.S. Bioindustrial Manufacturing and Design Ecosystem or BioMADE slogan could read, 'we don't make the products you buy, we make the products that you buy, with biology'. BioMADE is a non-profit public-private partnership between the U.S. government and the private sector to leverage the work already accomplished in industry, accelerate the bioindustrial revolution, and create a stronger, resilient, sustainable, and environmentally friendly manufacturing ecosystem. BioMADE endeavours to be a leader, an enabler, and a beacon for how contemporary manufacturing can be transformed with biology to mature the bioindustrial manufacturing ecosystem. The institute cannot go this path alone to solve all the problems and coalesce the existing ecosystem. It requires determination and commitment from the private sector, academia, non-profit research institutions and national laboratories; the entire community. Many technical challenges and adoption hurdles still loom high. Industry and consumers need to start accepting that engineering biology has a critical role to play in the manufacturing of many of the materials and products we use today.

Compensation of spatial inhomogeneities in a cavity soliton laser using a spatial light modulator.

Dissipative solitons are self-localized states which can exist anywhere in a system with translational symmetry, but in real systems this translational symmetry is usually broken due to parasitic inhomogeneities leading to spatial disorder, pinning the soliton positions. We discuss the effects of semiconductor growth induced spatial disorder on the operation of a cavity soliton laser based on a vertical-cavity surface-emitting laser (VCSEL). We show that a refractive index variation induced by an external, suitably spatially modulated laser beam can be used to counteract the inherent disorder. In particular, it is demonstrated experimentally that the threshold of one cavity soliton can be lowered without influencing other cavity solitons making two solitons simultaneously bistable which were not without control. This proof of principle paves the way to achieve full control of large numbers of cavity solitons at the same time.

Anisotropy-controlled topological stability of discrete vortex solitons in optically induced photonic lattices.

We realize an experimental control over the topological stability of three-lobe discrete vortex solitons by modifying the symmetry of a hexagonal photonic lattice optically induced in a photorefractive crystal. By continuously deforming the lattice wave in one transverse direction, we manipulate the coupling between lattice sites and induce or inhibit the reversal of soliton vorticity.

Associations between Gender, Alcohol Use and Negative Consequences among Korean College Students: A National Study.

This study examines Korean college students' rates and the severity of various negative consequences resulting from the frequency and quantity of alcohol consumption and the unique factors that are affecting this problem in the Korean context in comparison to other countries. It assesses how much gender, age and other associated respondent characteristics mediate alcohol use and the resulting negative consequences among the population. A stratified representative sample of 4803 valid student respondents attending 82 colleges participated in the alcohol consumption survey, of which 95% reported drinking in past 12 months. Drinking is measured by the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) screening tool. Based on this test, composite scores for each participant were computed and students were grouped into four risk groups: (a) nondrinkers, (b) light drinkers, (c) moderate drinkers and (d) heavy drinkers. Outcome measures include 21 validated items evaluating self-reported alcohol-related negative consequences. Rates of negative consequences are reported for each drinking risk group stratified by gender. Descriptive statistics, stepwise regression, multivariate linear regression and MANOVA tests were used to analyze the data. The study found that female respondents in the sample who consumed alcohol in the past 12 months drank 11.5 percent less than males (AUDIT-C score µ = 6.0 and 6.7, respectively), and there was a greater proportion of females (5.1 percent) who were nondrinkers than males (4.6 percent). Yet, when females drank, they experienced 11.8 percent more negative consequences on average than males (µ = 1.9 and 1.7, respectively). The study attempts to explain this apparent contradiction. The self-reported rates for many individual negative consequences also varied discernibly by gender. The study concludes with suggestions for how alcohol prevention on Korean college campuses would benefit from targeting females and males differently.

Remodeling of endothelial adherens junctions by Kaposi's sarcoma-associated herpesvirus.

Vascular endothelial cadherin (VE-cadherin) connects neighboring endothelial cells (ECs) via interendothelial junctions and regulates EC proliferation and adhesion during vasculogenesis and angiogenesis. The cytoplasmic domain of VE-cadherin recruits alpha- and beta-catenins and gamma-catenin, which interact with the actin cytoskeleton, thus modulating cell morphology. Dysregulation of the adherens junction/cytoskeletal axis is a hallmark of invasive tumors. We now demonstrate that the transmembrane ubiquitin ligase K5/MIR-2 of Kaposi's sarcoma-associated herpesvirus targets VE-cadherin for ubiquitin-mediated destruction, thus disturbing EC adhesion. In contrast, N-cadherin levels in K5-expressing cells were increased compared to those in control cells. Steady-state levels of alpha- and beta-catenins and gamma-catenin in K5-expressing ECs were drastically reduced due to proteasomal destruction. Moreover, the actin cytoskeleton was rearranged, resulting in the dysregulation of EC barrier function as measured by electric cell-substrate impedance sensing. Our data represent the first example of a viral protein targeting adherens junction proteins and suggest that K5 contributes to EC proliferation, vascular leakage, and the reprogramming of the EC proteome during Kaposi's sarcoma tumorigenesis.

Three-dimensional optically induced reconfigurable photorefractive nonlinear photonic lattices.

We experimentally investigate the formation of reconfigurable three-dimensional (3D) nonlinear photonic lattices in an externally biased cerium doped strontium barium niobate photorefractive crystal by a spatial light modulator-assisted versatile simplified single step optical induction approach. The analysis of the generated 3D nonlinear photonic lattices by plane wave guiding, momentum space spectroscopy, and far field diffraction pattern imaging is presented, which points to the embedded potential of these 3D structures as reconfigurable platform to investigate advanced nonlinear light-matter interaction in periodic structures.

Case study: weight of evidence evaluation of the human health relevance of thiamethoxam-related mouse liver tumors.

Thiamethoxam (CGA293343; 3-(2-chloro-thiazol-5-ylmethyl)-5-methyl-[1,3,5]oxadiazinan-4-ylidene-N-nitroamine) was shown to increase the incidence of mouse liver tumors in an 18-month study; however, thiamethoxam was not hepatocarcinogenic in rats. Thiamethoxam is not genotoxic, and, given the late life generation of mouse liver tumors, suggests a time-related progression of key hepatic events that leads to the tumors. These key events were identified in a series of studies of up to 50 weeks that showed the time-dependent evolution of relatively mild liver dysfunction within 10 weeks of dosing, followed by frank signs of hepatotoxicity after 20 weeks, leading to cellular attrition and regenerative hyperplasia. A metabolite, CGA330050, was identified as generating the mild hepatic toxicity, and another metabolite, CGA265307, exacerbated the initial toxicity by inhibiting inducible nitric oxide synthase. This combination of metabolite-generated hepatotoxicity and increase in cell replication rates is postulated as the mode of action for thiamethoxam-related mouse liver tumors. The relevance of these mouse-specific tumors to human health was assessed by using the framework and decision logic developed by ILSI-RSI. The postulated mode of action was tested against the Hill criteria and found to fulfill the comprehensive requirements of strength, consistency, specificity, temporality, dose-response, and the collective criteria of being a plausible mode of action that fits with known and similar modes of action. Whereas the postulated mode of action could theoretically operate in human liver, quantitation of the key metabolites in vivo and in vitro showed that mice, but not rats or humans, generate sufficient amounts of these metabolites to initiate the hepatic toxicity and consequent tumors. Indeed, rats fed 3000 ppm thiamethoxam for a lifetime did not develop hepatotoxicity or tumors. In conclusion, the coherence and extent of the database clearly demonstrates the mode of action for mouse liver tumorigenesis and also allows for the conclusion that thiamethoxam does not pose a carcinogenic risk to humans.