Vortex fluidic regulated phospholipid equilibria involving liposomes down to sub-micelle size assemblies.

Conventional channel-based microfluidic platforms have gained prominence in controlling the bottom-up formation of phospholipid based nanostructures including liposomes. However, there are challenges in the production of liposomes from rapidly scalable processes. These have been overcome using a vortex fluidic device (VFD), which is a thin film microfluidic platform rather than channel-based, affording ∼110 nm diameter liposomes. The high yielding and high throughput continuous flow process has a 45° tilted rapidly rotating glass tube with an inner hydrophobic surface. Processing is also possible in the confined mode of operation which is effective for labelling pre-VFD-prepared liposomes with fluorophore tags for subsequent mechanistic studies on the fate of liposomes under shear stress in the VFD. In situ small-angle neutron scattering (SANS) established the co-existence of liposomes ∼110 nm with small rafts, micelles, distorted micelles, or sub-micelle size assemblies of phospholipid, for increasing rotation speeds. The equilibria between these smaller entities and ∼110 nm liposomes for a specific rotational speed of the tube is consistent with the spatial arrangement and dimensionality of topological fluid flow regimes in the VFD. The prevalence for the formation of ∼110 nm diameter liposomes establishes that this is typically the most stable structure from the bottom-up self-assembly of the phospholipid and is in accord with dimensions of exosomes.

Vortex fluidic induced mass transfer across immiscible phases.

Mixing immiscible liquids typically requires the use of auxiliary substances including phase transfer catalysts, microgels, surfactants, complex polymers and nano-particles and/or micromixers. Centrifugally separated immiscible liquids of different densities in a 45° tilted rotating tube offer scope for avoiding their use. Micron to submicron size topological flow regimes in the thin films induce high inter-phase mass transfer depending on the nature of the two liquids. A hemispherical base tube creates a Coriolis force as a 'spinning top' (ST) topological fluid flow in the less dense liquid which penetrates the denser layer of liquid, delivering liquid from the upper layer through the lower layer to the surface of the tube with the thickness of the layers determined using neutron imaging. Similarly, double helical (DH) topological flow in the less dense liquid, arising from Faraday wave eddy currents twisted by Coriolis forces, impact through the less dense liquid onto the surface of the tube. The lateral dimensions of these topological flows have been determined using 'molecular drilling' impacting on a thin layer of polysulfone on the surface of the tube and self-assembly of nanoparticles at the interface of the two liquids. At high rotation speeds, DH flow also occurs in the denser layer, with a critical rotational speed reached resulting in rapid phase demixing of preformed emulsions of two immiscible liquids. ST flow is perturbed relative to double helical flow by changing the shape of the base of the tube while maintaining high mass transfer between phases as demonstrated by circumventing the need for phase transfer catalysts. The findings presented here have implications for overcoming mass transfer limitations at interfaces of liquids, and provide new methods for extractions and separation science, and avoiding the formation of emulsions.

Non-self mutation: double-stranded RNA elicits antiviral pathogenic response in a Drosophila model of expanded CAG repeat neurodegenerative diseases.

Inflammation is activated prior to symptoms in neurodegenerative diseases, providing a plausible pathogenic mechanism. Indeed, genetic and pharmacological ablation studies in animal models of several neurodegenerative diseases demonstrate that inflammation is required for pathology. However, while there is growing evidence that inflammation-mediated pathology may be the common mechanism underlying neurodegenerative diseases, including those due to dominantly inherited expanded repeats, the proximal causal agent is unknown. Expanded CAG.CUG repeat double-stranded RNA causes inflammation-mediated pathology when expressed in Drosophila. Repeat dsRNA is recognized by Dicer-2 as a foreign or 'non-self' molecule triggering both antiviral RNA and RNAi pathways. Neither of the RNAi pathway cofactors R2D2 nor loquacious are necessary, indicating antiviral RNA activation. RNA modification enables avoidance of recognition as 'non-self' by the innate inflammatory surveillance system. Human ADAR1 edits RNA conferring 'self' status and when co-expressed with expanded CAG.CUG dsRNA in Drosophila the pathology is lost. Cricket Paralysis Virus protein CrPV-1A is a known antagonist of Argonaute-2 in Drosophila antiviral defense. CrPV-1A co-expression also rescues pathogenesis, confirming anti-viral-RNA response. Repeat expansion mutation therefore confers 'non-self' recognition of endogenous RNA, thereby providing a proximal, autoinflammatory trigger for expanded repeat neurodegenerative diseases.

Inverted vortex fluidic exfoliation and scrolling of hexagonal-boron nitride.

Exfoliation or scrolling of hexagonal boron nitride (h-BN) occurs in a vortex fluidic device (VFD) operating under continuous flow, with a tilt angle of -45° relative to the horizontal position. This new VFD processing strategy is effective in avoiding the build-up of material that occurs when the device is operated using the conventional tilt angle of +45°, where the h-BN precursor and scrolls are centrifugally held against the wall of the tube. At a tilt angle of -45° the downward flow aided by gravity facilitates material exiting the tube with the exfoliation of h-BN and formation of h-BN scrolls then optimized by systematically varying the other VFD operating parameters, including flow rate and rotational speed, along with concentration of h-BN and the choice of solvent. Water was the most effective solvent, which enhances the green chemistry metrics of the processing.

Vortex fluidic mediated transformation of graphite into highly conducting graphene scrolls.

Two-dimensional graphene has remarkable properties that are revolutionary in many applications. Scrolling monolayer graphene with precise tunability would create further potential for niche applications but this has proved challenging. We have now established the ability to fabricate monolayer graphene scrolls in high yield directly from graphite flakes under non-equilibrium conditions at room temperature in dynamic thin films of liquid. Using conductive atomic force microscopy we demonstrate that the graphene scrolls form highly conducting electrical contacts to highly oriented pyrolytic graphite (HOPG). These highly conducting graphite-graphene contacts are attractive for the fabrication of interconnects in microcircuits and align with the increasing interest in building all sp2-carbon circuits. Above a temperature of 450 °C the scrolls unravel into buckled graphene sheets, and this process is understood on a theoretical basis. These findings augur well for new applications, in particular for incorporating the scrolls into miniaturized electronic devices.

Vortex Fluidic Mediated Synthesis of Macroporous Bovine Serum Albumin-Based Microspheres.

Macroporous bovine serum albumin (BSA) nanoparticles with controllable diameter were readily fabricated in a rapidly rotating angled glass tube in a vortex fluidic device (VFD). Systematically varying the rotational speed and the ratio of BSA, ethanol, and glutaraldehyde led to conditions for generating ca. 600 nm diameter macroporous particles that have intrinsic fluorescence emission at 520 nm when excited at 490 nm. The presence of the macropores increased the absorption efficiency of rhodamine B with potential applications for drug delivery purpose, compared with BSA nanoparticles having surfaces devoid of pores. Further control over the size of BSA nanoparticles occurred in the presence of C-phycocyanin protein during the VFD processing, along with control of their shape, from spheres to pockets, as established in exploring the parameter space of the microfluidic device.

Controlling the growth of fullerene C60 cones under continuous flow.

Micromixing of an o-xylene solution of C60 with N-N-dimethylformamide (DMF) at room temperature under continuous flow in a vortex fluidic device (VFD) results in the formation of symmetrical right cones in high yield with diameters 0.5 to 2.5 µm, pitch angle 25° to 55° and wall thickness 120 to 310 nm. Their formation is in the absence of surfactants and any other reagents, and is scalable. The cones are formed at specific operating parameters of the VFD, including rotational speed, flow rate and concentration, and varying these results in other structures such as grooved fractals. Other aromatic solvents in place of o-xylene results in the formation of rods, spicules and prisms, respectively for m-xylene, p-xylene and mesitylene.

Readability of patient information pamphlets in urogynecology.

OBJECTIVE: The purpose of this study was to determine the reading level of frequently used patient information pamphlets and documents in the field of urogynecology. METHODS: Urogynecology pamphlets were identified from a variety of sources. Readability was determined using 4 different accepted formulas: the Flesch-Kincaid Grade Level, the simple measure of gobbledygook Index, the Coleman-Liau Index, and the Gunning Fog index. The scores were calculated using an online calculator (http://www.readability-score.com). Descriptive statistics were used for analysis. The average of the 4 scores was calculated for each pamphlet. Subsequently, Z-scores were used to standardize the averages between the reading scales. RESULTS: Of the 40 documents reviewed, only a single pamphlet met the National Institutes of Health-recommended reading level. This document was developed by the American Urological Association and was specifically designated as a "Low-Literacy Brochure." The remainder of the patient education pamphlets, from both industry-sponsored and academic-sponsored sources, consistently rated above the recommended reading level for maximum comprehension. CONCLUSIONS: The majority of patient education pamphlets, from both industry-sponsored and academic-sponsored sources, are above the reading level recommended by the National Institutes of Health for maximum patient comprehension. Future work should be done to improve the educational resources available to patients by simplifying the verbiage in these documents.

Factors associated with the effectiveness of continuing education in long-term care.

PURPOSE: This article examines factors within the long-term-care work environment that impact the effectiveness of continuing education. DESIGN AND METHODS: In Study 1, focus group interviews were conducted with staff and management from urban and rural long-term-care facilities in southwestern Ontario to identify their perceptions of the workplace factors that affect transfer of learning into practice. Thirty-five people were interviewed across six focus groups. In Study 2, a Delphi technique was used to refine our list of factors. Consensus was achieved in two survey rounds involving 30 and 27 participants, respectively. RESULTS: Management support was identified as the most important factor impacting the effectiveness of continuing education. Other factors included resources (staff, funding, space) and the need for ongoing expert support. IMPLICATIONS: Organizational support is necessary for continuing education programs to be effective and ongoing expert support is needed to enable and reinforce learning.