Targeting orthotopic gliomas with renal-clearable luminescent gold nanoparticles

A major clinical translational challenge in nanomedicine is the potential of toxicity associated with the uptake and long-term retention of non-degradable nanoparticles (NPs) in major organs.The development of inorganic NPs that undergo renal clearance could potentially resolve this significant biosafety concern.However,it remains unclear whether inorganic NPs that can be excreted by the kidneys remain capable of targeting tumors with poor permeability.Glioblastoma multiforme,the most malignant orthotopic brain tumor,presents a unique challenge for NP delivery because of the blood-brain barrier and robust blood-tumor barrier of reactive microglia and macroglia in the tumor microenvironment.Herein,we used an orthotopic murine glioma model to investigate the passive targeting of glutathione-coated gold nanoparticles (AuNPs) of 3 nm in diameter that undergo renal clearance and 18-nm AuNPs that fail to undergo renal clearance.Remarkably, we report that 3-nm AuNPs were able to target intracranial tumor tissues with higher efficiency (2.3x relative to surrounding non-tumor normal brain tissues) and greater specificity (3.0x)than did the larger AuNPs.Pharmacokinetics studies suggested that the higher glioma targeting ability of the 3-nm AuNPs may be attributed to the longer retention time in circulation.The total accumulation of the 3-nm AuNPs in major organs was significantly less (8.4x) than that of the 18-nm AuNPs.Microscopic imaging of blood vessels and renal-clearable AuNPs showed extravasation of NPs from the leaky blood-tumor barrier into the tumor interstitium.Taken together,our results suggest that the 3-nm AuNPs,characterized by enhanced permeability and retention,are able to target brain tumors and undergo renal clearance.     

Diffusion-limited chronoamperometry at conical-tip microelectrodes

In this paper, we present simulated diffusion-limited time-variant currents at conical-tip microelectrodes fabricated by depositing a carbon film in and on pulled quartz capillaries. These mechanically strong microelectrodes are suitable probes for detecting neurotransmitters in vivo. The simulated results show that the currents obtained at conical-tip microelectrodes are larger than those at finite conical microelectrodes (e.g. etched carbon fibres protruding from an insulating plane) of comparable dimensions. The currents at conical-tip microelectrodes and finite conical microelectrodes both converge to that of a microdisk electrode at small cone heights and large cone angles, and to that of a cylindrical electrode portion of equal length and half the radius at large cone heights and small cone angles. At short times (scaled by the electrode dimensions), Cottrellian current is achieved at conical-tip microelectrodes and the current densities collapse to the expected chronoamperometric response at a microdisk electrode, subject to some simulation errors. Comparison between a simulated chronoamperogram and an experimental chronoamperogram then allows an estimate of parameters (such as electrode surface area and dimensions) that define the electrode geometry. Steady-state currents based on empirical functions have also been computed for conical-tip microelectrodes and finite conical microelectrodes.     

Unfrazzled by Fizziness: Identification of Beers Using Attenuated Total Reflectance Mid-infrared Spectroscopy and Multivariate Analysis

Mid-infrared (MIR) spectroscopy coupled with attenuated total reflectance (ATR) was used to analyse a series of different beer types in order to confirm their identity (e.g. ale vs lager, commercial vs craft beer). Multivariate data analyses such as principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were used to analyse and to discriminate the beer samples analysed based on their infrared spectra. Correct classification rates of 100% were achieved in order to differentiate between ale and lager and also between commercial and craft beer sample types, respectively. Overall, the results of this study demonstrated the capability of MIR spectroscopy combined with PLS-DA to classify beer samples according to style (ale vs lager) and production (commercial vs craft). Furthermore, dissolved gases in the beer products were proven not to interfere as overlapping artefacts in the analysis. The benefits of using MIR-ATR for rapid and detailed analysis coupled with multivariate analysis can be considered a valuable tool for researchers and brewers interested in quality control, traceability and food adulteration. The novelty of this study is potentially far reaching, whereby customs and agencies can utilise these methods to mitigate beverage fraud.     

Low Intensity Shockwave Treatment Modulates Macrophage Functions Beneficial to Healing Chronic Wounds

Extracorporeal Shock Wave Therapy (ESWT) is used clinically in various disorders including chronic wounds for its pro-angiogenic, proliferative, and anti-inflammatory effects. However, the underlying cellular and molecular mechanisms driving therapeutic effects are not well characterized. Macrophages play a key role in all aspects of healing and their dysfunction results in failure to resolve chronic wounds. We investigated the role of ESWT on macrophage activity in chronic wound punch biopsies from patients with non-healing venous ulcers prior to, and two weeks post-ESWT, and in macrophage cultures treated with clinical shockwave intensities (150–500 impulses, 5 Hz, 0.1 mJ/mm²). Using wound area measurements and histological/immunohistochemical analysis of wound biopsies, we show ESWT enhanced healing of chronic ulcers associated with improved wound angiogenesis (CD31 staining), significantly decreased CD68-positive macrophages per biopsy area and generally increased macrophage activation. Shockwave treatment of macrophages in culture significantly boosted uptake of apoptotic cells, healing-associated cytokine and growth factor gene expressions and modulated macrophage morphology suggestive of macrophage activation, all of which contribute to wound resolution. Macrophage ERK activity was enhanced, suggesting one mechanotransduction pathway driving events. Collectively, these in vitro and in vivo findings reveal shockwaves as important regulators of macrophage functions linked with wound healing. This immunomodulation represents an underappreciated role of clinically applied shockwaves, which could be exploited for other macrophage-mediated disorders.     

Microsurgical C-2 ganglionectomy for chronic intractable occipital pain

The P300 event-related brain potential (ERP) was elicited with visual stimuli using an oddball task in which the subjects made button press responses to discriminate target and standard stimuli. Each stimulus occurred randomly with a 0.50 probability, and 10 trial blocks were presented at 10-min inter-block-intervals (IBIs). P300 amplitude declined reliably across trial blocks, and an interaction between trial block number and electrode site was observed. No habituation effects were found for P300 latency or for N100, P200, or N200 amplitude. The results suggest that P300 amplitude from visual stimuli habituates when short IBIs and a sufficient number of trial blocks are employed. Theoretical implications are discussed with respect to attentional resource allocation and context updating.     

The influence of anger,impulsivity, sensation seeking and driver attitudes on risky driving behaviour among post-graduate university students in Durban,South Africa

Introduction

Road traffic accidents (RTAs) constitute a serious global health risk, and evidence suggests that young drivers are significantly overrepresented among those injured or killed in RTAs. This study explores the role of anger, impulsivity, sensation seeking and driver attitudes as correlates for risky driving practices among drivers, drawing comparisons between age and gender.

Method

The study used a cross-sectional survey design, with a sample of 306 post-graduate university students from two universities in Durban, South Africa, who completed the self-administered questionnaire.

Results

The results indicate that drivers with higher driver anger, sensation seeking, urgency, and with a lack of premeditation and perseverance in daily activities were statistically more likely to report riskier driving acts. Males reported significantly more acts of risky driving behaviour (RDB) than females. Driver attitudes significantly predicted self-reported acts of RDB on most indicators. Older drivers (25 years and older) had safer driver attitudes and a lower sense of sensation seeking and urgency in life.

Conclusion

Interventions targeting young drivers, which focus on impeding the manifestation of anger, impulsivity and sensation seeking are recommended. Also, the empirical support for the attitude–behaviour hypothesis evidenced in this study vindicates the development or continuation of interventions that focus on this dynamic.