Combined PTEN Knockdown and Local Insulin in Chronic Experimental Diabetic Neuropathy.

Unlabelled: Diabetic polyneuropathy (DPN) renders progressive sensory neurodegeneration linked to hyperglycemia and its associated metabolopathy. We hypothesized that there may be additive impacts of direct insulin signaling, independent of glycemia and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) knockdown on neuropathy. Our targets for combined interventions were neurons and Schwann cells (SCs) in vitro and chronic type 1 DPN in mice.

Using early health economic modeling to inform medical innovation development: a soft robotic sock in poststroke patients in Singapore.

Objectives: Based on a real-world collaboration with innovators in applying early health economic modeling, we aimed to offer practical steps that health technology assessment (HTA) researchers and innovators can follow and promote the usage of early HTA among research and development (R&D) communities.

Methods: The HTA researcher was approached by the innovator to carry out an early HTA ahead of the first clinical trial of the technology, a soft robotic sock for poststroke patients. Early health economic modeling was selected to understand the potential value of the technology and to help uncover the information gap.

In-situ vaccination using dual responsive organelle targeted nanoreactors.

The poor translation of nanomedicines from bench to bedside can be attributed to (i) lack of a delivery system with precise drug compositions with no batch-to-batch variations, (ii) off-target or undesirable release of payload, and (iii) lack of a method to monitor the fate of the specific drug of interest, which often has to be modified with a fluorescent tag or replaced with a model drug which can be tracked. To overcome these translation hurdles, we developed dual responsive organelle targeted nanoreactors (DRONEs) with precise drug composition, site specific payload release and which enable accurate in-vivo monitoring. DRONEs consist of a polyprodrug inner core composed of a dual responsive backbone containing a photosensitizer (Protoporphyrin IX) grafted with functionalized polyethylene glycol (PEG) outer shell to prolong blood circulation and a tumour homing pro-apoptotic peptide (CGKRK[KLAKLAK]) (THP).

Insulin enhances neurite extension and myelination of diabetic neuropathy neurons.

Background: The authors established an in vitro model of diabetic neuropathy based on the culture system of primary neurons and Schwann cells (SCs) to mimic similar symptoms observed in in vivo models of this complication, such as impaired neurite extension and impaired myelination. The model was then utilized to investigate the effects of insulin on enhancing neurite extension and myelination of diabetic neurons.

Methods: SCs and primary neurons were cultured under conditions mimicking hyperglycemia prepared by adding glucose to the basal culture medium.

Biodegradable rare earth fluorochloride nanocrystals for phototheranostics.

Rare earth (RE) doped inorganic nanocrystals have been demonstrated as efficient contrast agents for deep tissue shortwave-infrared (SWIR) imaging with high sensitivities leading to potential early detection of tumors. However, a potential concern is the unknown long-term toxicity and incompatibility of inorganic nanocrystals. In this work, biodegradable rare earth nanocrystals of Nd doped SrFCl coated with polydopamine (SrFCl:Nd@PDA) were designed.

Texture Discrimination with a Soft Biomimetic Finger Using a Flexible Neuromorphic Tactile Sensor Array That Provides Sensory Feedback.

The compliant nature of soft fingers allows for safe and dexterous manipulation of objects by humans in an unstructured environment. A soft prosthetic finger design with tactile sensing capabilities for texture discrimination and subsequent sensory stimulation has the potential to create a more natural experience for an amputee. In this work, a pneumatically actuated soft biomimetic finger is integrated with a textile neuromorphic tactile sensor array for a texture discrimination task.

Unveiling Stimulation Secrets of Electrical Excitation of Neural Tissue Using a Circuit Probability Theory.

Electrical excitation of neural tissue has wide applications, but how electrical stimulation interacts with neural tissue remains to be elucidated. Here, we propose a new theory, named the Circuit-Probability theory, to reveal how this physical interaction happen. The relation between the electrical stimulation input and the neural response can be theoretically calculated.

Mechanism and Applications of Electrical Stimulation Disturbance on Motoneuron Excitability Studied Using Flexible Intramuscular Electrode.

Wearable and implantable devices are irreplaceable components in the modern healthcare system. Electrical stimulation on the nervous and neuromuscular system, as a way of therapeutic interventions, has been widely applied to people with neurological disorders and neuromuscular disabilities. The conventional way to study electrical stimulation on the skeletal muscle employs single-channel wire electrodes, which have limited capability to explore the complicated motoneuron distribution in muscle tissue.

Enhanced penetration of pro-apoptotic and anti-angiogenic micellar nanoprobe in 3D multicellular spheroids for chemophototherapy.

Light irradiation is considered an ideal non-invasive stimulus that enables precise tumour treatment with flexible, facile, and spatiotemporal control. Photodynamic therapy (PDT) is an important clinically relevant therapeutic modality that has proven to compensate for the reduced therapeutic efficacy of conventional chemotherapy. However, oxygen consumption during PDT can result in an inadequate oxygen supply which reduces photodynamic efficacy.

A Neuroanatomically Grounded Optimal Control Model of the Compensatory Eye Movement System in Mice.

We present a working model of the compensatory eye movement system in mice. We challenge the model with a data set of eye movements in mice ( =34) recorded in 4 different sinusoidal stimulus conditions with 36 different combinations of frequency (0.1-3.

Megavoltage Radiosensitization of Gold Nanoparticles on a Glioblastoma Cancer Cell Line Using a Clinical Platform.

Gold nanoparticles (GNPs) have demonstrated significant dose enhancement with kilovoltage (kV) X-rays; however, recent studies have shown inconsistent findings with megavoltage (MV) X-rays. We propose to evaluate the radiosensitization effect on U87 glioblastoma (GBM) cells in the presence of 42 nm GNPs and irradiated with a clinical 6 MV photon beam. Cytotoxicity and radiosensitization were measured using MTS and clonogenic cellular radiation sensitivity assays, respectively.

Screen Printed Passives and Interconnects on Bio-Degradable Medical Hydrocolloid Dressing for Wearable Sensors.

The healthcare system is undergoing a noticeable transformation from a reactive, post-disease treatment to a preventive, predictive continuous healthcare. The key enabler for such a system is a pervasive wearable platform. Several technologies have been suggested and implemented as a wearable platform, but these technologies either lack reliability, manufacturing practicability or pervasiveness.

Soft Robotic Pad Maturing for Practical Applications.

Soft pneumatic actuators (SPAs) have existed for many years as one of the mainstream actuators. Along with the rise of soft robotics, the development in SPA designs in recent years was especially rapid and diverse. Particularly with innovations in SPA fabrication, there is an increasing variety of SPAs with different air chamber designs, varied scales, and distinctive motion modalities.

Expanding the Toolbox of Upconversion Nanoparticles for In Vivo Optogenetics and Neuromodulation.

Optogenetics is an optical technique that exploits visible light for selective neuromodulation with spatio-temporal precision. Despite enormous effort, the effective stimulation of targeted neurons, which are located in deeper structures of the nervous system, by visible light, remains a technical challenge. Compared to visible light, near-infrared illumination offers a higher depth of tissue penetration owing to a lower degree of light attenuation.

Engineering the Infrared Luminescence and Photothermal Properties of Double-Shelled Rare-Earth-Doped Nanoparticles for Biomedical Applications.

The nascent field of theranostics, which couples targeted therapy with diagnostics, has catalyzed efforts toward improved nanoprobe designs that facilitate both localized treatment and diagnostic imaging. Rare-earth-doped nanoparticles (RENPs) have emerged as a leading candidate for theranostics because of their versatile synthesis and modification chemistries, photostability, and relative safety. Furthermore, their bright, tunable fluorescence using near-infrared (NIR) excitation enables multispectral imaging with high signal-to-background ratios.

Investigation of Low-Current Direct Stimulation for Rehabilitation Treatment Related to Muscle Function Loss Using Self-Powered TENG System.

Muscle function loss is characterized as abnormal or completely lost muscle capabilities, and it can result from neurological disorders or nerve injuries. The currently available clinical treatment is to electrically stimulate the diseased muscles. Here, a self-powered system of a stacked-layer triboelectric nanogenerator (TENG) and a multiple-channel epimysial electrode to directly stimulate muscles is demonstrated.

Diabetic neuropathy research: from mouse models to targets for treatment.

Diabetic neuropathy is one of the most serious complications of diabetes, and its increase shows no sign of stopping. Furthermore, current clinical treatments do not yet approach the best effectiveness. Thus, the development of better strategies for treating diabetic neuropathy is an urgent matter.

Environmental Specification of Pluripotent Stem Cell Derived Endothelial Cells Toward Arterial and Venous Subtypes.

Endothelial cells (ECs) are required for a multitude of cardiovascular clinical applications, such as revascularization of ischemic tissues or endothelialization of tissue engineered grafts. Patient derived primary ECs are limited in number, have donor variabilities and their phenotypes and functions can deteriorate over time. This necessitates the exploration of alternative EC sources.

Fully automated leg tracking of Drosophila neurodegeneration models reveals distinct conserved movement signatures.

Some neurodegenerative diseases, like Parkinsons Disease (PD) and Spinocerebellar ataxia 3 (SCA3), are associated with distinct, altered gait and tremor movements that are reflective of the underlying disease etiology. Drosophila melanogaster models of neurodegeneration have illuminated our understanding of the molecular mechanisms of disease. However, it is unknown whether specific gait and tremor dysfunctions also occur in fly disease mutants.

Hydrogel Actuators and Sensors for Biomedical Soft Robots: Brief Overview with Impending Challenges.

There are numerous developments taking place in the field of biorobotics, and one such recent breakthrough is the implementation of soft robots-a pathway to mimic nature's organic parts for research purposes and in minimally invasive surgeries as a result of their shape-morphing and adaptable features. Hydrogels (biocompatible, biodegradable materials that are used in designing soft robots and sensor integration), have come into demand because of their beneficial properties, such as high water content, flexibility, and multi-faceted advantages particularly in targeted drug delivery, surgery and biorobotics. We illustrate in this review article the different types of biomedical sensors and actuators for which a hydrogel acts as an active primary material, and we elucidate their limitations and the future scope of this material in the nexus of similar biomedical avenues.

Effect of a Soft Robotic Sock Device on Lower Extremity Rehabilitation Following Stroke: A Preliminary Clinical Study With Focus on Deep Vein Thrombosis Prevention.

Background And Objective: Immobility of the lower extremity due to medical conditions such as stroke can lead to medical complications such as deep vein thrombosis or ankle contracture, and thereafter prolonged recovery process of the patients. In this preliminary clinical study, we aimed to examine the effect of a novel soft robotic sock device, capable of providing assisted ankle exercise, in improving blood flow in the lower limb to prevent the complication of strokes such as deep vein thrombosis and joint contracture.

Methods: Stroke patients were recruited ( = 17) to compare patients using the conventional pneumatic compression device with our robotic sock device on separate days.

Global signal regression strengthens association between resting-state functional connectivity and behavior.

Global signal regression (GSR) is one of the most debated preprocessing strategies for resting-state functional MRI. GSR effectively removes global artifacts driven by motion and respiration, but also discards globally distributed neural information and introduces negative correlations between certain brain regions. The vast majority of previous studies have focused on the effectiveness of GSR in removing imaging artifacts, as well as its potential biases.

Minimal clinically important difference of the EORTC QLQ-CIPN20 for worsening peripheral neuropathy in patients receiving neurotoxic chemotherapy.

Context/objectives: This is the first study to determine the minimal clinically important difference (MCID) of the European Organisation of Research and Treatment of Cancer Quality of Life Questionnaire-CIPN twenty-item scale (EORTC QLQ-CIPN20), a validated instrument designed to elicit cancer patients' experience of symptoms and functional limitations related to chemotherapy-induced peripheral neuropathy.

Methods: Cancer patients receiving neurotoxic chemotherapy completed EORTC QLQ-CIPN20 and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity [FACT/GOG-NTX] at baseline, second cycle of chemotherapy (T2, n = 287), and 12 months after chemotherapy (T3, n = 191). Anchor-based approach used the validated FACT/GOG-NTX neurotoxicity (Ntx) subscale to identify optimal MCID cutoff for deterioration.

Shape Programming Using Triangular and Rectangular Soft Robot Primitives.

This paper presents fabric-based soft robotic modules with primitive morphologies, which are analogous to basic geometrical polygons-trilateral and quadrilateral. The two modules are the inflatable beam (IB) and fabric-based rotary actuator (FRA). The FRA module is designed with origami-inspired V-shaped pleats, which creates a trilateral outline.