Highly Sensitive Composite Foam Bodily Sensors Based on the g-Putty Ink Soaking Procedure.

Electrically conductive composite materials are highlighted as a potential tech path toward future flexible devices for wearable health technologies. To be commercially viable, these materials must not only be mechanically soft, highly sensitive to deformation, and report a sustainable signal but also utilize manufacturing methods that facilitate large-scale production. An ideal candidate for these envisioned technologies is the viscous, electromechanically sensitive composite material g-putty. Inks based on g-putty here are shown to transform a commercial polymer foam into a sensitive strain sensing material through a simple, scalable soaking procedure. Foam composites reported here have sensitives as high as ∼20 in terms of compressive strain and ∼0.4 kPa-1 with respect to applied compressive stress; both values being comparable to the parent g-putty material. Through g-putty's self-adhering nature, the foams used acted as an elastic scaffolding that aided in overcoming many of the hysteresis effects associated with g-putty without the need for further encapsulation methods. From this, these composite foams were demonstrated to have a sustainable signal that allowed for effective impact and vital sign sensing.

Printable G-Putty for Frequency- and Rate-Independent, High-Performance Strain Sensors.

While nanocomposite electromechanical sensors are expected to display reasonable conductivity and high sensitivity, little consideration is given to eliminating hysteresis and strain rate/frequency dependence from their response. For example, while G-putty, a composite of graphene and polysiloxane, has very high electromechanical sensitivity, its extreme viscoelasticity renders it completely unsuitable for real sensors due to hysteretic and rate-/frequency-dependent effects. Here it is shown that G-putty can be converted to an ink and printed into patterned thin films on elastic substrates. A partial graphene-polymer phase segregation during printing increases the thin-film conductivity by ×106 compared to bulk, while the mechanical effects of the substrate largely suppress hysteresis and completely remove strain rate and frequency dependence. This allows the fabrication of practical, high-gauge-factor, wearable sensors for pulse measurements as well as patterned sensors for low-signal vibration sensing.

Dupilumab-associated ocular surface disease: presentation, management and long-term sequelae.

OBJECTIVES: To determine the presenting features of ocular surface disease in patients with atopic dermatitis (AD) treated with dupilumab at a tertiary, university hospital. To establish the need for treatment of dupilumab-associated ocular surface disease and report any long-term effects on the ocular surface. METHODS: A retrospective analysis of consecutive patients treated with dupilumab for AD between January 2017 and August 2019 was undertaken. Data were collected on demographics, incidence and type of ocular disease features, natural history and treatment. RESULTS: A total of 50% (14/28) patients developed ocular symptoms with a mean time of onset of 6.75 (±6.1) weeks from starting dupilumab. Of these, 69% (9/13) were diagnosed with conjunctivitis associated with cicatrisation in two patients and periorbital skin changes in four. Of these nine, four had prior history of atopic keratoconjunctivitis. All were treated with topical steroids; two required additional ciclosporin drops. In all, 67% (6/9) patients went on to have on-going ocular inflammation requiring maintenance drops at a mean of 16 (±6.9) months of follow-up. All patients had improvement in their AD severity; only one patient discontinued dupilumab due to ocular side effects. CONCLUSION: The rate of dupilumab-associated ocular surface disease was 32%. Periorbital skin changes and conjunctival cicatrisation were noted in association with conjunctivitis. Ocular surface disease improved on topical steroids and ciclosporin but 67% of patients needed on-going treatment. Close liaison with an ophthalmologist should be considered in those patients who develop conjunctivitis or have a past history of severe ocular surface disease.

Negative Gauge Factor Piezoresistive Composites Based on Polymers Filled with MoS2 Nanosheets.

Nanocomposite strain sensors, particularly those consisting of polymer-graphene composites, are increasingly common and are of great interest in the area of wearable sensors. In such sensors, application of strain yields an increase in resistance due to the effect of deformation on interparticle junctions. Typically, widening of interparticle separation is thought to increase the junction resistance by reducing the probability of tunnelling between conducting particles. However, an alternative approach would be to use piezoresistive fillers, where an applied strain modifies the intrinsic filler resistance and so the overall composite resistance. Such an approach would broaden sensing capabilities, as using negative piezoresistive fillers could yield strain-induced resistance reductions rather than the usual resistance increases. Here, we introduce nanocomposites based on polyethylene oxide (PEO) filled with MoS2 nanosheets. Doping of the MoS2 by the PEO yields nanocomposites which are conductive enough to act as sensors, while efficient stress transfer leads to nanosheet deformation in response to an external strain. The intrinsic negative piezoresistance of the MoS2 leads to a reduction of the composite resistance on the application of small tensile strains. However, at higher strain the resistance grows due to increases in junction resistance. MoS2-PEO composite gauge factors are approximately -25 but fall to -12 for WS2-PEO composites and roughly -2 for PEO filled with MoSe2 or WSe2. We develop a simple model, which describes all these observations. Finally, we show that these composites can be used as dynamic strain sensors.

Cyclodextrin-siRNA conjugates as versatile gene silencing agents.

Functional siRNAs (luciferase and PLK1) have been conjugated to ß-cyclodextrin and the ability of the conjugates to retain gene knockdown activity has been assessed by delivery to cancer cell lines using various formulations. Initially two formulations used complexation with polycations, namely Lipofectamine 2000 and an amphiphilic polycationic cyclodextrin. Gene knockdown results for human glioblastoma cells (U87) and prostate cancer cells (PC3, DU145) showed that conjugation to the cyclodextrin did not reduce gene silencing by the RNA. A third mode of delivery involved formation of targeted nanoparticles in which the conjugate was first complexed with adamantyl-PEG-ligands (targeting ligand RVG peptide or dianisamide) by adamantyl inclusion in the cyclodextrin cavities of the conjugates, followed by charge neutralisation with the cationic polymer chitosan. Enhanced knockdown was achieved by these ligand-targeted formulations. In summary, while this study illustrated the gene silencing efficacy of a simple cyclodextrin-siRNA conjugate it is envisaged that future studies will explore the use of conjugates with a modified cyclodextrin which would be self-delivering. Detailed data such as stability, lysosomal escape etc. will then be reported for each conjugate, since this will be appropriate for conjugates which are intended to exploit, rather than merely demonstrate, the concept. The present paper was intended to demonstrate the viability and generality of this novel concept.

Confirmation of extensive natural distribution of azaspiracids in the tissue compartments of mussels (Mytilus edulis).

Liquid chromatography multiple tandem mass spectrometry (LC-MS/MS) has been applied to demonstrate that azaspiracid (AZA1), its isomer, AZA6, and its methyl- and demethyl-analogues, AZA2 and AZA3 respectively, are distributed throughout mussel (Mytilus edulis) tissue compartments. Large differences in both the toxin content and the toxin profiles were observed in 20 individual mussels from the same batch. The toxin levels found in the hepatopancreas of mussels were, AZA1 (0.02-5.0 µg/g); AZA2 (0.12-1.9 µg/g), AZA3 (0.06-0.88 µg/g) and AZA6 (0.05-2.0 µg/g). This study also examined the toxin content in mussel tissue compartments and it was found that the gills contributed significantly to the overall level of toxins in mussels. Although polyether toxins are usually concentrated in the hepatopancreas of shellfish this is not always the situation with azaspiracids. The mean distribution of azaspiracids in mussels was; hepatopancreas (60.6%), gills (12.0%) and adductor muscle (27.4%).

Analysis of coffee bean extracts by use of ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry.

The number of flavour chemicals identified in coffee has reached over 1000 [1], [2]. Coffee is one of the world's most popular beverages [3], highly studied for its health-related properties [4], [5], [6]. Studies on coffee associated with human health have focused on the negative aspects, such as the toxicity of caffeine [7], [8]. Complex chemistry happens during coffee roasting and according to the literature, a number of compounds have been detected and quantified in coffee beans samples by UPLC-Q-TOF/MS [9], [10], [11], [12]. The following method offers a simple approach for the qualitative and quantitative analysis of coffee bean extracts using a Waters Acquity G2 UPLC-Q-TOF/MS instrument adapted from the method by Kenny et al., [12]. The following modifications were made:•The method by Kenny et al. was developed on a triple quadrupole mass spectrometer, the below method was developed on a Q-TOF MS.•A combination of utilising both base peak index and mass extraction at 0.05 Da allows for a sensitive, quantitative technique amidst poor background noise and poor separation with high mass accuracy (<5 ppm).•By use of MS(E) centroid experiment, greater mass spectral information for metabolite profiling could be obtained.

Amphidoma languida sp. nov. (Dinophyceae) reveals a close relationship between Amphidoma and Azadinium.

Toxic algae such as Alexandrium and Azadinium have an important ecological impact and have originated several times independently within the dinophytes. Their closest relatives, however, are mostly unknown at present. A new dinophyte species, Amphidoma languida sp. nov., was isolated from Bantry Bay (Ireland) during a period of elevated azaspiracid toxicity in mussels. The new species was described in detail, and its phylogenetic position was analysed, by using a combination of light and electron microscopy, chemical detection methods, and sequence comparison of concatenated ribosomal RNA sequence data. Morphological similarities, such as cingular and hypothecal plates, the number and arrangement of sulcal plates, and the characteristic apical pore complex with a small X-plate centrally invading the first apical plate, indicated a close relationship between Amphidoma and Azadinium. However, no known azaspiracid analogues were detected in A. languida by liquid chromatography coupled with tandem mass-spectrometry. In a molecular phylogeny, the Amphidomataceae including Amphidoma and Azadinium were an independent lineage among other monophyletic major groups of the dinophytes such as the Suessiales, Prorocentrales, Gonyaulacales, and Peridiniales. Thus, the taxonomic affiliation of Azadinium is clarified, and our data may prove helpful in the development of specific and reliable molecular detection methods of toxic Azadinium.

Mussels increase xenobiotic (azaspiracid) toxicity using a unique bioconversion mechanism.

Azaspiracid Poisoning (AZP) is a human toxic syndrome which is associated with the consumption of bivalve shellfish. Unlike other shellfish, mussels contain a large array of azaspiracid analogs, many of which are suspected bioconversion products. These studies were conducted to elucidate the metabolic pathways of azaspiracid (AZA1) in the blue mussel (Mytilus edulis) and revealed that the main biotransformation product was the more toxic demethyl analog, AZA3. To elucidate the mechanism of this C-demethylation, an unprecedented xenobiotic bioconversion step in shellfish, AZA1 was fed to mussels that contained no detectable azaspiracids. Triple quadrupole mass spectrometry (MS) and high resolution Orbitrap MS were used to determine the uptake of AZA1 and the toxin profiles in three tissue compartments of mussels. The second most abundant bioconversion product was identified as AZA17, a carboxyl analog of AZA3, which is a key intermediate in the formation of AZA3. Also, two pairs of isomeric hydroxyl analogs, AZA4/AZA5 and AZA7/AZA8, have been confirmed as bioconversion products for the first time. Ultra high resolution (100 k) MS studies showed that the most probable structural assignment for AZA17 is 22-carboxy-AZA3 and a mechanism for its facile decarboxylation to form AZA3 has been proposed.

Development and application of a high-performance liquid chromatography method using monolithic columns for the analysis of ecstasy tablets.

A rapid and selective HPLC method using monolithic columns was developed for the separation and quantification of the principal amphetamines in ecstasy tablets. Three monolithic (Chromolith RP18e) columns of different lengths (25, 50 and 100 mm) were assessed. Validation studies including linearity, selectivity, precision, accuracy and limit of detection and quantification were carried out using the Chromolith SpeedROD, RP-18e, 50 mm x 4.6 mm column. Column backpressure and van Deemter plots demonstrated that monolithic columns provide higher efficiency at higher flow rates when compared to particulate columns without the loss of peak resolution. Application of the monolithic column to a large number of ecstasy tablets seized in Ireland ensured its suitability for the routine analysis of ecstasy tablets.