Several studies have illustrated that transcutaneous vagus nerve stimulation (tVNS) can elicit therapeutic effects that are similar to those produced by its invasive counterpart, vagus nerve stimulation (VNS). VNS is an FDA-approved therapy for the treatment of both depression and epilepsy, but it is limited to the management of more severe, intervention-resistant cases as a second or third-line treatment option due to perioperative risks involved with device implantation. In contrast, tVNS is a non-invasive technique that involves the application of electrical currents through surface electrodes at select locations, most commonly targeting the auricular branch of the vagus nerve (ABVN) and the cervical branch of the vagus nerve in the neck. Although it has been shown that tVNS elicits hypo-and hyperactivation in various regions of the brain associated with anxiety and mood regulation, the mechanism of action and influence of stimulation parameters on clinical outcomes remains predominantly hypothetical. Suppositions are largely based on correlations between the neurobiology of the vagus nerve and its effects on neural activity. However, tVNS has also been investigated for several other disorders, including tinnitus, migraine and pain, by targeting the vagus nerve at sites in both the ear and the neck. As most of the described methods differ in the parameters and protocols applied, there is currently no firm evidence on the optimal location for tVNS or the stimulation parameters that provide the greatest therapeutic effects for a specific condition. This review presents the current status of tVNS with a focus on stimulation parameters, stimulation sites, and available devices. For tVNS to reach its full potential as a non-invasive and clinically relevant therapy, it is imperative that systematic studies be undertaken to reveal the mechanism of action and optimal stimulation modalities.
Attachment tendencies of Escherichia coli K12, Pseudomonas aeruginosa ATCC 9027, and Staphylococcus aureus CIP 68.5 onto glass surfaces of different degrees of nanometer-scale roughness have been studied. Contact-angle and surface-charge measurements, atomic force microscopy (AFM), scanning electron microscopy (SEM), and confocal laser scanning microscopy (CLSM) were employed to characterize substrata and bacterial surfaces. Modification of the glass surface resulted in nanometer-scale changes in the surface topography, whereas the physicochemical characteristics of the surfaces remained almost constant. AFM analysis indicated that the overall surface roughness parameters were reduced by 60-70%. SEM, CLSM, and AFM analysis clearly demonstrates that although E. coli, P. aeruginosa and S. aureus present significantly different patterns of attachment, all of the species exhibited a greater propensity for adhesion to the "nano-smooth" surface. The bacteria responded to the surface modification with a remarkable change in cellular metabolic activity, as shown by the characteristic cell morphologies, production of extracellular polymeric substances, and an increase in the number of bacterial cells undergoing attachment.
Raman microscopy systems are becoming increasingly widespread and accessible for characterising chemical species. Microfluidic systems are also progressively finding their way into real world applications. Therefore, it is anticipated that the integration of Raman systems with microfluidics will become increasingly attractive and practical. This review aims to provide an overview of Raman microscopy-microfluidics integrated systems for researchers who are actively interested in utilising these tools. The fundamental principles and application strengths of Raman microscopy are discussed in the context of microfluidics. Various configurations of microfluidics that incorporate Raman microscopy methods are presented, with applications highlighted. Data analysis methods are discussed, with a focus on assisting the interpretation of Raman-microfluidics data from complex samples. Finally, possible future directions of Raman-microfluidic systems are presented.
Infrared stimulation offers an alternative to electrical stimulation of neuronal tissue, with potential for direct, non-contact activation at high spatial resolution. Conventional methods of infrared neural stimulation (INS) rely on transient heating due to the absorption of relatively intense laser beams by water in the tissue. However, the water absorption also limits the depth of penetration of light in tissue. Therefore, the use of a near-infrared laser at 780 nm to stimulate cultured rat primary auditory neurons that are incubated with silica-coated gold nanorods (Au NRs) as an extrinsic absorber is investigated. The laser-induced electrical behavior of the neurons is observed using whole-cell patch clamp electrophysiology. The nanorod-treated auditory neurons (NR-ANs) show a significant increase in electrical activity compared with neurons that are incubated with non-absorbing silica-coated gold nanospheres and control neurons with no gold nanoparticles. The laser-induced heating by the nanorods is confirmed by measuring the transient temperature increase near the surface of the NR-ANs with an open pipette electrode. These findings demonstrate the potential to improve the efficiency and increase the penetration depth of INS by labeling nerves with Au NRs and then exposing them to infrared wavelengths in the water window of tissue.
The flat tip of an optical fiber is a unique and unconventional platform for micro and nanotechnologies. The small cross-section and large aspect ratio of the fiber provide an inherently light-coupled substrate that is uniquely suited to remote, in vivo and in situ applications. However, these same characteristics challenge established fabrication technologies, which are best suited to large planar substrates. This review presents a broad overview of strategies for patterning the flat tip of an optical fiber. Techniques discussed include self-assembly, numerous lithographies, through-fiber patterning, hybrid techniques, and strategies for mass manufacture, while the diverse applications are discussed in context throughout.
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