Development and Evaluation of a Reusable, Force Measuring Tool for the Robot-Assisted Insertion of Cochlear Implant Electrode Arrays.

Objective: Limitations in human kinematics during cochlear implantation induce pressure transients and increased forces on intracochlear structures. Herein, we present a novel head-mounted surgical tool designed for the motorized insertion of cochlear implant electrode arrays. The tool integrates a force measurement feature to overcome the lack of haptic feedback in current robotic solutions.

Uncovering Vulnerable Phases in Cochlear Implant Electrode Array Insertion: Insights from an In Vitro Model.

Objectives: The aim of this study is to improve our understanding of the mechanics involved in the insertion of lateral wall cochlear implant electrode arrays.

Design: A series of 30 insertion experiments were conducted by three experienced surgeons. The experiments were carried out in a previously validated artificial temporal bone model according to established soft surgery guidelines.

Cochlear implant electrode impedance subcomponents as biomarker for residual hearing.

Introduction And Objectives: Maintaining the structural integrity of the cochlea and preserving residual hearing is crucial for patients, especially for those for whom electric acoustic stimulation is intended. Impedances could reflect trauma due to electrode array insertion and therefore could serve as a biomarker for residual hearing. The aim of this study is to evaluate the association between residual hearing and estimated impedance subcomponents in a known collective from an exploratory study.

A Sleeve-Based, Micromotion Avoiding, Retractable and Tear-Opening (SMART) Insertion Tool for Cochlear Implantation.

Objective: In conventional cochlear implantation, the insertion of the electrode array is strongly affected by the local anatomy and human kinematics. Herein, we present a concept for an insertion tool that allows to optimize the insertion trajectory beyond anatomical constraints and stabilizes the electrode array in manual implantation. A novel sleeve-based design allows the instrument to be compliant and potentially protective to intracochlear structures, while a tear-open mechanism allows it to be removed after insertion by simply retracting the tool.

Robotic Cochlear Implantation for Direct Cochlear Access.

Robot-assisted systems offer great potential for gentler and more precise cochlear implantation. In this article, we provide a comprehensive overview of the clinical workflow for robotic cochlear implantation using a robotic system specifically developed for a minimally invasive, direct cochlear access. The clinical workflow involves experts from various disciplines and requires training to ensure a smooth and safe procedure.

Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults.

Targeting mitophagy to activate the recycling of faulty mitochondria during aging is a strategy to mitigate muscle decline. We present results from a randomized, placebo-controlled trial in middle-aged adults where we administer a postbiotic compound Urolithin A (Mitopure), a known mitophagy activator, at two doses for 4 months (NCT03464500). The data show significant improvements in muscle strength (∼12%) with intake of Urolithin A.

Effect of Urolithin A Supplementation on Muscle Endurance and Mitochondrial Health in Older Adults: A Randomized Clinical Trial.

Importance: Aging is associated with a decline in mitochondrial function and reduced exercise capacity. Urolithin A is a natural gut microbiome-derived food metabolite that has been shown to stimulate mitophagy and improve muscle function in older animals and to induce mitochondrial gene expression in older humans.

Objective: To investigate whether oral administration of urolithin A improved the 6-minute walk distance, muscle endurance in hand and leg muscles, and biomarkers associated with mitochondrial and cellular health.

Astrocyte-targeting RNA interference against mutated superoxide dismutase 1 induces motoneuron plasticity and protects fast-fatigable motor units in a mouse model of amyotrophic lateral sclerosis.

In amyotrophic lateral sclerosis (ALS) caused by SOD1 gene mutations, both cell-autonomous and noncell-autonomous mechanisms lead to the selective degeneration of motoneurons (MN). Here, we evaluate the therapeutic potential of gene therapy targeting mutated SOD1 in mature astrocytes using mice expressing the mutated SOD1 protein. An AAV-gfaABC D vector encoding an artificial microRNA is used to deliver RNA interference against mutated SOD1 selectively in astrocytes.

Direct supplementation with Urolithin A overcomes limitations of dietary exposure and gut microbiome variability in healthy adults to achieve consistent levels across the population.

Background: Urolithin A (UA) is produced by gut microflora from foods rich in ellagitannins. UA has been shown to improve mitochondrial health preclinically and in humans. Not everyone has a microbiome capable of producing UA, making supplementation with UA an appealing strategy.

In-Vitro Study of Speed and Alignment Angle in Cochlear Implant Electrode Array Insertions.

Objective: The insertion of the electrode array is a critical step in cochlear implantation. Herein we comprehensively investigate the impact of the alignment angle and feed-forward speed on deep insertions in artificial scala tympani models with accurate macro-anatomy and controlled frictional properties.

Methods: Motorized insertions (n=1033) were performed in six scala tympani models with varying speeds and alignment angles.

Fabrication of human anatomy-based scala tympani models with a hydrophilic coating for cochlear implant insertion experiments.

Electrode array insertion into the inner ear is a critical step in cochlear implantation, and artificial scala tympani models can be a valuable tool for studying the dynamics of this process. This technical note describes the fabrication of electrode array dummies and scala tympani models that address shortcomings of previously published cochlear models. In particular, we improve the reproduction of frictional properties with an easy-to-apply polymer brush coating that creates hydrophilic surfaces, and produce geometries with accurate macro-anatomy based on microtomographic scans.

Intraoperative Impedance-Based Estimation of Cochlear Implant Electrode Array Insertion Depth.

Objective: Cochlear implant impedances are influenced by the intracochlear position of the electrodes. Herein, we present an intuitive approach to calculate tissue resistances from transimpedance recordings, ultimately enabling to estimate the insertion depth of cochlear implant electrodes.

Methods: Electrode positions were measured in computed-tomography images of 20 subjects implanted with the same lateral wall cochlear implant model.

The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans.

Urolithin A (UA) is a natural dietary, microflora-derived metabolite shown to stimulate mitophagy and improve muscle health in old animals and in preclinical models of aging. Here, we report the results of a first-in-human clinical trial in which we administered UA, either as a single dose or as multiple doses over a 4-week period, to healthy, sedentary elderly individuals. We show that UA has a favourable safety profile (primary outcome).

Relationship between rheology and structure of interpenetrating, deforming and compressing microgels.

Thermosensitive microgels are widely studied hybrid systems combining properties of polymers and colloidal particles in a unique way. Due to their complex morphology, their interactions and packing, and consequentially the viscoelasticity of suspensions made from microgels, are still not fully understood, in particular under dense packing conditions. Here we study the frequency-dependent linear viscoelastic properties of dense suspensions of micron sized soft particles in conjunction with an analysis of the local particle structure and morphology based on superresolution microscopy.

Evolution of the neurochemical profiles in the G93A-SOD1 mouse model of amyotrophic lateral sclerosis.

In vivo H magnetic resonance spectroscopy (H-MRS) investigations of amyotrophic lateral sclerosis (ALS) mouse brain may provide neurochemical profiles and alterations in association with ALS disease progression. We aimed to longitudinally follow neurochemical evolutions of striatum, brainstem and motor cortex of mice transgenic for G93A mutant human superoxide dismutase type-1 (G93A-SOD1), an ALS model. Region-specific neurochemical alterations were detected in asymptomatic G93A-SOD1 mice, particularly in lactate (-19%) and glutamate (+8%) of brainstem, along with γ-amino-butyric acid (-30%), N-acetyl-aspartate (-5%) and ascorbate (+51%) of motor cortex.

Modulating the catalytic activity of AMPK has neuroprotective effects against α-synuclein toxicity.

Background: Metabolic perturbations and slower renewal of cellular components associated with aging increase the risk of Parkinson's disease (PD). Declining activity of AMPK, a critical cellular energy sensor, may therefore contribute to neurodegeneration.

Methods: Here, we overexpress various genetic variants of the catalytic AMPKα subunit to determine how AMPK activity affects the survival and function of neurons overexpressing human α-synuclein in vivo.

Jamming and overpacking fuzzy microgels: Deformation, interpenetration, and compression.

Tuning the solubility of fuzzy polymer microgels by external triggers, such as temperature or pH, provides a unique mechanism for controlling the porosity and size of colloidal particles on the nanoscale. As a consequence, these smart microgel particles are being considered for applications ranging from viscosity modifiers and sensing to drug delivery and as models for the glass and the jamming transition. Despite their widespread use, little is known about how these soft particles adapt their shape and size under strong mechanical compression.

Parkin functionally interacts with PGC-1α to preserve mitochondria and protect dopaminergic neurons.

To understand the cause of Parkinson's disease (PD), it is important to determine the functional interactions between factors linked to the disease. Parkin is associated with autosomal recessive early-onset PD, and controls the transcription of PGC-1α, a master regulator of mitochondrial biogenesis. These two factors functionally interact to regulate the turnover and quality of mitochondria, by increasing both mitophagic activity and mitochondria biogenesis.

Axonal Localization of Integrins in the CNS Is Neuronal Type and Age Dependent.

The regenerative ability of CNS axons decreases with age, however, this ability remains largely intact in PNS axons throughout adulthood. These differences are likely to correspond with age-related silencing of proteins necessary for axon growth and elongation. In previous studies, it has been shown that reintroduction of the α9 integrin subunit (tenascin-C receptor, α9) that is downregulated in adult CNS can improve neurite outgrowth and sensory axon regeneration after a dorsal rhizotomy or a dorsal column crush spinal cord lesion.

Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents.

The biological effects of urolithins remain poorly characterized, despite wide-spread human exposure via the dietary consumption of their metabolic precursors, the ellagitannins, which are found in the pomegranate fruit, as well as in nuts and berries. We identified urolithin A (UA) as a first-in-class natural compound that induces mitophagy both in vitro and in vivo following oral consumption. In C.

A subcutaneous cellular implant for passive immunization against amyloid-β reduces brain amyloid and tau pathologies.

Passive immunization against misfolded toxic proteins is a promising approach to treat neurodegenerative disorders. For effective immunotherapy against Alzheimer's disease, recent clinical data indicate that monoclonal antibodies directed against the amyloid-β peptide should be administered before the onset of symptoms associated with irreversible brain damage. It is therefore critical to develop technologies for continuous antibody delivery applicable to disease prevention.

Spinal cord stimulation improves forelimb use in an alpha-synuclein animal model of Parkinson's disease.

Neuromodulation by spinal cord stimulation has been proposed as a symptomatic treatment for Parkinson's disease. We tested the chronic effects of spinal cord stimulation in a progressive model of Parkinson's based on overexpression of alpha-synuclein in the substantia nigra. Adult Sprague Dawley rats received unilateral injections of adeno-associated virus serotype 6 (AAV6) in the substantia nigra to express alpha-synuclein.

In Vivo Evidence for a Lactate Gradient from Astrocytes to Neurons.

Investigating lactate dynamics in brain tissue is challenging, partly because in vivo data at cellular resolution are not available. We monitored lactate in cortical astrocytes and neurons of mice using the genetically encoded FRET sensor Laconic in combination with two-photon microscopy. An intravenous lactate injection rapidly increased the Laconic signal in both astrocytes and neurons, demonstrating high lactate permeability across tissue.