Optical coherence tomography in secondary progressive multiple sclerosis: cross-sectional and longitudinal exploratory analysis from the MS-SMART randomised controlled trial.

Background: Optical coherence tomography (OCT) inner retinal metrics reflect neurodegeneration in multiple sclerosis (MS). We explored OCT measures as biomarkers of disease severity in secondary progressive MS (SPMS).

Methods: We investigated people with SPMS from the Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial OCT substudy, analysing brain MRIs, clinical assessments and OCT at baseline and 96 weeks.

Investigating the relationship between thalamic iron concentration and disease severity in secondary progressive multiple sclerosis using quantitative susceptibility mapping: Cross-sectional analysis from the MS-STAT2 randomised controlled trial.

Background: Deep grey matter pathology is a key driver of disability worsening in people with multiple sclerosis. Quantitative susceptibility mapping (QSM) is an advanced magnetic resonance imaging (MRI) technique which quantifies local magnetic susceptibility from variations in phase produced by changes in the local magnetic field. In the deep grey matter, susceptibility has previously been validated against tissue iron concentration.

A numerical investigation of stress, strain, and bone density changes due to bone remodelling in the talus bone following total ankle arthroplasty.

Total ankle arthroplasty is the gold standard surgical treatment for severe ankle arthritis and fracture. However, revision surgeries due to the failure of the ankle implant are a serious concern. Extreme bone density loss due to bone remodelling is one of the main reasons for implant loosening, with aseptic loosening of the talar component being one of the primary reasons for total ankle arthroplasty revisions.

Finite element analysis of vertebroplasty in the osteoporotic T11-L1 vertebral body: Effects of bone cement formulation.

Vertebral compression fractures are one of the most severe clinical consequences of osteoporosis and the most common fragility fracture afflicting 570 and 1070 out of 100,000 men and women worldwide, respectively. Vertebroplasty (VP), a minimally invasive surgical procedure that involves the percutaneous injection of bone cement, is one of the most efficacious methods to stabilise osteoporotic vertebral compression fractures. However, postoperative fracture has been observed in up to 30% of patients following VP.

Vitamin D did not reduce multiple sclerosis disease activity after a clinically isolated syndrome.

Low serum levels of 25-hydroxyvitamin D [25(OH)D] and low sunlight exposure are known risk factors for the development of multiple sclerosis. Add-on vitamin D supplementation trials in established multiple sclerosis have been inconclusive. The effects of vitamin D supplementation to prevent multiple sclerosis is unknown.

Treatment reduces the incidence of newly appearing multiple sclerosis lesions evolving into chronic active, slowly expanding lesions: A retrospective analysis.

Background And Purpose: Newly appearing lesions in multiple sclerosis (MS) may evolve into chronically active, slowly expanding lesions (SELs), leading to sustained disability progression. The aim of this study was to evaluate the incidence of newly appearing lesions developing into SELs, and their correlation to clinical evolution and treatment.

Methods: A retrospective analysis of a fingolimod trial in primary progressive MS (PPMS; INFORMS, NCT00731692) was undertaken.

Longitudinal Metabolite Changes in Progressive Multiple Sclerosis: A Study of 3 Potential Neuroprotective Treatments.

Background: H-magnetic resonance spectroscopy (H-MRS) may provide a direct index for the testing of medicines for neuroprotection and drug mechanisms in multiple sclerosis (MS) through measures of total N-acetyl-aspartate (tNAA), total creatine (tCr), myo-inositol (mIns), total-choline (tCho), and glutamate + glutamine (Glx). Neurometabolites may be associated with clinical disability with evidence that baseline neuroaxonal integrity is associated with upper limb function and processing speed in secondary progressive MS (SPMS).

Purpose: To assess the effect on neurometabolites from three candidate drugs after 96-weeks as seen by H-MRS and their association with clinical disability in SPMS.

Excision of whole intact mouse brain.

Mechanical characterization experiments of brain tissue are performed to understand the mechanical behavior of brain tissue during normal physiology and pathophysiological processes including traumatic brain injury. Normal, healthy, undamaged, unfixed brain tissue specimens are required for these mechanical characterization experiments to ensure the properties being measured are not from damaged/diseased tissue which may lead to inaccurate and unreliable results regarding the mechanical behavior of healthy undamaged brain tissue. The process of excising brain tissue from the cranial vault of mouse cadavers can induce lacerations in the tissue that may affect its mechanical behavior.

Cardiovascular risk factors in secondary progressive multiple sclerosis: A cross-sectional analysis from the MS-STAT2 randomized controlled trial.

Background And Purpose: There is increasing evidence that cardiovascular risk (CVR) contributes to disability progression in multiple sclerosis (MS). CVR is particularly prevalent in secondary progressive MS (SPMS) and can be quantified through validated composite CVR scores. The aim was to examine the cross-sectional relationships between excess modifiable CVR, whole and regional brain atrophy on magnetic resonance imaging, and disability in patients with SPMS.

Effect of Uniaxial Compression Frequency on Osteogenic Cell Responses in Dynamic 3D Cultures.

The application of mechanical stimulation on bone tissue engineering constructs aims to mimic the native dynamic nature of bone. Although many attempts have been made to evaluate the effect of applied mechanical stimuli on osteogenic differentiation, the conditions that govern this process have not yet been fully explored. In this study, pre-osteoblastic cells were seeded on PLLA/PCL/PHBV (90/5/5 wt.

A finite element model of contusion spinal cord injury in rodents.

Traumatic spinal cord injuries result from high impact forces acting on the spine and are proceeded by an extensive secondary inflammatory response resulting in motor, sensory, and autonomic dysfunction. Experimental in vivo traumatic spinal cord injuries in rodents using a contusion model have been extremely useful in elucidating the underlying pathophysiology of these injuries. However, the relationship between the pathophysiology and the biomechanical factors is still not well understood.

A computational analysis of a novel therapeutic approach combining an advanced medicinal therapeutic device and a fracture fixation assembly for the treatment of osteoporotic fractures: Effects of physiological loading, interface conditions, and fracture fixation materials.

The occurrence of periprosthetic femoral fractures (PFF) has increased in people with osteoporosis due to decreased bone density, poor bone quality, and stress shielding from prosthetic implants. PFF treatment in the elderly is a genuine concern for orthopaedic surgeons as no effective solution currently exists. Therefore, the goal of this study was to determine whether the design of a novel advanced medicinal therapeutic device (AMTD) manufactured from a polymeric blend in combination with a fracture fixation plate in the femur is capable of withstanding physiological loads without failure during the bone regenerative process.

S-duct flow distortion with non-uniform inlet conditions.

Convoluted aero-engine intakes are often required to enable closer integration between engine and airframe. Although the majority of previous research focused on the distortion of S-duct intakes with undistorted inlet conditions, there is a need to investigate the impact of more challenging inlet conditions at which the intake duct is expected to operate. The impact of inlet vortices and total pressure profiles on the inherent unsteady flow distortion of an S-duct intake was assessed with stereo particle image velocimetry.

Remyelination varies between and within lesions in multiple sclerosis following bexarotene.

Objective: In multiple sclerosis chronic demyelination is associated with axonal loss, and ultimately contributes to irreversible progressive disability. Enhancing remyelination may slow, or even reverse, disability. We recently trialled bexarotene versus placebo in 49 people with multiple sclerosis.

Association of Slowly Expanding Lesions on MRI With Disability in People With Secondary Progressive Multiple Sclerosis.

Background And Objective: To explore the relationship between slowly expanding lesions (SELs) on MRI and disability in secondary progressive multiple sclerosis (SPMS).

Methods: We retrospectively studied 345 patients with SPMS enrolled in the MS-SMART trial. They underwent brain MRI at baseline and at 24 and 96 weeks.

Safety and efficacy of bexarotene in patients with relapsing-remitting multiple sclerosis (CCMR One): a randomised, double-blind, placebo-controlled, parallel-group, phase 2a study.

Background: Progressive disability in multiple sclerosis occurs because CNS axons degenerate as a late consequence of demyelination. In animals, retinoic acid receptor RXR-gamma agonists promote remyelination. We aimed to assess the safety and efficacy of a non-selective retinoid X receptor agonist in promoting remyelination in people with multiple sclerosis.

Efficacy and safety of temelimab in multiple sclerosis: Results of a randomized phase 2b and extension study.

Background: The envelope protein of human endogenous retrovirus W (HERV-W-Env) is expressed by macrophages and microglia, mediating axonal damage in chronic active MS lesions.

Objective And Methods: This phase 2, double-blind, 48-week trial in relapsing-remitting MS with 48-week extension phase assessed the efficacy and safety of temelimab; a monoclonal antibody neutralizing HERV-W-Env. The primary endpoint was the reduction of cumulative gadolinium-enhancing T1-lesions in brain magnetic resonance imaging (MRI) scans at week 24.

Mechanical Characterization and Modeling of the Porcine Cerebral Meninges.

The cerebral meninges, made up of the , and , is a tri-layer membrane that surrounds the brain and the spinal cord and has an important function in protecting the brain from injury. Understanding its mechanical behavior is important to ensure the accuracy of finite element (FE) head model simulations which are commonly used in the study of traumatic brain injury (TBI). Mechanical characterization of freshly excised porcine (DAM) was achieved using uniaxial tensile testing and bulge inflation testing, highlighting the dependency of the identified parameters on the testing method.

Efficacy of three neuroprotective drugs in secondary progressive multiple sclerosis (MS-SMART): a phase 2b, multiarm, double-blind, randomised placebo-controlled trial.

Background: Neurodegeneration is the pathological substrate that causes major disability in secondary progressive multiple sclerosis. A synthesis of preclinical and clinical research identified three neuroprotective drugs acting on different axonal pathobiologies. We aimed to test the efficacy of these drugs in an efficient manner with respect to time, cost, and patient resource.

Sex- and age-specific mechanical properties of liver tissue under dynamic loading conditions.

The liver is the most commonly injured abdominal organ following either blunt or penetrating impact. Current mechanical properties available in the literature are typically only measured at low strain rates, low strains, or use linear viscoelastic models. There is also a dearth of high-rate, large strain, viscoelastic data available for liver tissue which are required to model the deformation of the liver during high-rate impacts.

Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial (MS-SMART): a multiarm phase IIb randomised, double-blind, placebo-controlled clinical trial comparing the efficacy of three neuroprotective drugs in secondary progressive multiple sclerosis.

Introduction: The major unmet need in multiple sclerosis (MS) is for neuroprotective therapies that can slow (or ideally stop) the rate of disease progression. The UK MS Society Clinical Trials Network (CTN) was initiated in 2007 with the purpose of developing a national, efficient, multiarm trial of repurposed drugs. Key underpinning work was commissioned by the CTN to inform the design, outcome selection and drug choice including animal models and a systematic review.

Mechanical characterisation of brain tissue up to 35% strain at 1, 10, and 100/s using a custom-built micro-indentation apparatus.

Understanding the behaviour of soft tissues under large strains and high loading rates is crucial in the field of biomechanics in order to investigate tissue behaviour during pathological processes such as traumatic brain injury (TBI). It is, therefore, necessary to characterise the mechanical properties of such tissues under large strain and high strain rates that are similar to those experienced during injury. However, there is a dearth of large strain and high rate mechanical properties for brain tissue.