An open-label feasibility trial of transdermal cannabidiol for hand osteoarthritis.

Hand osteoarthritis (OA) is an irreversible degenerative condition causing chronic pain and impaired functionality. Existing treatment options are often inadequate. Cannabidiol (CBD) has demonstrated analgesic and anti-inflammatory effects in preclinical models of arthritis.

Comparison of strength profile representations using musculoskeletal models and their applications in robotics.

Musculoskeletal models provide an approach towards simulating the ability of the human body in a variety of human-robot applications. A promising use for musculoskeletal models is to model the physical capabilities of the human body, for example, estimating the strength at the hand. Several methods of modelling and representing human strength with musculoskeletal models have been used in ergonomic analysis, human-robot interaction and robotic assistance.

Effects of Different Orientation Angle, Size, Surface Roughness, and Heat Curing on Mechanical Behavior of 3D Printed Cement Mortar With/Without Glass Fiber in Powder-Based 3DP.

Powder-based (inkjet) three-dimensional printing (3DP) technology presents great promise in the construction industry. The capacity to build complex geometries is one of the most appealing features of the process without formwork. This article focuses on the vital aspect of using a modified powder (CP) instead of commercial powder (ZP 151).

Real-time Estimation of the Strength Capacity of the Upper Limb for Physical Human-Robot Collaboration.

In physical Human-Robot Collaboration (pHRC), having an estimate of the operator's strength capacity can help implement control strategies. Currently, the trend is to integrate devices that can measure physiological signals. This is not always a viable option, especially for highly dynamic tasks.

Preliminary Validation of Upper Limb Musculoskeletal Model using Static Optimization.

Musculoskeletal models are powerful analogues to simulate human motion through kinematic and dynamic analysis. When coupled with feature-rich software, musculoskeletal models form an attractive platform for the integration of machine learning for human motion analysis. Performing realistic simulations using these models provide an avenue to overcome constraints when collecting real-world data sets.

Approaches for Efficiently Detecting Frontier Cells in Robotics Exploration.

Many robot exploration algorithms that are used to explore office, home, or outdoor environments, rely on the concept of frontier cells. Frontier cells define the border between known and unknown space. Frontier-based exploration is the process of repeatedly detecting frontiers and moving towards them, until there are no more frontiers and therefore no more unknown regions.

Fitts' law in the presence of interface inertia.

Collaborative robots are advancing the healthcare frontier, in applications such as rehabilitation and physical therapy. Effective physical collaboration in human-robot systems require an understanding of partner intent and capability. Various modalities exist to convey such information between human agents, however, natural interactions between humans and robots are difficult to characterise and achieve.

Differential Effects of TPM, A Phosphorylated Tocopherol Mixture, and Other Tocopherol Derivatives as Excipients for Enhancing the Solubilization of Co-Enzyme Q10 as a Lipophilic Drug During Digestion of Lipid- Based Formulations.

Background: The tocopherol-based excipient, TPM, when incorporated into a medium-chain triglyceride (MCT)-based lipid formulation, has been previously shown to improve the solubilization of Coenzyme Q10 (CoQ10) during in vitro digestion which is strongly correlated with enhanced exposure in vivo.

Methods: The current study aimed to gain further understanding of the MCT + TPM co-formulation, by assessing the formulation performance under fasted and fed in vitro digestion conditions, with different drug and excipient loading levels. Natural and synthetic-derived TPM were equivalent, and with d-α- tocopherol polyethylene glycol 1000 succinate (TPGS) outperformed other derivatives in enhancing the solubilisation of CoQ10 during digestion.

A Study into the Effect of Different Nozzles Shapes and Fibre-Reinforcement in 3D Printed Mortar.

Recently, 3D printing has become one of the most popular additive manufacturing technologies. This technology has been utilised to prototype trial and produced components for various applications, such as fashion, food, automotive, medical, and construction. In recent years, automation also has become increasingly prevalent in the construction field.

Changes in Bioavailability of Omega-3 (DHA) through Alpha-Tocopheryl Phosphate Mixture (TPM) after Oral Administration in Rats.

Benefits of Omega-3 Docosahexaenoic acid (DHA) supplements are hindered by their poor solubility and bioavailability. This study investigated the bioavailability of various formulations of Omega-3 and tocopheryl phosphate mixture (TPM), following oral administration in rats, and assessed whether TPM could improve the oral absorption of DHA. The rats were administered with a high (265.

A Phase I study of the pharmacokinetics, safety and tolerability of a novel tocopheryl phosphate mixture/oxymorphone transdermal patch system.

Aim: Characterize the pharmacokinetic profile and tolerability of two tocopheryl phosphate mixture/oxymorphone patch formulations in healthy subjects, and the active metabolite (6-OH-oxymorphone).

Materials & Methods: Fifteen participants received a single application of oxymorphone patches +/- capsaicin for 72 h and were crossed-over for another 72 h.

Results: Plasma oxymorphone was detected approximately 7 h and 6-OH-oxymorphone after approximately 18-19 h postapplication of both formulations, respectively.

Pharmacokinetics, safety and tolerability of a novel tocopheryl phosphate mixture/oxycodone transdermal patch system: a Phase I study.

Aim: To characterize the pharmacokinetic profile and evaluate the safety and tolerability of a transdermal oxycodone patch containing tocopheryl phosphate mixture (TPM).

Patients & Methods: Eleven healthy subjects received a single application of three TPM/oxycodone patches applied to the torso for 72 h.

Results: Oxycodone was detected 8.

Transdermal oxycodone patch for the treatment of postherpetic neuralgia: a randomized, double-blind, controlled trial.

Aim: To evaluate the efficacy, systemic exposure, safety and tolerability of a transdermal oxycodone patch containing tocopheryl phosphate mixture (TPM) in patients with postherpetic neuralgia (PHN).

Patients & Methods: The study was a Phase IIa, multicenter, randomized, double-blind, vehicle-controlled crossover study.

Results: While the TPM/oxycodone patch did not significantly improve 'average' Numeric Pain Rating Scale scores versus vehicle patch, patients reporting high levels of paresthesia (n = 9) showed a trend toward improved pain reduction.

Tocopheryl phosphate mixture (TPM) as a novel lipid-based transdermal drug delivery carrier: formulation and evaluation.

Transdermal drug delivery is a useful route of administration that avoids first-pass metabolism and more invasive delivery options. However, many drugs require enhancers to enable sufficient drug absorption to reach therapeutic effect. Alpha-tocopheryl phosphate (TP) and di-alpha-tocopheryl phosphate (T2P) are two phosphorylated forms of vitamin E which form tocopheryl phosphate mixture (TPM) when combined, and have been proposed to enhance the dermal and transdermal delivery of actives of interest.

Topical application of a novel oxycodone gel formulation (tocopheryl phosphate mixture) in a rat model of peripheral inflammatory pain produces localized pain relief without significant systemic exposure.

This study was designed to assess the analgesic efficacy and systemic exposure of oxycodone administered topically in a novel tocopheryl phosphate mixture (TPM) gel formulation, to the inflamed hindpaws in a rat model of inflammatory pain. Unilateral hindpaw inflammation was induced in male Sprague-Dawley rats by intraplantar (i.pl.

Alpha-tocopheryl phosphate: a novel, natural form of vitamin E.

We have detected alpha-tocopheryl phosphate in biological tissues including liver and adipose tissue, as well as in a variety of foods, suggesting a ubiquitous presence in animal and plant tissue. Alpha-tocopheryl phosphate is a water-soluble molecule that is resistant to both acid and alkaline hydrolysis, making it undetectable using standard assays for vitamin E. A new method was therefore developed to allow the extraction of both alpha-tocopheryl phosphate and alpha-tocopherol from a single specimen.

F1F0-ATP synthase complex interactions in vivo can occur in the absence of the dimer specific subunit e.

Evidence suggests membrane bound F(1)F(0)-ATPase complexes form stable associations such that dimers can be retrieved from detergent lysates of mitochondria isolated from a range of sources including algae, higher plants, yeast and bovine heart, and plant chloroplasts. The physiological relevance of these interactions is not clear but may be connected with the formation and structure of mitochondrial cristae. We sought to demonstrate, in vivo, the association of F(1)F(0)-ATPases in yeast cells co-expressing two b subunits each fused at its C-terminus to a GFP variant appropriate for fluorescence resonance energy transfer (FRET; BFP as the donor and GFP as the acceptor fluorophore).

Cross-linking ATP synthase complexes in vivo eliminates mitochondrial cristae.

We have used the tetrameric nature of the fluorescent protein DsRed to cross-link F(1)F(O)-ATPase complexes incorporating a subunit gamma-DsRed fusion protein in vivo. Cells expressing such a fusion protein have impaired growth relative to control cells. Strikingly, fluorescence microscopy of these cells revealed aberrant mitochondrial morphology.

FRET reveals changes in the F1-stator stalk interaction during activity of F1F0-ATP synthase.

A stator is proposed as necessary to prevent futile rotation of the F(1) catalytic sector of mitochondrial ATP synthase (mtATPase) during periods of ATP synthesis or ATP hydrolysis. Although the second stalk of mtATPase is generally believed to fulfil the role of a stator capable of withstanding the stress produced by rotation of the central rotor, there is little evidence to directly support this view. We show that interaction between two candidate proteins of the second stalk, OSCP and subunit b, fused at their C-termini to GFP variants and assembled into functional mtATPase can be monitored in mitochondria using fluorescence resonance energy transfer (FRET).

An approach for reducing unwanted oligomerisation of DsRed fusion proteins.

Oligomerisation of the red fluorescent protein, DsRed, can interfere with the localisation and function of proteins to which it is fused. We demonstrate an approach that may help to reduce significantly the impact of oligomerisation on the biology of the protein fusion partner. Growth of yeast (Saccharomyces cerevisiae) cells expressing ATP synthase containing subunit gamma-DsRed fusion was compromised relative to control cells.

Subunit gamma-green fluorescent protein fusions are functionally incorporated into mitochondrial F1F0-ATP synthase, arguing against a rigid cap structure at the top of F1.

We have investigated the question of the presence of a cap structure located at the top of the F(1) alpha(3)beta(3) hexamer of the yeast mitochondrial F(1)F(0)-ATP synthase complex. Specifically, we sought to determine whether the putative cap has a rigid structure and occludes the central shaft space formed by the alpha(3)beta(3) hexamer or alternatively whether the cap is more flexible permitting access to the central shaft space under certain conditions. Thus, we sought to establish whether subunit gamma, an essential component of the F(1) central stalk housed within the central shaft space and whose N and C termini would both lie beneath a putative cap, could be fused at its C terminus to green fluorescent protein (GFP) without loss of enzyme function.