Perineural injections of incobotulinumtoxin-A for diabetic neuropathic pain of the lower extremities: protocol for a phase II, single-centre, double-blind, randomised, placebo-controlled trial (the PINBOT study).

INTRODUCTION: Diabetic neuropathic pain (DNP) is a debilitating complication affecting 15-20% of people with diabetes and is a predictor of depression, poor sleep and decreased quality of life. Current pharmacological treatments are often insufficient and have significant side-effects. Subcutaneous or intradermal botulinumtoxin-A (BonT-A) is an effective and safe treatment for neuropathic pain but is limited by the need to cover the entire affected area with injections. For large cutaneous areas, infiltration of the sensory nerve supply with BonT-A could provide similar effects, with a single injection. We aim to investigate the safety, efficacy, and effects on quality of life, physical activity, depressive symptoms and activities of daily living of perineural injections of BonT-A in patients with DNP of both lower extremities. METHODS: This study is a double-blind, randomised, placebo-controlled clinical trial. 80 participants with moderate to severe DNP of both legs will be randomised 1:1 to receive injections of either 100 units incobotulinumtoxin-A or a saline placebo around each distal sciatic nerve for two cycles of 12 weeks. Average daily pain scores will be recorded once a day from 1 week prior to the first treatment and through the entire study period. Primary outcomes are differences between groups in daily and weekly mean pain scores. Secondary outcomes are levels of physical activity, depression scores, health-related quality of life, activities of daily living, sensory profiles and motor function, recorded at baseline, 4, 12, 16 and 24 weeks. The use of rescue medication and adverse events will be recorded throughout the study period. ETHICS AND DISSEMINATION: The study is approved by the Danish Committee on Health Research Ethics and the Danish Medicines Agency. EU-Clinical Trial Information System (EU: 2022-500727-68-01), clinicaltrials.gov (ID: NCT05623111). Results will be published in peer-reviewed journals in open-access formats and data made available in anonymised form. TRIAL REGISTRATION NUMBER: NCT05623111.

Self-Assembly of Polymer-Modified FePt Magnetic Nanoparticles and Block Copolymers.

The fabrication of nanocomposites containing magnetic nanoparticles is gaining interest as a model for application in small electronic devices. The self-assembly of block copolymers (BCPs) makes these materials ideal for use as a soft matrix to support the structural ordering of the nanoparticles. In this work, a high-molecular-weight polystyrene-b-poly(methyl methacrylate) block copolymer (PS-b-PMMA) was synthesized through anionic polymerization. The influence of the addition of different ratios of PMMA-coated FePt nanoparticles (NPs) on the self-assembled morphology was investigated using transmission electron microscopy (TEM) and small-angle X-ray scattering (SAXS). The self-assembly of the NPs inside the PMMA phase at low particle concentrations was analyzed statistically, and the negative effect of higher particle ratios on the lamellar BCP morphology became visible. The placement of the NPs inside the PMMA phase was also compared to theoretical descriptions. The magnetic addressability of the FePt nanoparticles inside the nanocomposite films was finally analyzed using bimodal magnetic force microscopy and proved the magnetic nature of the nanoparticles inside the microphase-separated BCP films.

Embedding Photoacids into Polymer Opal Structures: Synergistic Effects on Optical and Stimuli-Responsive Features.

Opal films with their vivid structural colors represent a field of tremendous interest and obtained materials offer the possibility for many applications, such as optical sensors or anti-counterfeiting materials. A convenient method for the generation of opal structures relies on the tailored design of core-interlayer-shell (CIS) particles. Within the present study, elastomeric opal films were combined with stimuli-responsive photoacids to further influence the optical properties of structurally colored materials. Starting from cross-linked polystyrene (PS) core particles featuring a hydroxy-rich and polar soft shell, opal films were prepared by application of the melt-shear organization technique. The photoacid tris(2,2,2-trifluoroethyl) 8-hydroxypyrene-1,3,6-trisulfonate (TFEHTS) could be conveniently incorporated during freeze-drying the particle dispersion and prior to the melt-shear organization. Furthermore, the polar opal matrix featuring hydroxylic moieties enabled excited-state proton transfer (ESPT), which is proved by spectroscopic evaluation. Finally, the influence of the photoacid on the optical properties of the 3-dimensional colloidal crystals were investigated within different experimental conditions. The angle dependence of the emission spectra unambiguously shows the selective suppression of the photoacid's fluorescence in its deprotonated state.

Pathogenesis of and management strategies for postoperative delirium after hip fracture: a review.

BACKGROUND: Postoperative delirium is a frequent and serious complication in elderly patients following operation for hip fracture, leading to an increased risk of complications. The pathophysiological mechanisms are unresolved, but probably multifactorial. The purpose of this review is to summarize current knowledge about the pathogenesis of postoperative delirium with a view to finding strategies for prevention and management. METHOD: We conducted an Internet search through the Medline database (1966-March 2003) and supplemented it with a manual search. We included 12 studies which specifically discussed pathogenic factors or interventions against postoperative delirium following operation for hip fracture. RESULTS: 1,823 patients were included with an average incidence of delirium of 35%. We concentrated on pre-, intra-, and postoperative risk factors. Only advanced age and dementia met our fixed criterion of "strong evidence" for a significant association. Hence, from the studies that we reviewed we were unable to find intraoperative or postoperative factors with "strong evidence" for a significant association with delirium. INTERPRETATION: Postoperative delirium is a serious complication. The pathophysiology leading to delirium after hip fracture surgery still remains to be clarified and no single drug or surgical regimen has proven to be preventive. This calls for more detailed investigations of the differential role of different pathogenic mechanisms, as well as an aggressive multimodal approach to enhance recovery and reduce morbidity, as has proven to be successful in a variety of elective surgical procedures. Such multimodal interventional studies represent a major task for orthopedic departments in collaboration with anesthesiologists, geriatricians, physiotherapists and nursing staff.