Vaccine microarray patch self-administration: An innovative approach to improve pandemic and routine vaccination rates.

The high-density microprojection array patch (HD-MAP) is a novel vaccine delivery system with potential for self-administered vaccination. HD-MAPs provide an alternative to needle and syringe (N&S) vaccination. Additional advantages could include reduced cold-chain requirements, reduced vaccine dose, reduced vaccine wastage, an alternative for needle phobic patients and elimination of needlestick injuries. The drivers and potential benefits of vaccination by self-administering HD-MAPs are high patient acceptance and preference, higher vaccination rates, speed of roll-out, cost-savings, and reduced sharps and environmental waste. The HD-MAP presents a unique approach in pandemic preparedness and routine vaccination of adults. It could alleviate strain on the healthcare workforce and allows vaccine administration by minimally-trained workers, guardian or subjects themselves. Self-vaccination using HD-MAPs could occur in vaccination hubs with supervision, at home after purchasing at the pharmacy, or direct distribution to in-home settings. As a result, it has the potential to increase vaccine coverage and expand the reach of vaccines, while also reducing labor costs associated with vaccination. Key challenges remain around shifting the paradigm from medical professionals administrating vaccines using N&S to a future of self-administration using HD-MAPs. Greater awareness of HD-MAP technology and improving our understanding of the implementation processes required for adopting this technology, are critical factors underpinning HD-MAP uptake by the public.

Evaluation of the self-administration potential of high-density microarray patches to human skin: A preliminary study.

The high-density microneedle array patch (HD-MAP) is a novel vaccine delivery system with potential for self-administered vaccination. In this study, Vaxxas HD-MAPs were applied by both a trained user and self-administered with application sites compared to determine the response of skin and the level of engagement of the HD-MAP with human skin. Twenty healthy participants were enrolled, and the response of skin including erythema was observed at all application sites and no difference was found between trained user or self-administered applications. The majority of participants (70%) preferred the deltoid upper arm application site for applying HD-MAPs. Fluorescent dermatoscope images confirmed HD-MAPs engaged the skin surface and scanning electron microscopy (SEM) image analysis exhibited similar delivery characteristics for the upper arm and forearm sites when applied by either a trained user or self-administered. This study showed that noninvasive methods including dermatoscopy and SEM image analysis were able to estimate the engagement of HD-MAPs with human skin. HD-MAP self-vaccination technology has a unique proposition in pandemic preparedness by alleviating the need for health-care workers to administer vaccines, however greater awareness and understanding of the potential of this technology is required.

Exposure to solar ultraviolet radiation is associated with a decreased folate status in women of childbearing age.

In vitro studies indicate that folate in collected human blood is vulnerable to degradation after exposure to ultraviolet (UV) radiation. This has raised concerns about folate depletion in individuals with high sun exposure. Here, we investigate the association between personal solar UV radiation exposure and serum folate concentration, using a three-week prospective study that was undertaken in females aged 18-47years in Brisbane, Australia (153 E, 27 S). Following two weeks of supplementation with 500µg of folic acid daily, the change in serum folate status was assessed over a 7-day period of measured personal sun exposure. Compared to participants with personal UV exposures of <200 Joules per day, participants with personal UV exposures of 200-599 and >600 Joules per day had significantly higher depletion of serum folate (p=0.015). Multivariable analysis revealed personal UV exposure as the strongest predictor accounting for 20% of the overall change in serum folate (Standardised B=-0.49; t=-3.75; p=<0.01). These data show that increasing solar UV radiation exposures reduces the effectiveness of folic acid supplementation. The consequences of this association may be most pronounced for vulnerable individuals, such as women who are pregnant or of childbearing age with high sun exposures.

Inverse expression states of the BRN2 and MITF transcription factors in melanoma spheres and tumour xenografts regulate the NOTCH pathway.

The use of adherent monolayer cultures have produced many insights into melanoma cell growth and differentiation, but often novel therapeutics demonstrated to act on these cells are not active in vivo. It is imperative that new methods of growing melanoma cells that reflect growth in vivo are investigated. To this end, a range of human melanoma cell lines passaged as adherent cultures or induced to form melanoma spheres (melanospheres) in stem cell media have been studied to compare cellular characteristics and protein expression. Melanoma spheres and tumours grown from cell lines as mouse xenografts had increased heterogeneity when compared with adherent cells and 3D-spheroids in agar (aggregates). Furthermore, cells within the melanoma spheres and mouse xenografts each displayed a high level of reciprocal BRN2 or MITF expression, which matched more closely the pattern seen in human melanoma tumours in situ, rather than the propensity for co-expression of these important melanocytic transcription factors seen in adherent cells and 3D-spheroids. Notably, when the levels of the BRN2 and MITF proteins were each independently repressed using siRNA treatment of adherent melanoma cells, members of the NOTCH pathway responded by decreasing or increasing expression, respectively. This links BRN2 as an activator, and conversely, MITF as a repressor of the NOTCH pathway in melanoma cells. Loss of the BRN2-MITF axis in antisense-ablated cell lines decreased the melanoma sphere-forming capability, cell adhesion during 3D-spheroid formation and invasion through a collagen matrix. Combined, this evidence suggests that the melanoma sphere-culture system induces subpopulations of cells that may more accurately portray the in vivo disease, than the growth as adherent melanoma cells.

Laser conditioning of LaF(3)/MgF(2) dielectric coatings at 248 nm.

Highly reflective LaF(3)/MgF(2) systems for a wavelength of 248 nm on MgF(2) and crystalline quartz substrates were investigated. The influence of laser conditioning on damage threshold and absorptance was remarkable in those coatings that had a high initial absorptance. Monitoring with a laser calorimeter revealed the conditioning effect to be a function of the irradiation dose rather than of energy density or pulse rate. Furthermore, x-ray photoelectron spectroscopy and transmission electron microscopy investigations showed that conditioning induces stoichiometric and structural changes in the multilayers, especially in near-surface sublayers, whereas scanning electron microscopy and atomic force microscopy investigations indicated that the surface remains unchanged.

Investigations on the rectal absorption of chloramphenicol in rabbits after tenside use.

The rectal dose of 16 mg.kg-1 b.w. chloramphenicol (1) without additional tensides did not result in any detectable absorption of effective substance. In contrast, 0.04% of the N-lauroylleucine tenside allowed a rectal absorption having the same effect as that of an injection of the same quantities of effective substance. The tenside efficiency was not influenced by varied suppository masses (gelatine or Rosupol U, respectively), or by the pH value of the suppositories. Different particle sizes (less than 40 microns or greater than or equal to 40 up to less than 400 microns) of 1 did not change the absorption rate (AUC0-5h) significantly, but did change the plasma concentration-time profile considerably.

The protection of insulin against proteolytic processes after rectal application to normoglycemic rabbits.

In order to improve the bioavailability of insulin after rectal application to rabbits, the influence of surface-active amino acid-fatty acid condensate on absorption and, the effects of a protease inhibitor (aprotinine), of a disinfectant (methyl-hydroxybenzoate) and of chemotherapeutics (chloramphenicol, ambazone and metronidazole) were investigated. Only the application of methylhydroxybenzoate, ambazone and of metronidazole, which inhibit the anaerobic bacterial flora, improved bioavailability significantly. The examinations show that the proteolytic activity of the anaerobic bacterial flora causes the loss of the biological activity of peptides in the rectum.

[Scintigraphy of sustained-release agar-embedded insulin suppositories]. / Szintigraphische Verfolgung der retardierten Insulinliberation aus Agar-Einbettungen in Suppositorien.

In earlier publications [1-3] we reported on the retardation and protective effect of insulin-agar-embeddings in triglyceride suppositories by in vitro and in vivo tests on rabbits. The discovered effects were visually followed by gammascintigraphic test of adequate rectally applied 131I-insulin-specimens in the rectum and thyroid gland and, in relation with the glucose lowering course, the liberation, distribution and bioavailability of the immobilized hormone was illustrated.

[The application of insulin-agar embedding in suppositories for controlled hormone liberation and dose lowering]. / Uber die Verwendung von Insulin-Agar-Einbettungen in Suppositorien zur verzögerten Hormonliberation und Dosissenkung.

By embedding of insulin in agar a significant retardation as well as a protective effect for the hormone is obtained. As demonstrated on in vivo animal experiments, this embedding method in dependence on the insulin concentration and particle size of the polymeric matrix allows to prepare rectal insulin applications with remarkable depot effects. Alternatively in combination with resorption promoting tensides it permits to lower the administered hormone doses to a order of magnitude reaching those used for parenteral insulin applications.

Preferences for wavelength and intensity in rhesus monkeys: fact or artifact?

10 adult male rhesus monkeys were tested to determine whether systematic preferences existed for specific color or brightness of visual stimuli. In contrast with previous reports no significant preferences for either specific hues or brightness levels were found. Perhaps methodological or subject variables may be responsible for preferential responding in other situations and account for the present inability to confirm prior work on preferences for color and brightness.

[Development of swimming behavior in mice as a behavioral test in toxicology]. / Die Entwicklung des Schwimmverhaltens bei Mäusen als Verhaltenstest in der Toxikologie.

The development of the swimming behaviour in mice is described by 7 stages. The inbred strains and hybrids investigated showed differences in the progress of this development. In comparing the swimming behaviour of offspring from Cyclophosphamid- treated and untreated dams temporal differences have been registered, too. The swimming test is thought to be a suitable behavioural test within embryotoxicological investigations.