Stimulation efficiency of an actuator driven piston at the biological interface to the inner ear

Direct acoustic cochlear stimulation uses piston motion to substitute for stapes footplate (SFP) motion. The ratio of piston to stapes footplate motion amplitude, to generate the same loudness percept, is an indicator of stimulation efficiency. We determined the relationship between piston displacement to perceived loudness, the achieved maximum power output and investigated stapes fixation and obliteration as confounding factors. The electro-mechanical transfer function of the actuator was determined preoperatively on the bench and intraoperatively by laser Doppler vibrometry. Clinically, perceived loudness as a function of actuator input voltage was calculated from bone conduction thresholds and direct thresholds via the implant. The displacement of a 0.4 mm diameter piston required for a perception equivalent to 94 dB SPL at the tympanic membrane compared to normal SFP piston displacement was 27.6–35.9 dB larger, consistent with the hypothesis that the ratio between areas is responsible for stimulation efficiency. Actuator output was 110 ± 10 eq dB SPLFF @1Vrms ≤ 3 kHz and decreased to 100 eq dB SPLFF at 10 kHz. Output was significantly higher for mobile SFPs but independent from obliteration. Our findings from clinical data strongly support the assumption of a geometrical dependency on piston diameter at the biological interface to the cochlea.

Epigenome-wide association studies: current knowledge, strategies and recommendations

The aetiology and pathophysiology of complex diseases are driven by the interaction between genetic and environmental factors. The variability in risk and outcomes in these diseases are incompletely explained by genetics or environmental risk factors individually. Therefore, researchers are now exploring the epigenome, a biological interface at which genetics and the environment can interact. There is a growing body of evidence supporting the role of epigenetic mechanisms in complex disease pathophysiology. Epigenome-wide association studies (EWASes) investigate the association between a phenotype and epigenetic variants, most commonly DNA methylation. The decreasing cost of measuring epigenome-wide methylation and the increasing accessibility of bioinformatic pipelines have contributed to the rise in EWASes published in recent years. Here, we review the current literature on these EWASes and provide further recommendations and strategies for successfully conducting them. We have constrained our review to studies using methylation data as this is the most studied epigenetic mechanism; microarray-based data as whole-genome bisulphite sequencing remains prohibitively expensive for most laboratories; and blood-based studies due to the non-invasiveness of peripheral blood collection and availability of archived DNA, as well as the accessibility of publicly available blood-cell-based methylation data. Further, we address multiple novel areas of EWAS analysis that have not been covered in previous reviews: (1) longitudinal study designs, (2) the chip analysis methylation pipeline (ChAMP), (3) differentially methylated region (DMR) identification paradigms, (4) methylation quantitative trait loci (methQTL) analysis, (5) methylation age analysis and (6) identifying cell-specific differential methylation from mixed cell data using statistical deconvolution.

The Impact of Multiple Functional Layers in the Structure of Magnetic Nanoparticles and Their Influence on Albumin Interaction

In nanomedicine, hybrid nanomaterials stand out for providing new insights in both the diagnosis and treatment of several diseases. Once administered, engineered nanoparticles (NPs) interact with biological molecules, and the nature of this interaction might directly interfere with the biological fate and action of the NPs. In this work, we synthesized a hybrid magnetic nanostructure, with antibacterial and antitumoral potential applications, composed of a magnetite core covered by silver NPs, and coated with a modified chitosan polymer. As magnetite NPs readily oxidize to maghemite, we investigated the structural properties of the NPs after addition of the two successive layers using Mössbauer spectroscopy. Then, the structural characteristics of the NPs were correlated to their interaction with albumin, the major blood protein, to evidence the consequences of its binding on NP properties and protein retention. Thermodynamic parameters of the NPs–albumin interaction were determined. We observed that the more stable NPs (coated with modified chitosan) present a lower affinity for albumin in comparison to pure magnetite and magnetite/silver hybrid NPs. Surface properties were key players at the NP–biological interface. To the best of our knowledge, this is the first study that demonstrates a correlation between the structural properties of complex hybrid NPs and their interaction with albumin.

Rational Biological Interface Engineering: Amyloidal Supramolecular Microstructure-Inspired Hydrogel

Amyloidal proteins, which are prone to form fibrillar and ordered aggregates in vivo and in vitro, underlie the mechanism for neurodegenerative disorders and also play essential functions in the process of life. Amyloid fibrils typically adopt a distinctive β-sheet structure, which renders them with inherent extracellular matrix (ECM)-mimicking properties, such as powerful mechanical strength, promising adhesion, and antibacterial activity. Additionally, amyloidal proteins are a category of programmable self-assembled macromolecules, and their assembly and consequent nanostructure can be manipulated rationally. The above advantages motivate researchers to investigate the potential of amyloidal proteins as a novel type of hydrogel material. Currently, the amyloid-inspired hydrogel has become an emerging area and has been widely applied in a variety of biomedical fields, such as tissue repair, cell scaffolds, and drug delivery. In this review, we focus on the discussion of molecular mechanisms underlying the hydrogenation of amyloidal proteins, and introduce the advances achieved in biomedical applications of amyloid-inspired hydrogels.

A method to construct the dynamic landscape of a bio-membrane with experiment and simulation

Biomolecular function is based on a complex hierarchy of molecular motions. While biophysical methods can reveal details of specific motions, a concept for the comprehensive description of molecular dynamics over a wide range of correlation times has been unattainable. Here, we report a novel approach to construct the dynamic landscape of biomolecules, which describes the aggregate influence of multiple motions acting on various timescales and on multiple positions in the molecule. To this end, we use NMR relaxation and molecular dynamics simulation data for the characterization of lipid membranes, the most important biological interface. We develop a dynamics detector method that yields site-specific amplitudes, separated both by type and timescale of motion. This separation allows the detailed description of the dynamic landscape, which reveals vast differences in motion depending on molecular position. More generally, the method is applicable to a broad range of molecular systems, and can be adapted to other timescale-sensitive techniques.

Electrochemical Response of Cells Using Bioactive Plant Isolates

Traditional herbal medical practices continue to be part of the healthcare needs of the world especially residents of sub-Sahara Africa (sSA). However, the mechanism of action of the plant metabolites to elicit their potency continue to be a mystery due to the lack of standardized methods. The mechanism of plant bioactive compounds to cause cell death is gradually being linked to membrane polarization and depolarization behaviour. The current work seeks to probe the electrochemical response of model cells using bioactive compounds captured in bio-zeolites or membrane mimetics. The voltage and current fluctuations emanating from such studies will establish a correlation between cell death and membrane depolarization. It will be a useful biological interface sensing material with the potential to identify plant metabolites that can selectively detect and destroy diseased cells. Several model membranes have already been developed for biomedical applications and this new paradigm will elevate the usefulness of these model systems. The concept was investigated using extracts from Dioclea reflexa (DR) hook which belongs to the leguminous family. There are certain class of compounds in Dioclea reflexa (DR) that have clinical usefulness in both temperate and tropical regions, however the identity of the bioactive compounds responsible for inducing cell death continue to be a major challenge.

Cotton Fibers in Acrylic Facial Epithesis - a Thermal Analyze During Heat Exposure

Heat cured polymethylmethacrylate (PMMA) has been used as denture bases since 1937. PMMA is a vinyl polymer, made by free radical vinyl polymerization from the monomer methyl methacrylate [1]. After the success of using as prosthetic material in the mouth, PMMA began to be used in other areas, for example in facial prosthetics, for facial epitheses. The facial epitheses are exposed permanently to ambiental changes (temperature, air currents, humidity). Secondary, for a better esthetic effect, in facial epitheses PMMA often contain variables quantities of natural fibers (cotton, wool). Our study has analyzed how a PMMA facial epithesis reacts to temperature changes during heat exposure in the summer, especially depending on the amount of fiber it contains, considering that the biological interface between the prosthesis and facial tissues is sensitive to heat [2].

Assessment of Modern Excipients in Controlled Delivery of Proteins and Peptides

Polymeric micelles are highly proficient of modulating the function, distribution of drugs in the body, and can overcome biological barriers hence provoked as novel nanomedicine via various formulations. Current review emphasis on application of several polymers, biomaterials, lipids for the preparation of polymeric micelles formed by several molecular interactions between the block co-polymers and encapsulated molecules. Micellar carriers will be selected on basis of the type of polymer/payload interaction, which includes biological interface focused on the internal chemistry and fabrication of block-co polymers. Several features of these carriers can be manipulated to catering a broad range of drugs through active sensing of body targets. The fine-tuning of their properties in response to particular stimuli, modulating the activity of the loaded drugs at the targeted sites, even at the subcellular level. To end with, the future perspective and impending challenges for polymeric micelles as nanomedicine are elaborated, anticipating prompting further innovations. Keywords: Proteins, Peptides, Co-block Polymers, Lipids, Controlled, Drug Delivery.