Influence of Geometry on the Drug Release Profiles of Stereolithographic (SLA) 3D-Printed Tablets

Additive manufacturing (3D printing) permits the fabrication of tablets in shapes unattainable by powder compaction, and so the effects of geometry on drug release behavior is easily assessed. Here, tablets (printlets) comprising of paracetamol dispersed in polyethylene glycol were printed using stereolithographic 3D printing. A number of geometric shapes were produced (cube, disc, pyramid, sphere and torus) with either constant surface area (SA) or constant surface area/volume ratio (SA/V). Dissolution testing showed that printlets with constant SA/V ratio released drug at the same rate, while those with constant SA released drug at different rates. A series of tori with increasing SA/V ratio (from 0.5 to 2.4) were printed, and it was found that dissolution rate increased as the SA/V ratio increased. The data show that printlets can be fabricated in multiple shapes and that dissolution performance can be maintained if the SA/V ratio is constant or that dissolution performance of printlets can be fine-tuned by varying SA/V ratio. The results suggest that 3D printing is therefore a suitable manufacturing method for personalized dosage forms

Vat photopolymerization 3D printing for advanced drug delivery and medical device applications

Three-dimensional (3D) printing is transforming manufacturing paradigms within healthcare. Vat photopolymerization 3D printing technology combines the benefits of high resolution and favourable printing speed, offering a sophisticated approach to fabricate bespoke medical devices and drug delivery systems. Herein, an overview of the vat polymerization techniques, their unique applications in the fields of drug delivery and medical device fabrication, material examples and the advantages they provide within healthcare, is provided. The outstanding challenges and drawbacks presented by this technology are also discussed. It is forecast that the adoption of 3D printing could pave the way for a personalised health system, advancing from traditional treatments pathways towards digital healthcare and streamlining a new cyber era

Fabrication of drug-loaded hydrogels with stereolithographic 3D printing

3D printing (3DP) technologies have been attracting much recent interest as new methods of fabricating medicines and medical devices. Of the many types of 3DP available, stereolithographic (SLA) printing offers the unique advantage of being able to fabricate objects by cross-linking resins to form networked polymer matrices. Because water can be entrapped in these matrices, it is possible in principle to fabricate pre-wetted, drug-loaded hydrogels and devices. Here, SLA printing was used to prepare ibuprofen-loaded hydrogels of cross-linked polyethylene glycol diacrylate. Hydrogels containing up to 30% w/w water, and 10% w/w ibuprofen, were successfully printed. Dissolution profiles showed that drug release rates were dependent on water content, with higher water content hydrogels releasing drug faster. The conclusion is that SLA 3DP offers a new manufacturing route to pharmaceutical hydrogels

Deep Eyedentification: Biometric Identification using Micro-Movements of the Eye

We study involuntary micro-movements of the eye for biometric identification. While prior studies extract lower-frequency macro-movements from the output of video-based eye-tracking systems and engineer explicit features of these macro-movements, we develop a deep convolutional architecture that processes the raw eye-tracking signal. Compared to prior work, the network attains a lower error rate by one order of magnitude and is faster by two orders of magnitude: it identifies users accurately within seconds

Role of macrophage sialoadhesin in host defense against the sialylated pathogen group B <em>Streptococcus</em>

ABSTRACT: Several bacterial pathogens decorate their surfaces with sialic acid (Sia) residues within cell wall components or capsular exopolysaccharides. Sialic acid expression can promote bacterial virulence by blocking complement activation or by engagement of inhibitory sialic acid-binding immunoglobulin-like lectins (Siglecs) on host leukocytes. Expressed at high levels on splenic and lymph node macrophages, sialoadhesin (Sn) is a unique Siglec with an elongated structure that lacks intracellular signaling motifs. Sialoadhesin allows macrophage to engage certain sialylated pathogens and stimulate inflammatory responses, but the in vivo significance of sialoadhesin in infection has not been shown. We demonstrate that macrophages phagocytose the sialylated pathogen group B Streptococcus (GBS) and increase bactericidal activity via sialoadhesin-sialic-acid-mediated recognition. Sialoadhesin expression on marginal zone metallophillic macrophages in the spleen trapped circulating GBS and restricted the spread of the GBS to distant organs, reducing mortality. Specific IgM antibody responses to GBS challenge were also impaired in sialoadhesin-deficient mice. Thus, sialoadhesin represents a key bridge to orchestrate innate and adaptive immune defenses against invasive sialylated bacterial pathogens. KEY MESSAGE: Sialoadhesin is critical for macrophages to phagocytose and clear GBS. Increased GBS organ dissemination in the sialoadhesin-deficient mice. Reduced anti-GBS IgM production in the sialoadhesin-deficient mice. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00109-014-1157-y) contains supplementary material, which is available to authorized users

Identification of Colletotrichum species associated with anthracnose disease of coffee in Vietnam

Colletotrichum gloeosporioides, C. acutatum, C. capsici and C. boninense associated with anthracnose disease on coffee (Coffea spp.) in Vietnam were identified based on morphology and DNA analysis. Phylogenetic analysis of DNA sequences from the internal transcribed spacer region of nuclear rDNA and a portion of mitochondrial small subunit rRNA were concordant and allowed good separation of the taxa. We found several Colletotrichum isolates of unknown species and their taxonomic position remains unresolved. The majority of Vietnamese isolates belonged to C. gloeosporioides and they grouped together with the coffee berry disease (CBD) fungus, C. kahawae. However, C. kahawae could be distinguished from the Vietnamese C. gloeosporioides isolates based on ammonium tartrate utilization, growth rate and pathogenictity. C. gloeosporioides isolates were more pathogenic on detached green berries than isolates of the other species, i.e. C. acutatum, C capsici and C. boninense. Some of the C. gloeosporioides isolates produced slightly sunken lesion on green berries resembling CBD symptoms but it did not destroy the bean. We did not find any evidence of the presence of C. kahawae in Vietnam

Distinct phosphorylation requirements regulate cortactin activation by TirEPEC and its binding to N-WASP

<p>Abstract</p> <p>Background</p> <p>Cortactin activates the actin-related 2/3 (Arp2/3) complex promoting actin polymerization to remodel cell architecture in multiple processes (e.g. cell migration, membrane trafficking, invadopodia formation etc.). Moreover, it was called the Achilles' heel of the actin cytoskeleton because many pathogens hijack signals that converge on this oncogenic scaffolding protein. Cortactin is able to modulate N-WASP activation <it>in vitro </it>in a phosphorylation-dependent fashion. Thus Erk-phosphorylated cortactin is efficient in activating N-WASP through its SH3 domain, while Src-phosphorylated cortactin is not. This could represent a switch on/off mechanism controlling the coordinated action of both nucleator promoting factors (NPFs). Pedestal formation by enteropathogenic <it>Escherichia coli </it>(EPEC) requires N-WASP activation. N-WASP is recruited by the cell adapter Nck which binds a major tyrosine-phosphorylated site of a bacterial injected effector, Tir (translocated intimin receptor). Tir-Nck-N-WASP axis defines the current major pathway to actin polymerization on pedestals. In addition, it was recently reported that EPEC induces tyrosine phosphorylation of cortactin.</p> <p>Results</p> <p>Here we demonstrate that cortactin phosphorylation is absent on N-WASP deficient cells, but is recovered by re-expression of N-WASP. We used purified recombinant cortactin and Tir proteins to demonstrate a direct interaction of both that promoted Arp2/3 complex-mediated actin polymerization <it>in vitro</it>, independently of cortactin phosphorylation.</p> <p>Conclusion</p> <p>We propose that cortactin binds Tir through its N-terminal part in a tyrosine and serine phosphorylation independent manner while SH3 domain binding and activation of N-WASP is regulated by tyrosine and serine mediated phosphorylation of cortactin. Therefore cortactin could act on Tir-Nck-N-WASP pathway and control a possible cycling activity of N-WASP underlying pedestal formation.</p

Abnormal reward prediction-error signalling in antipsychotic naive individuals with first-episode psychosis or clinical risk for psychosis.

Ongoing research suggests preliminary, though not entirely consistent, evidence of neural abnormalities in signalling prediction errors in schizophrenia. Supporting theories suggest mechanistic links between the disruption of these processes and the generation of psychotic symptoms. However, it is unknown at what stage in the pathogenesis of psychosis these impairments in prediction-error signalling develop. One major confound in prior studies is the use of medicated patients with strongly varying disease durations. Our study aims to investigate the involvement of the meso-cortico-striatal circuitry during reward prediction-error signalling in earliest stages of psychosis. We studied patients with first-episode psychosis (FEP) and help-seeking individuals at-risk for psychosis due to sub-threshold prodromal psychotic symptoms. Patients with either FEP (n = 14), or at-risk for developing psychosis (n = 30), and healthy volunteers (n = 39) performed a reinforcement learning task during fMRI scanning. ANOVA revealed significant (p < 0.05 family-wise error corrected) prediction-error signalling differences between groups in the dopaminergic midbrain and right middle frontal gyrus (dorsolateral prefrontal cortex, DLPFC). FEP patients showed disrupted reward prediction-error signalling compared to controls in both regions. At-risk patients showed intermediate activation in the midbrain that significantly differed from controls and from FEP patients, but DLPFC activation that did not differ from controls. Our study confirms that FEP patients have abnormal meso-cortical signalling of reward-prediction errors, whereas reward-prediction-error dysfunction in the at-risk patients appears to show a more nuanced pattern of activation with a degree of midbrain impairment but preserved cortical function

The FIELDS Instrument Suite for Solar Probe Plus: Measuring the Coronal Plasma and Magnetic Field, Plasma Waves and Turbulence, and Radio Signatures of Solar Transients.

NASA's Solar Probe Plus (SPP) mission will make the first in situ measurements of the solar corona and the birthplace of the solar wind. The FIELDS instrument suite on SPP will make direct measurements of electric and magnetic fields, the properties of in situ plasma waves, electron density and temperature profiles, and interplanetary radio emissions, amongst other things. Here, we describe the scientific objectives targeted by the SPP/FIELDS instrument, the instrument design itself, and the instrument concept of operations and planned data products