The effect of laser repetition rate on the LASiS synthesis of biocompatible silver nanoparticles in aqueous starch solution.

Laser ablation-based nanoparticle synthesis in solution is rapidly becoming popular, particularly for potential biomedical and life science applications. This method promises one pot synthesis and concomitant bio-functionalization, is devoid of toxic chemicals, does not require complicated apparatus, can be combined with natural stabilizers, is directly biocompatible, and has high particle size uniformity. Size control and reduction is generally determined by the laser settings; that the size and size distribution scales with laser fluence is well described. Conversely, the effect of the laser repetition rate on the final nanoparticle product in laser ablation is less well-documented, especially in the presence of stabilizers. Here, the influence of the laser repetition rate during laser ablation synthesis of silver nanoparticles in the presence of starch as a stabilizer was investigated. The increment of the repetition rate does not negatively influence the ablation efficiency, but rather shows increased productivity, causes a red-shift in the plasmon resonance peak of the silver-starch nanoparticles, an increase in mean particle size and size distribution, and a distinct lack of agglomerate formation. Optimal results were achieved at 10 Hz repetition rate, with a mean particle size of ~10 nm and a bandwidth of ~6 nm 'full width at half maximum' (FWHM). Stability measurements showed no significant changes in mean particle size or agglomeration or even flocculation. However, zeta potential measurements showed that optimal double layer charge is achieved at 30 Hz. Consequently, Ag-NP synthesis via the laser ablation synthesis in solution (LASiS) method in starch solution seems to be a trade-off between small size and narrow size distributions and inherent and long-term stability

Clinical study protocol for a low-interventional study in intermediate age-related macular degeneration developing novel clinical endpoints for interventional clinical trials with a regulatory and patient access intention-MACUSTAR.

BACKGROUND: There is an unmet need for treatment options in intermediate age-related macular degeneration (iAMD). However, for any new interventions to be tested in clinical trials, novel currently unavailable clinical endpoints need to be developed. Thus, the MACUSTAR study aims to develop and evaluate functional, structural, and patient-reported candidate endpoints for use in future iAMD trials. METHODS: The protocol describes a low-interventional clinical multicenter study employing a novel two-part design. The cross-sectional part (total duration, 1 month) and the longitudinal part (total duration, 36 months) include participants with iAMD and control groups with early/late/no AMD. The cross-sectional part's primary objective is a technical evaluation of functional, structural, and patient-reported candidate outcomes. The longitudinal part's primary objective is to assess the prognostic power of changes in functional, structural, and patient-reported outcomes for progression from iAMD to late AMD. All data will be used to support a biomarker qualification procedure by regulatory authorities. DISCUSSION: The MACUSTAR study characterizes and evaluates much needed novel functional, structural, and patient-reported endpoints for future clinical trials in iAMD and will improve our understanding of the natural history and prognostic markers of this condition. TRIAL REGISTRATION: ClinicalTrials.gov NCT03349801 . Registered on 22 November 2017

MACUSTAR: Development and Clinical Validation of Functional, Structural, and Patient-Reported Endpoints in Intermediate Age-Related Macular Degeneration

Purpose: Currently, no outcome measures are clinically validated and accepted as clinical endpoints by regulatory agencies for drug development in intermediate age-related macular degeneration (iAMD). The MACUSTAR Consortium, a public-private research group funded by the European Innovative Medicines Initiative intends to close this gap. Procedures: Development of study protocol and statistical analysis plan including predictive modelling of multimodal endpoints based on a review of the literature and expert consensus. Results: This observational study consists of a cross-sectional and a longitudinal part. Functional outcome measures assessed under low contrast and low luminance have the potential to detect progression of visual deficit within iAMD and to late AMD. Structural outcome measures will be multimodal and investigate topographical relationships with function. Current patient-reported outcome measures (PROMs) are not acceptable to regulators and may not capture the functional deficit specific to iAMD with needed precision, justifying development of novel PROMs for iAMD. The total sample size will be n = 750, consisting mainly of subjects with iAMD (n = 600). Conclusions: As clinical endpoints currently accepted by regulators cannot detect functional loss or patient-relevant impact in iAMD, we will clinically validate novel candidate endpoints for iAMD

Bio-nanotechnology application in wastewater treatment

The nanoparticles have received high interest in the field of medicine and water purification, however, the nanomaterials produced by chemical and physical methods are considered hazardous, expensive, and leave behind harmful substances to the environment. This chapter aimed to focus on green-synthesized nanoparticles and their medical applications. Moreover, the chapter highlighted the applicability of the metallic nanoparticles (MNPs) in the inactivation of microbial cells due to their high surface and small particle size. Modifying nanomaterials produced by green-methods is safe, inexpensive, and easy. Therefore, the control and modification of nanoparticles and their properties were also discussed

Dielectrical Properties of CeO2 Nanoparticles at Different Temperatures

A template-free precipitation method was used as a simple and low cost method for preparation of CeO2 nanoparticles. The structure and morphology of the prepared nanoparticle samples were studied in detail using X-ray diffraction, Raman spectroscopy and Scanning Electron Microscopy (SEM) measurements. The whole powder pattern modelling (WPPM) method was applied on XRD data to accurately measure the crystalline domain size and their size distribution. The average crystalline domain diameter was found to be 5.2 nm, with a very narrow size distribution. UV-visible absorbance spectrum was used to calculate the optical energy band gap of the prepared CeO2 nanoparticles. The FT-IR spectrum of prepared CeO2 nanoparticles showed absorption bands at 400 cm(-1) to 450 cm(-1) regime, which correspond to CeO2 stretching vibration. The dielectric constant (er) and dielectric loss (tan delta) values of sintered CeO2 compact consolidated from prepared nanoparticles were measured at different temperatures in the range from 298 K (room temperature) to 623 K, and at different frequencies from 1 kHz to 1 MHz

Development of a voltammetric assay, using screen-printed electrodes, for clonazepam and its application to beverage and serum samples

© 2015 Elsevier B.V. All rights reserved. This paper describes the development of an electrochemical assay based on screen-printed carbon sensors for the determination of clonazepam in serum and in wine. The cyclic voltammetric behaviour of the drug was investigated and the effects of pH and scan rate on the peak current and peak potential determined. Two reduction peaks were recorded on the initial negative going scan, which were considered to result from the 2e-, 2 H+ reduction of the 4,5-azomethine and from the 4e-, 4 H+ reduction of the 7-NO2 to a hydroxylamine. On the return positive going scan an oxidation peak was seen, which was considered to result from the 2e-, 2 H+ oxidation (O1) of the hydroxylamine to the corresponding nitroso species. At pH 11 the solution of clonazepam was found to turn from clear to yellow in colour and the voltammetric signal of the O1 oxidation process was found to be adsorptive in nature, this was exploited in the development of an adsorptive stripping voltammetric assay. Experimental conditions were then optimised for the differential pulse adsorptive voltammetric measurement of clonazepam in wine and serum samples. It was shown that these analyses could be performed on only 100 μL of sample which was deposited on the sensor surface. Mean recoveries of 79.53% (%CV=9.88%) and 88.22% (%CV=14.1%) were calculated for wine fortified with 3.16 μg/mL and serum fortified with 12.6 μg/mL

Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders